MXPA06003892A

MXPA06003892A - 1-amino-2-oxy-substituted tetrahydronaphtalene derivatives, methods for the production thereof, and their use as antiphlogistics

Info

Publication number: MXPA06003892A
Application number: MXPA/A/2006/003892A
Authority: MX
Inventors: Skuballa Werner; Schmees Norbert; Berger Markus; Jaroch Stefan; Rehwinkel Hartmut; Schacke Heike; Baurle Stefan; Krolikiewicz Konrad; Nguyen Duy; Mengel Anne
Original assignee: Schering Aktiengesellschaft
Priority date: 2003-10-08
Filing date: 2006-04-06
Publication date: 2006-12-13

Abstract

The invention relates to polysubstituted tetrahydronaphtalene derivatives of formula (I), to methods for the production thereof, and to their use as antiphlogistics. The substituents are defined in Claim 1.

Description

DERIVATIVES 1-AMINO-2-OXI SUBSTITUTED FROM TETRAHYDRONAPHTHALENE, PROCEDURE FOR PREPARATION AND USE AS ANTI-INFLAMMATORY FIELD OF THE INVENTION The invention relates to derivatives of tetrahydro-naphthalene, with a procedure for its preparation and its use as an anti-inflammatory agent. . BACKGROUND OF THE INVENTION In the state of the art (DE 100 38 639 and W002 / 10143) open chain non-steroidal anti-inflammatories are known. In experiments, these compounds show dissociations between anti-inflammatory effects! and undesired metabolic effects and are superior to non-steroidal glucocorticoids or at least have an equally good effect. However, the selectivity and pharmacokinetic parameters of the compounds of the state of the art still need to be improved. Hence, the object of the present invention has been to create compounds whose selectivity with respect to the other steroid receptors and their pharmacokinetic properties are at least as good or better than those of the compounds of the state of the art. This object is achieved with the compounds of the present invention which are described in the claims.

DETAILED DESCRIPTION OF THE INVENTION The present invention therefore relates to stereoisomers of the general formula (I), where R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C? alkyl group or which can be substituted, a C alco-C? alkoxy group or can be substituted, an alkylthio-C? -C? group, a perfluoroalkyl-Cr-C5 group, a cyano group, a nitro group, or R1 and Rz together are a group selected from the groups -0- (CH2) n -0-, -0- (CH2) n-CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + ?, -N (C-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with ring carbon atoms directly adjacent, or are NR8R9, where R8 and R9 can be independently of each other, hydrogen-C-C5-alkyl or (CO) -alkyl-C? -C5, R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, an alkoxy- (C? -C? 0) group, an alkylthio- (Ci? -Cio) group, a perfluoroalkyl group uilo- (C1-C5), R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -Cl0) that can be substituted, an alkoxy- (C1- C10), R3 is an alkyl-C? -C? 0 group which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a cycloalkyl- (C3-C7) group that can be substituted, a heterocyclyl group that can be substituted, an aryl group that can be substituted, substituted, a mono- or bicyclic heteroaryl group which may be independently substituted by one or more groups selected from (C1-C5) alkyl groups (which may be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups) ), (C 1 -C 5) alkoxy groups, halogen atoms, hydroxy groups, NR 8 R 9 groups, exo ethylene groups, oxygen, which may contain 1-4 nitrogen atoms, and / or 1-2 oxygen atoms and / or 1 -2 sulfur atoms and / or 1-2 keto groups, where this group can be attached at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, an OR10 group or a group O (C0) R10 where R10 means any hydroxy protecting group or a C-C? alkyl group, R5 is an alkyl group o- (Ca-Cio), or a (C 1 -C 10) alkyl group which may be partially or fully fluorinated, a (C 3 -C 7) cycloalkyl group, an (C 1 -C 8) alkylocycloalkyl group (C 3) C7), a (C2-C8) alkenyl- (C3-C7) cycloalkyl group, a heterocyclyl group, an alkylheterocyclyl- (C? -8) group, an alkenylheterocyclyl- (C2-C8) group, a group aryl, an alkylaryl- (Ci- C8), an alkenylaryl- (C2-C8), alkynylaryl- (C2-C-) groups, a mono- or bicyclic heteroaryl group, an alkylheteroaryl- (C? -C8) or an alkenylheteroaryl- (C2-C8), an alkynylheteroaryl- (C2-C8) group which can be substituted by 1-2 keto groups, 1-2 (C1-C5) alkyl groups, 1-2 (C1-C5) alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene-no groups containing 1-3 nitrogen atoms and / or 1 -2-oxygen atoms and / or 1-2 sulfur atoms, where these groups can be bound at any position with the tetrahydronaphthalene system and which may be hydrogenated at one or several places, R6 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl- (C3-C6) ring. Another object of the present invention are stereoisomers of the general formula (I) of claim 2, wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-alkyl group. -C? Which can be substituted, an alkoxy-C? -C? Group which can be substituted, an alkylthio-C? -C? Group, a perfluoroalkyl-Ci- C5 group, a cyano group, a nitro group , or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + ?, -N (C-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in final position and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms, or is NR8R9, where R8 and R9 can be independently from each other, hydrogen, C-C5-alkyl or (CO) -alkyl -C? -C5, R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0 ) which can be substituted, an alkoxy- (C? -C? 0) group, an alkylthio- (Ci-Cio) group, a perfluoroalkyl- (C? -C5) group, R12 is a hydrogen atom, a hydroxy group , a halogen atom, a cyano group, an alkyl- (C? -C? 0) group which can be substituted, an alkoxy- (Ci-Cio) group, R3 is an alkyl-C? -C? group or it can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a cycloalkyl- (C3-C7) group which can be substituted, a heterocyclyl group which can be substituted, a group aryl that can be substituted, a mono- or bicyclic heteroaryl group which can be independently substituted by one or more groups selected from (C1-C5) alkyl groups (which can be substituted by 1-3 hydroxy groups or 1 -3 groups COOR13), where R13 is hydrogen or is -alkyl-C? -C5), alkoxy- (C1-C5) groups, halogen atoms, hydroxy groups, NR8R9 groups, exomethylene groups, oxygen, which can contain 1-3 atoms of nitrogen, and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group may be attached in any position to the amine of the tetrahydronaphthalene system and may be hydrogenated in one or several places, R4 is a hydroxy group, an OR10 group or an O (C0) R10 group where R10 means any hydroxy protecting group or a -C? -C? alkyl group, or R5 is an alkyl- (C? Cl 0), or a (C 1 -C 10) alkyl group which may be partially or fully fluorinated R 6 and R 7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system they are a C3-C6 cycloalkyl ring. Another object of the present invention are stereoisomers of the general formula (1), wherein R 1 and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group or , an alkoxy-C? -C? 0 group, an alkylthio-C? -C? group, a perfluoroalkyl-C? -C5 group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + ?, -N (alkyl-C? -C3) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms they are linked with ring carbon atoms directly adjacentOr is NR8R9, where R8 and R9 may be independently of one another, hydrogen, Ci-Cs alkyl-or (CO) -C-C? -C 5, R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group which can be substituted, an alkoxy- (C? -C? 0), an alkylthio- (Ci-Cio), a perfluoroalkyl- (C1-C5) group , R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, an alkoxy- (C? -C? O) group, R3 is an alkyl-C? -C? - group which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a (C3-C7) cycloalkyl group which can be substituted, a heterocyclyl group which may be substituted, an aryl group which may be substituted, a mono- or bicyclic heteroaryl group which may be substituted independently of one another by one or more (C1-C5) alky groups selected from groups-lo (which can be substituted p or 1-3 hydroxy groups or 1-3 COOR13 groups), (C1-C5) alkoxy groups, halogen atoms, exomethylene groups which may contain 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be bound in any position with the amine of the tetrahydronafat-talene system and can be hydrogenated in one or several places, R4 is a hydroxy group, a group OR10 or a group O (C0) R10 where R10 means any hydroxy-protecting group or a C-C-alkyl group or / R5 is an alkyl- (C? -C5) group, or an alkyl- (C1-C5) group ) partially or completely fluorinated, a (C3-C7) -cycloalkyl group, an alkyl- group (C? C8) -alkyl- (C3-C7) a (C2-C8) cycloalkyl (C3-C) group, a heterocyclyl group, a group alquilheterociclilo- (C? -C 8) a group alquenilheterociclilo- (C2-C8), a (C2-C8) alquinila- rilo- group, an aryl group, a C8-Ca-alkylaryl group; C2-C8 alkenylaryl group, a mono- or bi-heteroaryl group cyclic or an alkylheteroaryl- (C? -C8) or an alkenylheteroaryl- (C2-C8) group which can be substituted by 1-2 keto groups, 1-2 alkyl- (Cx-Cs) groups, 1-2 alkoxy groups - (C3-C5), 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms where these groups can be attached at any position to the tetrahydronaphthalene system and may be hydrogenated at one or more places R6 and R7 are independently of one another, hy- drogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring. Another object of the present invention are stereoisomers of the general formula (1), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C? or, an alkoxy-C? -C? group, an alkylthio-Cx-Cio group, a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the group consisting of groups -0- (CH2) n-0-, -0- (CH2) n -CH2 / -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + 1, -N (alkyl-C? -C3) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with carbon atoms of the directly adjacent ring, or is NR8R9, where R8 and R9 can be independently of each other, hydrogen, Ci-Cs-alkyl or (CO) -alkyl-C? -C5, R11 is a hydrogen atom , a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, an alkoxy- (Ci-Cio) group, an alkylthio group - (Ci-Cio), a perfluoroalkyl- (C 1 -C 5) group, R 12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a (C 1 -C 10) alkyl group which can be substituted , a (C1-C10) alkoxy group, R3 is a Cj-Cio alkyl group which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a cycloalkyl group - (C3-C7) that can be substituted, a heterocyclyl group which can be substituted, an aryl group which can be substituted, a mono- or bicyclic heteroaryl group which can be independently substituted by one or more groups selected from (C1-C5) alkyl groups (which can be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups), alkoxy- (C1-C5) groups, halogen atoms, exomethylene groups that can contain 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be attached in any position to the amine of the tetrahydronafatoten system and can be hydrogenated at one or several places, R4 is a hydroxy group , an OR10 group or an O (C0) R10 group where R10 signifies any hydroxy-protecting group or a -C? -C? -alkyl group, R5 is a (C1-C5) alkyl group, or an alkyl- (C1) group -C5) partially or fully fluorinated, R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring. Another object of the present invention are stereoisomers of the general formula (1), wherein R 1 and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group or which can be substituted, an alkoxy-C? -C? group, an alkylthio-C? -C? group, a per-fluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH - (CH2) n + ?, -N (C-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in final position and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms, or is it NR8R9, where R8 and R9 can be independently of one another, hydrogen, Ci-Cs-alkyl or (CO) -alkyl-C? -C5, R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0) group that can be substituted, an alkoxy- group (C? -C? 0), an alkylthio- (Ci-Cio) group, a perfluoroalkyl- (C1-C5) group, R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C?) Which can be substituted, an alkoxy- (C? -C? O) group, R3 is a C? -C? Alkyl group or can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, u a cycloalkyl- (C3-C7) group that can be substituted, a heterocyclyl group that can be substituted, an aryl group that can be substituted, a mono- or bicyclic heteroaryl group that can be independently substituted by one or more selected groups between (C 1 -C 5) alkyl groups (which may be substituted by 1-3 hydroxy groups or 1-3 COOR 13 groups where R 13 is hydrogen or C 1 -C 5 alkyl), (C 1 -C 5) alkoxy groups, atoms of halogen, exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be attached at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or several places, R4 is a hydroxy group, an OR10 group or an O (C0) R10 group where R10 means any hydroxy protecting group or a C-C? , R5 is a (C1-C5) alkyl group, or a partially or fully fluorinated (C1-C5) alkyl group, or a cyclsalkyl- (C3-C) group, a (C?-C8) cycloalkyl- (C3-C7) alkyl group, a (C2-C8) alkenyl- (C3-C7) cycloalkyl group, a heterocyclyl group, a group alkylheterocyclyl- (C? -C8), an alkenylheterocyclyl- (C2-C8), an alkenylaryl- (C2-C8), alkynylaryl- (C2-C8) groups, an aryl group, an alkylaryl-C- group? -C8, an alkenylaryl-c2-c8 group, a mono- or bicyclic heteroaryl group or an alkylhete-roaryl- (C? -C8) or an alkenylheteroaryl- (C2-C8) group which can be substituted by 1-2 groups keto, 1-2 (C1-C5) alkyl groups, 1-2 (C1-C5) alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1 -2 oxygen atoms and / or 1-2 sulfur atoms where these groups can be attached at any position with the tetrahydronaphthalene system and can be hydrogenated at one or several places R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the The carbon atom of the tetrahydronaphthalene system is a C3-C6 cycloalkyl ring with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the present invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C? which can be substituted, an alkoxy-Ci-C10 group, an alkylthio-C? -C? group or a perfluoroalkyl-C? -C5 group, a cyano group, a nitro group, or R1 and R2 together are a selected group of the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + 1, -N (C-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in final position and / or carbon atoms and / or atoms of nitrogen are attached with directly adjacent ring carbon atoms, or is NR8R9, where R8 and R9 can be independently of each other, hydrogen, C-C5-alkyl or (CO) -alkyl-C? -C5 / R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a (C1-C10) alkyl group which can be substituted, an alkoxy- (C? -C? 0) group, an alkylthio- (C1-C10) group, a perfluoroalkyl group - (C1-C5), R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, a (C1-C10) alkoxy group , R 3 is a C 1 -C 6 alkyl group or can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a cycloalkyl group that can be substituted, a group heterocyclyl which can be substituted, an aryl group which can be substituted, a mono- or bicyclic heteroaryl group which can be substituted by one or more groups selected from (C1-C5) alkyl groups (which can be substituted by 1- 3 hydroxy groups or 1-3 COOR13 groups), (C1-C5) alkoxy groups, halogen atoms, exomethylene groups having 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1- 2 sulfur atoms and / or 1-2 keto groups, where this group can be attached at any position to the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, an OR10 group or an O (C0) group R10 wherein R10 means any hydroxy-protecting group or a -C? -C? -alkyl group, R5 is a (C1-C5) alkyl group, or a partially or fully fluorinated (C? ~ C5) alkyl group, a group (C3-C7) -cycloalkyl, a (C? -C8) -cycloalkyl- (C3-C7) alkyl group, a (C2-C8) alkenyl- (C3-C7) cycloalkyl group, a heterocyclyl group, an alkylheterocyclic- (C? -C8), an alkenylhete-rocyclyl- (C2-C8), an alkenylaryl- (C2-C8), al-quinilaryl- (C2-C8) groups, an aryl group, an alkylaryl-Ci- group, C8, a C2-C8 alkenylaryl group, a mono- or bicyclic heteroaryl group or an alkylheteroaryl- (C? -8) group or an alkenylheteroaryl- (C2-C8) group which can be substituted by 1-2 keto groups, -2 alkyl groups- (C1-C5), 1-2 groups a lcoxy- (C1-C5), 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms where these groups can be bound in any position with the tetrahydronaphthalene system and may be hydrogenated at one or several places R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a cyc ring -cycloalkyl-C3-C6 with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the present invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C? which can be substituted, a C 1 -C 6 alkoxy group, a C 1 -C 0 alkylthio group, a C 1 -C 5 perfluoroalkyl group, a cyano group, a nitro group, or R 1 and R 2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2 / -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + 1, -N (CX-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or Nitrogen atoms are bonded with carbon atoms of the directly adjacent ring, or it is NR8R9, where R8 and R9 can be independently of each other, hydrogen, C-C5-alkyl or (CO) -alkyl-Cj-C5 / R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, an alkoxy group - (C? -C? 0), an alkylthio- (Ci-Cio) group, a perfluoroalkyl- (C1-C5) group, R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a (C1-C10) alkyl group which can be substituted, an alkoxy- (C? -C?) group, R3 is a C-C? alkyl group or can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a cycloalkyl- (C3-C7) group that can be substituted, a heterocyclyl group that can be substituted, an aryl group which can be substituted, a mono- or bicyclic heteroaryl group which can be substituted by one or more groups selected from (C1-C5) alkyl groups (which can be substituted by 1-3 hydroxy groups) or 1-3 groups COOR13), alkoxy- (C1-C5) groups, halogen atoms, exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be attached at any position to the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, an OR10 group or an O (C0) R10 group where R10 means any hydroxy protecting group or a C-C? alkyl group or R5 is a (C1-C5) alkyl group, or a partially or fully fluorinated (C? ~ C5) alkyl group, R6 and R7 are independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a ring or C3-C6 cycloalkyl with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the invention are stereoisomers of the general formula (I), wherein R 1 and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group, an alkoxy-C? -C? group, an alkylthio-C? C? group, a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups - 0- (CH2) n-0-, -0- (CH2) n-CH2, -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in position end and / or carbon atoms are bonded with carbon atoms of the directly adjacent ring, or is NR8R9, where R8 and R9 may independently be hydrogen, alkyl-Ci-Cs or (CO) -alkyl-Ci-Cs, R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, an alkoxy- (Ci-Cio) an alkylthio- (Ci-) group. Cio) / a perfluoroalkyl- (C1-C5) group, R12 is a hydrogen atom, a group by hydroxy, a halogen atom, a cyano group, a (C1-C10) alkyl group which can be substituted, a (C1-C10) alkoxy group, R3 is a C-C? alkyl group or to be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a phenyl or naphthyl group that can be substituted, a mono- or bicyclic heteroaryl group that can be substituted by 1-2 keto groups, 1-2 C -C5 alkyl groups, 1-2 (C1-C5) alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1 -2 oxygen atoms and / or 1-2 sulfur atoms, where these groups can be bound at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, R5 is a group (C 1 -C 5) alkyl, or a partially or fully fluorinated (C 1 -C 5) alkyl group, an aryl group, an alkylaryl- (C 1 -C 8) group, an (C 2 -C 8) alkenylaryl group, a group cycloalkyl- (C3-C7), a gr upo alkyl- (C? ~ C8) cycloalkyl (C3-C7), a (C2-C8) alkenyl group (C3-C7) cycloalkyl R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system they are a C3-C6 cycloalkyl ring, with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, an alkyl-Cj-Cio group, an alkoxy group -C? -C? O, an alkylthio-C? -C? O group, a perfluoroalkyl-C? -C5 group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups -0 - (CH2) p-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in final position and / or carbon atoms are bonded with ring carbon atoms directly adjacent, or is NR8R9, where R8 and R9 can be independently of each other, hydrogen, C-C5-alkyl or (CO) -alkyl-C? -C5, R11 is a hydrogen atom, a hydroxy group, a halogen atom , a cyano group, an alkyl- (Ci-Cio) group that can be substituted, an alkoxy- (C? -C? 0) group, an alkylthio- (Ci-Cio) group, a perfluoroalkyl- (C1-C5) group ), R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a (C1-C10) alkyl group that can be substituted, a (C1-C10) alkoxy group, R3 is an alkyl group -C? -C? Which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a phenyl group which can be substituted, a mono- or bicyclic heteroaryl group can be substituted by 1-2 keto groups, 1-2 C1-Cs alkyl groups, 1-2 (C1-C5) alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 atoms of nitrogen and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms, where these can be bound at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or several places, R4 is a hydroxy group, R5 is an alkyl group- (C3-C5), or an alkyl- (Ci-) group. C5) partially or fully fluorinated, an aryl group, an alkylaryl- (C? -C8) group, an (C2-C8) alkenylaryl group, a (C3-C7) cycloalkyl group, an alkyl- (C? C8) (C3-C7) cycloalkyl, a (C2-C8) alkenyl (C3-C7) cycloalkyl group R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the system tetrahydronaphthalene are a C3-C6 cycloalkyl ring with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, an alkyl-Ci-Cs group, an alkoxy group -Ci-Cs, a perfluoroalkyl group, a cyano group, or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms are bonded with directly adjacent ring carbon atoms, R11 is a hydrogen atom , a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, an alkoxy- (Ci-Cio), an al-quiltio- (Ci-Cio) group, a perfluoroalkyl- (C1-C5) group, R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a (C1-C10) alkyl group that can be substituted, an alkoxy group, (C1-C10), R3 is an alkyl-C? -C? 0 group which may be substituted by 1-3 hydroxy groups or halogen atoms, a phenyl, phthalidyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, dihydroisoquinolinyl, thiophthalidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolyl indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazolyl or indolyl which can be substituted by alkyl-Ci-Cs, halogen, hydroxy, alkoxy-Ci-Cs, where these groups they can be attached in any position to the amine of the tetrahydronaphthalene system and can be mono- or polysubstituted with 1-2 keto groups, 1-2-C-C3-alkyl groups, 1-2-C-C3-alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups and can be hydrogenated in one or several places, R4 is a hydroxy group, R5 is a (C1-C5) alkyl group, or an alkyl group (Ci-C5) partially or totally fluorinated, R6 and R7 are independently e between them, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C5-alkyl group, a C-C5-alkoxy group, a perfluoroalkyl-I0-C1 group -C5, a cyano group, a C-C5 alkoxy group or together are an alkylene dioxy-C-C2 group, where R1 and R2 must be directly adjacent, R11 is a hydrogen atom, a hydroxy group, an halogen, a cyano group, an alkyl- (Cj-Cio) group which can be substituted, an alkoxy- (Ci-Cio) group, an alkylthio- (C1-C10) group, a perfluoroalkyl-C? -C5 group, R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a (C1-C10) alkyl group that can be substituted, a (C1-C10) alkoxy group, R3 is a phenyl group , phthalidyl, isoindolyl, dihi-droindolyl, dihydroisoindolyl, dihydroisoquinolinyl, thiof-talidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, iso-quinolinyl, quinolonyl, isoquinolonyl indazolyl, benzothiazolyl, quinazolinyl, quino xalinyl, cinolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, dihydroindolonyl, dihydro-isoindolonyl, benzimidazolyl or indolyl which can be substituted with alkyl-Ci-Cs, halogen, hydroxy, alkoxy-Ci-Cs, where these groups they can be attached in any position with the amine of the tetrahydronaphthalene system and can be mono or polysubstituted with 1-2 keto groups, 1-2 C-C3 alkyl groups, 1-2 exomethylene groups and can be hydrogenated in one or several places , R 4 is a hydroxy group, R 5 is a (C 1 -C 5) alkyl group, or a (C 1 -C 5) alkyl group partially or fully fluorinated, R 6 and R 7 are independently from each other, a hydrogen atom, a group methyl or ethyl or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the invention are stereoisomers of the general formula (1), wherein R 1 and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group, an alkoxy-C? -C? group, an alkylthio-Ci-C10 group, a perfluoroalkyl-C? -C5 group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups -0 - (CH2) n-0-, -0- (CH2) n-CH2 / -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in final position and / or carbon atoms are bonded with directly adjacent ring carbon atoms, or is NR8R9, where R8 and R9 can be independently from each other, hydrogen, C-C5-alkyl or (CO) -alkyl-C? -C5 , R3 is a Ci-Cio alkyl group which can be substituted by a group selected from 1-3 hydroxy groups, halogen atoms, 1-3 C-C5 alkoxy groups, a phenyl or naphthyl group which can be substituted, a mono- or bicyclic heteroaryl group that can be substituted by 1-2 keto groups, 1-2 C -C5 alkyl groups, 1-2 (C1-C5) alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1 -2 oxygen atoms and / or 1-2 sulfur atoms, where these groups can be bound at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, R5 is an (C 1 -C 5) alkyl group, or a partially or fully fluorinated (C 1 -C 5) alkyl group, an aryl group, an alkylaryl- (C 1 -C 8) group, an (C 2 -C 8) alkenylaryl group, a (C3-C7) cycloalkyl group, a (C? ~ C8) cycloalkyl (C3-C7) alkyl group, a (C2-C8) alkenyl (C3-C7) cycloalkyl group, R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen . Another object of the invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, an alkyl-C? -C? group, an alkoxy-Ci-Cio group, an alkylthio-C-Cyclo group, a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms are bonded with directly adjacent ring carbon atoms, or it is NR8R9, where R8 and R9 can be independently from each other, hydrogen, C-C5-alkyl or (CO) ) -alkyl-C? -C5, R3 is an alkyl-C? -C? group or can be substituted by a group selected from 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a phenyl group which may be substituted, a mono- or bicyclic heteroaryl group which may be substituted by 1-2 keto groups, 1-2 C1-Cs alkyl groups, 1-2 (C1-C5) alkoxy groups, 1- 3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 atoms of sulfur, where these groups can be attached at any position to the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, R5 is a (C1-C5) alkyl group, or a a partially or fully fluorinated alkyl- (Ci- C5) group, an aryl group, an alkylaryl- (C? -C8) group, an (C2-C8) alkenylaryl group, a (C3-C7) cycloalkyl group, a group alkyl- (C? -C8) cycloalkyl (C3-C7), a (C2-C8) alkenyl (C3-C7) cycloalkyl group R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with The carbon atom of the tetrahydronaphthalene system is a C3-C6 cycloalkyl ring with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, an alkyl-Ci-Cs group, an alkoxy group -Ci-Cs, a perfluoroalkyl-I0-C1-C5 group, a cyano group, or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n- CH2 -0-.CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms are bonded with carbon atoms of the ring directly adjacent, R 3 is a C 1 -C 6 alkyl group or it can be substituted or 1-3 hydroxy groups, halogen atoms, a phenyl-, phthalidyl-, isoindolyl-, dihydroin-dolyl, dihydroisoindolyl, dihydroisoquinolinyl, thiophtalidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl, indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7 or 1,8-naphthyridinyl, dihydroindolonyl or, dihydroisoindoloyl, benzimidazolyl- or indolyl which can be substituted with C-C5-alkyl, halogen, hydroxy, alkoxy-Ci-Cs, where these groups can be attached in any position to the amine of the tetrahydronaphthalene system and they can be mono or polysubstituted with 1-2 keto groups, 1-2 C 1 -C 3 alkyl groups, 1-2 C 1 -C 3 alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups and they can be hydrogenated in one or several places, R 4 is a hydroxy group, R 5 is a (C 1 -C 5) alkyl group, or a partially or fully fluorinated (C 1 -C 5) alkyl group, R 6 and R 7 are independently one atom of hydrogen, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring, with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen . Another object of the invention are stereoisomers of the general formula (I), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C5 alkyl group, a group perfluoroalkyl-C? -C5, a cyano group, a C? -C5 alkoxy group or together are an alkylene dioxy-Ci- C2 group, where R1 and R2 must be directly adjacent, R3 is a phenyl group, phthalidylisoindolyl, dihydroindolyl, dihydroisoindolyl, dihydroisoquinolinyl, thiofetidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl, indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, dihydroindolonyl. , dihydroi-soindolonyl, benzimidazolyl or indolyl which can be substituted with Ci-Cs alkyl, halogen, hydroxy, alkoxy Ci-Cs, where these groups can be attached at any position with the amine of the tetrahydronaphthalene system and can be mono or polysubstituted with 1-2 keto groups, 1-2 C-C3 alkyl groups, 1-2 exomethylene groups and can be hydrogenated at one or several places, R4 is a hydroxy group, R5 is a (C1-C5) alkyl group , or a partially or fully fluorinated (C 1 -C 5) alkyl group, R 6 and R 7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a cycloalkane ring C3-C6 alkyl, with the proviso that at least three of the radicals R1, R2, R11 and R12 are not hydrogen. Another object of the present invention relates to stereoisomers of the general formula (I), where R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C? alkyl group or which can be substituted, a C alco-C? alkoxy group or can be substituted, an alkylthio-C? -C? 0 group, a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R1 and Y2 together are a group selected from the groups -0- (CH2) n -0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) a + 1, -N (alkyl? -C? -C3 ) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with carbon atoms of the directly adjacent rings, or are NR8R9, where R8 and R9 can be independently of each other, hydrogen, Ci-Cs-alkyl or (CO) -alkyl-Ci-Cs, R11 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0) group which can be substituted, an alkoxy- (Ci-Cio) group, an alkylthio- (C? -C? 0) group, a perfluo group R 5 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0) group which can be substituted, an alkoxy- (C1-C10), R3 is an alkyl-C? -C? 0 group which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-C? -C5 groups, a cycloalkyl group- (C3-C) which may be substituted, a heterocyclyl group which may be substituted, an aryl group which may be substituted, a mono- or bicyclic heteroaryl group which may be independently substituted by one or more groups selected from alkyl groups - (C1-C5) (which can be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups), (C1-C5) alkoxy groups, halogen atoms, exomethylene groups, oxygen, which can contain 1-3 nitrogen atoms, and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group may be attached in any position to the amine of the tetrahydron system aftalene and can be hydrogenated in one or several places, R4 is a hydroxy group, an OR10 group where R10 is a Ci-Cio alkyl group, R5 is a (C1-C5) alkyl group, or an alkyl- (Ci) group -C5) which may be partially or fully fluorinated, R6 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl- (C3-) ring C6). The stereoisomers of the formula II are included in the general formula 1. Another object of the present invention relates to stereoisomers of the general formula (II), where R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a Ci-Cio alkyl group, a Ci-Cio alkoxy group, an alkylthio-Ci- C? a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) "- CH2, - 0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + 1, -N (C-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms, or are NR8R9, where R8 and R9 can be independently yes, hydrogen, alkyl-Ci-Cs or (CO) -alkyl-C? -C5, R3 is an alkyl-C? -C? group or can be substituted by 1-3 hydroxy groups, halogen atoms, -3 alkoxy-Ci-Cs groups, a cycloalkyl- (C3-C7) group that can be substituted, a heterocyclyl group that can be substituted, an aryl group that can be substituted substituted, a mono- or bicyclic heteroaryl group which may be substituted by one or more groups selected from (C1-C5) alkyl groups (which may be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups), groups alkoxy- (C1-C5), halogen atoms, exomethylene groups, which may contain 1-3 nitrogen atoms, and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 groups keto, where this group can be linked in any position with the amine of the tetrahydronaphthalene system and can be hydrogenated in one or more places, R4 is a hydroxy group, an OR10 group where R10 is a C-C? -C alkyl group, R5 is a (C1-C5) alkyl group, or an alkyl- (C? ~ C5) group which can be partially or fully fluorinated, R6 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a (C3-C6) cycloalkyl ring. Another object of the invention are stereoisomers of the general formula (II), wherein R 1 and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group, an alkoxy-C? -C? group, an alkylthio-Ci-C? group, a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups - 0- (CH2) n-0-, -0- (CH2) n-CH2, -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in position and / or carbon atoms and / or nitrogen atoms are bonded with carbon atoms of the directly adjacent ring, or are NR8R9,. where R8 and R9 can be independently of each other, hydrogen, Ci-Cs-alkyl or (CO) -alkyl-Ci-Cs, R3 is a -C? -C? alkyl group or can be substituted by 1-3 hydroxy groups , halogen atoms, a phenyl group that can be substituted, a heteroaryl, a mono- or bicyclic heteroaryl group which can be substituted by 1-2 keto groups, 1-2 C-C5-alkyl groups, 1-2 C-alkoxy groups? -C5, 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms, where this group can be attached in any position with the amine of the tetrahydronaphthalene system and can be hydrogenated in one or several places, R4 is a hydroxy group, R5 is an alkyl- (C1-C5) group, or an alkyl- (Ci-C5) group which may be partial or fully fluorinated, an aryl group, a C-C8 alkylaryl group, a C2-C8 alkenylaryl group, a C3-C cycloalkyl group), a C3-C7 cycloalkyl- (C6-C8) alkyl group , an alkenyl- (C2-C8) group (C3-C7) -alkyl-, R6 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a (C3-C6) cycloalkyl ring. Another object of the present invention are stereoisomers of the general formula (II), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C-alkyl group A C 1 -C 6 alkoxy group, an alkylthio-C 1 -C 6 group, a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or R 1 and R 2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the atoms of oxygen in the final position and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms, or are NR8R9, where R8 and R9 can independently be hydrogen, alkyl-Ci-Cs or ( CO) -alkyl-Ci-Cs, R3 is an alkyl-C? -C? 0 group which can be substituted by 1-3 hydroxy groups or halogen atoms, a phenyl group which can be substituted, a heteroaryl group mono- or bicyclic that can be replaced by 1-2 groups keto, 1-2 gr C5-C5 alkyl groups, 1-2 C5-C5 alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms, where this group can be attached at any position to the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, R5 is an alkyl group (C1-C5) , or an alkyl- (C? -C5) group which may be partially or fully fluorinated, R6 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl-C3-C6 ring. Another object of the present invention are stereoisomers of the general formula (II), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, an Ci-Cs-alkyl group, a C-C5-alkoxy group, or R1 and R2 together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms are bonded with carbon atoms of the directly adjacent ring, R 3 is a C 1 -C 6 alkyl group or can be substituted by 1-3 hydroxy groups or halogen atoms, a phenyl, phthalidyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, dihydroisoquinolinyl group , thiophthalidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolyl indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazolyl or indolyl which can be to be substituted by alkyl-Ci-Cs, halogen, hydroxy, alkoxy-Ci-Cs, where these groups can be attached at any position with the a Mine of the tetrahydronaphthalene system and can be mono or polysubstituted with 1-2 keto groups, 1-2 C-C3-alkyl groups, 1-2 C-C3-alkoxy groups, 1-3 halogen atoms, 1-2 groups exomethylene and can be hydrogenated at one or more places, R4 is a hydroxy group, R5 is a (C1-C5) alkyl group, or a partially or fully fluorinated (Ci-C5) alkyl group, R6 and R7 are independently if, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring. Another object of the present invention are stereoisomers of the general formula (II), wherein R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C5 alkyl group, a alkoxy-C? -C5 group, or together are an alkylene dioxy-C? -C2 group where R1 and R2 must be directly adjacent, R3 is a phenyl, phthalidyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, dihydroisoquinolinyl, thiofidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl, indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7- or 1, 8-naphthyridinyl, dihydroindolonyl, dihydroisodinyl, benzimidazolyl or indolyl which can be substituted by alkyl- C? -C5, halogen, hydroxy, alkoxy-Ci-Cs, where these groups can be attached at any position with the amine of the tetrahydronaphthalene system and can be mono or polysubstituted with 1-2 keto groups, 1-2 C-alkyl groups ? -C3, 1-2 exomethylene groups and can be hydrogenated at one or several places, R4 is a hydroxy group, R5 is an alkyl group (C? -C5), or a partial- (C? -C5) alkyl group or fully fluorinated, R6 and R7 are independently from each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system are a C3-C6 cycloalkyl ring. A particular object of the invention are stereoisomers of claim 1, which on the aromatic ring of the tetrahydronaphthalene system carry substituents selected from the group consisting of C 1 -C 5 alkyl, C 1 -C 5 alkoxy, COOR 13, NR 8 R 9 , perfluoroalkyl-C? -C5, halogen, hydroxy, cyano, nitro, 0- (CH2) n-0, 0- (CH2) nCH2, 0-CH = CH, (CH2) n + 2, NH- (CH2) n + ?, N (C? -C3-alkyl) - (CH2) n +? NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in final position and / or carbon atoms and / or Nitrogen atoms are bonded with carbon atoms of the ring directly adjacent. Therefore the two linker radicals of the invention should be counted as two substituents, R 13 is hydrogen or C 1 -C 6 alkyl or C 1 -C 5. When R1 / R2 is COOR13, R13 is preferably tert-butyl. A particular object is that R3 is formed by a radical containing COOR13 as a substituent, where R13 is -alkyl-C? -C? O- or C? -C5. Another object of the invention are stereoisomers of claim 2 which carry three substituents in the tetrahydronaphthalene system ring, selected from the -alkyl group -C? -C5-, C alco-C5-alkoxy, C perf-C5 perfluoroalkyl, halogen, hydroxy, cyano-, nitro, O- (CH2) n-0, O- (CH2) n -CH2, 0-CH = CH, (CH2) ) n + 2, NH- (CH2) n + ?, N (C? -C3-alkyl) - (CH2) p + ?, NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in position end and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms. Whereby, the radicals with two bonds of the invention should be counted as two substituents. A subgroup of these stereoisomers are the stereoisomers of the formula I or II of claim 2, where R1 and R2 together are the radicals 0- (CH2) n -0.0- (CH2) n -CH2, 0-CH = CH, (CH2) n + 2, NH- (CH2) n +? -, N (C? -C3-alkyl) - (CH2) n + 1, -NH- N = CH. The atoms which in each case are in the final position of the groups with two bonds mentioned above are linked with carbon atoms directly adjacent to the tetrahydronaphthalene system. A subgroup are the stereoisomers of claim 2, wherein R 1, R 2, R 11 or R 12 are selected from the group consisting of C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 perfluoroalkyl, halogen, hydroxy, cyano, nitro. Another subgroup are the stereoisomers of claim 1 or 2, in which R1, R2, R11 or R12 are selected from the group consisting of alkyl-Ci-Cs which can be substituted, al-coxy-Ci-Cs which can be substituted, perfluoroalkyl-C? -C5, halogen, hydroxy, cyano. Another subgroup are the stereoisomers of formula I or II of claim 2, in which the alkyl radicals R1 and R2 mean (CH2) n + 2 and thus form a ring of 5 to 6 members with the carbon atom of the chain . A particular object of the invention are stereoisomers of the general formula I or II, which carry one or two substituents on the aromatic ring of the tetrahydronaphthalene system, selected from the group C-C5-alkyl, C-C5-alkoxy, perfluoroalkyl-C ? -C5, halogen, hydroxy, nitro, 0- (CH2) n -0.0 (CH2) n -CH2, 0 -CH = CH, (CH2) n + 2, NH- (CH2) n +? N ( C? -C3-alkyl) - (CH2) n +? -NHN = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with carbon atoms of the ring directly adjacent. A subgroup are stereoisomers of the general formula 1, which carry two substituents on the aromatic ring of the tetrahydronaphthalene system, selected from the group C1-C5 alkyl, C1-Cs alkoxy, perfluoroalkyl-Ci-Cs, halogen, hydroxy, cyano-, nitro, 0- (CH2) n -0, 0- (CH2) n-CH2-, 0-CH = CH, (CH2) n + ?, -NH- (CH2) n + ?, N (C? -C3-alkyl) - (CH2) n + ?, NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with carbon atoms of the ring directly adjacent. With which the radicals. of two bonds of the invention should be counted as two substituents. Another object of the invention are stereoisomers of the general formula I or II according to claim 1 or 2, where R 3 is a C 1 -C 6 alkyl group or can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy- (C 1 -C 5) groups, a C 3 cycloalkyl group C7) which can be substituted, a heterocyclyl group which can be substituted, a mono- or bicyclic heteroaryl group which can be substituted by one or more (C1-C5) alkyl groups, (C1-C5) alkoxy groups, halogen, exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be attached in any position with the amine of the system and can be hydrogenated in one or more places. Another object of the invention are stereoisomers of the formula I or II, where R3 is a C-C6alkyl group, which can be substituted by 1-3 hydroxy groups, halogen atoms, a phenyl group which can be substituted , a mono- or bicyclic heteroaryl group which can be substituted by one or more (C1-C5) alkyl groups, (C1-C5) alkoxy groups, halogen atoms, exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be attached at any position to the amine of the system and can be hydrogenated at one or several places. An object of the invention are stereoisomers of the general formula I or II, wherein R3 is a phenyl or naphthyl group which can be substituted by one or more radicals of the group Ci-Cs alkyl, Ci-Cs alkoxy, hydroxy, halogen, cyano, CF3, nitro, COOR13, NR8R9. A preferred object of the present invention are compounds of the general formula I or II according to claims 1-6, wherein R3 means a group that can be substituted by one or more groups, independently of each other, selected from alkyl- groups. C? -C5, which in turn can be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups, where R13 is hydrogen or C? -C5 alkyl, a mono- or bicyclic heteroaryl group substituted by alkoxy-Ci groups -Cs, halogen atoms, hydroxy groups, NR8R9 groups, exomethylene groups, oxygen, which may contain 1-4 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1 -2 keto groups, where this group can be linked in any position with the amine of the tetrahydronaphthalene system and can be hydrogenated in one or several places. Another preferred object of the present invention are compounds of the general formula I or II according to claims 1-6, wherein R3 signifies a group that can be substituted by one or several groups independently selected from C -C5 alkyl groups, which they may in turn be replaced by 1-3 hydroxy groups or 1-3 COOR13 groups, where R 13 signifies hydrogen or alkyl-CiCs, is mono- or bicyclic heteroaryl groups substituted with alkoxy-CiCs, halogen atoms, hydroxy groups, NR8R9 groups, exomethylene groups, oxygen, containing 1-4 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group. it may be attached at any position to the amine of the tetrahydronaphthalene system and may be hydrogenated at one or more places and R5 may be a partially or fully fluoro-Ci-Cs alkyl group. A preferred object of the invention are stereoisomers of the general formula 1, wherein R3 is a C-C? 0 alkyl group which can be substituted with 1-3 hydroxy groups, halogen atoms, a phenyl, naphthyl, phthalidyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, dihydroisoquinolinyl, dihydroquinolinyl, thiophthalidyl, benzoxazinonyl group , phthalazino-nyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl, indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazolyl or indolyl which can be substituted by C-alkyl? -C5, halogen, hydroxy, alkoxy-Ci-Cs. A particular object of the invention are stereoisomers of the general formula I or II, wherein R3 is an alkylo-Ci-Cio group, which can be substituted by 1-3 hydroxy groups, halogen atoms, a phenyl group, phthalidyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, dihydroisoquinolinyl, thiophthalidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl, indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7 or 1,8 naphthyridinyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazole or indolyl which can be substituted with C-C5-alkyl, halogen, hydroxy, C-C5-alkoxy. Another object of the invention are stereoisomers of the formula (I), wherein R 3 is a phtalidyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, thiophthalidyl, indazolyl, benzothiazolyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazolyl or indolyl group. Another object of the invention are stereoisomers of the formula (I), wherein R3 is a dihydroisoquinolinyl, dihydroquinolinyl, benzoxazinonyl, phthalazinonyl, quinoli-nyl, isoquinolinyl, quinolonyl, isoquinolonyl quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1.7 or 1 group. 8-naphthyridinyl. Another object of the invention are stereoisomers of the general formula I wherein R3 is an isoquinolonyl quinolonyl, quinazolinyl or phthalazinyl group. Another object of the invention are stereoisomers of the general formula I or 11 wherein R3 is an isoquinolonyl, quinolonyl, quinazolinyl, phthalazinyl-, indazolyl, quinolinyl, isoquinolinyl, isoquinolonyl, dihydroindolonyl, dihydroindolyl, dihydroindolonyl, naphthyl, pyridyl group. phthalidil, which can be substituted. Another object of the invention are stereoisomers of the general formula 1 wherein R3 is an isoquinolin-1 (2H) -on-5-yl, quinolin-2 (lH) -on-5-yl-, 8- or 7-fluoro group -2-methyl-quinazoline, 7, 8-difluoro-4-methyl-quinazoline, 7,8-difluoro-2-methylquinazoline or 2-methyl-phthalazin-1-one. The radical R3 is attached to the tetrahydronaphthalene system through the amine. When the radical R3 has several chemically possible positions to be linked to the ring system, the present invention encompasses all those possibilities.

The radical R3 is also encompassed by the present invention when it is hydrogenated at one or more places. The substituents of the mono- or bicyclic heteroaryl group (heterocyclic groups) R 3 defined above can be, at chemically appropriate positions, for example hydroxy, halogen atoms, particularly fluoro and chloro, Ci-Cs-alkyl groups (which in turn they can be substituted by hydroxy groups, C 1 -C 5 alkoxy groups or COOR 13 groups, where R 13 is hydrogen or C 1 -C 5 alkyl), particularly methyl, C 2 -C 2 alkenyl groups, C-alkyl groups ? -C5 partially or completely fluorinated, particularly CF3, CFH2, or C2F5, alkoxy-Ci-Cs groups, particularly methoxy and ethoxy, groups NR8R9, particularly NH2, N (CH3) 2 or NH (CH3), cyano groups and keto groups which are formed with a carbon atom of a ring of the heteroaryl group and oxygen, and which forms an N-oxide with a ring nitrogen atom that may be present. Therefore, the preferred substituent groups of the radical R3, as defined in claim 1 and for all other claims, are fluorine, chlorine, OH, CH3, CF3 CFH2, or C2F5, OCH3, OC2H5, NH2, N (CH3) 2 and N (CH3) 2 and NH (CH3), cyano, keto, oxygen. As substituents of the heterocyclic groups R3, as defined above in the objects of the invention, they are used in appropriate positions, for example halogen atoms, alkyl-Ci-Cs groups (which in turn are substituted by groups hydroxy or COOR13, where R13 is hydrogen or C1-C5-alkyl), C2-Cs-alkenyl groups, fluorinated C-C5-alkyl groups, alkoxy-Ci-Cs groups or cyano groups. An equally preferred object are stereoisomers of the general formula I or II, where R3 is a phenyl or naphthyl group, phthalidyl, thiophthalidyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazolyl- or indolyl which can be substituted with alkyl-Ci-Cs, halogen, hydroxy, alkoxy-Ci-Cs. A particularly preferred object is stereoisomers of the general formula I, wherein R3 is a phenyl-, phthalidyl-, thiophthalidyl, benzoxazinonyl, phthalazinonyl, quinoli-nyl, isoquinolinyl, quinolonyl, isoquinolonyl, indazolyl, benzothiazolyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl group. , 7- or 1, 8-naphthyridinyl, dihydroindolonyl, dihydroisoindolonyl, benzimidazolyl or indolyl which can be substituted with Ci-Cs-alkyl, halogen, hydroxy, C-C5-alkoxy. The heterocyclyl group R3 is not aromatic and can be, for example, pyrrolidine, imidazolidine, pyrazolidine, piperidine. The hydroxy group of R 4 may be present in a form protected by one of the hydroxy protecting groups known to the person skilled in the art, such as, for example, silyl ether or ester of organic acids C1-C10, or as ether-C-C5 or benzyl ether , preferably in the form of one of the usual hydroxy protecting groups or as ether-Ci-Cs- The hydroxy group is particularly preferred as radical R4. The usual hydroxy protecting groups are described in detail in T.W. Greene, P.G.M. Wuts "Protective Groups in Organizational Synthesis", 2.Ed., John Wiley & Sons, 1991). The protecting groups are preferably alkyl-, aryl- or mixed alkylaryl-substituted silyl groups, for example the trimethylsilyl groups (TMS), triethylsilyl (TES), tert-butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS) or triisopropylsilyl (TIPS) ) or another protecting group of ordinary hydroxy (methoxymethyl, methoxyethoxymethyl, ethoxyethyl, tetrahydrofuranyl, tetrahydropyranyl groups) The radical R5 is directly linked to the tetrahydronaphthalene system When the radical R5 has several chemically possible positions to be bound to the ring system, the present invention It encompasses all those possibilities Another object of the invention are stereoisomers of the general formula I wherein R5 is a C-C5-alkyl group or an Ci-Cs-alkyl group which may be partially or fully fluorinated, a C3-C7 cycloalkyl group, a (C? ~ C8) cycloalkyl (C3-C7) alkyl group, a (C2-C8) alkenyl (C3-C7) cycloalkyl group, a heterocyclyl group, an alkylheterocyclyl group -Ci- C8, an alkenylheterocyclyl-C2-C8 group, an aryl group, a C-C8 alkylaryl group, a C2-C8 alkenylaryl group). Another subgroup of the invention are stereoisomers of the general formula I of claim 1, wherein R5 is a C3-C7 cycloalkyl group, a C3-C8-C3-C3-C7 cycloalkyl group, a C2-alkenyl group -C8-C3-C7 cycloalkyl, a heterocyclyl group, an alkylheterocyclyl-C? -C8 group, a C2-C8 alkenylheterocyclyl group, an aryl group, an alkylaryl-C? -C8 group, an alkenylaryl-C2 group -C8, a mono- or bicyclic heteroa-ryl group, a C-C8 alkylheteroaryl group or a C-C8 alkenylheteroaryl group, an alkynylheteroaryl-C2-C8 group which may be substituted by 1-2 keto groups , 1-2 C1-Cs alkyl groups, 1-2 C1-C5 alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms, where these groups can be attached at any position with the tetrahydronaphthalene system and can be hydrogenated at one or several places. An object of the invention are stereoisomers of the general formula I, wherein R5 is a C-C5-alkyl group or an Ci-Cs-alkyl group which may be partially or fully fluorinated, an aryl group, an alkylaryl-C group? -C8, a C2-C8 alkenylaryl group, a C3-C7 cycloalkyl group, a C-C8-C8-cycloalkyl-C3-C, a (C2-C8) alkenyl-C2-C8-cycloalkyl group -C3-C7 Another object of the invention are stereoisomers of the general formula I or II of claims 1 to 6, in which R5 is a C-C? 0 alkyl group or a C-C? -alkyl group. or which may be partially or fully fluorinated, preferably, an alkyl-Ci-Cs group or an alkyl-Ci-Cs group which may be partially or fully fluorinated, with particular preference a C-C3-alkyl group or an alkyl- C? -C3 which can be partially or fully fluorinated, very especially CF3 or C2Fs. Another object of the invention are stereoisomers of the general formula I or II according to claims 5 and 6 wherein R5 is a Ci-Cs alkyl group or a Ci-C5 alkyl group which may be partially or fully fluorinated. Preferably R5 represents the trifluoromethyl or pentafluoroethyl group. Stereoisomers are preferred according to claims 1 to 6, which radical R5 can be a partially or fully fluorinated alkylalkyl group, particularly a partially or fully fluorinated C-C3 alkyl group. An especially preferred subgroup, such as those disclosed in the present invention, are the radicals and all of their subcombinations which are documented with examples. The designation of halogen atom or halogen means a fluoro, chloro, bromo or iodo atom. A fluorine, chlorine or bromine atom is preferred. The C alquilo-C ?o or C?-C5 alkyl groups R 1, R 2, R 4, R 5, R 6, R 7, R 11, R 12 and R 13 can be straight or branched chain derivatives and can represent, for example, a methyl, ethyl or n-methyl group. - propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl or n-pentyl, 2,2-dimethylpropyl, 2-methylbutyl or 3-methylbutyl and the group hexyl, heptyl, nonyl, decyl and any of their branched derivatives. A methyl or ethyl group is preferred. The alkyl groups mentioned above can be substituted by 1-5 selected groups, independently of hydroxy, cyano, nitro, COOR 13, C 1 -C 5 alkoxy groups, halogen, NR 8 R 9, a partial C 1 -C 3 alkyl group or fully fluorinated; a subgroup are the substituents 1-3 halogen atoms and / or 1-3 hydroxy groups and / or 1-3 cyano groups and / or 1-3 COOR13 groups. A preferred subgroup is a fluoro atom, hydroxy, methoxy and / or cyano groups. The alkyl groups can be substituted only by 1-3 hydroxy groups and / or 1-3-groups COOR13. In this case, hydroxy groups are preferred. As partial or fully fluorinated C 1 -C 3 alkyl group the following partially or fully fluorinated groups can be used: fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, 1,1-difluoroethyl, 1,2-difluoroethyl, 1,1,1-trifluoroethyl , tetrafluoroethyl, pentafluoroethyl. Of these, the trifluoromethyl or pentafluoroethyl groups are preferred. With which, the fully fluorinated group is also called the perfluororalyl group. The reagents that can be used during the synthesis are commercially available and the published synthesis of the respective reagents belongs to the state of the art or can be used analogously. The C 1 -C 0 alkoxy or C 1 -C 5 alkoxy groups can be straight or branched chain and represent, for example, a methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, ter- butoxy or n-pentoxy, 2, 2-dimethylpropoxy, 2-methylbutoxy or 3-methylbutoxy. The C1-C5 alkoxy group is preferred. A methoxy or ethoxy group is particularly preferred. The alkoxy groups mentioned above can be substituted with 1-3 groups selected from halogen, particularly fluorine, chlorine, hydroxy and cyano. The alkylthio-Ci-Cs groups can be straight-chain or branched and represent, for example, a methylthio group, ethylthio, n-propylthio, iso-propylthio, n-butylthio, iso-butylthio, tert-butylthio or n-penthylthio, 2, 2-dimethylpropylthio, 2-methylbutylthio or 3-methylbutylthio. A methylthio or ethylthio group is preferred. The substituent NR8R9 means, for example, NH2, NH (CH3), N (CH3) 2, NH (C2H5), N (C2H5) 2 / NH (C3H7), N (C3H7) 2, NH (C4H9), N (C4H9) ) 2, NH (C5H), N (C5Hu) 2, NH (C0) CH3, NH (CO) C2H5, NH (CO) C3H7, NH (CO) C4H9, NH (CO) C5Hu. The cycloalkyl group means a cyclic group saturated with 3 to 7 carbon atoms in the ring as p. ex. cyclopropyl, methylcyclopropyl, cyclobutyl, methylcyclobutyl, cyclopentyl, methylcyclopentyl, cyclohexyl methylcyclohexylcycloheptyl, ε-retylcycloheptyl which can be substituted by one or more hydroxy groups, halogen atoms, C alquilo-C5 alkyl groups, C alco alkoxy groups ? -C5, groups NR8R9, groups COOR13, CHO, cyano. A C 1 -C 8 -cycloalkyl-C 3 -C 7 group) is a cycloalguyl group which is linked to the ring system by means of a linear or branched C 1 -C 8 -alkyl unit. The term "C2-C8 alkenyl-C3-C3-cycloalkyl group, R5" means a cycloalkyl group which is linked to the ring system via a linear or branched C2-C8 alkenyl unit. The heterocyclyl group is non-aromatic and may be, for example, pyrrolidine, imidazolidine, pyrazolidine, piperidine. Also included in the heterocyclyl groups are the perhydroquinoline and perhydroisoquinoline groups. The substituents that can be used for the heterocyclyl and heteroaryl groups can be, for example, substituents of the C 1 -C 5 alkyl group, hydroxy, C 1 -C 5 alkoxy, NR 8 R 9, halogen, cyano, COOR 13, CHO which can be substituted. The substituents may also be attached to the nitrogen atom; in that case also the N-oxides are included in the definition. The aryl groups described in the invention are aromatic or aromatic carbocyclic groups with 6 to 14 carbon atoms which have a ring such as, for example, phenyl or phenylene or several condensed rings, such as naphthyl or anthranil. We will mention as examples, phenyl, naphthyl, tetralinyl, anthranil, indanyl and indenyl. The aryl groups may be substituted at any appropriate site leading to a stable stereoisomer, by one or more radicals from the group consisting of hydroxy, halogen, alkyl-Ci-Cs, alkoxy-Ci-Cs, cyano, CF3, nitro which, if necessary, can be substituted by 1-3 hydroxy groups or COOR13 groups. Substituted phenyl and naphthyl groups are preferred. An alkylaryl-C? -C8 group is an aryl group as described above, which is linked to the ring system through a straight or branched C? -C8 alkyl unit.

A C2-C8 alkenylaryl group is an aryl group as described above, which is linked to the ring system through a linear or branched C2-C8 alkenyl unit. A C2-C8 alkynylaryl group is an aryl group as described above, which is linked to the ring system through a linear or branched C2-C8 alkynyl unit. The mono- or bicyclic heteroaryl group can be substituted by one or more substituents selected from a C-C5-alkyl group, Ci-Cs alkoxy, halogen, exomethylene which can be substituted by 1-3 hydroxy groups or 1-3 groups COOR13. The substituents may also be directly attached to the heteroatom. Also the N-oxides are included in the present invention.

The mono- or bicyclic heteroaryl group may contain 0-9 groups of nitrogen atoms, oxygen atoms, sulfur atoms or keto groups, of which at least it may contain max. 3 (4?) Nitrogen atoms, max. 2 oxygen atoms, max. 2 sulfur atoms and max. 2 groups keto. Any sub-collection of these groups is possible. The heteroaryl group can be hydrogenated at one or more places.

Monocyclic heteroaryl groups may be for example pyridine, pyrazine, pyrimidine, pyridazine, triazine, azaindolizine, 2H- and 4H-pyran, 2H- and 4H-thiopyran, furan, thiophene, and 4H-pyrazole IH, 1H- and 2H- pyrrole, oxazole, thiazole, furazane, IH- and 4H-imidazole, isoxazole, isothiazole, oxadiazole, thiazole, tetrazole, thiadiazole. The bicyclic heteroaryl groups can be, for example, phthalidyl, thioftadilyl, indolyl, isoindolyl, dihydroindolyl, dihydroisoindolyl, indazolyl, benzothiazolyl, indolonyl, dihydroindolonyl, isoindolonyl, dihydroisoindolonyl, benzofuranyl, benzimidazolyl, dihydroisoquinolinyl, dihydroquinolinyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl groups. , quinolonyl, isoquinolonyl, quinazolinyl, quinoxalinyl, cinolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, coumarinyl, isocoumarinyl, indolizinyl, isobenzofuranyl, azaindolyl, azaisoindolyl, furanopyridyl, furanopyrimidinyl, furanopyrazinyl, furanopyridazinyl, dihydrobenzofuranyl, dihydrofuranopyridyl, dihydrofuranopi-rimidinyl, dihydrofuranopyrazinyl, dihydrofuranopyridazini- 10, dihydrobenzofuranyl. If the heteroaryl groups are partially or totally hydrogenated, then the stereoisomers of the formula I or 11 wherein R3 is tetrahydropyranyl, pyranyl 2H-, 4H-pyranyl, piperidyl, tetrahydropyridyl, dihydropyridyl, lH-pyridin-2-onyl, lH-pyridin-4-onyl, 4-aminopyridyl, lH-pyridin-4-onyl, 4 -aminoipiridilo, lH-pyridin-4-ilidenaminilo, chromanyl, isochromanyl, thiochromanyl, decahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, 5, 6, 7, 8-tetrahydro-lH-quinolin-4-onyl, decahydroisoquinolinyl, tetrahydroisoquinolinyl, dihydroisoquinolinyl, 3, 4 -dihydro-2H-benz [1,4] oxazinyl, 1,2-dihydro [1, 3] benzoxazin-4-onyl, 3,4-dihydrobenz [1,4] oxazin-4-onyl, 3,4-dihydro -2H-benzo [1, 4] thiazinyl, 4H-benzo [1, 4] thiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, lH-cinnolin-4-onyl, 3H-quinazolin-4-onyl, lH-quinazolin -4-onyl 3, 4-dihydro-lH-quinoxalin-2-onyl, 2, 3-1, 2, 3, 4-tetrahydro [1, 5] naphthyridinyl, dihydro-lH- [1, 5] naphthyridyl, ÍH- [1, 5] naphthyrid-4-ynyl, 5,6,7,8-tetrahydro-lH-naphthyridin-4-ynyl, 1,2-dihydropyrido [3,2-d] [1,3] oxazin- 4-onyl, octahydro-lH-indolyl , 2, 3-dihydro-lH-indolyl, octahydro-2H-isoindolyl, 1, 3-dihydro-2H-isoindolyl, 1, 2-dihidroindazolilo, lH-pyrrolo t2, 3-b] pyridyl, 2, 3-dihydro- lH-pyrrolo [2, 3-b] pyridyl, 2,2-dihydro-lH-pyrrolo [2, 3] pyridin-3-onyl are included in the present invention. An alkylheteroaryl-Ci-Cs group is a heteroaryl group as described above, which is linked to the ring system through a linear or branched C 1 -C 8 alkyl unit. A C2-C8 alkenylheteroaryl group is a heteroaryl group as described above, which is linked to the ring system through a linear or branched C2-C8 alkenyl unit. A C2-C8 alkynylheteroaryl group is a heteroaryl group as described above, which is linked to the ring system through a linear or branched C2-C8 alkynyl unit. A C 1 -C 8 alkylheterocyclyl group is a heterocyclyl group as described above, which is linked to the ring system through a linear or branched C 1 -C 8 -alkyl unit. An alkenylheterocyclyl-C? -C8 group is a heterocyclyl group as described above, which is linked to the ring system through a linear or branched C2-C8 alkenyl unit. The stereoisomers of the general formula I or II of the invention can be present as stereoisomers thanks to the presence of asymmetry centers. All possible diastereomers (e.g., RR, RS, SR, SS), as well as racemates and free-enantiomers are the subject of the present invention. The term "stereoisomers" includes all possible diastereomers, regioisomers and tautomers (e.g. keto-enol tautomers), in which the stereoisomers of the invention may be present, and which are therefore also subject of the invention. The stereoisomers of the invention can also be present in the form of salts with physiologically tolerable anions, for example in the form of hydrochlorides, sulfates, nitrates, phosphates, pivalates, maleates, fumarates, tartrates, benzoates, mesylates, citrates or succinates. . The stereoisomers of the invention are prepared by generating the open chain precursors of the general formula III according to methods known in the state of the art, ('(I) which are then cyclized, either without another reagent, in a solvent, preferably chlorinated hydrocarbons such as, for example, methylene chloride or dichloroethane or concentrated organic acids, preferably acetic acid, or by adding inorganic or organic acids or Lewis acids at temperatures between -70 ° C and + 80 ° C (preferably between -30 ° C and + 80 ° C), to obtain the stereoisomers of the general formula I or II. of a compound III in which only two substituents are carried in the tetrahydronaphthalene ring, a compound of the formula II is obtained.Therefore, a process for preparing the stereoisomers of the general formula I or 11 is also the subject of the present invention. , which is characterized in that imines of the general formula III are cyclized, either without another reagent, in a concentrated organic solvent or acids or by adding inorganic or organic acids or Lewis acids at temperatures of re -70 ° C and + 80 ° C (preferably between -30 ° C and + 80 ° C) to obtain the stereoisomers of the general formula I or II as well as their previous compounds of the formula III. The new imines for cyclization are likewise object of the present invention, particularly those that are revealed by means of examples. The binding of substances to the glucocorticoid receptor (GR) and other steroid hormone receptors (mineral corticosteroid receptor (MR), progesterone receptor (PR) and androgen receptor (AR)) is analyzed with the help of recombinantly prepared receptors. For linkage analyzes, cytosol preparations of Sf9 cells previously infected with recombinant baculovirus encoding GR are used. In comparison with the reference substance [3 H] -dexametasone, the substances have a high affinity with GR. Thus, for example, for the compound of Example 285 it was found that IC50 (GR) = 86 nM and ICS0 (PR) = > 1000 and for the compound of Example 49, IC50 (GR) = 95 nM and IC50 (PR) = 460.

It is considered that the essential molecular mechanism that is responsible for the anti-inflammatory effect of glucocorticoids is the inhibition of the transcription of cytokines, adhesion molecules, enzymes and other pro-inflammatory factors through the GR. This inhibition is caused by an interaction of GR with other transcription factors, for example AP-1 and NF-cappa-B (for a summary see Cato ACB &Wade E, BioEssays 18, 371-378 1996). The stereoisomers of the general formula I of the invention inhibit the secretion initiated by lipopolysaccharide (LPS) of the cytokine IL-8 in the human monocytic cell line THP-1. The concentration of the cytokine was determined in the supernatant with ELISA sets obtained in commerce. The compound of example 285 exhibits an inhibition ICSo (IL8) = 40 nM (79% ef), the compound of example 49 exhibits an inhibition IC5o (IL8) = 19 nM. The anti-inflammatory effect of the stereoisomers of the general formula I was tested in animal experiments by means of rat-and-mouse crotone-induced inflammation assays. (J. Exp. Med. (1995), 182, 99-108). To this end, croton oil was applied topically in ethanolic solution in the ears of the animals. Simultaneously or two hours before applying the croton oil, the test substances were applied topically or systemically. After 16-24 hours, the weight of the ear was checked as a measure of inflammatory edema, the activity of peroxidase as a measure of granulocyte invasion and the activity of elastase as a measure of the invasion of neutrophil granulocytes. In this test, the stereoisomers of the general formula I inhibited the three inflammation parameters mentioned above, both after topical and systemic application. One of the most frequent undesirable effects of a glucocorticoid therapy is the so-called "spheroid diabetes" [see, Hatz, HJ, Glucocorticoid: Immunologische Grundlagen, Pharmakologie und Therapierichtlinien, Wissens-chafliche Verlagsgesellschaft mbH, Stuttgart, 1998]. The origin of this is the stimulation of gluconeogenesis in the liver by induction of the enzymes responsible for it and the free amino acids that result from the disintegration of proteins (catabolic effect of glucocorticoids). Thi-rosinaminotransferase (TAT) is a key enzyme of catabolic metabolism in the liver. The activity of this enzyme can be determined by photometry from liver homogenates and is a good measure for the undesired metabolic effects of glucocorticoids. To measure the induction of TAT, the animals are sacrificed 8 hours after the test substance is administered, the liver is removed and the activity of the TAT in the homogenate is measured. In this test, the stereoisomers of the general formula I, in effective doses as antiinflammatories, or induce tyrosineamine transferase or only do so to a limited extent.

As a result of its anti-inflammatory and also anti-allergic, in suppressive and antiproliferative effect, the stereoisomers of the general formula I of the invention can be used as a medicament for the treatment or prophylaxis of the following diseases in mammals and humans. The term "disease" applies to the following indications: (i) Pulmonary diseases manifested with inflammatory, allergic and / or proliferative processes: - Chronic obstructive pulmonary diseases of any genesis, especially bronchial asthma - Bronchitis of different origins - All forms of restrictive lung diseases, especially allergic alveolitis, - All forms of pulmonary edema, especially toxic pulmonary edema - Sarcoidosis and granulomatosis, particularly Boeck (ii) Rheumatic diseases / autoimmune diseases / joint diseases manifested with inflammatory, allergic and / or proliferative processes: - All forms of rheumatic diseases, particularly rheumatoid arthritis, acute rheumatic fever, rheumatic polymyalgia - Reactive arthritis - Diseases of soft inflammatory parts of other origins - Arthritic symptoms in degenerative joint diseases (osteoarthritis) - Traumatic arthritis - Collagenosis of any genesis, for example systemic lupus erythroblast, scleroderma, polymyositis, dermatomyositis, Sjögren's syndrome, Still's syndrome, Felty syndrome (iii) Allergies manifested with inflammatory and / or proliferative processes: - All forms of allergic reactions, for example Quincke's edema, hay fever, insect bites, allergic reactions to medications, blood derivatives, means of contrast etc., anaphylactic shock, urticaria , contact dermatitis (iv) Vascular inflammation (vasculitis) - Panarteritis nodosa, temporal arteritis, erythema nodosum (v) Dermatological diseases that manifest themselves with inflammatory, allergic and / or proliferative processes: - Atopic dermatitis (especially in children) - Psoriasis - Pityriasis rubra pilaris - Erythematous diseases initiated by different noxies, eg radiation, chemicals, burns etc. - Bullous dermatoses - Lichennoid type diseases, - Pruritus (eg of allergic origin) - Seborrheic eczema - Rosacea - Pemphigus vulgaris - Exudative multiform erythema - Balanitis - Vulvitis - Hair loss as alopecia areata - Cutaneous T-cell lymphomas ( vi) Kidney diseases that manifest with inflammatory, allergic and / or proliferative processes: - Nephrotic syndrome - All nephritis (vii) Liver diseases that manifest with inflammatory, allergic and / or proliferative processes: - Acute destruction of liver cells - Acute hepatitis of different origins, for example viral, toxic, drug-induced - Chronic aggressive hepatitis and / or chronic intermittent hepatitis (viii) Gastrointestinal diseases manifested with inflammatory, allergic and / or proliferative processes: - Regional enteritis (Crohn's disease) - Ulcerative colitis - Gastritis - Reflux esophagitis - Gastroenteritis of other origins eg celiac sprue (ix) Proctological diseases manifested with inflammatory, allergic and / or proliferative processes: - Anal eczema - Fissures - Hemorrhoids - Idiopathic proctitis (x) Eye diseases that manifest with inflammatory, allergic and / or proliferative processes: - Allergic keratitis, uveitis, iritis, - Conjunctivitis - Blepharitis - Optic nerve neuritis - Corioditis - Sympathetic ophthalmia (xi) Diseases of ear, nose and throat that manifest with inflammatory, allergic and / or proliferative processes: - Allergic rhinitis, hay fever - Otitis externa, for example by contact eczema, infection etc. - Otitis media (xii) Neurological diseases that manifest with inflammatory, allergic and / or proliferative processes: - Cerebral edema, especially cerebral edema by tumor - Multiple sclerosis - Acute encephalomyelitis - Meningitis - Different forms of seizures, for example BNS seizures (xiii) Hematological diseases that manifest with inflammatory, allergic and / or proliferative processes: - Acquired hemolytic anemia - Idiopathic thrombocytopenia (xiv) Tumor diseases that manifest with inflammatory, allergic and / or proliferative processes: - Acute lymphatic leukemia - Malignant lymphomas - Lymphogranulomatosis - Lymphosarcomas - Extensive metastasis, especially in cases of breast, bronchial carcinoma and prostate (xv) Endocrine diseases manifested with inflammatory, allergic and / or proliferative processes: - Endocrine orbitopathy - Thyroid toxic crisis - Quervain thyroiditis - Hashimoto's thyroiditis - Basedow's disease (xvi) Transplants of organs and tissues, graft disease - versus-host (xvii) Severe shock states, for example anaphylactic shock, Systemic inflammatory response syndrome (SIRS) (xviii) Substitution therapy in case of: - Congenital primary adrenal insufficiency, eg congenital adrenogenital syndrome - Adrenal insufficiency primary education, for example Add disease ison, autoimmune adrenalitis, post-infectious, tumors, metastasis etc. - Congenital secondary adrenal insufficiency, for example hypopituitarism - Acquired secondary adrenal insufficiency, eg post-infectious, tumors etc. (xix) Emesis, which manifests with inflammatory, allergic and / or proliferative processes: - for example in combination with a 5-HT3 antagonist in cases of vomiting conditioned by cytostatics. (xx) Pains of inflammatory origin, for example lumbago In addition, the stereoisomers of the general formula I of the invention can be used for the therapy and prevention of other diseases not mentioned above, for which synthetic glucocorticoids are currently used (cf. this, Hatz, HJ, Glucocorticoid: Immunologische Grundlagen, Pharmakologie u Therapierichtlinien, Wissenschafliche Ver-lagsgesellschaft mbH, Stuttgart, 1998). All the indications mentioned (i) to (xx) are described in detail in Hatz, HJ, Glucocorticoid: Immu-nologische Grundlagen, Pharmakologie u. Therapierichtlinien, Wissenschafliche Verlagsgesellschaft mbH, Stuttgart, 1998. The dose of therapeutic effect for the diseases mentioned is different and depends, for example, on the effectiveness of the compound of the general formula I, on the patient, on the form of administration and on the type and the severity of the conditions treated, as well as their use as preventive or therapeutic. The invention relates to the use of the claimed compounds / stereoisomers for the preparation of medicaments. The invention further provides (i) the use of one of the compounds / stereoisomers of the formula I of the invention or its mixture for preparing a medicament for the treatment of a DISEASE; (ii) a method for treating a DISEASE, comprising administering an amount of the compound of the invention, the amount of which suppresses the disease and is administered to a patient in need of such a medication; (iii) a pharmaceutical composition for the treatment of a DISEASE, whose treatment comprises the administration of one of the compounds of the invention or its mixture and at least one auxiliary substance and / or pharmaceutical carrier. In animals generally satisfactory results can be expected when the daily dose comprises from 1 μg to 100,000 μg of the compounds of the invention per kg of body weight. For large mammals, such as, for example, humans, the recommended daily dose ranges from 1 μg to 100,000 μg per kg of body weight. A dose of 10 to 30,000 μg per kg of body weight, more preferably 10 to 10,000 μg per kg body weight is preferred. Conveniently, this dose is administered several times per day. For the treatment of an acute shock (eg anaphylactic shock) doses can be administered clearly superior to the mentioned doses. The formulation of the pharmaceutical preparations based on the new compounds is carried out in a known manner by preparing the active substance with the vehicles, fillers, disintegration agents, absorption agents, aglu-financiers, humectants, glidants, flavor correctors, dyes, etc. galenically customary and taking them to the desired form of administration. For this we refer to Remington's Pharmaceutical Science, 15. Ed. Mack Publishing Company, East Pennsylvania (1980). For oral application, particularly tablets, coated tablets, capsules, pills, powders, granules, pills, suspensions, emulsions or solutions are used.

Injectable and infusion preparations are possible for parenteral application. For intra-articular injection, properly prepared glass suspensions can be used. For intramuscular injection, injectable, aqueous or oily solutions or suspensions and corresponding depot preparations can be used. For rectal application, the new compounds can be used in the form of suppositories, capsules, solutions (eg in the form of an enema) and ointments, both for systemic and local therapy. For the pulmonary application of the new compounds, they can be used in the form of aerosols and inhalants. For local application in the eyes, outer ear, middle ear, nasal passages and sinuses, the new compounds can be used in the form of drops, ointments and tinctures in corresponding pharmaceutical preparations. For topical application, formulations in the form of gels, ointments, ointments, creams, pastes, powders, milk and tinctures are possible. In these preparations, the dosage of the compounds of the general formula I should be 0.01% -20% to achieve a sufficient pharmacological effect. The invention also comprises the compounds of the general formula I of the invention in the form of a therapeutic active substance. The invention also encompasses the compounds of the general formula I of the invention in the form of a therapeutic active together with auxiliaries and pharmaceutically tolerable and acceptable vehicles. The invention also comprises a pharmaceutical composition containing one of the pharmaceutically active compounds of the invention or its mixture or its pharmaceutically tolerable salt and a pharmaceutically tolerable salt or pharmaceutically tolerable auxiliaries and vehicles. EXPERIMENTAL PART Example 1 4-. { [8-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -2, 3-dihydroisoindol-1-one 4-amino-2,3-dihydroisoindol-l -one Methyl ester of 2-methyl-3-nitrobenzoic acid 30 g (165.6 mmol) of 2-methyl acid are introduced -3-Nitrobenzoic acid in 150 ml of methanol and, after the addition of 2.9 ml of concentrated sulfuric acid, is refluxed for two days. After cooling, the crystallizate is extracted (25.55 g = 79%) and used as such in the next step. ? -NMR (300 MHz, DMSO-de): d = 2.50 (3H), 3.85 (3H), 7.56 (IH), 8.00 (IH), 8.05 (1H). 2- (Bromomethyl) -3-nitrobenzoic acid methyl ester 25.55 g (130.9 mmol) of 2-methyl-3-nitrobenzoic acid methyl ester are introduced into 300 ml of carbon tetrachloride, and mixed with carbon tetrachloride. , 6 grams (141.7 mmol) of N-bromsuccinimide and 62.8 mg of benzoyl peroxide. After refluxing for seven days, the succinimide is extracted and then the filtrate is centrifuged until it is dried. In this way the desired compound is obtained, which is used in the rough in the next step. ^ - MR (300 MHz, CDC13): d = 4.00 (3H), 5.66 (2H), 7.55 (IH), 7.95 (IH), 8.10 (IH). 2- (Azidomethyl) -3-nitrobenzoic acid methyl ester 10 g (36.5 mmol) of 2- (bromomethyl) -3-nitrobenzoic acid methyl ester in 36 ml of N, N-dimethylformamide are introduced with 24 ml of Water. After the addition of 3.54 g of sodium azide, the preparation is stirred overnight. The reaction mixture is diluted with methyl-tert-butyl ether, washed twice with water and once with saline. After drying with sodium sulfate, it is filtered and the solvent is removed. The desired acid is obtained in a yield of 89.6% (7.72 g) and is used raw in the next step. XH-NMR (300 MHz, CDC13): d = 4.00 (3H), 4.93 (2H), 7.58 (HH), 7.96 (ÍH), 8.12 (HH). 4-amino-2,3-dihydroisoindole-1-one 1 g (4.2 mmol) of 2- (azidomethyl) -3-nitrobenzoic acid methyl ester in 10 ml of ethanol and 2 ml of ethyl acetate are introduced. and it is mixed with 148.5 mg of Pd / C. After stirring overnight at room temperature under a hydrogen atmosphere, the catalyst is removed on a glass fiber filter and the filtrate is concentrated to dryness. The residue is subjected to flash chromatography (elution medium). 391.5 mg (62.4%) of the desired compound are obtained.

X H-NMR (300 MHz, DMSO-d 6): d = 4.10 (2 H), 5.36 (2 H), 6.75 (H), 6.85 (H), 7.15 (H), 8 , 35 (ÍH). 4- (5-f luoro-2-methoxy-enyl) -2-hydroxy-4-methyl-2-trifluoromethyl) -pentanal 6.55 g (21.11 mmol) of rac-4- (5-fluoro) are dissolved. -2-methoxyphenyl) -4-methyl-2-trifluoromethyl) -pentan-1,2-diol (WO 00/32584) in 224 ml of dichloromethane and room temperature is mixed with 74 ml of dry dimethylsulfoxide and 10.68 g ( 105.55 mmol) of triethylamine. At 15 to 18 ° C, 10.08 g (63.33 mmol) of the S03 / pyridine complex are added in portions over the course of 40 minutes in the vessel. After stirring overnight at room temperature, 84 ml of a saturated solution of ammonium chloride are added. The mixture generates a slight heat. After stirring for 15 minutes at room temperature, it is extracted twice with 300 ml of diethyl ether each. The organic phases are washed with water and saline, and dried (sodium sulfate). After filtering and removing the solvent, the residue is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). Then 5.85 g (90%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.46 (3H), 2.22 (HH), 3.38 (ÍH), 3.59 (HH), 3.86 (HH), 6.70-6.80 (ÍH), 6.82-6.97 (2H), 9.05 (HH). 4-. { [4- (5-f luoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} 2,3-dihydroisoindol-1-one 400 mg (1.297 mmol) of rac-4- (5-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2"trifluoromethyl) -pentanal are stirred with 192.1 mg (1.297 mmol) of 4-amino-2,3-dihydroisoindol-1-one in 1.89 ml of ethyl acetate for four days at room temperature The mixture is combined with toluene and concentrated on a rotary evaporator until The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane) 429.7 mg (75.5%) of the desired compound are isolated XH-NMR (300 MHz, CDC13): d = 1.37 (3H), 1.52 (3H), 2.22 (ÍH), 3.42 (ÍH), 3.84 (3H), 4.37 (2H), 4.68 (HH) 6,53-6,68 (3H), 6,72-6,95 (2H), 7,37 (ÍH), 7,49 (ÍH), 7,75 (ÍH). Fluoro-2-hydroxy-5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amino.} -2,3-dihydroisoindole-1- ona (Diastereomer A); 4- { [8-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino}. -2,3-dihydroisoindole-lo na (Diastereomer A); 4-. { [8-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amino} -2,3-dihydroisoindol-1-one (Diastereomer B) 420 mg (0.95'8 mmol) of the mixture described in the previous step of 4- are mixed. { [4- (5-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} -2, 3-dihydroisoindol-1-one with 9.6 ml of an ÍM solution of boron tribromide in dichloromethane, and stir for one hour and three quart at room temperature. The reaction mixture is combined at -30 ° C by dripping with a saturated solution of sodium bicarbonate until reaching pH 8. After diluting with ethyl acetate, the ice bath is removed and stirred vigorously for 15 minutes. After extracting twice with ethyl acetate, the organic phases are washed with water and saturated sodium chloride solution. After drying (sodium sulfate) and removing the solvent, the residue is subjected to flash chromatography (silica gel, NH2 phase) (elution medium: dichloromethane / methanol). 67.7 mg (16.6%) of 4- are isolated. { [8-fluoro-2-hydroxy-5-methoxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2, 3-dihydroisoindol-1-one (Diastereomer A, Fl); 12.9 mg (3.2%) of 4-. { [8-fluoro-2,5-dihydroxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2, 3-dihydroisoindol-1-one (Diastereomer A, F2) and 32.2 mg (7.9%) of 4-. { [8-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino) -2,3-dihydroisoindol-1-one ( Diastereomer B, F3). Fl: ^ -NMR (300 MHz, MeOD): d = 1.47 (3H), 1.60 (3H), 2.07 (1H), 2, 25 (ÍH), 3,49 (3H), 4,19-4,40 (2H), 5,20 (ÍH), 6,31 (ÍH), 7,00 (ÍH), 7,15-7 , 30 (2H), 7.38 (ÍH). F2: ^? - R (300 MHz, MeOD): d = 1.50 (3H), 1.59 (3H), 2.05 (IH), 2.28 (1H), 4.20-4.42 (2H), 5.18 (ÍH), 6.61 (ÍH), 6.80-6.90 (HH), 7.15 (ÍH), 7.20-7.40 (2H). F3: ^ -NMR (300 MHz, MeOD): d = 1.52 (3H), 1.69 (3H), 2.03 (1H), 2.23 (1H), 4.20-4.39 ( 2H), 5.18 (1H), 6.65-6.80 (2H), 7.10-7.23 (2H), 7.35 (1H). Example 2 5-. { [7-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -isoquinolin-1 (2H) -one 5-amino-isoquinolin-l (2H) -one 5-nitroisocoumarin 16.4 g (84.03 mmol) of the methyl ester of 2-methyl-3-nitrobenzoic acid, described in Example 1, with 26.8 g (225.1 mmol) of N, N-dimethylformamide dimethylacetal in 85 ml of dimethylformamide for 12 hours at 130 ° C. The solvent is removed in a rotary evaporator, the residue is taken up with methyl-tert-butyl ether and washed three times with water. After washing with a saturated solution of NaCl, the organic phase is dried. After filtering the drying media and removing the solvent, the residue is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 8.73 g (54.4%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 7.39 (ÍH), 7.45 (ÍH), 7.68 (1H), 8.49 (ÍH), 8.65 (ÍH). 5-Nitroisoquinolin-1 (2H) -one 2.51 g (13.13 mmol) of 5-nitroisocoumarin are introduced into 100 ml of ethanol and ammonia is introduced under pressure into the autoclave. The product precipitates and is extracted. 1.98 g (79.7%) of the desired compound are isolated. ^? - NMR (300 MHz, DMSO-de): d = 6.97 (ÍH), 7.45 (HH), 7.65 (ÍH), 8.43 (HH), 8.57 (ÍH), 11.5 (ÍH). 5-aminoisoquinolin-1 (2H) -one 268.3 mg (1.51 mmol) of 5-nitroisoquinolinyl (2H) -one are mixed with 376.5 mg of ammonium chloride and 2.6 ml of water 14 ml of ethanol and 5.4 ml of tetrahydrofuran. After stepwise addition of 1.23 g of tin powder (with heating between 30 and 35 ° C), stir for two hours. The reaction mixture is extracted on a glass fiber filter and washed again with ethyl acetate. After washing the filtrates with water and saturated sodium chloride solution, the organic phase is dried using conventional means. The filtration of the drying media and the removal of the solvents makes it possible to obtain 196.5 mg (88.1%) of the desired amines. ^ -NMR (300 MHz, DMSO-d6): d = 5, 6 (2H), 6,68 (1H), 6,87 (ÍH), 7,00 (ÍH), 7,17 (ÍH), 7 , 39 (ÍH), 11,7 (ÍH). 4- (4-Chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentan-1-ol A solution of 3 g of ethyl ester of 2-hydroxy-4-methylene is mixed -2- (trifluoromethyl) valeric in 22 ml of 3-chloranisole with aluminum trichloride, in portions at room temperature. After stirring for 48 hours at room temperature, the mixture is mixed with 2N hydrochloric acid and hexane, and stirred for an additional hour. After washing with 2N hydrochloric acid and water, the excess of 3-chloranisole is distilled in vacuo. The remaining residue is purified by chromatography on silica gel (elution medium: hexane / acetic acid). 2.85 g of a mixture of 4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -alleric acid ethyl ester and the regioisomer of ethyl ester of 4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) acid are obtained. (2-Chloro-4-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) valeric as a yellow oil. This mixture of substances is incorporated in 90 ml of ether at 0 ° C with 445 mg of lithium aluminum hydride, and stirred for 12 hours. The preparation is poured into a saturated solution of sodium bicarbonate and filtered with diatomaceous earths. The phases are separated and the aqueous phase is extracted with ethyl acetate. Wash with water and saline, dry with sodium sulfate and concentrate in vacuo. After using chromatography on silica gel (elution medium: hexane / acetic acid), a first fraction of 1.87 g of the desired compound of 4- (4-chloro-2-methoxyphenyl) -2-hydroxy- is obtained. 4-methyl-2- (trifluoromethyl) pentan-1-ol and a second fraction of 160 mg of the regioisomer, 4- (2-chloro-4-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentan-1-ol, as a colorless oil. First fraction: XH-NMR (CDC13), d = 1.41 (3H), 1.51 (3H), 2.24 (ÍH), 2.51 (ÍH), 2.84 (ÍH), 3.36 (ÍH), 3.48 (ÍH), 3.85 (3H), 6.88 (ÍH), 6.92 (ÍH), 7.24 (ÍH). Second fraction: XH-NMR (CDC13), d = 1.52 (3H), 1.62 (3H), 2.18 (HH), 2.76 (1H), 2.93 (ÍH), 3.33 (ÍH), 3.55 (ÍH), 3.80 (3H), 6.78 (ÍH), 6.90 (ÍH), 7.38 (ÍH). 4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (tri-fluoromethyl) pentanal In a hot flask, 854.6 mg (6.733 mmol) of oxalyl chloride are introduced in 14.5 ml of dichloromethane. At -70 ° C, 1.05 ml of DMSO are added dropwise, dissolved in 3 ml of dichloromethane and the preparation is again stirred for five minutes. Subsequently, 2 g (6.12 mmol) of 4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentan-1-ol, dissolved in six milliliters of dichloromethane, are added dropwise. . After stirring for 20 minutes, the preparation is carefully mixed with 4.24 ml (30.61 mmol) of triethylamine and the temperature is adjusted between -70 and -60 ° C.

After stirring for five minutes at -70 ° C, the reaction mixture is allowed to stand at room temperature. 25 ml of water are added and the preparation is stirred for another hour at room temperature. After separating the phases, the aqueous phase is stirred once with 100 ml of dichloromethane. Wash the combined organic extracts with 1% sulfuric acid, % sodium bicarbonate and saline. Using conventional procedures, 1.92 g (96.9%) of the desired aldehyde is obtained, which is used in the crude in the next step. XH-NMR (300 MHz, CDC13): d = 1.37 (3H), 1.45 (3H), 2.22 (1H), 3.35 (1H), 3.59 (1H), 3.90 (3H), 6.80-6.92 (2H), 7.04 (1H), 9.02 (1H). 5-. { [(4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} isoquinolin-1 (2H) -one 300 mg (0.924 mmol) of 4- (4-chloro-2-methoxy-phenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal are stirred with 148 mg (0.924 mmol) of 5-amino-isoquinolin-1-one in 1.33 ml of ethyl acetate for four days at room temperature. It is combined three times with toluene and concentrated in a rotary evaporator until dry. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 382.4 mg (88.6%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.37 (3H), 1.58 (3H), 2.26 (1H), 3.43 (1H), 3.85 (3H), 4.80 (ÍH), 6.43 (ÍH), 6.59 (ÍH), 6.70-6.77 (2H), 7.00 (ÍH), 7.15-7.25 (1H), 7.30 -7.45 (2H), 8.32 (HH), 11.00 (HH). 5-. { [1-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amin} Isoquinolin-1 (2H) -one 50 mg (0.107 mmol) of the mixture described in the previous step of 5- are mixed. { [4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} 2, 3-isoquinolin-l-one at -20 ° C with 2.1 ml of an ÍM solution of boron tribromide in dichloromethane, and is stirred for two and a half hours at a temperature between -20 ° C and 0 ° C. The reaction mixture is added dropwise at -20 ° C, with a saturated solution of sodium bicarbonate. After diluting with ethyl acetate, the mixture is allowed to warm to room temperature, stirred for 15 minutes and extracted twice with ethyl acetate. The combined organic extracts are washed with water and saturated NaCl solution. After drying with sodium sulfate, the solvent is removed and the residue is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 12.5 mg (25%) of the desired compound are isolated. XH-NMR (300 MHz, MeOD): d = 1.55 (3H), 1.65 (3H), 2.03-2.20 (2H), 5.13 (1H), 6.73 (1H) , 6.80 (ÍH), 6.87 (ÍH), 7.09 (ÍH), 7.19 (ÍH), 7.40 (ÍH), 7.70 (ÍH). Example 3 (+) - 6-fluoro-1- (lH-indazol-4-yl) amino] -4, -dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2,5- diol and (-) - 6-fluoro-1- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3-tetrahydronaf-alen-2, 5 -diol 2, 6-difluoranisole 20 g (153.74 mmol) of 2,6-difluorophenol are dissolved in 200 ml of acetone and mixed under nitrogen with 42.5 g (307.48 mmol) of potassium carbonate. After the addition of 19.1 ml of methyl iodide (2 equivalents), the mixture is refluxed. After cooling, the reaction mixture is filtered, the filter residue is washed with acetone and the filtrate is centrifuged until it is dried. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 17.27 g (77.9%) of the desired product are obtained. It should be noted that the product is somewhat volatile. The temperature of the bath must not exceed 30 ° C, and the vacuum must be adjusted in the rotary evaporator. XH-NMR (300 MHz, CDC13): d = 4.00 (3H), 6.80-7.00 (3H). 2- (3-f luoro-2-methoxyphenyl) -2-methylpropanonitrile 10 g (69.39 mol) of 2,6-difluoroanisole are dissolved in 200 ml of toluene and mixing at room temperature with 5.75 g (83.27 mmol) of nitroisobutyric acid. 166.5 ml of a 0.5 molar solution of he-xa ethyldisilazide of potassium in toluene are added dropwise over 35 minutes.

There is a decrease in temperature to 27.5 ° C.

After stirring for 16 hours at room temperature, the reaction mixture is combined with 200 ml of water and 400 ml of ethyl acetate, and the pH is acidified with 10% sulfuric acid to pH 4. The organic phase is separated and The aqueous phase is stirred once in ethyl acetate (200 ml). The combined organic extracts are stirred with water and saline. After drying, filtering and removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 7.66 g are isolated (57.1%) of the desired compound. ^ -NMR (300 MHz, CDC13): d = 1.76 (6 H), 4.08 (3H), 6.95-7.13 (3H). 2- (3-f luoro-2-methoxy-enyl) -2-methylpropanal 7.66 g (39.64 itimol) of the nitrile previously described are dissolved in 158 ml of toluene. At -65 to -60 ° C, 49.5 ml of a 1.2 molar solution of DIBAH in touluol are added dropwise over 40 minutes. After stirring for one hour at this temperature, 493 ml of a 10% solution of L- (+) - tartaric acid are added dropwise. After 100 milliliters, the temperature is increased to -10 ° C. The rest of the tartaric acid solution is quickly added and the preparation is stirred thoroughly for two hours at room temperature. The reaction mixture is combined twice with 400 ml of diethyl ether each time. The combined organic extracts are poured into water and saline, dried, and the solvent is removed. The remaining residue (7.8 g = 102%) is used raw in the next step. XH-NMR (300 MHz, CDC13): d = 1.40 (6 H), 3.88 (3H), 6.95-7.10 (3H), 9.60 (1H). Ethyl ester (E / Z) -4- (3-fluoro-2-methoxyphenyl) -4-methylpent-2-enoic To a solution of 9.87 g (39.75 mmol) of 2-ethoxy-triethyl ester of Phosphoacetic acid in 40 ml of absolute THF is added dropwise to 21.3 ml of a 2 molar solution of LDA in THF at 0 ° C. After stirring for 30 minutes at 0 ° C, 7.8 g (39.75 pmol) of 2- (3-fluoro-2-methoxyphenyl) -2-methylpropanal dissolved in 26 ml of THF are added dropwise at 0 ° C. ° C. The ice bath is removed and the preparation is stirred for 16 hours at room temperature. The reaction mixture is poured into water and extracted twice with ethyl acetate. The combined organic extracts are washed with water and saline, dried and the solvent is removed after filtering the drying media. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 8.39 g (68.2%) of the desired compound are isolated. MS (Cl): 328 (29%), 265 (100%), 181 (56%), 167 (42%). Acid (E / Z) -4- (3-f luoro-2-methoxy-enyl) -4-methylpent-2-enoic 8.39 g (27.03 mmol) of ethyl ester of acid are mixed (E / Z) -4- (3-fluoro-2-methoxyphenyl) -4-methylpent-2-enoic with 270 ml of IN NaOH in ethanol / water (2: 1) and stir for two days at room temperature. The ethanol is removed in a rotary evaporator and the residue is extracted twice with 150 ml of diethyl ether each. The combined organic extracts are washed with water and subjected to a DC control. The aqueous phase is acidified with concentrated hydrochloric acid to pH 3 and extracted twice with 300 ml of diethyl ether each. The ether extracts are washed with water and saline, dried, the solvent is removed and the residue is used (5.89 g = 77.2%) in the rough in the next step. MS (Cl): 300 (100%), 282 (10%), 237 (27%), 167 (26%). 4- (3-F-luoro-2-methoxy-enyl) -4-methyl-2-oxo-pentenoic acid 5.89 g (20.86 -timol) of (E / Z) -4- (3-fluoro) acid are mixed. -2-methoxyphenyl) -4-methylpent-2-enoic at room temperature with 126 ml of a 1 molar solution of sulfuric acid, and after the addition of 21 ml of ethyl acetate, is stirred for 15 hours with a water bath. a temperature of 90 ° C. The reaction mixture is carefully combined in a cooling bath (large amount of foam) with solid potassium carbonate at pH 9. It is extracted twice with diethyl ether. The combined organic extracts are washed with water and subjected to DC. The combined aqueous phases are acidified with hydrochloric acid to pH 4 and extracted twice with 300 ml of diethyl ether each. The ether extracts are washed with saline solution, they are dried and the solvent is removed. Since the residue still contains acetic acid, it is centrifuged twice with 100 ml of toluene at a time. The remaining residue (4.14 g = 78.1%) is used raw in the next step. ^ -NMR (300 MHz, CDC13): d = 1.50 (6 H), 3.53 (2H), 3.93 (3H), 6.90-7.10 (3H). Ethyl 4- (3-fluoro-2-methoxyphenyl) -4-methyl-2-oxo-pentaneic acid ester 4.14 g (16.28 itimol) of 4- (3-fluoro-2-methoxyphenyl) acid are dissolved. ) -4-methyl-2-oxo-pentanoic acid in 97 ml of ethanol, mixed with 1.79 ml of sulfuric acid and refluxed for four hours. The ethanol is removed in a rotary evaporator and the residue is carefully mixed with a saturated solution of sodium bicarbonate until obtaining pH 9. It is extracted twice with 100 rl of ethyl acetate each, and the combined organic extracts are washed with water and then with saline. After drying, filtering the drying media and removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 4.16 g (90.6%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.29 (3H), 1.48 (6H), 3.40 (2H), 3.98 (3H), 6.89-7.09 (3H) ). Ethyl 4- (3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-trimethylsilyloxy-pentanoic acid ester 4.16 g (14.74 inmol) of ethyl ester of acid are dissolved 4- (3-fluoro-2-methoxyphenyl) -4-methyl-2-oxo-pentanoic acid in 24 ml of THF and mixed at 0 ° C with 2.51 g (17.68 mmol) of (trifluoromethyl) -trimethylsilane and 36.1 mg of tetrabutylammonium fluoride. After stirring for two hours at 0 to 5 ° C, the preparation is poured into 50 ml of ice water. It is extracted twice with 150 ml of diethyl ether each, and the combined organic extracts are processed using conventional means. Chromatography on silica gel (elution medium: ethyl acetate / hexane) makes it possible to obtain 5.24 g (83.8%) of the desired compound. MS (Cl): 442 (100%), 425 (41%). 4- (3-f luoro-2-methoxy-enyl) -4-methyl-2- (trifluoromethyl) -2-trimethylsilyloxy-pentan-1-ol 5.24 g (12.34 mmol) of ethyl ester are dissolved in water. 4- (3-fluoro-2-methoxyphenyl) -4-methyl-2-trifluoromethyl-2-trimethylsilyloxy-pentanoic acid in 45 ml of diethyl ether and mixed in portions between 0 and 5 ° C with 936.9 mg (24, 69 mmol) of LiAlH4. After stirring for four and a half hours at room temperature, the reaction mixture is carefully combined with cooling in an ice bath with a saturated solution of NaHCO 3, stirred for one hour in the cold and overnight at room temperature. Processing using conventional means allows to obtain 4.11 g (87.1%) of a mixture of the desired compound and a compound from which the silyl ether has migrated. The compound is used raw in the next step. 4- (3-f luoro-2-methoxy-enyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentan-1-ol 4.11 g (10.75 itimol) of 4- ( 3-fluoro-2-methoxyphenyl) -4-methyl-2-trifluoromethyl-2-trimethylsilyloxy-pentan-1-ol in 61 ml of THF, mixed with 3.39 g (10.746 mmol) of Bu4NF trihydrate and stirred for one hour at room temperature. The reaction mixture is poured into water and extracted twice with diethyl ether. The organic phases are washed with water and saline using conventional means. After drying, filtering and filtering the drying media and removing the solvent, the residue is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 2.71 g (81.4%) of the desired compound are isolated. ZH-NMR (300 MHz, CDC13): d = 1.45 (3H), 1.54 (3H), 2.20 (HH), 2.54 (ÍH), 2.90 (ÍH), 3.30. -3.50 (2H), 3.98 (3H), 6.90-7.13 (3H). 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal In a hot flask, 765 mg (6.03 mmol) of oxalyl chloride are introduced into 13 ml of dichloromethane. At -78 ° C drip 0.855 ml of DMSO dissolved in 2.5 ml of dichloromethane, and the preparation is stirred for five minutes. Then 1.7 g (5.48 mmol) of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanol dissolved in five milliliters of dichloromethane are added dropwise. After stirring for 15 minutes, the preparation is carefully mixed with 3.79 ml (27.40 mmol) of triethylamine, for five minutes at -78 ° C, and then left to stand at room temperature. 20 ml of water are added and the preparation is further stirred for an additional hour at room temperature. After separating the phases, the aqueous phase is combined once with 100 ml of dichloromethane. The combined organic extracts are washed with 1% sulfuric acid, with a 5% solution of sodium bicarbonate and with saline. Using conventional procedures, 1.617 g (96.2%) of the aldehyde which is used in the crude in the next step is obtained. ^ - MR (300 MHz, CDC13): d = 1.40 (3H), 1.49 (3H), 2.29 (IH), 3.29 (IH), 3.59 (IH), 4.00 (3H), 6.85-7.08 (3H), 9.13 (1H). l, 1, l-trifluoro-4- (3-fluoro-2-methoxyphenyl) -2- [(1H-indazol-4-yl) iminomethyl] -4-methylpentan-2-ol. 1.46 g (4,746 g. mmol) of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal with 632 mg (4.746 mmol) of 4-aminoindazole in 6.78 ml of acetic acid per two days at room temperature. The reaction mixture is combined three times with toluene in a rotary evaporator and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). They are isolated 147 g (73.5%) of the desired compound. MS (ES +): 424 (100%). (+) - 6-fluoro-5-methoxy-l- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalene- 2-ol and (-) - 6-fluoro-5-methoxy-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4 -tetrahydronaphthalen-2-ol 1.32 g (3.117 mmol) of the previously described imine and 1,1-trifluoro-4- (3-fluoro-2-methoxyphenyl) -2- [(1H-indazole) are dissolved. -4-yl) iminomethyl] -4-methylpentan-2-ol in 22.8 ml of dichloromethane. To this solution is added 9.35 ml of an ITM solution of TIC14 in dichloromethane (3 equivalents) at -30 ° C, and then the mixture is placed under nitrogen for 15 minutes. The reaction mixture is stirred for three and a half hours at -30 - -15 ° C. The preparation is mixed at -30 ° C by dripping with a saturated solution of sodium bicarbonate. After. dilute with ethyl acetate, stir for 15 minutes at room temperature. After extracting twice with 150 ml of ethyl acetate each, the organic phases are washed (water, saline), dried (Na2SO4) and the solvent is removed. After chromatography on silica gel (elution medium: dichloromethane / methanol), 1.07 g (81.1%) of the desired product is obtained as a racemate. The product is separated into its enantiomers (Chiralpak AD 5 g; elution medium: hexane / ethanol). The (+) enantiomer has an optical rotation [a] D = + 1.6 ° (c = 1, MeOH) and the enantiomer (-) has an optical rotation [a] D = -1.3 ° (c = 1) , MeOH). (+) - 6-fluoro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3-tetrahydronaphthalene-2,5-diol 200 mg (0.472 mmol) of (+) - 6-fluoro-5-me-toxy-1- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1 are mixed , 2, 3, -tetrahydronaphthalen-2-ol previously described with 4.7 ml of an IVM solution of BBr3 in dichloromethane at room temperature, and stirred for three and a half hours at room temperature. The reaction mixture is combined at -30 ° C by dripping with a saturated solution of sodium bicarbonate, and the pH is adjusted to 8. After diluting with ethyl acetate, the ice bath is removed and the preparation is stirred thoroughly for 15 minutes. After stirring twice with ethyl acetate, the combined organic extracts are washed with water and saturated saline. After drying with sodium sulfate, filtering and removing the solvent, the residue is chromatographed on silica gel (elution medium: dichloromethane / methanol). 171.3 mg (88.6%) of the desired compound are obtained. The rotation, measured at room temperature, is [a] D - +7.3 (c = 1, MeOH). (+ -6-fluoro-l-l (lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2,5-diol 200 mg (0.472 mmol) of (-) - 6-fluoro-5-me-toxy-1- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1 are mixed , 2, 3, 4-tetrahydronaphthalen-2-ol previously described with 4.7 ml of an IM solution of BBr3 in dichloromethane at room temperature, and stirred for three hours and three quart at room temperature. -30 ° C drip with a saturated solution of sodium bicarbonate, and then adjust the pH to 8. After diluting with ethyl acetate, remove the ice bath and stir the preparation thoroughly for 15 minutes. shake twice with ethyl acetate, wash the combined organic extracts with water and saturated saline solution.Salt with sodium sulfate, filter and remove the solvent, the residue is chromatographed on silica gel (elution medium: dichloromet anion / methanol) 179.4 mg (92.8%) of the desired compound are obtained. The rotation, measured at room temperature, is [a] D = -7.8 (c = 1, MeOH). Example 4 4-. { [8-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -6-fluoro-2, 3-dihydroisoindol-l-one 4-amino-6-fluoro-2,3-dihydroisoindol-l-one 2-Methyl-5-fluoro-3-nitrobenzoic acid 116 ml of acid are mixed sulfuric acid with 14.70 g (95.37 mmol) of 5-fluoro-2-methylbenzoic acid, at -15 ° C in portions. To this mixture is added dropwise a mixture of nitric acid (4.79 ml of fuming nitric acid and 21.8 ml of concentrated sulfuric acid), at -15 - -10 ° C over a period of 90 minutes. After stirring for three hours, the reaction mixture is poured into ice water and stirred thoroughly for about half an hour. The crystallized precipitate is extracted, washed neutral with water and dried. A yield of 8.56 g (45.1%) of a mixture of different regioisomers and by-products is obtained. This mixture is used crude in the next step (esterification) and purified in this step. Methyl ester of 2-methyl-5-fluoro-3-nitrobenzoic acid 8.56 g (42.99 mmol) of 2-methyl-5-fluoro-3-nitrobenzoic acid are introduced into 76 ml of N, N-dimethylformamide and it is mixed with 9.15 g (64.48 mmol) of methyl iodide and 8.91 g. (64.48 mmol) of potassium carbonate. After stirring for 65 hours at room temperature, the reaction mixture is poured into ice water and extracted several times with ethyl acetate. The combined organic extracts are washed with water and saline. After drying (sodium sulfate), the drying media is removed and the solvent is removed. Repeat chromatography on silica gel (elution medium: ethyl acetate / hexane) several times to obtain the desired compound in a yield of 25.9% (2.37 g). XH-NMR (300 MHz, CDC13): d = 2.60 (3H), 3.96 (3H), 7.61 (1H), 7.77 (1H). Methyl ester of 2- (bromomethyl) -5-fluoro-3-nitrobenzoic acid 2.37 g (11.12 mmol) of 5-fluoro-methyl ester of 2-methyl-3-nitrobenzoic acid in 35 ml are introduced. of carbon tetrachloride, and mixed with 2.24 grams (12.24 mmol) of N-bromsuccinimide and 5.4 mg of benzoyl peroxide. After refluxing for four days, the succinimide (fiberglass filter) is removed and the filtrate is then centrifuged to dry. Flash chromatography allows to obtain 2.47 g (75.9%) of the desired compound. XH-NMR (300 MHz, CDC13): d = 4.01 (3H), 5.13 (2H), 7.72 (1H), 7.87 (1H). Methyl ester of 2- (azidomethyl) -5-f luoro-3-nor trobenzoic acid 2.47 g (8.46 mmol) of 2- (bromomethyl) -5-fluoro-3-nitrobenzoic acid methyl ester are mixed with 8.3 ml of N, N-dimethylformamide and 5.5 ml of water. After the addition of 0.82 g (12.66 mmol) of sodium azide, the preparation is stirred overnight. The reaction mixture is poured into water and extracted three times with methyl-tert-butyl ether. The combined organic extracts are washed with water and saline. After drying with sodium sulfate, it is filtered and the solvent is removed. Flash chromatography makes it possible to obtain 2.06 g (95.8%) of the desired azides. ^ -NMR (300 MHz, CDC13): d = 4.00 (3H), ,, 90 (2H), 7.73 (ÍH), 7.87 (ÍH). 4-amino-6-fluoro-2,3-dihydroisoindol-l-one 1.86 g (7.32 mmol) of 2- (azidomethyl) -5-fluoro-3-nitrobenzoic acid methyl ester in 46 ml are introduced. of ethanol and 3.4 ml of ethyl acetate, and mixed with 256.6 mg of Pd / C. After stirring overnight at room temperature under a hydrogen atmosphere, the catalyst is removed on a glass fiber filter and the filtrate is concentrated to dryness. The residue, 1.18 mg (97.5%) of the desired compound, is used crude in the next step. ^ -NMR (300 MHz, DMSO-d6): d = 4.10 (2H), 5.75 (2H), 6.46-6.57 (2H), 8.50 (1H). 4-. { [4- (5-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} 6-f luoro-2, 3-dihydroisoindol-1-one 400 mg (1.297 mmol) of rac-4- (5-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) are stirred. pentanal with 215.5 mg (1.297 mmol) of 4-amino-6-fluoro-2,3-dihydroisoindol-1-one in 1.89 ml of ethyl acetate for four days at room temperature. As the DC indicates that contaminated material is still present, the reaction mixture is mixed with toluene and subjected to a precipitation with water for 20 hours. The mixture is combined three times with toluene and concentrated in a rotary evaporator to dryness. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 383.4 mg (64.7%) of the desired compound are isolated. 1 H-NMR (300 MHz, CDC13): d = 1.37 (3H), 1.53 (3H), 2.20 (HH), 3.47 (ÍH), 3.88 (3H), 4.32. (2H), 4.57 (HH), 6.22 (ÍH), 6.63-6.88 (4H), 7.42 (1H), 7.48 (1H). 4- . { [8-fluoro-2, 5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-1-yl] amino} -6-fl uoro-2,3-dihydroisoindol-l-one 380 mg (0.832 mmol) of 4- are mixed. { [4- (5-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} 6-fluoro-2,3-dihydroisoindol-1-one at room temperature with 8.3 ml of an IVM solution of BBr3 in dichloromethane, and stirred for one hour at the temperature of an ice bath. The conditioning of the preparation is carried out as described in example four. After subjecting the crude product to flash chromatography (amine phase; elution medium: methanol / dichloromethane), 9.2 mg (2.7%) of the desired compound are obtained. ^ -NR (300 MHz, CD3OD): d = 1.53 (3H), 1.69 (3H), 2.02 (IH), 2.22 (IH), 4.28 (2H), 5.09 (ÍH), 6.60-7.00 (4 H). Example 5 4-. { [5-fluoro-2,6-dihydroxy-, 4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amino} -2,3-dihydroisoindol-1-one 2-fluoro-3-methoxybenzaldehyde 27 ml (240.62 mmol) of 2-fluoranisole are dissolved in 700 ml of tetrahydrofuran. 200 ml of BuLi (1.3M solution in cyclohexane) are added dropwise at -70 ° C. It is stirred for one hour at -70 ° C and then 152 ml of N, N-dimethylformamide dissolved in 50 ml of tetrahydrofuran are added dropwise at this temperature. After stirring for an additional hour at -70 ° C, 380 ml of hydrochloric acid (10%) are added dropwise. Thereafter, the preparation is allowed to slowly reach room temperature. After stirring overnight at room temperature, methyl tert-butyl ether is added and, after thorough stirring, the organic phase is separated. The aqueous phase is still extracted twice with methyl-tert-butyl ether. The combined organic extracts are washed with saline and dried. After filtering the drying media, the solvent is removed and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 25.66 g (69.2%) of the desired compound are isolated. 1 H-NMR (300 MHz, CDC13): d = 3.95 (3H), 7.13-7.26 (2H), 7.38-7.45 (HH), 10.4 (HH). 2-Fluoro-3-methoxybenzene alcohol 25.66 g (166.47 mmol) of 2-fluoro-3-methoxybenzaldehyde are dissolved in 140 ml of ethanol and mixed at 0 ° C with 3.15 g (83.35 mmol ) of sodium borohydride in portions.

After stirring for one hour at room temperature, the reaction mixture is mixed with water and extracted three times with methyl-tert-butyl ether. The combined organic extracts are washed with water and saline, dried, the drying media removed and the solvent removed. The remaining residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 24.79 g (95.3%) of the desired compound are obtained. H-NMR (300 'MHz, CDC13): d = 3.90 (3H), 4.78 (2H), 6.87-7.10 (3H). 2-Fluoro-3-methoxybenzyl chloride 24.79 g (158.75 mmol) of 2-fluoro-3-methoxybenzene alcohol in 35 ml of dichloromethane are dissolved. 58.4 ml of thionyl chloride are added with slight cooling, and then the preparation is stirred overnight at room temperature. The reaction mixture is centrifuged to dryness, the residue is dissolved in methyl tert-butyl ether and stirred twice with a half saturated solution of potassium carbonate. The aqueous phase is extracted once with methyl-tert-butyl ether. The combined organic extracts are processed using conventional means. The remaining residue is used raw in the next step. XH-NMR (300 MHz, CDC13): d = 3.90 (3H), 4.65 (2H), 6.90-7.10 (3H). 2-Fluoro-3-methoxybenzyl cyanide 24.89 g (142.56 mmol) of 2-fluoro-3-methoxybenzene chloride in 200 ml of DMSO are stirred with 8.38 g (171.07 mmol) of cyanide sodium for three hours at 90 ° C. The reaction mixture is poured into water and extracted four times with methyl-tert-butyl ether. The combined organic phases are washed with saline, dried, the drying media removed and the solvent removed. First, only a part of the crude residue (21.43 g) is used in the next step. ^ -NMR (300 MHz, CDC13): d = 3.77 (2H), 3.90 (3H), 6.89-7.07 (2H), 7.08-7.15 (ÍH). 2- (2-f'-Loro-3-methoxy-enyl) -2-methylpropanonitrile 4 g (24.22 mmol) of 2-fluoro-3-methoxybenzyl cyanide are dissolved in 38 ml of N, N-dimethylformamide and mix with 6.87 g (48.35 mmol) of methyl iodide. 2.11 g (48.35 mmol) of sodium hydride (55%) are added in portions at 0 ° C for 45 minutes. After stirring for 20 hours at room temperature, the preparation is poured into ice water and extracted three times with 200 ml of diethyl ether each. The organic phases are washed with water and saline, and dried. After filtering the drying media and removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 4.66 g (99.5%) of the desired compound are isolated. ^? - NMR (300 MHz, CDC13): d = 1.80 (6 H), 3.90 (3H), 3.92-7.02 (IN), 7.02-7.11 (2H). 2- (2-f 'luoro -3-methoxy-enyl) -2-methylpropanal 4.66 g (24.12 mmol) of 2- (2-fluoro-3-methoxyphenyl) -2-methylpropanonitrile in 96 ml are dissolved. of toluene. At -65 ° C and -60 ° C, 30 ml (36.18 mmol) of a 1.2 molar solution of DIBAH in 96 ml of toluene are added dropwise. After stirring for three and a half hours at -65 ° C, 276 ml of a 10% solution of L (+) - tartaric acid is added dropwise at this temperature. With this the temperature rises to 0 ° C. The ice bath is removed and the preparation is stirred for one hour at room temperature. The reaction mixture is extracted three times with 300 ml of diethyl ether each. The combined organic extracts are processed using conventional means (water, saline, drying). After removing the solvent, 4.78 g (just over 100%) of the desired compound are obtained. ^? - NMR (300 MHz, CDC13): d = 1.46 (6 H), 3.89 (3 H), 6.85-6.7.00 (2 H), 7.08-7.15 (1 H) ), 9.65 (ÍH). E / Z-4- (2-fluoro-3-methoxyphenyl) -4-methylpent-2-enoic acid methyl ester 20.26 g (111.26 mmol) of phosphoacetic acid methyl ester in 68 ml of tetrahydrofuran are introduced. . 61 ml of a 2 M solution of LDA in THF / heptane / ethylbenzene are added dropwise at 0 ° C. After stirring for 45 minutes at 0 ° C, 21,83 g (111.26 mmol) of 2- (2-fluoro-3-methoxyphenyl) -2-methylpropanal are added dropwise., dissolved in 68 ml of tetrahydrofuran. After stirring overnight, the reaction mixture is stirred in an ice-water bath and extracted three times with methyl-tert-butyl ether. The combined organic extracts are processed using conventional means and the resulting residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 23.30 g (75.8%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.50 (6 H), 3.73 (3 H), 3.88 (3 H), 5.74 (1 H), 5.80 (OH), 6, 80-7.10 (3H). 4- (2-Fluoro-3-methoxyphenyl) -4-methylpentanoic acid methyl ester 23.30 g (84.33 mmol) of E / Z-4- (2-fluoro-3-methoxyphenyl) methyl ester are mixed. ) -4-methylpent-2-enoic in 310 ml of ethanol with 1.2 g of palladium on carbon, and stir under a hydrogen atmosphere overnight at room temperature. The catalyst is removed by filtration on a glass fiber filter and after concentrating the residue is left which is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 19.58 g (83.4%) of the desired compound are isolated. aH-NMR (300 MHz, CDC13): d = 1.48 (6 H), 2.00-2.18 (4 H), 3.60 (3 H), 3.90 (3 H), 6.78- 7.03 (3H). 4- (2-Fluoro-3-methoxyphenyl) -2-hydroxy-4-methylpentanoic acid methyl ester 19.58 g (77 mmol) of 4- (2-fluoro-3-methoxyphenyl) methyl ester are introduced. 4-methylpentanoic in 245 ml of tetrahydrofuran and the reaction mixture is cooled to -70 ° C. In the course of one hour, 220.7 ml of a 0.5 molar solution of potassium bis- (trimethylsilylamide) in toluene are added dropwise, and then the reaction mixture is stirred for 45 minutes at -70 ° C. 28.3 g (107.79 mmol) of Davis's reagent, dissolved in 245 ml of tetrahydrofuran, are added dropwise over 40 minutes. After stirring for two hours at -70 ° C, 250 ml of a saturated solution of ammonium chloride are slowly added dropwise and the preparation is brought to room temperature. After extracting with methyl-tert-butyl ether, the combined organic extracts are processed with water and saline using conventional means. After removing the solvent, the residue is chromatographed several times on silica gel (elution medium: ethyl acetate / hexane). Finally, 12.14 g (58.3%) of the desired compound are isolated. ^ -NMR (300 MHz, CDC13): d = 1.45 (3H), 1.49 (3H), 1.90-2.01 (ÍH), 2.38-2.50 (2H), 3, 70 (3H), 3.90 (3H), 3.92-4.03 (HH), 6.80-7.08 (3H). Methyl 4- (2-f luoro-3-methoxyfenyl) -4-methyl-2-oxopentananoate 11.14 g (41.22 mmol) of 4- (2-fluoro-3-methoxyphenyl) -2- are introduced. Methyl hydroxy-4-methyl-pentanoate in 260 ml of dichloromethane and 71.3 ml of dimethyl sulfoxide. After the addition of 20.8 g (205.78 mmol) of triethylamine, the mixture is mixed with 13 g (81.71) of S03 / pyridine complex, and then stirred overnight at room temperature. The reaction mixture is combined with 100 ml of saturated ammonium chloride solution, with slight cooling, and stirred thoroughly. After extracting twice with methyl-tert-butyl ether, the combined organic phases are processed using conventional means. The residue remaining after removing the solvent is chromatographed on silica gel (elution medium: ethyl acetate / hexane) together with the residue of the test preparation (1 g). 10.03 g (83.2%, of both preparations) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.49 (6 H), 3.39 (2 H), 3.73 (3 H), 3.89 (3 H), 6.80-6.91 (2 H) ), 6.95-7.07 (ÍH). 4- (2-f luoro-3-methoxy-enyl) -4-methyl-2- (trifluoromethyl) -2- (trimethylsilyloxy) -pentanoate methyl. 10.03 g (37.39 mmol) of 4- (2) are dissolved. methyl-3-ethoxyphenyl) -4-methyl-2-oxopentanoate in 63 ml of tetrahydrofuran, mixed with 5.68 g (39.98 mmol) of (trifluoromethyl) -trimethylsilane and then with 82.3 mg of tetrabutylammonium fluoride. After stirring overnight at room temperature, the preparation is placed in ice water, extracted with methyl tert-butyl ether and the combined organic extracts are processed using conventional means. After removing the solventThe residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). In addition to 6.94 g (45.2%) of the desired product, 2.75 g of initial material (contaminated) is isolated, which is processed once again using the method described. In this way, another 1.91 g of methyl 4- (2-fluoro-3-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2- (trimethylsilyloxy) -pentanoate are obtained.

MS (C1): 428 (100%), 395 (67%). 4- (2-f luoro-3-methoxy-enyl) -4-methyl-2- (trifluoromethyl) -2- (trimethyl-silyloxy) -pentan-1-ol and 4- (2-fluoro-3-methoxyphenyl) -4-methyl -2- (trifluoromethyl) -1- (trimethylsilyloxy) pentan-2-ol 8.85 g (21.56 mmol) of 4- (2-fluoro-3-methoxyphenyl) -4-methyl-2- are dissolved. (trifluoromethyl) -2- (trimethylsilyloxy) -pentanoate methyl in 77 ml diethyl ether. To this solution is added 1.64 g (43.12 mmol) of lithium aluminum hydride at 0 ° C per portion. After stirring for four hours at room temperature, it is cooled to 0 ° C and approximately 80 ml of saturated sodium bicarbonate solution are carefully added dropwise. Then it is agitated exhaustively for one hour at room temperature. The preparation is extracted several times with methyl tert-butyl ether. The combined organic extracts are washed with water and then with saline. After drying with sodium sulfate, the drying media is removed, the solvent is centrifuged and the residue (7.36 g, mixture of both regioisomers of silylether) crude is used in the next step. 4- (2 ~ fluoro-3-methoxy phenyl) -4-methyl-2- (trifluoromethyl) pentan-1,2-diol 7.36 g (19.24 mmol) of the mixture of both regioisomers of silylether are dissolved in 108 ml of tetrahydrofuran, is mixed with 6.07 g (19.24 mmol) of tetrabutylammonium fluoride and stirred overnight at room temperature. The reaction mixture is diluted with methyl tert-butyl ether, washed with water and saline, and then the solvents are centrifuged after drying. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 5.3 g (88.8%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.45 (3H), 1.58 (3H), 2.20 (1H), 2.38 (2H), 2.93 (1H), 3.30 -3.40 (ÍH), 3.50-3.60 (ÍH), 3.89 (3H), 6.85-6.98 (2H), 6.98-7.09 (HH). 4- (2-f luoro-3-methoxy-enyl) -2-hydroxy-2- (trifluoromethyl) -pentanal 2.5 g (8.06 mmol) of rac-4- (2-fluoro-3-) are mixed. methoxyphenyl) -4-methyl-2- (trifluoromethyl) pentan-1,2-diol with 52 ml of dichloromethane, 14 ml of dimethyl sulfoxide and 4.08 g (40.29 mmol) of triethylamine. 2.57 g (16.11 mmol) of S03 / pyridine complex are added at room temperature, and the preparation is stirred overnight at this temperature. The reaction mixture is combined with a saturated solution of ammonium chloride and stirred thoroughly. After processing using conventional means, 2.11 g (85%) of the desired aldehyde are obtained. XH-NMR (300 MHz, CDC13): d = 1.45 (3H), 1.50 (3H), 2.30 (HH), 3.12 (1H), 3.62 (ÍH), 3.89 (3H), 6.75 (ÍH), 6.90 (1H), 7.00 (ÍH), 9.15 (ÍH). 4- . { [5-fluoro-2-hydroxy-6-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-1-yl] amino} -2, 3-dihydroisoindol-1-one 150 mg (0.487 mmol) of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-2-trifluoromethyl-pentanal are mixed in 0.9 ml of glacial acetic acid with 72.7 mg (0.487 mmol) of 4-amino-2,3-dihydroisoindol-1-one, and stir for two days at room temperature. The preparation is centrifuged to dryness and the residue is subjected to chromatography (flash). 119.8 mg (56.2%) of the desired cyclic compound are isolated. 1 H-NMR (300 MHz, CDC13): d = 1.50 (3H), 1.65 (3H), 2.05 (HH), 2.20 (ÍH), 3.83 (3H), 4.29. (2H), 4.40 (ÍH), 5.00 (1H), 6.79 (1H), 6.93 (ÍH), 7.00-7.12 (2H), 7.21 (ÍH), 7.35 (1H). 4- . { [5-fluoro-2,6-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2, 3-dihydroisoindol-1 -one. 109.8 mg (0.250 mmol) of (rae.) 4- are mixed. { [5-fluoro-2-hydroxy-6-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2, 3-dihydroisoindol-1-one with 3.4 ml of an IVM-solution of BBr3 in dichloromethane, and stirred for four hours at room temperature. The preparation is mixed at 0 ° C with a saturated solution of sodium bicarbonate and extracted twice with ethyl acetate. The combined organic extracts are dried with sodium sulfate. After filtering the drying media and removing the solvent, the residue is subjected to flash chromatography. 15.6 mg (14.7%) of final product are isolated. ^ -NMR (300 MHz, CD3OD): d = 1.53 (3H), 1.67 (3H), 2.03-2.20 (2H), 4.28-4.43 (2H), 5, 13 (HH), 6.78 (1H), 6.90 (2H), 7.18 (HH), 7.38 (HH).

Example 6 4_-. { [7-bromo-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -l, 3-dihydroindol-2-one-4-amino-l, 3-dihydroindol-2-one dimethyl 2- (2,6-dinitro-phenyl) -malone To dissolve 42.95 g (311.03 mmol) of dimethyl malonate in 300 ml of N, N-dimethylformamide and mixed in portions with 35.15 g (296.22 mmol) of potassium tert-butylate. The terbutanol formed is distilled, and then the reaction mixture is cooled to 20 ° C. 30 g are added to the mixture (148.11 mmol) of 2,6-dichlorobenzene in portions continuously. After stirring for three hours at 90 ° C, it is stirred overnight at room temperature. The reaction mixture is poured into 800 ml of a 1% solution of NaOH (cooled with ice) and extracted three times with methyl-tert-butyl ether. The remaining ether phase is subjected to DC control and discarded. The aqueous phase is carefully acidified in a bath of ice water with concentrated nitric acid (w = 65%). It is extracted six times with methyl-tert-butyl ether and the combined organic extracts are processed using conventional means (water, saline, drying, filtration and elimination of the solvents) to obtain a residue, which is subjected to a gel chromatography. silica (elution medium: ethyl acetate / hexane). 12.09 g (27.09%) of the desired compound are isolated. ? -NMR (300 MHz, CDC13): d = 3.82 (6 H), 5.39 (H), 7.75 (H), 8.27 (2 H). (2,6-dinitrophenyl) -methyl acetate 10.08 g (33.8 mmol) of dimethyl 2- (2,6-dinitrophenyl) -malonate in 54 ml of ethyl acetate are mixed with 2.7 ml. of perchloric acid and heated to reflux at 125 ° C. The ethyl acetate formed is distilled. After 90 minutes, the reaction is aborted and it is confirmed by DC that no initial materials are left. The reaction mixture is poured into ice water and extracted three times with ethyl acetate. The combined organic extracts are stirred with a solution % sodium bicarbonate, with water and saline.

After drying the organic phase, filtering the drying media and removing the solvent, a residue is obtained, which is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 4.69 g of acid are isolated (2,6-dinitrophenyl) -acetic acid, which is again esterified with methanol (16 ml) and concentrated sulfuric acid (0.4 ml). For this, the acid and the reactants are heated for seven hours at reflux. The methanol is centrifuged and the residue is processed using conventional means. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 4.43 g (89%) of the desired esters are obtained. ^? - NMR (300 MHz, CDC13): d = 3.75 (3H), 4.20 (2H), 7.69 (IH), 8.19 (2H). 4-amino-l, 3-dihydroindol-2-one 4.43 g (18.45 mmol) of methyl (2,6-dinitrophenyl) -acetate are mixed in 38.8 ml of ethyl acetate, 11 ml of water, mixed with 3.75 g of iron powder and stirred again for four hours. Then warm between 40 and 60 ° C. The reaction mixture is poured into ice water, mixed with ethyl acetate and stirred for ten minutes thoroughly. The mixture is filtered through a glass fiber filter, the organic phase is separated and the aqueous phase is extracted twice with ethyl acetate. The combined organic extracts are washed with saline, dried and the solvent is centrifuged after filtering the drying media. The residue is chromatographed on silica gel (elution medium: methanol / dichloromethane). 2.38 g of 4-nitro-indol-2-one are isolated. The nitro compound is again mixed in glacial acetic acid / water with 2.7 g of iron powder, and the cyclic previously described is again met. 1.63 g of the desired amines are isolated. XH-NMR (300 MHz, DMSO-d6): d = 3.19 (2H), 5.03 (2H), 6.08 (IN), 6.22 (1H), 6.85 (1H), 10 , 10 (ÍH). 4- (4-bromo-2-methoxy-enyl) -4-methyl-2- (trifluoromethyl) -pentan-1,2-diol 2.55 g (6, 17 mmol) of 4- (4-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanoic acid ethyl ester (synthesized in two steps from 4- (4- bromine-2-methoxyphenyl) -2-oxopentanoic acid, WO 98/54159) in 102 ml of diethyl ether, mixed at 0 to -5 ° C in portions with 351.3 mg (9.256 mmol) of lithium aluminum hydride, and it is stirred for three and a half hours at room temperature. The reaction mixture is combined dropwise, in an ice water bath with a saturated solution of sodium bicarbonate, kept at 5 ° C for 15 minutes and then stirred for one hour at room temperature. The formed precipitate is extracted, washed again with diethyl ether and the filtrate is concentrated in a rotary evaporator. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). Approximately 308 mg of aldehyde (see the next step) make it possible to obtain 2.025 g (88.4%) of diols. 4- (4-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal 2.03 g (5.442 mmol) of 4- (4-bromo-2-methoxyphenyl) are oxidized. ) -4-methyl-2- (trifluoromethyl) -pentan-1,2-diol to give aldehyde, using the Swern method described in Example 3. 1.839 g (91.4%) of the desired compound are isolated. ^ -NMR (300 MHz, CDC13): d = 1.39 (3H), 1.45 (3H), 2.23 (ÍH), 3.35 (ÍH), 3.58 (ÍH), 3.90 (3H), 6.93-7.09 (3H), 9.03 (1H). 4- . { [4- (4-bromo-2-methoxy phenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} -1,3-dihydroindol-2-one 300 mg (0.812 mmol) of 4- (4-bromo-2-methoxy-phenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal are stirred at 1.5 ml of glacial acetic acid with 120.4 mg (0.812 mmol) of 4-amino-1,3-dihydroindol-2-one, for a weekend at room temperature. The reaction mixture is concentrated to dryness and the residue is subjected to flash chromatography. 235.9 mg (58.1%) of the desired imines are isolated. ^ -NR (300 MHz, CDC13): d = 1.35 (3H), 1.53 (3H), 2.20 (1H), 3.30 (ÍH), 3.42 (2H), 3.85 (3H), 4.71 (ÍH), 6.05 (ÍH), 6.78 (ÍH), 6.80-6.90 (2H), 6.98 (1H), 7.19 (ÍH), 7.45 (HH), 8.25 (ÍH). 4- [(1-bromo-2,5-dihydroxy-, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl) amino] -1,3-dihydroindole-2- One 235.9 mg of 4- is mixed. { [4- (4-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} -1, 3-dihydroindol-2-one at 0 ° C with 6.42 ml of an ÍM solution of BBr3 in dichloromethane, and stirred for four hours at room temperature. A saturated solution of sodium bicarbonate is carefully added by dripping. After extracting three times with ethyl acetate, the organic phase is dried with sodium sulfate. The drying media is removed and the solvent is removed. The residue is subjected to flash chromatography. 125.4 mg (54%) of the desired compound are isolated. 1 H-NMR (300 MHz, CD 3 OD): S = 1.52 (3H), 1.65 (3H), 1.98-2.18 (2H), 3.25-3.49 (2H), 4, 98 (1H), 6.37 (1H), 6.47 (ÍH), 6.87 (ÍH), 7.02 (HH), 7.11 (1H). Example 7 (+) -4-. { [7-hydroxy-9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9-te-rahydronaphthyl-1,2-dH, 3-dioxol-6-yl] amino]} -2, 3-dihydroisoindol-1-one and (-) -4-. { [7-hydroxy-9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9-e-rahydronaf-1, 2-dH, 3-dioxol-6-yl] amino} -2, 3-dihydroisoindol-1-one Methyl ester of l, 3-benzodioxol-4-carbonic acid 50 g of 2,3-dihydroxybenzoic acid in 450 ml of methanol are mixed with 50 ml of thionyl chloride at room temperature drip. The solution is then heated for five hours at 60 ° C and further stirred overnight at room temperature. The solvent is completely removed under vacuum, the remaining oil is taken up in diethyl ether and extracted with a saturated solution of sodium bicarbonate. After washing with saline, it is dried with sodium sulfate and the solvents are removed in vacuo to obtain 46 g of 2,3-dihydroxybenzoic acid methyl ester. This is mixed in 575 ml of DMF and 20.2 ml of dibromomethane with 56.7 g of potassium carbonate, and heated for five hours under argon at 100 ° C. Then it is stirred overnight at room temperature. After mixing water, it is extracted three times with ethyl acetate. The organic phases are washed several times with water and dried with sodium sulfate. The solvent is removed under vacuum to obtain 50.2 g of 1,3-benzodioxole-4-carbonic acid methyl ester as a brown solid. Melting point: 55-57 ° C 4- (1,3-Benzodioxol-4-yl) -4-methyl-2-oxopentanoic acid ethyl ester 4.76 g of methyl ester of acid 1, 3 are added dropwise -benzodioxol-4-carbonic acid in 65 ml of dry THF to a solution of 21 ml of 3M methylmagnesium chloride in THF under argon. The reaction mixture is stirred for three hours and then slowly mixed with IN hydrochloric acid. After extracting with ethyl acetate and washing the organic phase with water, it is dried with sodium sulfate and the solvent is removed in vacuo. 5 g of 1- (1,3-benzodioxol-4-yl) -1-methylethanol is obtained as a brown oil. The tertiary alcohol (27.17 mmol) is mixed with 7.8 g (41.6 mmol) of 2- (trimethylsilyloxy) -acrylic acid ethyl ester in 100 mL of dichloromethane at -70 ° C with 5.4 g. (20.8 mmol) of tin tetrachloride. After stirring for 15 minutes at -70 ° C, the solution is poured into a semi-saturated solution of sodium carbonate, mixed with ethyl acetate and stirred vigorously. The phases are separated and the aqueous phase is extracted twice with ethyl acetate. The organic phases are washed with saline, dried with sodium sulfate and the solvent is removed in vacuo. 7.15 g of a yellow oil are obtained, which is distilled together with the products of other preparations of similar magnitude. Ethyl 4- (1, 3-benzodioxol-4-yl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanoic acid ester 6.1 g (21.91 mmol) of 4- (1-ethyl ester , 3-benzodioxol-4-yl) -4-methyl-2-oxopentanoic acid in 130 ml of tetrahydrofuran, are transformed with 9.5 ml (65.7 mmol) of (trifluoromethyl) trimethylsilane and 4.42 ml of a solution 1M tetrabutylammonium fluoride in tetrahydrofuran. The reaction process and the subsequent processing is carried out as described in Example 3. The resulting crude product is purified with that of a preparation of similar magnitude [9.19 g (33.02 mmol) of ethyl ester of acid. 4- (1,3-benzodioxol-4-yl) -4-methyl-2-oxopentanoic acid as starting material] by chromatography on silica gel (elution medium: ethyl acetate / hexane). 16.45 g (86%) of the desired product are isolated from both combined preparations. 4- (1,3-benzodioxol-4-yl) -4-methyl-2- (trifluoromethyl) pentan-1,2-diol. 12.5 g (36.03 mmol) of 4-ethyl ester are incorporated. (1, 3-benzodioxol-4-yl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanoic acid in 430 ml of diethyl ether, and mixed with 2.05 g (54.1 mmol) of sodium hydride. aluminum and lithium at 0 ° C per portion. After stirring overnight at room temperature, pour the preparation carefully into a solution of sodium bicarbonate. The solvents are filtered with diatomaceous earth and extracted three times with ethyl acetate. The combined organic extracts are washed with saline, dried and the solvent is centrifuged after filtering the drying media. Chromatography of the residue on silica gel (elution medium: ethylacetate / hexane) makes it possible to obtain 6.7 g (61%) of the desired alcohol. 4- (1,3-benzodioxol-4-yl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal 2.26 g (7.38 mmol) of 4- (1,3-benzodioxole) are oxidized. -4-yl) -4-methyl-2- (trifluoromethyl) pentan-1,2-diol to give aldehyde, according to the Swern method described in Example 3. After performing a processing using conventional means, the residue undergoes flash chromatography. 1.85 g (82.3%) of the desired aldehyde are obtained. ^ -NMR (300 MHz, CDC13): d = 1.39 (3H), 1.48 (3H), 2.27 (IH), 3.10 (IH), 3.67 (IH), 5.92 -6.02 (2H), 6.60-6.70 (1H), 6.70-6.88 (2H), 9.06 (1H). (+) -4-. { . { 1-Hydroxy-, 9-dimethyl-1- (trifluoromethyl) -6,7,8,9-tetrahydronaphtho (1,2-d) -1,3-dioxol-6-yl] amino} -2, 3-dihydroisoindol-1-one and (-) -4-. { [1-hydroxy-9,9-dimethyl-1- (trifluoromethyl) -6,7,8,9-tetrahydronaphtho (1,2-d) -1,3-dioxol-6-yl] amino} -2, 3-dihydroisoindole-1 -one. 800 mg (2.63 mmol) of 4- (1,3-benzodioxol-4-yl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal are stirred in 5.2 ml of glacial acetic acid with 389 mg (2.63 mmol) of 4-amino-2,3-dihydroisoindol-1-one overnight at room temperature. The reaction mixture is centrifuged to dryness, and the residue is subjected to flash chromatography. 725 mg (62.8%) of the desired compound is isolated as racemate. The separation of the racemate (Chiralpak AD 20 g, elution medium: hexane / ethanol / diethylamine) makes it possible to obtain 279.2 mg of the (+) enantiomers. { . { to} D = +20.7 (c = 1.03, methanol)} and 297.5 mg of the (-) enantiomers. { [α] D = -23.4 (c = 1.02, methanol)} Example 8 5-. { [8-chloro-2,5-dihydroxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} - isoquinolin-1 (2H) -one 4- (5-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (tri-fluoromethyl) pentanal. 2 g (6.12 mmol) of 4 are oxidized. (5-chloro-2-methoxyphenyl) -hydroxy-4-methyl-2-trifluoromethyl-pentan-1-ol with 854.6 mg (6.733 mmol) of oxalyl chloride and 1.05 ml (14.812 mmol) of DMSO using the Swern method, as described in Example 2. After further processing, 1.95 g (98.4%) of the desired aldehyde is obtained, which is used in the rough in the next step. XH-NMR (300 MHz, CDC13): d = 1.39 (3H), 1.49 (3H), 2.27 (IH), 3.32 (1H), 3.59 (1H), 3.88 (3H), 6.78 (ÍH), 7.10 (1H), 7.20 (ÍH), 9.09 (HH). 5- . { [4- (5-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl] -pentylideneamino} isoquinolin-1 (2H) -one 300 mg (0.924 mmol) of 4- (5-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal are stirred with 148 mg (0.924 mmol). ) of 5-amino-isoquinolin-1-one in 1.33 ml of crystalline acetic acid for four days at room temperature. The mixture is extracted three times with toluene and concentrated in a rotary evaporator to dryness. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 345.8 mg (80.1%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.39 (3H), 1.57 (3H), 2.29 (1H), 3.49 (ÍH), 3.83 (3H), 4.82. (1H), 6.57-6.65 (2H), 6.72 (ÍH), 6.89 (ÍH), 7.03 (1H), 7.18-7.29 (HH), 7.36 (ÍH), 7.40 (ÍH), 8.32 (ÍH), 10.98 (ÍH). 5-. { (8-Chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-1-yl] amino) -isoquinolin-1 (2H) -one mix 50 mg (0.107 mmol) of the mixture described in the previous step of 5-. { [4- (5-Chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino) 2,3-isoquinolin-l-one at -20 ° C with 2.1 ml of an ÍM solution of boron tribromide in dichloromethane, and is stirred in a temperature range between -20 ° C and 0 ° C. The reaction mixture is combined at -20 ° C by dripping with a saturated solution of sodium bicarbonate. After diluting with ethyl acetate, the ice bath is removed and the preparation is stirred for 15 minutes at room temperature. It is extracted twice with 30 ml of ethyl acetate each. The combined organic extracts are washed with water and a saturated solution of NaCl. After drying with sodium sulfateThe solvent is removed and the remaining residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 16.5 mg (33%) of the desired compound are isolated. MS (ES +): 453, 455 Example 9 8-bromo-l- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaf alen-2, 5-diol Ethyl ester of 4- (5-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanoic acid 34.45 g (258.91 mmol) are incorporated. of aluminum trichloride in 354.35 g (237.02 mmol) of 4-bromoanisole. To this mixture is added 38.95 g (172.19 mmol) of 2-hydroxy-4-methylene-2- (trifluoromethyl) pentanoic acid ethyl ester by dripping for one hour. After stirring overnight at room temperature, pour the preparation into ice water and acidify with 10% hydrochloric acid. After extracting three times with ethyl acetate, the combined organic extracts are washed with 1N hydrochloric acid and saline. After drying over magnesium sulfate, the solvent is removed. Most of the remaining 4-bromoanisoles are distilled (10 mbar; Bath temperature: 110 ° C). After chromatography on silica gel (elution medium: ethyl acetate / hexane), 36.87 g (51.8%) of the desired compound are obtained. ^? - NMR (300 MHz, CDC13): d = 1.39 (3H), 1.46 (3H), 2.49 (IH), 2.85 (IH), 3.48 (IH), 3, 62-3.75 (1H), 3.85 (3H), 4.02-4.15 (HH), 6.73 (1H), 7.23-7.33 (2H). 4- (5-Bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentan-1-ol 3 g (7.25 mmol) of ethyl ester of 4- (5-methyl) acid are dissolved. -bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanoic acid in 120 ml of diethyl ether and the reaction mixture is cooled to 0 ° C. 426.5 mg (10.89 mmol) of lithium aluminum hydride are added in portions. After stirring for two hours at room temperature there is no initial material left. The preparation is mixed in an ice bath with a saturated solution of sodium bicarbonate, the precipitate is removed and washed with diethyl ether. After centrifugation, the residue is subjected to flash chromatography. They are isolated, starting from about 540.5 mg of 4- (5-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal, 1.14 g of the desired alcohol (also contained in the bromine compound). 4- (5-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal 1.13 g (3.06 mmol) of 4- (5-bromo-2-methoxyphenyl) are incorporated. ) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentan-1-ol in 20 ml of dichloromethane and 5.4 ml of DMSO. After mixing with 1.55 g (15.32 mmol) of triethylamine and 975.28 mg (6.13 mmol) of S03 / pyridine complex, the preparation is stirred overnight at room temperature. After DC, another spatula measure of S03 / pyrelin complex is added and stirred a few more hours. The reaction mixture is combined with a saturated solution of ammonium chloride and stirred three times with methyl-tert-butyl ether. The combined organic extracts are washed with water and saline. After drying and removing the solvent, the residue is subjected to flash chromatography. 902.7 mg (79.81%) of the desired aldehyde are isolated (together with the bromine compound). ^ -NMR (300 MHz, CDC13): d = 1.40 (3H), 1.50 (3H), 2.28 (ÍH), 3/30 (ÍH), 3.87 (3H), 6.73 (1H), 7.22 (1H), 7.35 (1H), 9.09 (1H). 1, 1, 1-tri-fluoro-4- (5-bromo-2-methoxy phenyl) -2- [(1 H -indazol-4-yl) iminomethyl] -4-methylpentan-2-ol 300 mg (0.813) are mixed mmol) of 4- (5-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal in 1.19 ml of glacial acetic acid with 108.2 mg (0.813 mmol) of 4- aminoindazole, and stir for four days at room temperature. The preparation is centrifuged to dryness and the residue is extracted three times with toluene. Chromatography on silica gel (elution medium: ethyl acetate / hexane) makes it possible to obtain 352.5 mg (89.5%) of the desired imines (together with the imine of the bromine compound). ^ -NMR (300 MHz, CDC13): d = 1.48 (3H), 1.55 (3H), 2.28 (ÍH), 3.44 (ÍH), 3.80 (3H), 4.98 (1H), 6.35 (1H), 6.53 (1H), 6.99 (ÍH), 7.30 (ÍH), 7.29-7.40 (HH), 7.55 (1H), 7.99 (1H), 10.28 (ÍH). 8-bromo-5-methoxy-1- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-2-ol Dissolve 100 mg (0.206 mmol) of 1,1-l-trifluoro-4- (5-bromo-2-methoxyphenyl) -2- [(lH-indazol-4-yl) iminomethyl] -4-methylpentan-2-ol in 1 milliliter of dichloromethane and the reaction mixture is cooled to -30 ° C. Four milliliters of an ICM solution of BBr3 in dichloromethane are added dropwise over 15 minutes, and then the preparation is stirred for 45 minutes at -30 ° C. Approximately 10 ml of a saturated solution of sodium bicarbonate at -30 ° C is carefully added dropwise. After diluting with ethyl acetate, it is stirred for ten minutes and then extracted twice with 50 ml of ethyl acetate each. The combined organic extracts are washed with water and saline. After drying and removing the solvent, the residue which is obtained after drying and centrifugation is subjected several times to chromatography on silica gel (elution medium: ethyl acetate / dichloromethane). 21 mg of the desired compound are isolated (together with the corresponding bromo compound). ? -NMR (300 MHz, CD30D): d = 1.55 (3H), 1.67 (3H), 2.10 (1H), 2.43 (1H), 3.89 (3H), 5.25 (ÍH), 6.72 (ÍH), 6.83 (1H), 6.90 (ÍH), 7.22 (ÍH), 7.49 (1H), 8.25 (ÍH). 8-bromo-l - [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalene-2,5-diol. mg (0.043 mmol) of 8-bromo-5-methoxy-1 - [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -, 2, 3, 4-tetrahydronaphthalene- 2-ol at room temperature with 0.4 ml of a 1M solution of BBr3, and stir for 19 hours at room temperature. After combining the reaction mixture with ice, a saturated solution of sodium bicarbonate is added dropwise and diluted with ethyl acetate. The organic phases are washed in neutral form using conventional means and the residue that remains after centrifuging the solvents, is subjected to chromatography on silica gel (elution medium: methanol / dichloromethane). 17.1 mg (83.8%) of the desired compound are isolated (together with the bromine compound). ^ -NMR (300 MHz, CD30D): d = 1.59 (3H), 1.71 (3H), 2.10 (ÍH), 2.42 (ÍH), 5.25 (ÍH), 6.64-6.78 (2H) ), .6.83 (ÍH), 7.20-7.34 (2H), 8.25 (HH). Example 10 l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaph alen-2-ol 2 -hydroxy-4-methyl -4-phenyl-2- (trifluoromethyl) pentanal 10.4 g of 4-methyl-2-oxo-4-phenyl-pentanoic acid (W098 / 54159) are mixed in 250 ml of dimethylformamide at -5 ° C with 4 , 1 ml of thionyl chloride, and then for 15 minutes with 4 ml of methanol. After standing for 15 hours at room temperature, the preparation is diluted with water and extracted with ethyl acetate. The organic extracts are washed with water, dried (Na 2 SO 4) and concentrated, which yields 9.3 g of methyl ester of 4-methyl-2-oxo-4-phenylpentanoic acid. This is mixed in 558 ml of DMF at -5 ° C with 15.5 ml (104.63 mmol) of (trifluoromethyl) trimethylsilane and 20.5 g (63.28 mmol) of cesium carbonate, and is stirred for 16 hours. hours at room temperature. Water is added, extracted with ethyl acetate, the organic phases are washed with water and dried (Na2SO4). The concentrated intermediate product is taken with 200 ml of THF and 50 ml of a 1M solution of tetrabutylammonium fluoride in THF are added. Stir for 2 hours, add water, extract with ethyl acetate, wash the organic phase with water and dry (Na 2 SO). After chromatography on silica gel with hexane-ethyl acetate (0-30%), 8.35 g of 2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) pentanoic acid methyl ester are obtained. The ester (8.3 g, 28.59 mmol) is dissolved in 180 ml of THF and 1.52 g (36.20 mmol) of lithium aluminum hydride are added in small portions, over a period of 2, 5 hours. After the reaction is completed, 5 ml of ethyl acetate are added dropwise and, after a further 10 minutes, 10 ml of water are added. The precipitate obtained is filtered and washed carefully with ethyl acetate. After chromatography on silica gel with hexane-ethyl acetate (0-35%), 5.40 g of 4-methyl-4-phenyl-2- (trifluoromethyl) pentan-1,2-diol are obtained. To 2.5 g (9.53 mmol) of diol in 75 ml of dichloromethane and 28 ml of DMSO are added 5.7 ml (40.3 mmol) of triethylamine and 5 g of pyridine / S03 complex in portions over 20 minutes . It is stirred for two hours and 40 ml of an ammonium chloride solution are added. The mixture is stirred for another 15 minutes, the phases are separated and extracted with dichloromethane. It is washed with water and dried with sodium sulfate. The solvent is removed under vacuum to obtain 3 g of product. XH-NMR (300 MHz, CDC13): d = 1.34 (s, 3H), 1.44 (s, 3H), 2.34 (d, 2H), 2.66 (d, ÍH), 3, 64 (s, ÍH), 7.03-7.41 (m, 4H), 8.90 (s, ÍH). l, l, l-trifluoro-4-phenyl-2- [(1H-indazol-4-yl) iminomethyl] -4-methntan-2-ol 130 mg (0.50 mmol) of 2-hydroxy-4 are dissolved -methyl-4-phenyl-2- (trifluoromethyl) pentanal in 15 ml of toluene, is mixed with 73 mg (0.55 mmol) of 4-amino-indazole and 0.22 ml of titanium tetraethylate, and is stirred at 100 ° C for 2.5 hours under argon. After the usual work-up, the reaction solution is mixed with 1 ml of saturated sodium chloride solution and stirred for 30 minutes. Subsequently, the suspension is extracted in Celite and washed with 200 ml glacial acetic acid. The organic phases are washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo to obtain 246 g. Column chromatography on silica gel with pentane-acetic acid yields 190 mg of product. ^? - NMR (300 MHz, DMSO-de): d = 1.35 (s, 3H), 1.47 (s, 3H), 2.26 (d, ÍH), 2.73 (d, ÍH) , 6,13 (s, ÍH), 6,24 (d, ÍH), 6,94 (t, 1H), 7,06 (t, 2H), 7,23 (t, ÍH), 7,34- 7.40 (m, 3H), 7.56 (s, ÍH), 8.00 (s, ÍH), 13.17 (s, ÍH). 1- [(lH-Indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-2-ol 190 mg (0.51 mmol) are dissolved ) of 1,1-l-trifluoro-4-phenyl-2- [(1H-indazol-4-yl) iminomethyl] -4-methntan-2-ol in 100 ml of dichloromethane and cooled to -70 ° C. The solution is mixed for 10 minutes with 9 ml of titanium tetrachloride (1 molar in dichloromethane) and stirred for 1 hour at -70 ° C. The cold solution is then poured into 200 ml of saturated sodium bicarbonate solution and stirred for 15 minutes. After the usual work-up, the mixture is extracted with dichloromethane, the organic phase is washed with a saturated sodium chloride solution, dried with sodium sulfate and concentrated in vacuo to obtain 208 mg. Column chromatography with dichloromethane-methanol gives 53 mg (28%) of the desired product. ? -NMR (300 MHz, DMSO-de): d = 1.36 (s, 3H), 1.51 (s, 3H), 2.08 (d, 2H), 5.35 (d, 1H), 5.93 (s, ÍH), 6.24 (d, HH), 6.32 (d, HH), 6.74 (d, 1H), 7.05-7.12 (m, 2H), 7 , 21-7.28 (m, 2H), 7.43 (d, ÍH), 8.15 (s, ÍH), 12.81 (s, 1H). EXAMPLE 11 1- [(2-Methylbenzothiazol-7-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaph alen-2-ol l, l, l-trifluoro -4-phenyl-2- [(2-methybenzothiazolyl-7-11) iminomethyl] -4-methntan-2-ol? -NMR (300 MHz, DMSO-de): d = 1.33 (s, 3H) , 1.47 (s, 3H), 2.24 (d, ÍH), 2.71 (d, 1 H 2.82 (s, 3H), 6.19, (s, 1H), 6.54 ( d, ÍH), 6.91 (t, ÍH), 7.02 (t, 2H), 7.31-7.40 (m, 3H), 7.51 (s, ÍH), 7.78 (d , HH). 1- [(2-Methyl-il-benzoth-iazol-7-yl) -amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol? -NMR. (300 MHz, DMSO-de): d = 1.34 (s, 3H), 1.47 (s, 3H), 1.99-2.12 (m, 2H), 2.78 (s, 3H), 5.38 (d, 1H), 5.68 (d, ÍH), 6.10 (s, ), 6.78 (dd, 1H), 7.07-7.16 (m, 2H), 7.20-2.28 (m, 3H), 7.41 (d, 1H). Example 12 6- [(lH-indazol-4-yl) amino] -9,9-dimethyl-7- (ri luorome il) -6 7 8 9-tetrahydro-naph alen-l, 2-dH, 3-dioxol -7-ol 4- (1, 3-benzodioxol-4-yl) -1,11-tri-fluoro-2- [1 H- (indazolyl-4-yl) iminomethyl] -4-methylpentan-2-ol ^ -NMR (300 MHz, DMSO-d6): d = 1.34 (s, 3H), 1.48 (s, 3H), 2.28 (d, ÍH), 2.93 (d, ÍH), 5.90 (s, 2H), 6.15 (s, ÍH), 6. 29 (d, ÍH), 6,45 (t, ÍH), 6,56 (dd, ÍH), 6,62 (d, ÍH), 7,23 (t, ÍH), 7,40 (d, ÍH) ), 7.74 (s, 1H), 8.00 (s, ÍH), 13.17 (s, ÍH). 6- [(lH-indazol-4-yl) amino] -9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9-tetrahydro-naphtho (1,2-d] -1, 3- dioxol-7 -ol XH-NMR (300 MHz, DMSO-d6): d = 1.43 (s, 3H), 1.55 (s, 3H), 2.04-2.12 (m, 2H), 5.26 (d, 1H), 5.95 (s, 1H), 6.00 (s, 2H), 6.19 (d, ÍH), 6.29 (d, 1H), 6.70-6 , 78 (m, 3H), 7.07 (t, ÍH), 8.12 (s, ÍH), 12.81 (s, 1H).

EXAMPLE 13 1- [(2-Methylquinolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-2-ol 1, 1, 1-tri fluoro-4-phenyl-2- [(2-methylquinolin-5-yl) iminomethyl] -4-methylpentan-2-ol. 120 mg of 2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) are stirred. pentanal, 67 mg of 5-amino-2-methylquinoline and 163 ml of titanium tetraethylate in 8 ml of toluene for 2 hours at 100 ° C. After cooling, the preparation is mixed with 2 ml of water, stirred for 15 minutes at room temperature and concentrated in vacuo. Column chromatography on silica gel with cyclohexane-ethyl acetate gives 111 mg of product. ^ TÍ-NMR (300 MHz, CDC13): d = 1.35 (s, 3H), 1.55 (s, 3H), 2.45 (d, ÍH), 2.75 (s, 3H), 2 , 80 (d, ÍH), 5.00 (s, 1H), 6.15 (d, ÍH), 6.9-7.1 (m, 3H), 7.30 (m, 3H), 7, 35 (d, ÍH), 7.45 (t, ÍH), 7.90 (d, ÍH), 8.35 (d, ÍH). 1- [(2-methylquinolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol To a solution of 111 mg of 1, 1, 1-Trifluoro-4-phenyl-2- [(2-methylquinolin-5-yl) iminomethyl] -4-methylpentan-2-ol in 84 ml of CH2C12 is added dropwise to 5.1 ml of an titanium tetrachloride-CH2Cl2 at -78 ° C. After resting 1 hour at -78 ° C, mix the preparation with concentrated NaHC03 and warm to room temperature. The phases are separated, the aqueous phase is extracted with CH2C12, the combined organic phases are dried (Na2SO4) and concentrated in vacuo. Column chromatography on silica gel with cyclohexane-ethyl acetate yields 94 mg of product. XH-NMR (300 MHz, CDC13): d = 1.45 (s, 3H), 1.60 (s, 3H), 2.15 (d, 1H), 2.20 (d, 1H), 2, 75 (s, 3H), 3.05 (br., 1H), 4.85 (br.d, 1H), 5.20 (d, ÍH), 6.85 (d, ÍH), 7.10 ( t, ÍH), 7,20 (d, ÍH), 7,30 (t, ÍH), 7,40 (d, ÍH), 7,50 (d, ÍH), 7,55 (t, ÍH), 8.05 (d, 1H). Example 14 1- [(quinolin-5-yl) amino] -, 4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaph alen-2-ol l, l, l ~ trifluoro-4- phenyl-2- [(quinolin-5-yl) iminomethyl] -4-methylpentan-2-ol. Analogously to that described in example 13, 120 mg of 2-hydroxy-4-methyl-4-phenyl- are converted 2-trifluoromethylpentanal and 61 mg of 5-aminoquinoline in 95 mg of product.

XH-NMR (300 MHz, CDC13): d = 1.35 (s, 3H), 1.60 (s, 3H), 2.45 (d, ÍH), 2.80 (d, ÍH), 5.00 (s, ÍH), 6.20 (d, 1H), 6.95-7.1 (m, 3H), 7.30 (m, 2H), 7.50 (m, 2H), 8.00 (d, 1H), 8.45 (d, ÍH), 8 , 95 (m, ÍH). 1- [(quinolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol. Analogously to that described in example 13, convert 95 mg of 1,1-l-trifluoro-4-phenyl-2- [(quinolin-5-yl) iminomethyl] -4-methylpentan-2-ol to 90 mg of product. aH-NMR (300 MHz, CDC13): d = 1.45 (s, 3H), 1.60 (s, 3H), 2.15 (d, 1H), 2.20 (d, ÍH), 3, 25 (br., 1H), 4.95 (br.d, ÍH), 5.20 (d, ÍH), 6.90 (dd, ÍH), 7.10 (t, ÍH), 7.25- 7.35 (m, 4H), 7.40 (d, 1H), 7.60 (m, 2H), 8.15 (d, 1H), 8.90 (m, ÍH). Example 15 5-. { [2-hydroxy-4, -dimethyl-2- (trifluoromethyl) -1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one 5-. { [2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) pentylidene] amino} quinolin-2 (1H) -one Analogously to that described in example 13, 600 mg of 2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) pentanal and 337 mg of 5-aminoquinolin- 2 (1H) -one (52313) in 570 mg of product. ^ -NMR (300 MHz, CDC13): d = 1.35 (s, 3H), 1.55 (s, 3H), 2.40 (d, ÍH), 2.80 (d, ÍH), 4, 70 (br.s, 1H), 5.80 (d, ÍH), 6.75 (d, 1H), 7.05 (t, 1H), 7.15 (t, 2H), 7.30 (m , 4H), 8.00 (d, ÍH), 9.05 (br. S, ÍH). 5-. { [2-hydroxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one Analogously to the one described in example 13, 23 mg of 5- are converted. { [2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) pentylidene] amino} quinolin-2 (1H) -one in 11 mg of product. ^? - NMR (300 MHz, DMSO-de): d = 1.35 (s, 3H), 1.50 (s, 3H), 2.00 (d, 1H), 2.10 (d, 1H) , 5.35 (d, 1H), 6.05 (s, 1H), 6.20 (d, ÍH), 6.40 (d, 1H), 6.55 (t, ÍH), 7.25 ( m, 2H), 7.45 (d, ÍH), 8.20 (d, ÍH), 11.60 (br.s, ÍH). EXAMPLE 16 1- [(2-methoxyquinolin-5-yl) amino] -4, -dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaph alen-2-ol l, l, l-trifluoro- 4-phenyl-2- [(2-methoxyquinolin-5-yl) iminomethyl] -4-methylpentan-2-ol. Analogously to that described in example 13, 200 mg of 2-hydroxy-4-methyl- 4-phenyl-2- (trifluoromethyl) pentanal and 122 mg of 5-amino-2-methoxyquinoline in 190 mg of product. 2H-NMR (300 MHz, CDC13): d = 1.35 (s, 3H), 1.55 (s, 3H), 2.45 (d, 1H), 2.80 (d, 1H), 4, 10 (s, 3H), 5.00 (s, 1H), 6.10 (d, 1H), 6.90 (d, 1H), 6.95 (t, ÍH), 7.05 (t, 2H) ), 7.30 (d, 2H), 7.35 (t, ÍH), 7.70 (d, 1H), 8.30 (d, ÍH). l - [(2-methoxyquinolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-2-ol analogously to that described in the example 13, 185 mg of 1,1-l-trifluoro-4-phenyl-2- [(2-methoxy-quinolin-5-yl) iminomethyl] -4-methylpentan-2-ol are converted into 127 mg of product. ^ - MR (300 MHz, CDC13): d = 1.45 (s, 3H), 1.60 (s, 3H), 2.15 (d, ÍH), 2.20 (d, ÍH), 3, 10 (s, ÍH), 4.10 (s, 3H), 4.75 (br.d, ÍH), 5.20 (d, ÍH), 6.75 (d, ÍH), 6.85 (d , HH), 7.1 (t, 1H), 7.25-7.45 (m, 4H), 7.50 (t, HH), 8.00 (d, 1H). Example 17 [1-phenylamino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol 1,1,1-fluoro-4-phenyl-2- [( phenyl) iminomethyl] -4-methylpentan-2-ol. Analogously to that described in example 1, 200 mg are converted. of 2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) pentanal and 64 ml of aniline in 180 mg of product. -NMR (300 MHz, CDC13): d = 1.35 (s, 3H), 1.50 (s, 3H), 2.35 (d, ÍH), 2.70 (d, 1H), 5.05 (s, 1H), 6.65 (d, 2H), 7.05 (t, ÍH), 7.15-7.30 (m, 7H). 1 - [(Phenylamino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol To a solution of 175 mg of 1,1-trifluoro-4-phenyl -2- [(phenyl) iminomethyl] -4-methylpentan-2-ol in 160 ml of CH2C12 is added 9.6 ml of a 1M solution of titanium tetrachloride-CH2C12 at -78 ° C. First stirring is carried out for 1 hour. -78 ° C and after adding another 10 ml of titanium tetrachloride-CH2Cl2 solution, it is stirred for 60 hours at room temperature, the mixture is mixed with concentrated NaHCO3, the phases are separated, the aqueous phase is extracted with CH2C12, the combined organic phases are dried (Na2SO) and concentrated in vacuo, column chromatography on silica gel with cyclohexane-ethyl acetate yields 45 mg of product XH-NMR (CDC13): d = 1.40 (s) , 3H), 1.50 (s, 3H), 2.00 (d, ÍH), 2.20 (d, 1H), 3.40 (s, ÍH), 3.80 (d, 1H), 4.95 (d, ÍH), 6.80 (d, 2H) , 6.85 (t, 1H), 7.15 (m, ÍH), 7.20-7.30 (m, 4H), 7.40 (d, ÍH). Example 18 4-. { [2-hydroxy-, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2- (trifluoromethyl) benzonitrile 1,1, 1-tri-fluoro-4-phenyl-2- [(4-cyano-3- (trifluoromethyl) phenyl) iminomethyl] -4-methylpentan-2-ol analogously to the one described in example 13, 120 mg of 2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) pentanal and 78 mg of 4-cyano-3- (trifluoromethyl) aniline in 71 mg of product. XH-NMR (300 MHz, CDC13): d = 1.35 (s, 3H), 1.55 (s, 3H), 2.40 (d, ÍH), 2.75 (d, ÍH), 4, 55 (s, 1H), 6.75 (dd, ÍH), 6.95 (d, 1H), 7.10 (t, 1H), 7.20 (m, 3H), 7.30 (m, 2H) ), 7.70 (d, 1H). 4-. { [2-hydroxy-4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amino} -2- (trifluoromethyl) benzonitrile In a manner analogous to that described in example 13, 71 mg of 1,1-l-trifluoro-4-phenyl-2- [(4-cyano-3- (trifluoromethyl) phenyl) iminomethyl] -4-methylpentan- 2-ol in 58 mg of product. XH-NMR (300 MHz, CDC13): d = 1.40 (s, 3H), 1.50 (s, 3H), 2.15 (s, 2H), 2.60 (s, ÍH), 5, 05 (d, 1H), 5.10 (d, ÍH), 6.85 (dd, ÍH), 7.00 (d, ÍH), 7.20 (s, 2H), 7.35 (m, ÍH) ), 7.40 (d, ÍH), 7.60 (d, ÍH). Example 19 5-. { [5-Bromo-2-hydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-e-rahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one (2-bromophenyl) -acetonitrile 25 g (100 mmol) of 2-brombenzyl bromide are mixed in 100 ml of N, N-dimethylformamide and 64 ml of water with 9.75 g (150 mmol) of potassium cyanide, and it is stirred overnight at room temperature. The reaction mixture is poured into ice water. After extracting three times with methyl-tert-butyl ether, the combined organic extracts are washed with saline, dried and the solvent is removed. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 18.9 g (96.4%) of the desired compound are obtained. ? -NMR (300 MHz, CDC13): d = 3.85 (2H), 7.23 (1H), 7.48 (ÍH), 7.55 (ÍH), 7.62 (1H). 2- (2-bromo-phenyl) -2-methyl-yl-propionityl. 18.9 g (96.41 mmol) of (2-bromophenyl) -acetonitrile and 31.41 g (221.74 mmol) of methyl iodide are dissolved. in 150 ml of N, N-dimethylformamide. 8.87 g (221.74 mmol) of sodium hydride (as a 60% suspension in oil) are added at 0 ° in portions, and the preparation is stirred overnight at room temperature. The reaction mixture is poured into ice water and processed using conventional means. Since the compound isolated after chromatography (20.9 g) in addition to the desired product also contains 2- (2-bromophenyl) -propionitrile, the batch is converted once again using the same reagents. This reaction also results in material that still contains mono-methyl compound. After carrying out another alkylation with 15 g of methyl iodide and 4.45 g of sodium hydride in 150 ml of N, N-dimethylformamide, 18.57 g of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.91 (6 H), 7.20 (HH), 7.35 (1H), 7.49 (ÍH), 7.68 (ÍH). 2- (2-bromo-phenyl) -2-methyl-propanal. 18.57 g (82.21 mmol) of 2- (2-bromophenyl) -2-methyl-propionitrile in 325 ml of toluene are reduced with 102.72 ml of a 1.2 M solution of DIBAH in toluene, as described in Example 3. After carrying out the usual work-up, 18.17 g (97.34%) of the desired aldehyde, which is used in the crude form, is isolated. next step. ^? - NMR (300 MHz, CDC13): d = 1.51 (6 H), 7.20 (1H), 7.33-7.45 (2H), 7.61 (IH), 9.8 ( ÍH). Ethyl (E / Z) -4- (2-bromophenyl) -4-methylpent-2-enoic acid ester 18.17 g (80.02 mmol) of 2- (2-bromophenyl) -2-methyl- propanal, using a method analogous to that described in Example 3, with a Horner-Wittig reaction. After performing the usual processing as described therein, and following chromatography on silica gel (elution medium: ethyl acetate / hexane), 22.3 g (81.67%) of the desired product are isolated.

(E / Z) -4- (2-bromo-phenyl) -4-met-ilpent-2-enoic acid 22.3 g (65.349 mmol) of ethyl ester of (E / Z) -4- (2-bromophenyl) are saponified ) -4-methylpent-2-enoic, as described in Example 3, with 650 ml of sodium bicarbonate solution (IN in ethanol / water 2: 1). After carrying out the usual processing, 14.32 g (69.9%) of the desired acid are isolated. 4- (2-Bromophenyl) -4-methyl-2-oxo-pentanoic acid. 14.32 g (45.72 mmol) of (E / Z) -4- (2-bromophenyl) -4-methylpentyl acid are converted. 2-enoic, with the aid of sulfuric acid in ethyl acetate, as described in Example 3, in the desired ketocarbonic acid. 13 g (99.6%) are isolated. XH-NMR (300 MHz, CDC13): d = 1.60 (6 H), 3.91 (2 H), 7.09 (1 H), 7.30 (H), 7.49 (1 H), 7, 57 (ÍH). Ethyl 4- (2-bromophenyl) -4-methyl-2-oxo-pentanoic acid ester 13 g (45.59 mmol) of 4- (2-bromophenyl) -4-methyl-2-oxo-pentanoic acid are converted , with ethanol and concentrated sulfuric acid, in ester. After carrying out the usual workup (according to example 3) and carrying out chromatography on silica gel, 13.01 g (91.1%) of the desired compound are obtained. 2H-NMR (300 MHz, CDC13): d = 1.30 (3H), 1.60 (6H), 3.72 (2H), 4.17 (2H), 7.05 (1H), 7, 27 (1H), 7.47 (1H), 7.57 (1H). 4- (2-bromo-phenyl) -4-methyl-2- (trifluoromethyl) -pentan-1, 2-diol. 13 g (41.5 mmol) of ethyl ester of 4- (2-bromophenyl) -4- are processed. Methyl-2-oxo-pentanoic acid with the Ruppert reagent, as described in Example 3. After the usual work up and chromatography on silica gel (elution medium: ethyl acetate / hexane), they are isolated 16.15 g (85.6%) of the desired compound. To a solution of 6.1 g (35.45 mmol) of the trifluoromethylalcohol described above in 148 ml of toluene are added dropwise, 73.6 ml (88.39 mmol) of a DIBAH solution (1.2 M) toluene) at -10 ° C (35 minutes). After stirring for thirty minutes at a temperature between -10 ° C and -5 ° C, 24.2 ml of isopropanol are carefully added dropwise at -10 ° C, and then water is added. After stirring thoroughly for two hours at room temperature, the resulting precipitate is extracted on a G4 filter, washed with ethyl acetate and the filtrate is centrifuged until dry. The residue (mixture of regioisomers of both silyl ether compounds: 14.5 g = 95.4% = 35.08 mmol) is processed as described in Example 3, with tetrabutylammonium trihydrate fluoride in tetrahydrofuran at room temperature. After carrying out the usual work up using conventional means and chromatography, 5.26 g of the desired compound are isolated. ^ -NMR (300 MHz, CDC13): d = 1.62 (3H), 1.70 (3H), 2.19 (1H), 2.90-3.01 (2H), 3.27-3, 89 (1H), 3.59 (ÍH), 7.09 (ÍH), 7.30 (ÍH), 7.53 (HH), 7.60 (ÍH). 4- (2-bromophenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal 2 g (5.86 mmol) of 4- (2-bromophenyl) -2-hydroxy-4-methyl-2- are oxidized. trifluoromethyl-pentan-l-ol with S03-pyridine complex, as described in Example 1. 1.72 g (86.8 mmol) of the desired aldehyde are isolated. ^ -NMR (300 MHz, CDC13): d = 1.60 (6 H), 2.29 (ÍH), 3.65 (ÍH), 3.78 (ÍH), 7.09 (ÍH), 7, 25 (HH), 7.34 (1H), 7.58 (ÍH), 9.20 (HH). 4- . { [4- (2-bromophenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} isoquinolin-1 (2H) -one 200 mg (0.589 mmol) of 4- (2-bromophenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal are stirred with 94.3 mg (0.589 mmol) of 5- aminoisoquinolin-l (2H) -one (Example 2) in 0.86 ml of glacial acetic acid for five days at room temperature. After performing the usual work-up using conventional means and chromatography on silica gel (elution medium: ethyl acetate / hexane), 170.8 mg (60.2%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.59 (3H), 1.70 (3H), 2.29 (HH), 3.86 (1H), 4.89 (ÍH), 6.58 (1H), 6.70-6.90 (3H), 7.15-7.37 (3H), 7.48 (IH), 7.59 (1H), 8.30 (1H), 11.00 (1 HOUR) . 5- . { [5-bromo-2-hydroxy-4, 4-dimethyl-2- (trifluoromethyl) -1, 2, 3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one 50 mg (0.104 mmol) of 4- are mixed. { (4- (2-Bromophenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino} - isoquinoline-1 (2H) -one with one milliliter of an IVM solution of BBr3 in dichloromethane, and stirring one hour and quarter at room temperature After carrying out the usual processing using conventional means (according to example 2) and carrying out chromatography on silica gel (elution medium: methanol / dichloromethane), 49.2 mg are obtained (98.4%) of the desired compound XH-NMR (300 MHz, DMS0-d6): d = 1.67 (3H), 1.79 (3H), 2.09 (1H), 2.21 (1H) ), 5.48 (ÍH), 6.02 (1H), 6.26 (ÍH), 6.81 (1H), 7.00-7.30 (5H), 7.49-7.62 (ÍH). 2H), 11.25 (1H) By applying the starting aldehyde and the corresponding amines described in the above examples, the following cyclic compounds can be obtained by means of the imines: Example 20 5-bromo-l- [(lH- indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaf alen-2-ol The product is obtained after cyclization as was described in Example 19. XH-NMR (300 MHz, CD30D): d = 1.73 (3H), 1.88 (3H), 2.10-2.30 (2H), 5.30 (1H) , 6.39 (1H), 6.85 (ÍH), 7.01 (ÍH), 7.24 (1H), 7.48 (ÍH), 7.58 (ÍH), 8.13 (ÍH). Example 21 5-bromo-4,4-dimethyl-l-propylamino-2- (trifluoromethyl) -1,2,3,4-e-rahidronaf alen-2-ol The product is obtained after cyclization as described in Example 19. XH-NMR (300 MHz, CD30D): d = 0.90-1.02 (3H), 1.48-1.60 (2H), 1.63 (3H), 1.70 (3H) , 1.91 (ÍH), 2.15 (ÍH), 2.65-2.78 (ÍH), 2.91-3.05 (ÍH), 7.12 (ÍH), 7.45 (ÍH) , 7.56 (ÍH). Example 22 5-Bromo-l- [(3-hydroxypropyl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol The product is obtained after cyclization as was described in Example 19. XH-NMR (300 MHz, CD3OD): d = 1.63 (3H), 1.71 (3H), 1.94 (1H), 1.99-2.11 (2H) , 2.17 (ÍH), 2.84-2.98 (HH), 3.09-3.20 (ÍH), 3.55 (2H), 7.13 (1H), 7.49 (HH) 7.59 (1H). Example 23 5-. { [8-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -isoqt? inolin-1 (2H) -one The product is obtained after cycling as described in example 19. MS (ES +, ACN / H20 + 0.01% TFA): 437 (100%) Example 24 4 -. { [7-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -6-fluoro-2, 3-dihydroisoindol-1-one The product is obtained after cyclization as described in example 19. 1H-NMR (300 MHz, CD3OD): d = 1.58 (3H), 1.65 (3H), 2.01-2.10 (2H), 4.20-4.45 (2H), 5, 10 (1H), 6.70-6.89 (4H). Example 25 5-. { [6-fluoro-2-hydroxy-5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alan-1-yl] amino} Isoquinolin-1 (2H) -one The product is obtained after cyclization as described in example 3.? -NMR (300 MHz, CD3OD): d = 1.53 (3H), 1.58 (3H), 2.14 (2H), 3.99 (3H), 5.15 (ÍH), 6.84 (ÍH), 6.95 (ÍH), 7.00-7.10 (2H), 7.18 ( ÍH), 7.39 (ÍH), 7.69 (ÍH). The obtained product is separated into its enantiomers (Chiralpak AD 20p, elution medium: hexane / ethanol / DEA) and these are subjected to ether separation (analogous procedure to that described in example 3): 5-. { [6-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one (cis, enantiomer A) XH-NMR (300 MHz, CD3OD): d = 1.62 (3H), 1.72 (3H), 2.04-2.21 (2H) ), 5.13 (ÍH), 6.75-6.92 (3H), 7.05 (ÍH), 7.18 (ÍH), 7.39 (1H), 7.69 (1H). 5- . { [6-fluoro-2, 5-dihydroxy-4, 4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one (cis, enantiomer B)? -NMR (300 MHz, CD3OD): d = 1.62 (3H), 1.72 (3H), 2.04-2.21 (2H) ), 5.13 (ÍH), 6.75-6.92 (3H), 7.05 (ÍH), 7.18 (ÍH), 7.39 (ÍH), 7.69 (ÍH). Example 26 4-. { (6-fluoro-2, 5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2, 3,4-tetrahydronaph alen-1-yl] amino.} -2,3-dihydroisoindole-1 -one The product is obtained after cycling and separating in ether as described in example 3. XH-NMR (300 MHz, CD3OD): d = 1.60 (3H), 1.69 (3H), 1.99 -2.20 (2H), 4.23-4.45 (2H), 5.13 (IH), 6.80-7.03 (3H), 7.18 (IH), 7.39 (1H) Example 27 6-Chloro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-te rahydronaphthalene-2,5-diol 3-Chloro-2-methoxybenzyl cyanide To 31.6 g (201.7 mmol) of 3-chloro-2-methoxytoluene in 500 ml of CC1 is added 39.4 g (221.3 mmol) of NBS and 100 mg of benzoyl peroxide, heated at reflux for 16 hours, allowed to cool and filtered, the filtrate is freed from the solvents and dissolved in 214 ml of N, N-dimethylformamide and 142 ml of water. g (322.1 mmol) of potassium cyanide at 0 ° C and stirred for 16 hours.The reaction mixture is diluted with water and extracted several times with water. tert-butyl methyl ether. The organic phase is washed several times with a saturated solution of sodium chloride and dried over sodium sulfate.The solvent is removed in vacuo and, after purification by chromatography on silica gel (hexane / ethyl acetate 20%), 29.7 g of product are obtained. 1 H-NMR (CDC13): d = 3.76 (s, 2H), 3.95 (s, 3H), 7.08 (t, ÍH), 7.31 (d, ÍH), 7.37 (d , ÍH). 4- (3-chloro-2-methoxy-phenyl) -4-methyl-2- (trifluoromethyl) -pentan-1,2-diol. 29.7 g (163.7 mmol) of 4-chloro cyanide are mixed. 2-methoxybenzyl and 46.5 g (327.4 mmol) of methyl iodide in 260 ml of DMF with 13.2 g (327.4 mmol) of sodium hydride (60% in oil), at 0 ° C by portions. It is stirred overnight and then mixed with water and glacial acetic acid. The phases are separated and the aqueous phase is extracted several times with crystalline acetic acid. It is washed with water and saturated sodium chloride solution, dried with sodium sulfate and concentrated in vacuo. After chromatography on silica gel (hexane / ethyl acetate 95: 5), 32.4 g of 2- (4-chloro-2-methoxy-phenyl) -2-methylpropionitrile are obtained as a colorless oil. 7 g (33.4 mmol) of the nitrile in toluene are mixed with 41.6 ml (50.1 mmol) of a solution of diisobutylaluminum hydride (20% in toulol), slowly at -78 ° C, and after Allow 3 hours to pass at -78 ° C, 5.55 ml of isopropanol are added dropwise. Allow to warm to -5 ° C and add 380 ml of an aqueous solution of 10% tartaric acid. After diluting with ether, the mixture is thoroughly stirred, the organic phase is separated off and the aqueous phase is extracted several times with ether. Wash with saline, dry with sodium sulfate and concentrate in vacuo. After chromatography on silica gel (hexane / ethyl acetate 95: 5), 7.1 g of 2- (4-chloro-methoxy-phenyl) -2-methylpropanal are obtained as a colorless oil. A solution of 8.95 g (33.4 mmol) of 2-diethylphosphono-2-ethoxyacetic acid ethyl ester in 30 ml of tetrahydrofuran is mixed with 19 ml (38 mmol) of a 2 M solution of lithium diisopropylamide in tetrahydrofuran. -heptane-toluene, in an ice bath for 20 minutes, and stirred for 15 minutes at 0 ° C. After 30 minutes, 7.1 g (33.4 mmol) of 2- (3-chloro-2-methoxyphenyl) -2-methylpropanal in 27 ml of tetrahydrofuran at 0 ° C are added dropwise. After standing for 20 hours at room temperature, water is added and extracted several times with ether and ethyl acetate. It is washed with a saturated solution of ammonium chloride, dried (Na 2 SO 4) and concentrated. The crude product is purified by column chromatography on silica gel (hexane / 10% ethyl acetate) to obtain 8.5 g of 4- (3-chloro-2-methoxy-phenyl) -4 ethyl ester. -methyl-3-ethoxy-2-en-valeric. The intermediate product is saponified with 80 ml of 3M sodium hydroxide / 160 ml of ethanol. 5.3 g of acid are obtained, which is stirred with 80 ml of 2 N sulfuric acid at 90 ° C for 16 hours. After cooling, basify with potassium carbonate, wash with ether and acidify with hydrochloric acid. After extracting with ethyl acetate, washing with a saturated solution of sodium chloride and removing the solvent, 4.0 g of 4- (3-chloro-2-methoxyphenyl) -4-methyl-2-oxo- valeric 6.6 g (24.3 mmol) of 4- (3-chloro-2-methoxy-phenyl) -4-methyl-2-oxo-valeric acid and 2.74 ml (51.4 mmol) of acid are heated. sulfuric (96%) in 150 ml of ethanol, for 5 hours at reflux. The preparation is concentrated in vacuo and the residue is taken up in a saturated solution of sodium bicarbonate. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium bicarbonate, dried (sodium sulfate) and concentrated in vacuo. After purification by chromatography on silica gel (hexane / 10% ethyl acetate), 5.9 g of 4- (3-chloro-2-methoxy-phenyl) -4-methyl-2-ethyl ester are obtained. -oxo-valeric. This ester and 3.4 g (23.8 mmol) of (trifluoromethyl) -trimethylsilane in 34 ml of THF are mixed with 49 mg of tetrabutylammonium fluoride at 0 ° C. Stir for 16 hours at room temperature and place the reaction mixture in water. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. 2.96 g of 4- (3-chloro-2-methoxy-phenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid ethyl ester are obtained as a yellow oil. This oil is mixed in 24 ml of diethyl ether at 0 ° C with 510 mg of lithium aluminum hydride, and stirred for 4 hours at room temperature. To the preparation, 20 ml of saturated sodium bicarbonate solution are carefully added at 0 ° C and stirred vigorously for another 1 hour.

It is extracted several times with tert-butyl methyl ether, washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The crude product is mixed in 33 ml of THF with 1.83 (5.79 mmol) of tetrabutylammonium fluoride trihydrate and stirred for 16 hours. It is poured into ice water, extracted several times with tert-butyl methyl ether, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 25%), 1.81 g of 4- (3-chloro-2-methoxy-phenyl) -4-methyl-2-trifluoromethyl-pentan- are obtained. 1,2-diol. ^ - MR (300 MHz, CDC13), d = 1.47 (s, 3H), 1.56 (s, 3H), 2.21 (d, ÍH), 2.54 (d, 1H), 2, 91 (s, 1H), 3.31 (dd, ÍH), 3.42 (d, ÍH), 4.01 (s, 3H), 7.00 (t, ÍH), 7.20-7.35 (m, 2H). 4- (3-chloro-2-methoxy-phenyl) -2-hid oxy -met-il-2- (trifluoromethyl) -pentanal To 1.2 g (3.7 mmol) of diol in 24 ml of dichloromethane and 6.4 ml of DMSO, 1.87 g (18.5 mmol) of triethylamine and 1.17 g (7.4 mmol) of pyridine complex and S03 are added in portions over 10 minutes. Stir for 5 hours and add 30 ml of a concentrated solution of ammonium chloride. The mixture is stirred for another 15 minutes, the phases are separated and extracted with tert-butyl methyl ether. It is washed with water and dried with sodium sulfate. The solvent is removed in vacuo and, after purification by chromatography on silica gel (hexane / ethyl acetate, 0-50%), 0.98 g of product are obtained. XH-NMR (CDC1): d = 1.44 (s, 3H), 1.50 (s, 3H), 2.29 (d, 2H), 3.28 (d, ÍH), 3.55 (s) , ÍH), 4.01 (s, 3H), 6.95 (t, 1H), 7.07 (dd, 1H), 7.30 (dd, HH), 8.90 (s, HH). 1, 1, l-trifluoro-4- (3-chloro-2-methoxyphenyl) -2- [(1 H -indazol-4-yl) iminomethyl] -4-methylpentan-2-ol. 125 mg (0.385 mmol) are mixed. of 4- (3-chloro-2-methoxy-phenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal in 0.7 ml of ethyl acetate with 51.3 mg (0.385 mmol) of -a inoindazole and stir overnight at room temperature. After concentrating to dryness, it is subjected to flash chromatography. 11.9 mg (74.1%) of the desired compound are isolated. 6-chloro-l- [(lH-indazol-4-yl) amino] -5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol Dissolve 116.9 mg (0.285 mmol) of imine in 2.6 ml of dichloromethane at -25 ° C with 1.13 ml of an ITM solution of titanium tetrachloride in dichloromethane. After stirring for six hours at -20 ° C to + 10 ° C, it is mixed with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic phase is centrifuged to dryness with sodium sulfate. Flash chromatography of the residue allows to obtain 91.9 mg (78.6%) of the desired cyclic compounds (together with the dechlorinated compound). 6-chloro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2,5-diol 69 are mixed, 9 mg (0.159 mmol) of 6-chloro-l- [(1 H -indazol-4-yl) amino] -5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4- Tetrahydronaphthalen-2-ol with 1.45 ml of an ImM BBr3 solution in dichloromethane, and stir for five hours at room temperature. After carrying out the usual processing using conventional means, the residue is subjected to flash chromatography. 28.1 mg (41.5%) of the desired compound are isolated. Melting point: 112-120 ° C Example 28 cis-7-chloro-l- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3, -te rahidronaf alen-2-ol 4- (4-chlorophenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal 2- (4-chlorophenyl) -2-methylpropanal 10 g of 4-chlorbenzyl cyanide are mixed and 14.3 ml of methyl iodide in 140 ml of DMF with sodium hydride (60% in oil), at 0 ° C in portions. It is stirred overnight, and then mixed with water and ethyl acetate. The phases are separated and the aqueous phase is extracted with ethyl acetate. It is completely extracted with water, washed with saline, dried with sodium sulfate and concentrated in vacuo. After chromatography on silica gel (hexane / ethyl acetate 95: 5), 11.73 g of 2- (4-chlorophenyl) -2-methylpropionitrile is obtained as a colorless oil. This is slowly mixed in toulol at -78 ° C with 55.4 ml of a solution of diisobutylaluminum hydride (20% in toulol), and after 4 hours at -78 ° C, 50 ml are added dropwise. of ethyl acetate. Stir with warming to room temperature overnight and add water. It is filtered through diatomaceous earths to separate the phases, and the aqueous phase is extracted with ethyl acetate. Wash with water and saline, dry with sodium sulfate and concentrate in vacuo. After chromatography on silica gel (hexane / ethyl acetate 95: 5), 10.2 g of 2- (4-chlorophenyl) -2-methylpropanal are obtained as a colorless oil. ^ -NMR (300 MHz, CDC13) d = 1.46 (s, 6H), 7.20 (d, 1H), 7.29-7.43 (m, 3H), 9.48 (s, 1H) . 4- (4-Chlorophenyl) -4-methyl-2-oxo-valeric acid A solution of 15.04 g of 2-diethylphosphono-2-ethoxyacetic acid ethyl ester in 50 ml of tetrahydrofuran is mixed with 30 ml of a solution 2 M lithium diisopropylamide in tetrahydrofuran-heptane-toluene, in an ice bath for 20 minutes, and stir for 15 minutes at 0 ° C. In the course of 30 minutes, a solution of 10.2 g of 2- (4-chlorophenyl) -2-methylpropanal in 50 ml of tetrahydrofuran at 0 ° C is added dropwise. After 20 hours at room temperature, 2N sulfuric acid is added, extracted with ethyl acetate, dried (Na2SO4) and concentrated. The crude product is saponified with 200 ml of 2 M sodium hydroxide / 400 ml of ethanol. 13.8 g of acid are obtained, which is heated under reflux with 300 ml of 2 N sulfuric acid and 100 ml of ethyl acetate under vigorous stirring at reflux for 3 hours. After extracting with ethyl acetate and washing with water, 10.9 g of 4- (4-chlorophenyl) -4-methyl-2-oxo-valeric acid is obtained as a red oil. XH-NMR (300 MHz, CDC13), d = 1.47 (s, 6H), 3.28 (s, 2H), 7.28 (m, 4H), 7.73 (bs, ÍH). 4- (4-chlorophenyl) -4-methyl-2- (trifluoromethyl) -pentan-1, 2-diol Using a procedure analogous to that used in the synthesis of 4- (3-chloro-2-methoxy-phenyl) -2 -hydroxy-4-methyl-2-trifluoromethyl-pentanal (Example 27), the esterification of 10.9 g of 4- (4-chlorophenyl) -4-methyl-2-oxo-valeric acid in ethanol / sulfuric acid is effected. , the transformation of the product with (trifluoromethyl) trimethylsilane and tetrabutylammonium fluoride, and reduction of the hydroxyesters with lithium aluminum hydride to obtain 4.22 g of 4- (4-chlorophenyl) -4-methyl-2- (trifluoromethyl) pentan-1,2-diol as a colorless oil. XH-NMR (CDC13), d (ppm) = 1.39 (s, 3H), 1.49 (s, 3H), 2.07 (d, ÍH), 2.19 (d, 1H), 2, 83 (bs, ÍH), 3.27 (d, 1H), 3.41 (d, 1H), 7.26-7.38 (m, 4H). 4- (4-chlorophenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal To 2 g (6.7 mmol) of diol in 50 ml of dichloromethane and 22 ml of DMSO, 6.8 are added ml (33.3 mmol) of triethylamine and 1.5 g of pyridine complex and S03 in portions for 20 minutes. It is stirred for 5 hours and 40 ml of a concentrated solution of ammonium chloride are added. The mixture is stirred for another 15 minutes, the phases are separated and extracted with dichloromethane. It is washed with water and dried with sodium sulfate. The solvent is removed in vacuo and, after chromatography on silica gel (hexane / 30% ethyl acetate), 1.27 g of product are obtained. XH-NMR (300 MHz, CDC13): d = 1.34 (s, 3H), 1.44 (s, 3H), 2.34 (d, 2H), 2.66 (d, ÍH), 3.64 (s, 1H), 7.23-7.31 (m, 4H), 8.90 (s, ÍH). 7-Chloro-l- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol Starting with the aldehyde previously described , the desired compound is synthesized from the imine, as described in Example 83. XH-NMR (300 MHz, CDC13); d = 1.45 (s, 3H), 1.63 (s, 3H), 2.19 (d, ÍH), 2.31 (d, ÍH), 2.87 (s, 3H), 5.05 (d, ÍH), 5.98 (d, ÍH), 6, 78 (d, 1H), 7.28-7.37 (m, 4H), 7.76 (t, ÍH), 9.36 (s, ÍH). Example 29 5, 8-difluoro-1- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-2-ol 4- (2, 5-difluoromethyl) -4-methyl-2-trif luoromethyl pentan-1,2-diol 5.4 g (15.5 mmol) of 4- (2,5-difluorophenyl) ethyl ester are dissolved. ) -2-hydroxy-4-methyl-2-trifluoromethyl-valeric (WO 02/10143) in diethyl ether at 0 ° C and mixed with 1.76 g (46.5 mmol) of lithium aluminum hydride for 20 minutes . Stir for 4 hours, carefully add a quantity of saturated NaHCO 3 solution until no gas formation is observed. The mixture is diluted with ethyl acetate, stirred for another 15 minutes and then the precipitate obtained is filtered. It is then concentrated and chromatographed on silica gel with hexane / ethyl acetate (50%). 2.45 g of 2,5-difluorophenyl) -4-methyl-2-trifluoromethyl-pentan-1,2-diol are obtained as a yellowish oil capable of crystallizing. 4- (2,5-difluoromethyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal. 800 mg (2.8 mmol) of 4- (2,5-difluorophenyl) -4- are introduced. methyl-2-trifluoromethyl-pentan-1,2-diol in 20 ml of dichloromethane and 9.5 ml of DMSO and 1.95 ml of triethylamine are added at 0 ° C. The solution is slowly mixed with 1.34 g (8.4 mmol) of S03-pyridine complex and stirred for 2 hours at 0 ° C. The mixture is dispersed between a saturated solution of ammonium chloride and MTBE, the phases are separated and the aqueous phase is extracted with MTBE. The combined organic phases are washed with water and a saturated solution of NaCl, and dried with NaS0. Concentrate and chromatograph on silica gel with hexane / ethyl acetate (30%). 710 mg of the desired product are obtained. XH-NMR (300 MHz, CDC13): d = 1.41 (s, 3H), 1.48 (s, 3H), 2.39 (d, 2H), 3.02 (d, ÍH), 3, 61 (s, ÍH), 6.84-7.18 (m, 3H), 9.23 (s, ÍH). 5, 8-difluoro-l- [(2-methylquinazolin-5-yl) amino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol The compound is synthesized desired from the imine (Diastereomer A). XH-NMR (300 MHz, CDC13): d = 1.51 (s, 3H), 1.68 (s, 3H), 2.11 (d, J = 15 Hz, 1H), 2.23 (d, J = 15 Hz, 1H), 2.84 (s, 3H), 4.23 (s, br, ÍH), 4.84 (d, J = 8 Hz, ÍH), 5.32 (d, J = 8 Hz, HH), 6.80-6.90 (m, HH), 6.95-7.02 (m, 1H), 7.05 (d, J = 8 Hz, HH), 7.39 ( d, J = 8 Hz, HH), 7.77 (dd, J = 8 Hz / 8 Hz, HH), 9.19 (s, HH). Example 30 5-. { [4,4-dimethyl-6-fluoro-2-hydroxy-5-methoxy-2-trifluorome-1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one 5-aminoquinolin-2 (1H) -one 4.5 g of 5-nitroquinolin-2 (1H) -one are completely hydrogenated (Chem. Pharm. Bull. (1981), 29, pp. 651-56) in 200 ml of ethyl acetate and 500 ml of methanol, in the presence of 450 mg of palladium on activated carbon as catalyst, under normal pressure with hydrogen. The catalyst is removed by filtration through diatomaceous earth and the reaction solution is concentrated in vacuo. You get 3, 8 g of the title compound as a yellow solid. XH-NMR (DMSO): d = 5.85 (bs, 2H), 6.27 (d, ÍH), 6.33 (d, ÍH), 6.43 (d, ÍH), 7.10 (t , 1H), 8.07 (d, ÍH), 11.39 (bs, 1H) 5-. { [4,4-dimethyl-6-fluoro-2-hydroxy-5-methoxy-2-trifluoromethyl-1,2,4,4-tetrahydronaphthalen-1-yl] amino} - quinolin-2 (1H) -one Using a procedure analogous to that described in Example 3, the corresponding imine is prepared from 500 mg of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl -2-trifluoromethyl-pentanal and 260 mg of 5-aminoquinolin-2 (1H) -one. By reacting 80 mg of the imines with 0.5 ml of titanium tetrachloride (1M in dichloromethane), 20 mg of the title compound are obtained. Examples 31 and 32 5-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one, Diastereomer B 5-. { [2,5-dihydroxy-4,4-dimethyl-2-trifluoromethyl-1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one, Diastereomer A 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal 19.3 g of ethyl ester of 4- (2-methyl) acid are mixed. -methoxyphenyl) -4-methyl-2-oxo-pentanoic acid (WO 00/32584) in 630 ml of diethyl ether with 3.3 g of lithium aluminum hydride, in portions at 0 ° C. After stirring for 10 hours, a saturated bicarbonate solution is added and filtered through diatomaceous earths. The phases are separated and the aqueous phase is extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na 2 SO) and evaporated. After chromatography on silica gel (hexane / ethyl acetate 0 - >); 10%), 16.3 g of diol are obtained as a yellow oil. 2.0 g of diol, 5.2 ml of triethylamine and 5.12 g of sulfur-pyridine oxide complex in 24 ml of DMSO are stirred at room temperature for 48 hours. 0.5N hydrochloric acid is added and extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO4) and concentrated in vacuo. After chromatography on silica gel (hexane / ethyl acetate 0-> 4) 3%), 1.44 g of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal is obtained as a yellow oil. XH-NMR (300 MHz, CDC13), d = 1.40 (s, 3H), 1.47 (s, 3H), 2.2 (d, ÍH), 3.46 (d, 1H), 3, 60 (s, ÍH), 3.88 (s, 3H), 6.83-6.94 (m, 2H), 7.13 (dd, 1H), 7.24 (dt, ÍH), 8.94 (s, 1H). 5- . { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1,2,3- tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one, Diastereomer B, and 5-. { [2,5-dihydroxy-4,4-dimethyl-2-trifluoromethyl-1,2,4,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (IB.) -one, Diastereomer A Using a procedure analogous to that described in example 2, the corresponding imine is prepared from 1.0 g of 4- (2-methoxyphenyl) -2-hydroxy-4 -methyl-2- (trifluoromethyl) pentanal and 553 mg of 5-aminoquinolin-2 (1H) -one. By reaction of 50 mg of imine and 0.22 ml of BBr3 (1N in dichloromethane), 21 mg of 5- are obtained. { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one as fraction 1 and 5 mg of 5-. { [2,5-dihydroxy-4,4-dimethyl-2-trifluoromethyl-l, 2,3,4-tetrahydro-naphthalen-1-yl] amino} -quinolin-2 (1H) -one as fraction 2. Fraction 1: ^ -NMR (300 MHz, CD3OD): d = 1.50 (s, 3H), 1.63 (s, 3H), 2.04 (d, ÍH), 2.12 (d, 1H), 3.83 (s, 3H), 5.17 (s, ÍH), 6.48 (d, ÍH), 6.60 (d, ÍH) , 6.67 (d, ÍH), 6.90 (d, ÍH), 6.92 (d, 1H), 7.10 (t, ÍH), 7.35 (t, ÍH), 8.20 ( d, 1H) Melting point = 269-270 ° C Fraction 2: ^ -NMR (300 MHz, CD3OD): d = 1.39 (s, 3H), 1.52 (s, 3H), 2.05 ( d, ÍH), 2.23 (d, ÍH), 5.28 (s, ÍH), 6.38 (d, ÍH), 6.58 (d, 1H), 6.68 (d, ÍH), 6.92 (d, HH), 7.00 (d, 1H), 7.11 (t, 1H), 7.38 (t, HH), 8.14 (d, HH). Examples 33 and 34 (-) -5-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one (+) -5- { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluorome-1, 2,3, 4-tetrahydronaph-alen-1-yl] amino} -quinolin-2 (ÍH) -one Separation of (+/-) -5-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1,2,4,4-tetrahydronaphthalen-1-yl] amino} - quinolin-2 (IH) -one: The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, Fa DAICEL) with hexane / ethanol (90:10, v / v). In this way the (-) enantiomer is obtained: MS (ESI): M + + 1 = 433, [a] D -70.1 ° (c = 1.0, CHC13) and the enantiomer (+): MS (ESI) ): M + + 1 = 433, [a] D + 78.5 ° (c = 1.0, CHC13). Example 35 (+) -5-. { [2,5-dihydroxy-4,4-dimethyl-2-trifluoromethyl-1,2,3,4-tetrahydronaph-alen-1-yl] amino]} -quinolin-2 (1H) -one, Diastereomer B Analogously to that described in example 3, 5 mg of the title compound are obtained by reaction of 50 mg of (+) - 5 -. { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one and 0.22 ml of BBr3 (IM in dichloromethane). ^ - MR (300 MHz, CD3OD): d = 1.56 (s, 3H), 1.68 (s, 3H), 2.06 (d, ÍH), 2.15 (d, ÍH), 5, 15 (s, 1H), 6.51 (d, ÍH), 6.62 (d, ÍH), 6.68 (d, ÍH), 6.70 (d, ÍH), 6.81 (d, 1H) ), 6.95 (t, 1H), 7.37 (t, ÍH), 8.23 (d, ÍH) Example 36 (-) -5-. { [2,5-dihydroxy-4,4-dimethyl-2-trifluoromethyl-1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one, Diastereomer B Analogously to that described in example 3, 32 mg of the title compound are obtained by reaction of 70 mg of (~) -5-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one and 0.32 ml of BBr3 (1M in dichloromethane). aH-NMR (300 MHz, CD3OD): d = 1.57 (s, 3H), 1.68 (s, 3H), 2.05 (d, ÍH), 2.14 (d, 1H), 5, 15 (s, ÍH), 6.51 (d, ÍH), 6,62 (d, ÍH), 6,67 (d, ÍH), 6,68 (d, 1H), 6,81 (d, ÍH) ), 6.95 (t, ÍH), 7.37 (t, ÍH), 8.22 (d, ÍH). Example 37 5-. { [7-chloro-2,5-dihydroxy-4,4-dimethyl-2-trifluoromethyl-l, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (HH) -one Using a procedure analogous to that described in example 2, the corresponding imine is obtained from 1.0 g of 4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4 methyl-2- (trifluoromethyl) pentanal and 492 mg of 5-aminoquinolin-2 (1H) -one. By reaction of 300 mg of imine with 3.2 ml of BBr3 (1N in dichloromethane), 20 mg of the title compound are obtained. ^ -NMR (300 MHz, DMSO): d = 1.46 (s, 3H), 1.58 (s, 3H), 1.95 (d, ÍH), 2.05 (d, ÍH), 5, 28 (d, ÍH), 6.08 (s, ÍH), 6.20 (d, 1H), 6.40 (d, ÍH), 6.50-6.66 (m, 3H), 6.77 (s, ÍH), 7.24 (t, 1H), 7.35 (t, ÍH), 8,19 (d, ÍH), 10.04 (bs, ÍH), 11.57 (bs, ÍH). Example 38 5-. { [2,5-dihydroxy-4, -dimethyl-6-fluoro-2-trifluoromethyl-1, 2,3,4-tetrahydronaph-alen-1-yl] amino} -quinolin-2 (HH) -one Using a procedure analogous to that described in example 2, the corresponding imine is obtained from 1.0 g of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4 methyl-2- (trifluoromethyl) pentanal (Example 3) and 520 mg of 5-aminoquinolin-2 (lH) -one. By reaction of 300 mg of imine with 3.3 ml of BBr3 (IN in dichloromethane), 255 mg of the title compound are obtained. XH-NMR (300 MHz, CD30D): d = 1.58 (s, 3H), 1.70 (s, 3H), 2.07 (d, ÍH), 2.15 (d, 1H), 5, 13 (s, ÍH), 6.51 (d, ÍH), 6.60 (d, ÍH), 6.68 (d, ÍH), 6.74-6.95 (m, 2H), 7.36 (t, 1H), 8.22 (d, ÍH). Examples 39 and 40 (-) -5-. { [2,5-dihydroxy-4,4-dimethyl-6-fluoro-2-trifluorome-1, 2,3, 4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (lH) -one and (+) - 5 -. { [2,5-dihydroxy-4,4-dimethyl-6-fluoro-2-trifluoromethyl-1, 2,3,4-te rahidronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one Separation of (+/-) -5-. { [2,5-dihydroxy-4,4-dimethyl-6-fluoro-2-trifluoromethyl-1,2,3-tetrahydronaphthalen-1-yl] amino} -quinolin- (1H) -one The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, Fa DAICEL) with hexane / ethanol (90:10, v / v). In this way the (-) enantiomer is obtained: MS (El): M + = 436, [a] D -23.6 ° (c = 1.0, CHC13) and the enantiomer (+): MS (El): M + = 436, [a] D + 25.0 ° (c = 1.0, CHC13). Example 41 5-. { [4,4-dimethyl-5-methoxy-7-methyl-2-trifluoromethyl-2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one, Diastereomer A Ethyl 4- (2-methoxy-4-methylphenyl) -4-methyl-2-oxopentanoic acid ester Analogously to that described in example 7, methyl ester is prepared of 2-methoxy-4-methylbenzoic acid from 30 g of 2,4-cresotinic acid and 58.6 ml of methyl iodide, which is combined with 124.3 g of potassium carbonate in 643 ml of DMF. The ester is converted to a reaction with 141 ml of methyl magnesium chloride (3M in THF) in 475 ml of THF to obtain 1- (2-methoxy-4-methylphenyl) -1-methylethanol. 5 g of the product obtained are converted with 6.4 g of 2- (trimethylsilyloxy) -acrylic acid ethyl ester in 102 ml of dichloromethane at -70 ° C, with 2.3 ml of tin tetrachloride, in 4.84 g. of the title compound. XH-NMR (300 MHz, CDC13): d = 1.44 (s, 6H), 2.31 (s, 3H), 3.38 (s, 2H), 3.81 (s, 3H), 6, 66 (s, 1H), 6.72 (d, ÍH), 7.12 (d, 1H). 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal. Analogously to the one described in Example 7, 4.84 g of ethyl ester of 4-acid are converted. (2-methoxy-4-methylphenyl) -4-methyl-2-oxopentanoic acid in 7 ml of trifluoromethyltrimethylsilane and 3 ml of a solution of tetrabutylammonium fluoride (IM in THF) in 56 ml of THF, in 4.14 g of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanoic acid ethyl ester. The product is reduced with 856 mg of lithium aluminum hydride in 170 ml of diethyl ether to obtain 3.58 g of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanol The oxidation of the diol according to the procedure analogous to that described in Example 7, with 1.1 ml of oxalyl chloride, 2.1 ml of DMSO and 8.0 ml of triethylamine under Swern conditions, makes it possible to obtain 3.01 g of the title compound. aH-NR (300 MHz, CDC13): d = 1.38 (s, 3H), 1.43 (s, 3H), 2.18 (d, 1H), 3.45 (d, 1H), 3 , 87 (s, 3H), 6.67 (s, 1H), 6.70 (d, 1H), 6.98 (d, 1H), 8.92 (s, ÍH). 5-. { [4,4-dimethyl-5-methoxy-7-methyl-2-trifluoromethyl-1, 2,3,4-tetrahydronaphthalen-1-yl} Not me} -quinolin-2 (1H) -one Using a procedure analogous to that described in example 2, the corresponding imine is obtained from 280 mg of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl -2- (trifluoromethyl) pentanal and 156 mg of 5-aminoquinolin-2 (1H) -one. This is stirred at room temperature with 93 mg of aluminum chloride for 2.5 hours. The preparation is introduced into a saturated bicarbonate solution and extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO4) and concentrated in vacuo.

After chromatography on silica gel (dichloromethane / 2-propanol 0-> 5%), 24 mg of the title compound are obtained. XH-NMR (300 MHz, CD3OD): d = 1.50 (s, 3H), 1.62 (s, 3H), 2.04 (d, ÍH), 2.13 (d, ÍH), 2, 20 (s, 3H), 3.85 (s, 3H), 5.13 (s, ÍH), 6.51 (d, ÍH), 6.62 (d, ÍH), 6.70 (d, ÍH) ), 6.75 (s, ÍH), 6.78 (s, ÍH), 7.39 (t, ÍH), 8.23 (d, ÍH) Example 42 5-. { [4,4-dimethyl-7-fluoro-2-hydroxy-5-methoxy-2-trifluoromethyl-1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one 4- (4-f luoro-2-methoxy-enyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal 16.8 g of ethyl ester of 4-acid are mixed (4-fluoro-2-methoxyphenyl) -4-methyl-2-oxo-pentanoic acid (WO 00/32584) in 600 ml of diethyl ether with 2.7 g of lithium aluminum hydride, in portions at 0 ° C. After stirring for 10 hours, a saturated bicarbonate solution is added and filtered through diatomaceous earths. The phases are separated and the aqueous phase is extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO4) and evaporated.

After chromatography on silica gel (hexane / ethyl acetate 0-> 10%), 6.7 g of diol and 2.65 g of the title compound are obtained. The preparation of the title compound from the corresponding diol is carried out by reacting 3.0 g of diol, 6.6 ml of triethylamine and 6.5 g of sulfur-pyridine oxide complex in 34 ml of DMSO a room temperature, with a reaction period of 48 hours. 0.5N hydrochloric acid is added and extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO4) and concentrated in vacuo. After chromatography on silica gel (hexane / ethyl acetate 0-> 15%), 2.7 g of the title compound are obtained as a yellow oil. XH-NMR (300 MHz, CDC13), d = 1.38 (s, 3H), 1.46 (s, 3H), 2.19 (d, ÍH), 3.37 (d, ÍH), 3, 58 (s, 1H), 3.87 (s, 3H), 6.55-6.64 (m, 2H), 7.06 (dd, ÍH), 8.97 (s, 1H). 5- . { [4,4-dimethyl-7-fluoro-2-hydroxy-5-methoxy-2-trifluoromethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one Using a procedure analogous to that described in example 41, the corresponding imine is obtained from 500 mg of 4- (4-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl -2- (trifluoromethyl) pentanal and 260 mg of 5-aminoquinolin-2 (1H) -one. By reaction of 220 mg of imine with 197 mg of aluminum chloride, 10 mg of the title compound are obtained. XH-NMR (CD3OD): d = 1.51 (s, 3H), 1.63 (s, 3H), 2.07 (d, ÍH), 2.14 (d, ÍH), 5.15 (s) , HH), 6.53 (d, 1H), 6.58-6.77 (m, 4H), 7.40 (t, HH), 8.23 (d, HH). Example 43 (+) -5-. { [2,5-dihydroxy-4,4-dimethyl-2-trifluoromethyl-1,2,4,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (HH) -one Analogously to that described in example 3, 5 mg of the title compound are obtained by reaction of 50 mg of (+) - 5. { [4,4-dimethyl-2-hydroxy-5-methoxy-2-trifluoromethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one and 0.22 ml of BBr3 (IM in dichloromethane). XH-NMR (300 MHz, CD3OD): d = 1.57 (s, 3H), 1.69 (s, 3H), 2.06 (d, 1H), 2.15 (d, ÍH), 5, 16 (s, ÍH), 6.51 (d, ÍH), 6.62 (d, 1H), 6.69 (d, ÍH), 6.71 (d, ÍH), 6.82 (d, 1H) ), 6.95 (t, 1H), 7.37 (t, ÍH), 8.23 (d, 1H). Example 44 4-. { [2-hydroxy-4,4-dimethyl-5-methoxy-2-trifluoromethyl-1,2,3,4-tetrahydronaph alen-1-yl] amino} -f alida Using a procedure analogous to that described in example 10, the corresponding imine is obtained from 600 mg of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 308 mg of 4-amino-phthalide (Bull. Soc. Sci. Bretagne 26, 1951, special edition 5, p.7, 96) .. As in example 2, 650 mg of imine are mixed by reaction with 7.7. ml of BBr3 (IM in dichloromethane) to obtain 165 mg of the title compound. 1 H-NMR (300 MHz, DMSO-d 6): d = 1.30 (s, 3 H), 1.46 (s, 3H), 1.93 (d, ÍH), 2.18 (d, ÍH), 3.57 (s, 3H), 5.10 (d, ÍH), .20 (d, 1H), 5.32 (d, ÍH), 5.55 (d, ÍH), 5.81 (s, ÍH), 6.80 (d, ÍH), 7.03 (d , HH), 7.04 (d, HH), 7.20 (d, 1H), 7.27 (t, ÍH), 7.37 (t, ÍH).

Example 45 7-Chloro-l- [(lH-indazol-4-yl) amino] -4, -dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaph alen-2,5-diol Using a procedure analogous to that described in Example 2, the corresponding imine is obtained from 410 mg of 4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 168 mg of 4-aminoindazole. By reaction of 200 mg of imine with 6.7 ml of BBr3 (IN in dichloromethane), 98 mg of the title compound are obtained. XH-NMR (300 MHz, DMSO-d6): d = 1.48 (s, 3H), 1.59 (s, 3H), 1.97 (d, ÍH), 2.07 (d, ÍH), 5.27 (d, ÍH), 5.95 (s, 1H), 6.21 (d, ÍH), 6.31 (d, ÍH), 6.72 (s, ÍH), 6.74 (d , 1H), 6.76 (s, ÍH), 7.08 (t, 1H), 8.13 (s, 1H), 9.94 (s, 1H), 12.83 (s, ÍH).

Examples 46 and 47 (-) -7-chloro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (tri-loromethyl) -1,2,3,4-tetrahydronaphthalene- 2,5-diol (+) - 7-chloro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3, 4-tetrahydronaf alen -2, 5-diol Separation of (+/-) -7-chloro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3 , 4-tetrahydronaphthalene-2,5-diol The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, Fa DAICEL) with hexane / ethanol (90:10, v / v). In this way, the (-) enantiomer is obtained: MS (El): M + = 425/427, [] D -3.0 ° (c = 1.0, CHC13) and the (+) enantiomer: MS (El) : M + = 425/427, [a] D + 5.0 ° (c = 1.0, CHC13). Examples 48 and 49 7-fluoro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3, 4-te rahidronaf alen -2-ol 7-fluoro-1- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaf-alen-2, 5- diol Using a procedure analogous to that described in example 2, and starting from 1.8 g of 4- (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 780 mg of 4-aminoindazole, the corresponding imine is obtained. By reaction of 300 mg of imine with 10.6 ml of BBr3 (1N in dichloromethane), 13 mg of 7-fluoro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl- 5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol as fraction 1 and 30 mg of 7-fluo-ro-1- [(lH-indazol-4-yl) amino] ] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2,5-diol as fraction 2. Fraction 1: XH-NMR (300 MHz, CDC13): d = 1 , 48 (s, 3H), 1.62 (s, 3H), 2.05 (d, 1H), 2.16 (d, 1H), 3.85 (s, 3H), 4.62 (d, ÍH), 5,07 (d, ÍH), 6,43 (d, 1H), 6,55 (dd, 1H), 6,71 (dd, ÍH), 6,92 (d, ÍH), 7, 27 (t, ÍH), 8.01 (s, ÍH) Fraction 2: ^ H-NMR (300 MHz, CDC13): d = 1.54 (s, 3H), 1.65 (s, 3H), 2 , 07 (d, ÍH), 2.17 (d, 1H), 4.62 (d, ÍH), 5.07 (d, ÍH), 6.37-6.47 (m, 2H), 6, 72 (dd, ÍH), 6.94 (d, ÍH), 7.28 (t, ÍH), 8.02 (s, ÍH).

Examples 50 and 51 (-) -7-fluoro-1- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3, 4-tetrahydronafallen- 2,5-diol (+) - 7-fluoro-1- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalene- 2,5-diol Separation of (+/-) -7-fluoro-l- [(1 H -indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3, 4-tetrahydronaphthalen-2, 5-diol: The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, Fa DAICEL) with hexane / ethanol (90:10, v / v). In this way the (-) enantiomer is obtained: MS (El): M + = 409, [a] D -40.5 ° (c = 0.2, CHC13) and the enantiomer (+): MS (El): M + = 409. Examples 52 and 53 5-fluoro-1- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2,3, 4-tetrahydronafallen- 2,5-diol, Diastereomer A 5-fluoro-1- [(lH-indazol-4-yl) amino] -4, -dimethyl-2- (trifluoromethyl) -1,2,3, 4-te rahidronaftalen-2 , 5-diol, Diastereomer B 4- (2-f luoro-methoxy-enyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal 4.12 g of ethyl ester of 4- ( 2-fluoro-4-methoxyphenyl) -4-methyl-2-oxo-pentanoic acid in 140 ml of diethyl ether with 666 mg of lithium aluminum hydride, in portions a 0 ° C. After stirring for 10 hours, a saturated bicarbonate solution is added and filtered through diatomaceous earths. The phases are separated and the aqueous phase is extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na 2 SO) and evaporated. After chromatography on silica gel (hexane / ethyl acetate 0 - >); 10%), 2.74 g of diol and 416 mg of the title compound are obtained. The preparation of the title compound from the obtained diol is carried out by reaction of 3.0 g of diol, 6.6 ml of triethylamine and 6.5 g of sulfur-pyridine oxide complex in 34 ml of DMSO a room temperature, for a period of 48 hours. 5N hydrochloric acid is added and extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO) and concentrated in vacuo. After chromatography on silica gel (hexane / ethyl acetate 0-> 15%), 1.73 g of the title compound is obtained as a yellow oil. XH-NMR (300 MHz, CDC13), d = 1.39 (s, 3H), 1.46 (s, 3H), 2.26 (d, ÍH), 3.09 (d, ÍH), 3, 63 (s, ÍH), 3.78 (s, 3H), 6.52-6.65 (m, 2H), 7.03 (t, ÍH), 9.04 (s, ÍH). 5-fluoro-l- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2, 5-diol, Diastereomer A, and 5-fluoro-l- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -l, 2, 3, 4-tetrahydronaphthalen-2, 5-diol, Diastereomer B Using a procedure analogous to that described in example 2, and starting with 1.7 g 4- (2-fluoro-4-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 736 mg of 4- aminoindazole, the corresponding imine is obtained. By reaction of 300 mg of imine with 10.6 ml of BBr3 (IN in dichloromethane), 12 mg of 5-fluoro-l- [(lH-indazol-4-yl) amino] -4, 4- are obtained. dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydro-naphthalene-2,5-diol, Diastereomer B, as fraction 1, and 90 mg of 5-fluoro-l- [(lH-indazole- 4-yl) amino] -4,4-dimethyl-2- (tri-fluoromethyl) -1, 2,3-tetrahydronaphthalene-2,5-diol, Diastereomer A, as fraction 2. Fraction 1: ^ -NMR (300 MHz, CDC13): d = 1.48 (s, 3H), 1.58 (s, 3H), 2.06 (d, ÍH), 2.23 (d, 1H), 4.95 (d , 1 H), 5,11 (d, 1 H), 6,37 (d, ÍH), 6,48 (dd, ÍH), 6,64 (d, ÍH), 6,75 (s, ÍH), 7 , 25 (t, ÍH), 7.48 (s, 1H). Fraction 2: ^ -NMR (300 MHz, CDC13): d = 1.48 (s, 3H), 1.58 (s, 3H), 2.05 (d, ÍH), 2.24 (d, ÍH) , 5.04 (d, 1H), 5.12 (d, 1H), 6.37 (d, ÍH), 6.48 (dd, ÍH), 6.58 (dd, ÍH), 6.78 ( d, ÍH), 7.24 (t, 1H), 7.29 (s, ÍH). Example 54 [(lH-indazol-4-yl) amino] -4,4-dimethyl-5-methoxy-2- (rifluoromethyl) -1,2,3, 4-etrahydronaphthalen-2-ol, Diastereomer A Using a procedure analogous to the one described in example 41, the imine is obtained. corresponding from 850 mg of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 390 mg of 4-aminoindazole. By reaction of 500 mg of imine with 495 mg of aluminum chloride, 138 mg of the title compound are obtained. XH-NMR (300 MHz, CDC13), d = 1.52 (s, 3H), 1.66 (s, 3H), 2.05 (d, ÍH), 2.16 (d, ÍH), 3, 85 (s, 3H), 4.57 (d, 1H), 5.23 (d, 1H), 6.48 (d, 1H), 6.82 (d, ÍH), 6.92 (d, 1H) ), 6.95 (d, ÍH), 7.12 (t, ÍH), 7.29 (t, ÍH), 7.97 (s, 1H) Example 55 [(lH-indazol-4-yl) amino] ] -4,4-Dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaf-alen-2-ol, Diastereomer B Using a procedure analogous to that described in Example 2, 300 mg are converted of the imine described in example 54 with 11 ml of BBr3 (IN in dichloromethane) in 24 mg of the title compound. ^? - NMR (300 MHz, CD3OD), d = 1.42 (s, 3H), 1.55 (s, 3H), 2.08 (d, ÍH), 2.23 (d, ÍH), 3 , 33 (s, 3H), 5.33 (s, 1H), 6.63 (d, ÍH), 6.72 (d, ÍH), 6.88 (d, ÍH), 7.06 (d, ÍH), 7.20-7.31 (m, 2H), 8.17 (s, ÍH). Example 56 1- [(lH-indazol-4-yl) amino] -4, -dimethyl-2- (trifluoromethyl) -1,2,3, 4-te rahidronaftalen-2, 5-diol Convert 100 mg of the compound of Example 54, employing a procedure analogous to that described in example 1, with 3.7 ml of BBr3 (IN in dichloromethane) in 47 mg of the title compound.

XH-NMR (300 MHz, CD3OD), d = 1.40 (s, 3H), 1.54 (s, 3H), 2.10 (d, ÍH), 2.25 (d, ÍH), 5, 36 (s, ÍH), 6.60 (d, ÍH), 6.94 (d, 1H), 7.12 (t, ÍH), 7.18-7.33 (m, 3H), 8.20 (Yes H) . Example 57 7-Chloro-l- [(1H-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-2-ol Using a procedure analogous to that described in Example 2, and starting with 350 mg of 4- (4-chlorophenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 158 mg of 4-aminoindazole, the corresponding imine is obtained. By reaction of 50 mg of imine with 1.8 ml of BBr3 (IN in dichloromethane), 29 mg of the title compound are obtained. XH-NMR (300 MHz, CDC13), d = 1.41 (s, 3H), 1.54 (s, 3H), 2.10 (d, ÍH), 2.19 (d, 1H), 4, 63 (d, ÍH), 5,14 (d, ÍH), 6,43 (d, ÍH), 6,95 (d, 1H), 7,23-7,37 (m, 4H), 8,03 (Yes H) . Example 58 1- [(l-Methyl-indazol-4-yl) amino] -4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol 4- amino-1-methylindazole 6.5 g of 4-nitroindazole (Chem. Ber. (1904), are stirred. 37, 2583), 1.9 ml of methyl iodide and 14.4 g of cesium carbonate in 110 ml of DMF for 2 hours at 0 ° C, and then for 12 hours at room temperature. The mixture is introduced into water and extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO4) and evaporate. The residue is recrystallized from ethyl acetate / hexane. 2.49 g of l-methyl-4-nitroindazole are obtained. This is hydrogenated in 70 ml of THF with 420 mg of palladium on activated carbon, under normal pressure with hydrogen. The preparation is filtered through diatomaceous earth and evaporates completely. 2.1 g of the title compound are obtained. XH-NMR (300 MHz, CD3OD), d = 3.96 (s, 3H), 6.35 (d, ÍH), 6.75 (d, ÍH), 7.16 (d, ÍH), 8, 06 (s, ÍH). [(1-methyl-indazol-4-yl) amino] -4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol Using a procedure analogous to that described in Example 3, the corresponding imine is obtained from 296 mg of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 150 mg of 4-amino-1-methylindazole. By reaction of 100 mg of imine with 0.5 ml of titanium tetrachloride, 100 mg of the title compound are obtained. Melting point: 172-174 ° C Examples 59 and 60 7-ethyl-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1, 2,3,4-tetrahydronaph alen-2-ol 7-ethyl-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4 -tetrahydronaf alen-2-ol 2-hydroxy-4- (4-iodo-2-methoxyphenyl) -4-met il-2-trifluoromethylvaleric acid methyl ester 3 g of 4- (4-iodo-2-acid methoxyphenyl) -4-methyl-2-oxovaleric acid (WO 98/54159) in a solution of 1, 3 ml of thionyl chloride in 12 ml of methanol at 0 ° C, and stir for 10 hours at room temperature. A saturated bicarbonate solution is added and extracted with ethyl acetate. The organic phases are washed with a solution of bicarbonate and saline, dried (Na 2 SO 4) and evaporated. 3.2 g of 4- (4-iodo-2-methoxyphenyl) -4-methyl-2-oxovaleric acid methyl ester are obtained as the crude product. This ester is mixed with 4.5 ml of trifluoromethyltrimethylsilane in 70 ml of DMF and 1.63 g of cesium carbonate at 0 ° C, and stirred for 10 hours at room temperature. 20 mg of tetrabutylammonium fluoride are added and the mixture is stirred for another 30 minutes at room temperature. The preparation is poured into water and extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO) and evaporated. After chromatography on silica gel (hexane / ethyl acetate 0 - >); 15%), 1.47 g of the title compound is obtained as a yellow oil. ? -NMR (300 MHz, CDC13), d = 1.34 (s, 3H), 1.42 (s, 3H), 2.30 (d, 1H), 2.97 (d, ÍH), 3, 36 (s, 3H), 3.84 (s, 3H), 6.88 (dd, 1H), 7.13 (dd, ÍH), 7.23 (dd, ÍH). 4- (4-ethyl-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethylpentanal 1 g of methyl ester of 2-hydroxy-4- (4-iodo-2-methoxyphenyl) - are heated at reflux 4-methyl-2-trifluoromethyl-valeric acid, 860 mg of tributylvinyltin, 103 mg of palladium-dibenzylidene ketone complex and 30 mg of triphenylphosphine in 17 ml of THF, under an argon atmosphere for 57 hours. It is filtered through diatomaceous earth and evaporates completely. After chromatography on silica gel (hexane / ethyl acetate 0-> 2%), 339 mg of methyl ester of 2-hydroxy-4- (2-methoxy-4-vinylphenyl) -4- are obtained. methyl-2-trifluoromethylvaleric. This is stirred with 56 mg of lithium aluminum hydride in 11 ml of diethyl ether at room temperature for 10 hours. It is introduced in a saturated bicarbonate solution, filtered through diatomaceous earth and extracted with ethyl acetate. The organic phases are washed with a solution of bicarbonate and saline, dried (Na 2 SO) and evaporated. After chromatography on silica gel (hexane / ethyl acetate 0-> 10%), 148 mg of 2-hydroxy-4- (2-methoxy-4-vinylphenyl) -4-methyl-2- are obtained trifluoro-methylpentanol. This is hydrogenated in 4.3 ml of ethyl acetate with 14 mg of palladium on active carbon, at normal pressure with hydrogen. The preparation is filtered through diatomaceous earth and evaporates completely. 127 mg of 4- (4-ethyl-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethylpentanol are obtained. The corresponding diol is obtained with 0.29 ml of triethylamine and 280 mg of sulfur-pyridine oxide complex in 1.3 ml of DMSO at room temperature, in a reaction period of 10 hours. It is introduced into a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic phases are washed with water and saline, dried (Na2SO4) and concentrated in vacuo. After chromatography on silica gel (hexane / ethyl acetate 0-> 3%), 94 mg of the title compound is obtained as a colorless oil. ^? - MR (300 MHz, CDC13), d = 1.24 (t, 3H), 1.38 (s, 3H), 1.44 (s, 3H), 2.17 (d, 1H), 2 , 62 (q, 2H), 3.46 (d, 1H), 3. 88 (s, 3H), 6.68 (s, ÍH), 6.72 (d, ÍH), 7.02 (d, ÍH), 8.91 (s, 1H). 7-ethyl-l- 1 (lH-indazol-4-yl) amino] -4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-2-ol and 7 -ethyl-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol Using a procedure analogous to that described in Example 2, and starting from 90 mg of 4- (4-ethyl-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 38 mg of 4-aminoindazole, the corresponding imine is obtained. By reaction of 68 mg of imine with 0.39 ml of BBr3 (IN in dichloromethane), 16 mg of 7-ethyl-1 - [(1H-indazol-4-yl) amino] -4,4-dimethyl- 5-methoxy-2- (trifluoromethyl) -1, 2,3,4-tetrahydronaphthalen-2-ol as fraction 1 and 7 mg of 7-ethyl-1- [(lH-indazol-4-yl) amino] - 4, 4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-2-ol as fraction 2. Fraction 1: ^ -NMR (300 MHz, CDC13), d = 1.24 (t , 3H), 1.42 (s, 3H), 1.51 (s, 3H), 2.03 (d, ÍH), 2.14 (d, 1H), 2.63 (q, 2H), 3.18 (s, 3H), 3.74 (bd, ÍH), 5.33 (bd, ÍH), 6.48 (s, ÍH), 6.70 (d, ÍH) , 6.85 (s, ÍH), 6.98 (d, ÍH), 7.32 (t, 2H), 7. 89 (s, ÍH).

Fraction 2: XH-NMR (300 MHz, CDC13), d = 1.00 (t, 3H), 1.55 (s, 3H), 1.65 (s, 3H), 2.04 (d, ÍH), 2.18 (d, ÍH), 2.36 (q, 2H), 3.18 (s, 3H), 4.65 (bd, 1H), 5.09 (bd, 1H), 6.47 (d, ÍH), 6.48 (s, ÍH), 6.76 (s, ÍH), 6.92 (d, 1H), 7.29 (t, 2H), 8.00 (s, 1H). Example 61 1- [(1-methyl-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2, 5-diol Using an analogous procedure to that described in example 2, 163 mg of the imine described in example 58 are converted with 0.97 ml of BBr3 (1N in dichloromethane) to 44 mg of the title compound. XH-NMR (300 MHz, CD3OD), d = 1.56 (s, 3H), 1.68 (s, 3H), 2.05 (d, ÍH), 2.14 (d, 1H), 4, 02 (s, 3H), 5.15 (s, ÍH), 6.34 (d, ÍH), 6.67 (d, ÍH), 6.78 (d, ÍH), 6.82-6.98 (m, 2H), 7.25 (t, 2H), 8.07 (s, ÍH). Examples 62 and 63 5-. { [7-fluoro-2-hydroxy-4,4-dimethyl-5-methoxy-2- (rifluoromethyl) -1,2,3,4-tetrahydrona-alen-1-yl] amino} -isoquinolin-1 (2H) -one 5-. { [7-fluoro-2, 5-dihydroxy-4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one Using a procedure analogous to that described in example 2, and starting from 385 mg of 4- (4-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 200 mg of 5-aminoisoquinolin-1 (2H) -one, the corresponding imine is obtained. By reaction of 300 mg of imine with 10.0 ml of BBr3 (IN in dichloromethane), 10 mg of 5- are obtained. { [7-fluoro-2-hydroxy-4, -dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one as fraction 1 and 100 mg of 5-. { [7-fluoro-2, 5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one as fraction 2. Fraction 1: XH-NMR (300 MHz, DMSO-d6), d = 1.32 (s, 3H), 1.47 (s, 3H), 1 , 95 (d, ÍH), 2.24 (d, 1H), 3.44 (s, 3H), .01-5.14 (m, 2H), 5.85 (s, ÍH), 6.70 (dd, ÍH), 6.78 (d, ÍH), 6.86 (dd, ÍH), 6.98 (dd, ÍH), 7.22 (d, ÍH), 7.31 (t, ÍH), 7.52 (d, ÍH), 11.10 (bd, ÍH). Fraction 2: XH-NMR (300 MHz, DMSO-d6), d = 1.47 (s, 3H), 1.58 (s, 3H), 1.97 (d, ÍH), 2.08 (d, ÍH), 5,30 (d, ÍH), 5,94 (d, ÍH), 6,13 (s, 1H), 6,35 (dd, ÍH), 6,54 (dd, ÍH), 6, 81 (d, 1H), 7.03 (d, 1H), 7.17 (dd, ÍH), 7.25 (t, ÍH), 7.51 (d, ÍH), 9.98 (bs, 1H ), 11.25 (bd, ÍH). Examples 64 and 65 (~) -5-. { [7-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one (+) - 5 -. { [7-fluoro-2, 5-dihydroxy-4,4-dimethyl-2- (rifluoromethyl) -1,2,3,4-te rahidronaf alen-1-yl] amino} -isoquinolin-1 (2H) -one Separation from (+/-) -5-. { [7-fluoro-2, 5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-l (2H) -one: The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, DAICEL Fa) with hexa-no / ethanol (90:10, v / v). In this way, the (-) eantiomer is obtained: MS (El): M + = 436, [a] D -62.5 ° (c = 0.5, CHC13) and the enantiomer (+): MS (El): M + = 436, [a] D + 75.6 ° (c = 0.8, CHC13). Example 66 5-. { [6-fluoro-2-hydroxy-, 4-dimethyl-5-methoxy-2- (rifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer A 5-amino-2-methyl-phthalazin-1-one 3-bromo-4-nitrophthalide 5.37 g of 4-nitrofta-lide are refluxed in the light. (Tetrahedron Lett. (2001), 42, pp. 1647-50), 8.04 g of N-bromsuccinimide and 196 mg of benzoyl peroxide in 80 ml of benzoyl trifluoride until complete transformation. It is poured into water, extracted with dichloromethane, washed several times with water, dried and the solvent is removed under vacuum. 7.24 g of 3-bromo-4-nitro-phthalide is obtained as a solid. XH-NMR (300 MHz, CDC13), d = 7.26 (s, HH), 7.88 (t, HH), 8.3 (d, HH), 8.56 (d, HH). -nitro-phthalazin-1-one 18.25 g of hydrazine sulfate and 14.88 g of sodium carbonate in 300 ml of DMF are stirred at 100 ° C for 1 hour. Then 7.24 g of 3-bromo-4-nitro-phthalide in 100 ml of DMF are added and the mixture is stirred at 100 ° C. for a further 4 hours. It is introduced into water, extracted several times with ethyl acetate and the organic phases are washed with water and saline. It is dried and the solvent is removed in vacuo. After recrystallization from ethyl acetate, 2.35 g of 5-nitro-phthalazin-1-one is obtained as a solid. XH-NMR (300 MHz, DMSO-d5), d = 8.05 (t, ÍH), 8.57-8.66 (m, 2H), 8.73 (s, ÍH), 13.13 (bs) , ÍH). 2-methy-5-nitro-phthalazin-1-one 1.6 g of 5-nitro-phthalazin-1-one and 2.31 g of potassium carbonate are stirred for 10 minutes at room temperature in 60 ml of DMF. 1.1 ml of methyl iodide are added and the mixture is stirred overnight. It is introduced into water, extracted several times with ethyl acetate and the organic phases are washed with water and saline. It is dried and the solvent is removed in vacuo. 1.57 g of 2-methy-5-nitro-phthalazin-1-one is obtained as a yellow solid. XH-NMR (300 MHz, DMSO-d6), d = 3.73 (s, 3H), 8.05 (t, ÍH), 8.62 (d, 2H), 8.75 (s, ÍH). 5-amino-2-methyl-phthalazin-1 -one 1.57 g of 2-methyl-5-nitro-phthalazin-1-one and 130 mg of palladium on active carbon are suspended in 45 ml of ethyl acetate, hydrogenates with hydrogen at normal pressure. It is filtered through diatomaceous earth and the solvent is removed under vacuum. 1.26 g of 5-amino-2-methyl-phthalazin-1-one is obtained as a yellow solid. XH-NMR (300 MHz, CDC13), d = 3.81 (s, 3H), 7.0 (d, 1H), 7.5 (t, ÍH), 7.8 (d, ÍH), 8, 16 (s, ÍH). 5- . { (6-fluoro-2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino.} -2-methylphthalazine-1 -one Using a procedure analogous to that described in example 10, the corresponding imine is obtained from 200 mg of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 114 mg of 5-amino-2-methyl-phthalazin-1-one. As in Example 3, 50 mg of imine is converted by reaction with 0.23 ml of titanium tetrachloride to obtain 12 mg of the compound of the invention. Title: Melting point: 262-263 ° C Example 67 5- { [6-Fluoro-2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1, 2,3,4 -tetrahydronaf alen-1-yl] amino.}. -f-alazin-1 (2H) -one 5-amino-phthalazin-1-one 980 mg of 5-nitro-phthalazin-1-one are suspended (example 66) and 100 mg of palladium on active carbon in 50 ml of ethyl acetate and 1 ml of triethylamine, and hydrogenated with hydrogen at normal pressure. It is filtered through diatomaceous earth and the solvent is removed under vacuum. 830 g of 5-amino-phthalazin-1-one are obtained as solid crude product. ? -NMR (300 MHz, DMSO-de), d = 6.26 (bs, 2H), 7.00 (d, ÍH), 7.32 (d, ÍH), 7.44 (t, ÍH), 8.48 (s, ÍH), 12.35 (bs, ÍH). 5-. { (6-fluoro-2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino.} - phthalazine-1 (2H) -one Using a procedure analogous to that described in example 10, the corresponding imine is obtained from 200 mg of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 105 mg of 5-amino-phthalazin-1-one. As in Example 3, 50 mg of imine is processed in a reaction with 0.22 ml of titanium tetrachloride, and 36 mg of the title compound are obtained. XH-NMR (300 MHz, CD3OD), d = 1.53 (s, 3H), 1.64 (s, 3H), 2.12 (s, 2H), 3.94 (d, 3H), , 24 (s, ÍH), 6.96 (dd, ÍH), 7.03 (dd, ÍH), 7.24 (dd, ÍH), 7.58-7.65 (m, 2H), 8, 55 (s, ÍH) Example 68 5- { [7-chloro-2,5-dihydroxy-4,4-dimethyl-2- (rifluoromethyl) -1,2,3, 4-te rahidronaf alen-1 -yl] amino.} -2-methylphthalazin-1-one Using a procedure analogous to that described in Example 10, the corresponding imine is obtained from 200 mg of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 108 mg of 5-amino-2-methyl-phthalazin-1-one. As in Example 2, 225 mg of imine is processed by reaction with 2.3 ml of BBr3 (1M in dichloromethane), and 12 mg of the title compound are obtained.

'H-NMR (300 MHz, CD3OD), d = 1.55 (s, 3H), 1.66 (s, 3H), 2.08 (d, ÍH), 2.14 (d, ÍH), 5.22 (s, ÍH), 6.74 (s, 1H), 6.78 (s, ÍH), 7.18-7.27 (m, ÍH), 7.62-7.72 (m, 2H), 8.57 (s, ÍH). Example 69 5-. { [6-fluoro-2-hydroxy-4,4-dimethyl-5-methoxy-2- (rifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -2-methylphthalazin-1-on, Diastereomer B Using a procedure analogous to that described in example 10, the corresponding imine is obtained from 200 mg of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4 -methyl-2- (trifluoromethyl) pentanal and 114 mg of 5-amino-2-methyl-phthala-zin-1-one. As in Example 2, 112 mg of imine is processed by reaction with 0.36 ml of BBr3 (IM in dichloromethane), and 38 mg of the title compound are obtained. XH-NMR (300 MHz, CDC13), d = 1.53 (s, 3H), 1.64 (s, 3H), 2.11 (d, ÍH), 3.85 (s, 3H), 3, 97 (d, 3H), 5.02 (d, ÍH), 5.13 (d, ÍH), 6.97 (d, ÍH), 7.00 (dd, ÍH), 7.08 (d, ÍH) ), 7.61 (t, 1H), 7.83 (d, ÍH), 8.15 (s, ÍH). Example 70 5-. { [6-fluoro-2,5-dihydroxy-4, -dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] apine} -2-I-N-phthalazin-1-one 29 mg of the compound of Example 69 are converted using an analogous procedure to that described in Example 1, with 0.13 ml of BBr3 (IN in dichloromethane), in 18 mg of the title compound. XH-NMR (300 MHz, CD3OD), d = 1.60 (s, 3H), 1.71 (s, 3H), 2.09 (d, ÍH), 2.16 (d, ÍH), 3, 83 (s, 3H), 5.23 (s, ÍH), 6.79 (dd, ÍH), 6.90 (dd, ÍH), 7.22 (dd, 1H), 7.59-7.68 (, 2H), 8.56 (s, ÍH). Example 71 5-. { [6-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -f alazin-1 (2H) -one 80 mg of the compound of Example 67 are converted using a procedure analogous to that described in Example 1, with 0.35 ml of BBr3 (1N in dichloromethane), in 15 mg of the title compound . ? -NMR (300 MHz, CD3OD), d = 1.60 (s, 3H), 1.71 (s, 3H), 2.14 (d, 2H), 5.23 (s, ÍH), 6, 80 (dd, 1H), 6.90 (dd, 1H), 7.25 (dd, 1H), 7.58-7.68 (m, 2H), 8.56 (s, 1H). Examples 72 and 73 5-. { [2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -f alazin-1 (2H) -one 5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph-alen-1-yl] amino} -f alazin-1 (2H) -one Using a procedure analogous to that described in example 10, starting with 500 mg of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 277 mg of 5- amino-phthalazine-1-on, the corresponding imine is obtained. As in Example 2, 32 mg of 5- are obtained by conversion of 470 mg of imine with 5.4 ml of BBr3 (IM in dichloromethane). { [2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -ftalazin-1 (2H) -one as fraction 1 and 35 mg of 5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydro-naphthalen-1-yl] amino} -ftalazin-1 (2H) -one as fraction 3. Fraction 1: XH-NMR (300 MHz, DMSO-d6), d = 1.32 (s, 3H), 1.50 (s, 3H), 1.96 (d, 1H), 2.23 (d, 1H), 3.47 (s, 3H), .17 (d, 1H), 5.93 (s, ÍH), 6.06 (d, ÍH), 6.78 (d, ÍH), 7.04 (d, 1H), 7.27 (t, ÍH), 7.37 (d, ÍH), 7.44 (d, 1H), 7.62 (t, ÍH), 8.67 (s, 1H) , 12.39 (s, ÍH). Fraction 3: XH-NMR (300 MHz, CD3OD), d = 1.57 (s, 3H), 1.69 (s, 3H), 2.07 (d, ÍH), 2.15 (d, ÍH) , 5.24 (s, 1H), 6.72 (d, ÍH), 6.81 (d, ÍH), 6.96 (t, ÍH), 7.24 (dd, ÍH), 7.57- 7.70 (m, 2H), 8.57 (s, ÍH). Examples 74, 75 and 76 5-. { [2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -2-methylphthalazin-1-one -. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -2-methylf alazin-1-one, Diastereomer A 5-. { [2,5-Dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -2-methylf Alazin-1-one, Diastereomer B Using a procedure analogous to that described in example 10, starting with 500 mg of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) ) pentanal and 302 mg of 5-amino-2-methylphthalazin-1-one, the corresponding imine is obtained. As in Example 2, 158 mg of 5- are obtained by converting 570 mg of imine with 6.4 ml of BBr3 (IM in dichloromethane). { [2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one as fraction 1, 66 mg of 5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahi-dronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer A, as fraction 4, and 77 mg of 5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-on, Diastereomer A, as fraction 5. Fraction 1: XH-NMR (300 MHz, CD3OD), d = 1.42 (s, 3H), 1.58 (s, 3H), 2.08 (d, ÍH), 2.26 (d, ÍH), 3.47 (s, 3H), 3.77 (s, 3H), 5.33 (s, ÍH), 6.76 (d , 1H), 7.07 (d, ÍH), 7.29 (t, ÍH), 7.52 (dd, ÍH), 7.60-7.71 (m, 2H), 8.51 (s, ÍH). Fraction 4: XH-NMR (300 MHz, CD3OD), d = 1.42 (s, 3H), 1.56 (s, 3H), 2.09 (d, ÍH), 2.27 (d, ÍH) , 3.78 (s, 3H), 5.33 (s, ÍH), 6.62 (d, ÍH), 6.95 (d, ÍH), 7.14 (t, ÍH), 7.56 ( dd, ÍH), 7.59-7.70 (m, 2H), 8.54 (s, ÍH).

Fraction 5: XH-NMR (300 MHz, CD3OD), d = 1.57 (s, 3H), 1.68 (s, 3H), 2.07 (d, ÍH), 2.14 (d, ÍH) , 3.77 (s, 3H), 5.33 (s, ÍH), 6.71 (d, 1H), 6.80 (d, 1H), 6.96 (t, ÍH), 7.22 ( dd, ÍH), 7.58-7.69 (m, 2H), 8.56 (s, ÍH). Examples 77 and 78 (-) -5-. { [2-hydroxy-4,4-dimethyl-5-methoxy-2- (rifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one (+) -5-. { [2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Separation of (+/-) -5-. { [2-hydroxy-4, -dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one: The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, Fa DAICEL) with hexane / ethanol (90:10, v / v). In this way the (-) enantiomer is obtained: MS (El): M + = 447, [a] D -48.0 ° (c = 0.7, CHC13) and the enantiomer (+): MS (El): M + = 447, [a] D + 45.6 ° (c = 0.8, CHC13). Examples 79 and 80 (-) -5-. { [2,5-Dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer A (+) -5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer A Separation from (+/-) -5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer A: The mixture of enantiomers is separated by chromatography on chiral substrate (CHIRALPAK ADID, Fa DAICEL) with hexane / ethanol (85: 15, v / v). In this way the (-) enantiomer is obtained: MS (El): M + = 433, [a] D -25.3 ° (c = 1.0, CHC13) and the enantiomer (+): MS (El): M + = 433. Examples 81 and 82 (-) -5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydrona-alen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer A (+) -5-. { [2,5-Dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer A Separation of (+/-) -5-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrah.idronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer B: The mixture of enantiomers is separated by chromatography on chiral substrate (CHIRALPAK ADID, Fa DAICEL) with hexane / ethanol (90: 10, v / v). In this way the (-) enantiomer is obtained: MS (El): M + = 433, [a] D -10.1 ° (c = 0.8, CHC13) and the enantiomer (+): MS (El): M + = 433, [a] D + 5.8 ° (c = 0.9, CHC13). Example 83 cis-1- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (rifluoromethyl) -1,2, 3,4-tetrahydronaphthalen-2-ol (Markus Berger) 5 - amino-2-methylquinazoline 12.7 g (62 mmol) of 2-methyl-5-nitro-3H-quinazolin-4-one (MT Bogert, VJ Chambers J. Org Chem. 1905, 649-658) are heated to reflux. and 37.5 g of phosphorus pentachloride in 75 ml of phosphoryl chloride for 20 hours. After cooling, it is poured into saturated NaHCO 3 solution and extracted with ethyl acetate. The organic phase is dried and the solvent is removed. 14 g of 4-chloro-2-methyl-5-nitroquinazoline are obtained, of which 4.5 g (20.2 mmol) are dissolved in 225 ml of ethyl acetate and 22.5 ml of triethylamine. 2 g of palladium on carbon are added and stirred in an ice bath for 4 hours under a hydrogen atmosphere at normal pressure. The solution is freed from the catalyst by filtration over Celite, then washed with 200 ml of ethanol and evaporated. After chromatography on silica gel with ethyl acetate-ethanol (0-10%), 530 mg of product are obtained. XH-NMR (300 MHz, CDCl 3), d = 2.87 (s, 3H), 4.52 (br., 2H), 6.77 (d, ÍH), 7.33 (d, ÍH), 7 , 65 (t, ÍH), 9.40 (s, ÍH). (rae) -1, 1, 1, - trifluoro-4-phenyl -2- [(E / Z) - (2-methyl-quinazol-5-yl) iminomethyl] -4-methyl-pentan-2 -ol To 140 mg (0.54 mmol) of 2-hydroxy-4-methyl-4-phenyl-2- (trifluoromethyl) -pentanal and 100 mg (0.63 mmol) of 5-amino-2-methylquinazoline in 15 ml of toluene 0.3 ml of titanium tetraethylate are added, and the mixture is heated for 2 hours at 100 ° C. After cooling, pour in water and shake vigorously. The suspension is filtered through Celite and then thoroughly washed with ethyl acetate. The phases of the filtrate are separated and extracted once more with ethyl acetate. Dry with sodium sulfate and remove the solvent in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 0-60%), 123 mg of (rae) -1,1,1, -trifluoro-4-phenyl-2- [(E / Z) are obtained. ) - (2-methyl-quinazol-5-yl) iminomethyl] -4-methyl-pentan-2-ol. cis-1- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol 82 mg (0.20 mg) are taken mmol) of imine in 7 ml of dichloromethane and cooled to -70 ° C. 0.8 ml (0.8 mmol) of an ITM solution of titanium tetrachloride in dichloromethane are added dropwise over 10 minutes and the mixture is stirred for another 6 hours at -65 ° C. The solution is poured into a saturated solution of sodium bicarbonate and stirred vigorously for 5 minutes. It is extracted with dichloromethane, washed with a saturated solution of sodium chloride and dried with sodium sulfate. After concentration and chromatography on silica gel (0-65% hexane / ethyl acetate), 46 mg of the desired product are obtained.

XH-NMR (300 MHz, CDC13); d = 1.46 (s, 3H), 1.63 (s, 3H), 2.19 (d, ÍH), 2.29 (d, ÍH), 2.87 (s, 3H), 5.14 (d, ÍH), 5.97 (d, ÍH), 6.81 (d, 1H), 7.15 (t, ÍH), 7.36-7.43 (m, 2H), 7.42 ( d, 1H), 7.75 (t, ÍH), 9.42 (s, 1H). Example 84 trans-5-methoxy-1- [(2-methylquinazolin-5-yl) mino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol This compound is prepared using a procedure analogous to that described in Example 83. XH-NMR (300 MHz, CDC13); d = 1.43 (s, 3H), 1.54 (s, 3H), 2.07 (d, ÍH), 2.18 (d, ÍH), 2.84 (s, 3H), 3.21 (s, 3H), 4.31 (d, 1H), 5.38 (d, ÍH), 6.63 (d, ÍH), 7.05 (d, ÍH), 7.18 (d, 1H) , 7.31 (t, ÍH), 7.43 (d, 1H), 7.81 (t, lH), 9.13 (s, 1H). Example 85 cis-6-chloro-5-methoxy-l- [(2-methoxquinazolxn-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2 -ol This compound is prepared using a procedure analogous to that described in Example 83. ^? - NMR (300 MHz, CDC13); d = 1.58 (s, 3H), 1.74 (s, 3H), 2.14 (d, ÍH), 2.25 (d, ÍH), 2.88 (s, 3H), 3.97 (s, 3H), 5.05 (d, 1H), 5, 92 (d, ÍH), 6.79 (d, 1H), 7.09 (d, ÍH), 7.19 (d, ÍH), 7.30 (d, ÍH), 7.75 (t, ÍH) ), 9.39 (s, ÍH). Example 86 cis-6-fluoro-5-methoxy-l- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) "1,2,3,4-tetrahydronaphthalene-2 -ol This compound is prepared using a procedure analogous to that described in Example 83. XH-NMR (CDC13): d = 1.57 (s, 3H), 1.74 (s, 3H), 2.13 (d, ÍH), 2.26 (d, ÍH), 2.88 (s, 3H), 3.97 (s, 3H), 5.02 (d, ÍH), 5.85 (d, ÍH), 6, 79 (d, ÍH), 6.93 (dd, ÍH), 7.07 (dd, ÍH), 7.29 (d, ÍH), 7.74 (d, 1H), 9.33 (s, ÍH) Example 87 cis -6- [(2-methylquinazolin-5-yl) amino] -9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9 -tehydro-naphthyl-1,2- dH, 3-dioxol-7-ol This compound is synthesized using a procedure analogous to that described in Example 83. XH-NMR (300 MHz, CDC13), d = 1.52 (s, 3H), 1.66 (s) , 3H), 2.10 (d, ÍH), 2.26 (d, 1H), 2.88 (s, 3H), 5.04 (d, ÍH), 5.94 (d, ÍH), 5, 99 (d, 2H), 6.65 (d, ÍH), 6.80 (d, 1H), 6.86 (d, ÍH), 7.76 (t, 1H), 9.52 (s, ÍH) ). Example 88 cis-6-chloro-l- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluor ethyl) -1,2,3-tetrahydronaphthalene-2,5-diol This compound is prepared by separation in ether, as described in example 3. XH-NMR (300 MHz, CDC13); d = 1.54 (s, 3H), 1.68 (s, 3H), 2.06 (d, ÍH), 2.20 (d, 1H), 2.81 (s, 3H), 4.98 (d, 1H), 5.81 (d, ÍH), 5.91 (br., ÍH), 6.73 (d, 1H), 6.86 (d, 1H), 7.08 (d, 1H) ), 7.23 (d, ÍH), 9.35 (s, 1H). Example 89 cis-6-fluoro-1- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2,5-diol This compound is prepared by separation in ether, as described in example 3. XH-NMR (300 MHz, CDC13); d = 1.62 (s, 3H), 1.77 (s, 3H), 2.13 (d, 1H), 2.27 (d, ÍH), 2.88 (s, 3H), 5.03 (d, 1H), 5.67 (br, HH), 5.78 (d, 1H), 6.79 (d, HH), 6.91 (d, 2H), 7.29 (d, 1H) , 7.73 (t, 1H), 9.35 (s, ÍH). EXAMPLE 90 cis-6- [(7-Fluoro-2-methylquinazolin-5-yl) amino] -9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9-tetrahydro-naphthyl-1, 2 -dH, 3-dioxol-7-ol-5-amino-7-fluoro-2-methyquinazoline 17 g (70.5 mmol) of 3,6-difluoro-2-N-pivaloylaminobenzaldehyde are combined (L. Florvall, I Fagervall , L.-G-Larsson, SB Ross, Eur.J. Med. Chem. 34 (1999) 137-151), 9.2 g of acetamidine hydrochloride, 13.4 g of potassium carbonate and 10.4 g of molecular sieves (4A) in 70 ml of butyronitrile. Heat with vigorous stirring for 17 hours at 145 ° C and remove the solvent in vacuo. After chromatographing the residue on silica gel with hexane / ethyl acetate (0-70%), 4.5 g of 7- fluoro-5-N-pivaloylamino-2-methyquinazoline are obtained. Dissolve 1 g (3.82 mmol) of 7-fluoro-5-N-pivaloylamino-2-methyquinazoline in 74 ml of toluene and cool to -70 ° C. 9.5 ml (11.4 mmol) of a 1.2 M solution of diisobutylaluminum hydride in toulol are added dropwise over 30 minutes. Allow the reaction mixture to warm to -40 ° C and stir for 4 hours at -40 ° C. Water is slowly added and stirred 30 minutes at room temperature to form a precate. Solvents are removed by filtration over Celite. The phases are separated, washed with a saturated solution of sodium chloride and dried with sodium sulfate. After chromatography on silica gel with hexane-ethyl acetate (0-100%), 64 mg of product are obtained. XH-NMR (300 MHz, CDC13); d = 2.83 (s, 3H), 4.67 (br., 2H), 6.50 (dd, ÍH), 6.93 (dd, 1H), 9.23 (s, 1H). To 60 mg (0.46 mmol) of racemic 4- (1,3-benzodioxol-4-yl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal and 32 mg (0.18 mmol) of 5-amino-7-fluoro-2-methylquinazoline in 7 ml of toluene is added 0.1 ml of titanium tetraethylate and the mixture is heated for 2.5 hours at 100 ° C. After cooling, pour into water and shake vigorously. The suspension is filtered through Celite, washed thoroughly with ethyl acetate. The phases of the filtrate are separated and extracted once more with ethyl acetate. Dry with sodium sulfate and remove the solvent in vacuo. 4- (1,3-Benzodioxol-4-yl) - 1,1, 1-trifluoro-2- [(E / Z) - (7-fluoro-2-methylquinazolin-5-yl) iminomethyl] -4- The crude methyl-pentan-2-ol obtained in this way is taken up in 8 ml of dichloromethane and cooled to -70 ° C. 1.1 ml (1.1 mmol) of a 1M solution of titanium tetrachloride in dichloromethane are added dropwise over 10 minutes and stirred an additional 1 hour at -70 ° C. The solution is poured into a saturated solution of sodium bicarbonate and stirred vigorously for 5 minutes. It is extracted with dichloromethane, washed with a saturated solution of sodium chloride and dried with sodium sulfate. After concentrating and chromatographing on silica gel (hexane / ethyl acetate 0-75%), 26 mg of the desired product are obtained. XH-(300 MHz, CDC13); d = 1.53 (s, 3H), 1.66 (s, 3H), 2.12 (d, ÍH), 2.27 (d, ÍH), 2.84 (s, 3H), 4.94 (d, 1H), 5.99 (s, 1H), 6.00 (s, 1H), 6.02 (d, ÍH), 6.50 (dd, 1H), 6.68 (d, ÍH) , 6.83 (d, 1H), 6.89 (dd, ÍH), 9.26 (s, ÍH). EXAMPLE 91 Trans-5-methoxy-1- [(7-fluoro-2-methylquinazolxn-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene- 2-ol This compound is prepared using a procedure analogous to that described in Example 83. H-(300 MHz, CDC13); d = 1.42 (s, 3H), 1.55 (s, 3H), 2.07 (d, ÍH), 2.17 (d, ÍH), 2.80 (s, 3H), 3.33 (s, 3H), 4.57 (d, ÍH), 5.31 (d, 1H), 6.66 (d, ÍH), 6.88 (dd, 1H), 7.00 (dd, ÍH) , 7.05 (d, ÍH), 7.30 (t, 1H), 9.03 (s, ÍH).

Example 92 cis-6-chloro-l- [(7-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) "1, 2, 3, 4-tetrahydronaphthalene-2 , 5-diol This compound is prepared by separation in ether, as described in example 3. XH-(300 MHz, CDC13), d = 1.60 (s, 3H), 1.73 (s, 3H) , 2.12 (d, ÍH), 2.24 8d, ÍH), 2.84 (s, 3H), 4.96 (d, ÍH), 5.98 (d, ÍH), 6.01 (s) , 1H), 6.51 (dd, 1H), 6.88 (d, 1H), 6.91 (dd, ÍH), 7.17 (d, ÍH), 9.23 (s, ÍH). 93 cis-6-fluoro-l- [(7-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2, 5-diol This compound is prepared by separation in ether, as described in example 3. 2H-(300 MHz, CD3OD), d = 1.61 (s, 3H), 1.72 (s, 3H), 2.15 (m, 2H), 2.78 (s, 3H), 5.30 (s, 1H), 6.72-6.82 (m, 3H), 6.92 (dd, 1H), 9 55 (s, 1H) Example 94 trans-7-fluoro-1- [(7-fluoro-2-methylquinazolin-5-yl) amino] -5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene- 2-ol XH-(300 MHz, CD3OD), d = 1.40 (s, 3H), 1.53 (s, 3H), 2.07 (d, ÍH), 2.18 (d, 1H) , 2.81 (s, 3H), 3.34 (s, 3H), 4.52 (d, ÍH), 5.25 (d, 1H), 6.41 (dd, 1H), 6.74 ( dd, ÍH), 6.86 (dd, ÍH), 7.01 (dd, ÍH), 9.03 (s, 1H). Example 95 cis-6-chloro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-etrahydronaphthalen-2 , 5-diol 5-amino-8-fluoro-2-methylquinazoline To a solution of 3.35 g (20.25 mmol) of hydrochloride and 21.27 g (149.7 mmol) of sodium sulphate in 72 ml of water is added to a warm solution at 50 ° C of 2.4 g (18.6 mmol) of 2,5-difluoroaniline in 11 ml of water and 1.6 ml of concentrated hydrochloric acid (37%), which is stirred at this temperature for 1 hour. Stir for another 30 minutes at room temperature, heat with the addition of 4.09 g (58.9 mmol) of ammonium hydroxyl chloride in 19 ml of water, for 45 minutes at 125 ° C, and keep at this temperature for 5 minutes . After cooling and filtering for one hour the brown chestnut precipitate obtained, it is washed with water and dried. 3.0 g (15.0 mmol) of hydroxylimine are obtained as an intermediate product, which is dissolved in portions in 15 ml of concentrated sulfuric acid at 60 ° C. After the addition is over, the residue is heated for 2 hours at 80 ° C, and for 4 hours at 90 ° C. Allow to cool and pour the solution into 100 g of ice. It is extracted with ethyl acetate, the organic phases are washed with water, dried over sodium sulfate and concentrated. After chromatography on silica gel with hexane-ethyl acetate (0-45%), 1.2 g (7.1 mmol) of 4,7-difluorisatin are obtained. To the isatin, 30 ml of a 1 molar solution of sodium hydroxide are added dropwise over 10 minutes with 1.8 ml of a 30% solution of hydrogen peroxide. After stirring for 2 h at room temperature, it is cooled to 0 ° C and 5 ml of a 4 molar solution of hydrochloric acid are added and diluted with 50 ml of water. It is extracted with ethyl acetate, dried over sodium sulfate, concentrated and 1.27 g of 3,6-difluoroanthranilic acid are obtained quantitatively, which are used without further purification. The 3,6-difluorrantranilic acid is heated in 8 ml of acetic acid anhydride for 45 minutes at 100 ° C. After cooling, the remaining acetic acid and excess acetic acid anhydride are removed by azeotropy with toluene under vacuum. The residue is mixed in an ice bath with 40 ml of a 25% ammonia solution and stirred for 72 hours. It is diluted with water and acidified with acetic acid. It is extracted with ethyl acetate, the organic phases are washed with water, dried over sodium sulfate and concentrated. The 1.03 g (5.25 mmol) of 5,8-difluoro-2-methyl-3H-quinazolin-4-one and the 6 g of phosphorus pentachloride obtained in this way are heated in 20 ml of phosphoryl chloride for 12 hours at 125 ° C. After cooling, it is poured into a concentrated solution of NaHCO 3 and extracted with ethyl acetate. The organic phase is dried and the solvent is removed. 1.7 g of 4-chloro-5,8-difluoro-2-methylquinazoline are obtained quantitatively, this compound is dissolved in 60 ml of ethyl acetate and 5 ml of triethylamine. 600 mg of palladium on charcoal is added and stirred for 2 hours (480 ml of nitrogeno absorption) under a hydrogen atmosphere at normal pressure. The solution is freed from the catalyst by filtration in Celite, then washed with 100 ml of ethanol and evaporated. After chromatography on silica gel with hexane-ethyl acetate-ethanol (0-40%), 550 mg of 5,8-difluoro-2-methylquinazoline are obtained. To 240 mg (1.3 mmol) of 5,8-difluoro-2-methylquinazoline, 300 mg (1.13 mmol) of 18-crown-6 in 10 ml of DMF and 890 mg (13.7 mmol) are added. of sodium azide, and the mixture is heated for 8 hours at 125 ° C. The solvent is removed under vacuum and chromatography on silica gel with ethyl acetate to obtain 52 mg of product. XH-NMR (300 MHz, CDC13); d = 2.92 (s, 3H), 4.31 (br., 2H), 6.67 (dd, 1H), 7.38 (dd, ÍH), 9.37 (s, 1H). To 140 mg (0.46 mmol) of 4- (3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal and 100 mg (0.56 mmol) of 5-amino -8-fluoro-2-methylquinazoline in 14 ml of toluene is added 0.23 ml (1.1 mmol) of titanium tetraethylate, and the mixture is heated for 2 hours at 100 ° C. After cooling, pour into water and shake vigorously again. The suspension is filtered on Celite and exhaustively washed with ethyl acetate. The phases are separated in the filtrate and extracted once more with ethyl acetate. Dry with sodium sulfate and remove the solvent in vacuo. 4- (3-chloro-2-methoxyphenyl) -1,11-trifluoro-2- [(E / Z) - (8-fluoro-2-methylquinazolin-5-yl) iminomethyl] -4-methyl is obtained -pentan-2-ol as crude product, it is taken in 23 ml of dichloromethane and cooled to -30 ° C. 7.8 ml (7.8 mmol) of a 1M solution of boron tribromide in dichloromethane are added dropwise over 10 minutes, left to stand at room temperature for 1 hour and stirred for another 16 hours. The solution is poured into a mixture of ice and saturated sodium bicarbonate solution, and stirred vigorously for a prolonged 15 minutes. It is extracted with dichloromethane, washed with a saturated solution of sodium chloride and dried with sodium sulfate. After concentrating and chromatographing on silica gel (hexane / ethyl acetate 0-50%), 64 mg of the desired product are obtained. XH-NMR (300 MHz, CDC13); d = 1.60 (s, 3H), 1.74 (s, 3H), 2.07 (d, ÍH), 2.26 (d, ÍH), 2.93 (s, 3H), 4.99 (d, ÍH), 5.66 (d, ÍH), 5.99 (br., 1 H), 6.67 (dd, 1H), 6.91 (d, ÍH), 7.16 (d, ÍH), 7.49 (dd, 1H), 9.41 (s, ÍH). Example 96 cis-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol XH- NMR (300 MHz, CDC13); d = 1.45 (s, 3H), 1.61 (s, 3H), 2.17 (d, ÍH), 2.26 (d, ÍH), 2.92 (s, 3H), 5.08 (d, HH), 5.69 (d, 1H), 6.69 (dd, HH), 7.16 (t, 1H), 7.35 (m, 2H), 7.42 (d, HH) 7.49 (t, ÍH), 9.44 (s, 1H). Example 97 trans-8-fluoro-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4 - tetrahydronaphthalen-2-ol XH-NMR (300 MHz, CDCl 3); d = 1.50 (s, 3H), 1.63 (s, 3H), 2.14 (s, 2H), 2.89 (s, 3H), 3.21 (s, 3H), 4.25 (d, ÍH), 5,21 (d, ÍH), 6,59 (dd, ÍH), 6,98 (dd, ÍH), 7,04 (dd, ÍH), 7,52 (dd, 1H) , 9.21 (s, ÍH). Example 98 cis-7-chloro-l- [(-8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene- 2-ol XH-NMR (300 MHz, CDC13); d = 1.44 (s, 3H), 1.60 (s, 3H), 2.18 (d, ÍH), 2.27 (d, ÍH), 2.93 (s, 3H), 5.00 (d, ÍH), 5.71 (d, ÍH), 6, 66 (dd, 1H), 7.28-7.37 (m, 3H), 7.50 (dd, 1H), 9.39 (s, 1H). Example 99 cis-6-chloro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4 -tetrahydronaphthalen-2-ol XH-NMR (300 MHz, CDC13); d = 1.57 (s, 3H), 1.72 (s, 3H), 2.12 (d, ÍH), 2.22 (d, ÍH), 2.93 (s, 3H), 3.97 (s, 3H), 4.99 (d, ÍH), 5, 65 (d, 1H), 6.67 (dd, 1H), 7.07 (d, ÍH), 7.21 (d, ÍH), 7.49 (dd, ÍH), 9.39 (s, ÍH) ). Example 100 cis-6-fluoro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4 -tetrahydronaphthalen-2-ol XH-NMR (300 MHz, CDC13); d = 1.56 (s, 3H), 1.71 (s, 3H), 2.11 (d, 1H), 2.22 (d, 1H), 2.93 (s, 3H), 3.97. (s, 3H), 4.97 (d, ÍH), 5.60 (d, ÍH), 6.67 (dd, ÍH), 6.93 (dd, ÍH), 7.06 (dd, ÍH) 7.48 (dd, 1H), 9.37 (s, ÍH). Example 101 cis-6- [(8-fluoro-2-methylquinazol-5-xl) amino] -9,9-dimethyl-7- (trifluoromethyl) -6,7,8, -tetrahydro-naphthol- [1,2 -d] -l, 3-dioxol-7-ol aH-NMR (300 MHz, CDC13); d = 1.52 (s, 3H), 1.67 (s, 3H), 2.10 (d, ÍH), 2.27 (d, ÍH), 2.94 (s, 3H), 4.96 (d, 1H), 5.67 (d, 1H), 5.99 (s, ÍH), 6.01 (s, ÍH), 6.67 (d, 1H), 6.68 (dd, ÍH) , 6.86 (d, ÍH), 7.49 (dd, ÍH), 9.44 (s, ÍH). Example 102 cis-6-fluoro-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2 , 5-diol XH-NMR (300 MHz, CD30D); d = 1.60 (s, 3H), 1.72 (s, 3H), 2.09 (d, ÍH), 2.17 (d, ÍH), 2.86 (s, 3H), 5.23 (s, ÍH), 6.80-6.93 (m, 3H), 7.57 (dd, ÍH), 9.66 (s, ÍH). Example 103 cis-6- [(2-methylquinolin-5-yl) amino] -9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9-tetrahydro-naph or [1,2-d] -l, 3-dioxol-7-ol XH-NMR (300 MHz, CDC13); d = 1.50 (s, 3H), 1.60 (s, 3H), 2.08 (d, ÍH), 2.20 (d, 1H), 2.73 (s, 3H), 4.85 (d, 1H), .09 (d, ÍH), 5.98 (s, 1H), 5.99 (s, ÍH), 6.62 (d, ÍH), 6.81 (m, 2H), 7.22 (d, ÍH), 7.50 (d, 1H), 7.56 (t, ÍH), 8.09 (d, 1 HOUR) . EXAMPLE 104 cis-6- [(2-methyl-1, 7-naphidin-5-yl) amino] -9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9-tetrahydro-naphtho [ 1,2-d] -1,3-dioxol-7-ol aH-NMR (300 MHz, CD30D); d = 1.48 (s, 3H), 1.57 (s, 3H), 2.02 (d, ÍH), 2.17 (d, ÍH), 2.76 (s, 3H), 5.06 (s, ÍH), 5.96 (s, 2H), 6.61 (d, ÍH), 6.82 (d, ÍH), 7.50 (d, ÍH), 7.90 (s, ÍH) , 8.33 (d, 1H), 8.69 (s, 1H) Example 105 Rae. -5, 8-difluoro-l- [(lH-indazol-4-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol (Diastereomer B ) Melting point: 209-211 ° C Example 106 Rac-5-fluoro-l- [(2-methylquinazolin-5-yl) amino] -6-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1 , 2,3,4-tetrahydronaph alen-2-diol, (Diastereomer B) Melting point: 115 ° C Example 107 Rac-5-fluoro-1- [(2-methylquinazolin-5-yl) amino] -4, 4- dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2,5-diol (Diastereomer B) XH-NMR (300 MHz, CD30D); d = 1.51 (s, 3H), 1.66 (s, 3H), 2.08 (d, J = 14 Hz, ÍH), 2.18 (d, J = 14 Hz, ÍH), 2.82 (s, 3H), 5.21 (s, ÍH), 6 , 71-6.93 (m, 3H), 7.19 (d, J = 8 Hz, ÍH), 7.77 (dd, J = 9 Hz / 8 Hz, 1H), 9.57 (s, ). Example 108 Rae. -5-fluoro-l- [(2-methylquinazolin-5-yl) amino] -6-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-diol ( Diastereomer A) MS (ESI): 4590 (M + l) Example 109 6-fluoro-l-. { [(2-Hydroxymethyl) -quinolin-5-yl) amino]) -5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol Methyl ester of acid 5- [4- (3-Fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-ethylideneamino] -quinolin-2-carbonyl ester A solution of 4- (3-fluoro-2) is stirred. -methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethylpentanal (872 mg, 2.84 mmol) and 5-aminoquinoline-2-carbonic acid methyl ester (570 mg, 2.84 mmol) in 5, 0 ml of concentrated acetic acid for two days at room temperature. After coevaporating several times with toluene, the residue is concentrated on silica gel with hexane / ethyl acetate (0-100% ethyl acetate). 820 mg (59% of theory) of the product are obtained. XH-NMR (300 MHz, CDC13): d = 1.41 (s, 3H), 1.59 (s, 3H), 2.35 (d, 1H), 3.33 (d, 1H), 4.00 (d, 3H), 4.11 (s, 3H), 4.76 (s, 1H), 6, 32-6.39 (m, 1H), 6.49-6.56 (m, ÍH), 6.66 (d, ÍH), 6.81 (d, 1H), 7.60-7.65 (m, 2H), 8.14-8.24 (m, 2H), 8.52 (d, ÍH). 5- (6-Fluoro-2-hydroxy-5-methoxy-4,4-dimethyl-2-trifluoromethyl-1,2,3,4-tetrahydro-naphthalene-1-ylamino) -quinolin- methyl ester 2 -carbonic 5- [4- (3-Flusro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoroethylpentylidene-mino] -quinolin-2-carbonic acid methyl ester (120 mg, 0.243) is dissolved. mmol) in 2.0 ml of dichloromethane. Titanium tetrachloride (1M solution in dichloromethane, 0.73 ml, 0.73 mmol) is added dropwise over 15 minutes at -30 ° C. The reaction mixture is then stirred for 3 hours between -30 ° C and -15 ° C. After adding a saturated solution of sodium bicarbonate at -30 ° C, the reaction is stopped. Extract with ethyl acetate, wash the combined organic phases with water and saturated sodium chloride solution. After drying with sodium sulfate, removing the empty solvent and purifying on silica gel with dichloromethane / methanol (0-3% methanol), 70 mg (58% of theory) of the product are obtained. XH-NMR (300 MHz, CD30D): d = 1.56 (s, 3H), 1.68 (s, 3H), 2.16 (s, 2H), 3.96 (d, 3H). 4.08 (s, 3H), 5.28 (s, ÍH), 6.91-6.99 (m, 2H), 7.03-7.09 (m, ÍH), 7.57 (d, 1H), 7.68 (t, 1H), 8.12 (d, ÍH), 8.72 (d, 1H). 6-fluoro-l-. { [(2-hydroxymethyl) -quinolin-5-yl] amino} -5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol 5- (6-fluoro-2-hydroxy-5-) methyl ester is dissolved methoxy-4,4-dimethyl-2-trifluoromethyl-1, 2,3,4-tetrahydro-naphthalen-1-ylamino) -quinolin-2-carbonic acid (70 mg, 0.14 mmol) in 5.0 ml of methanol and mixed with sodium borohydride (22 mg, 0.57 mmol). Equal amounts of sodium borohydride are added after one and two hours, respectively (total amount: 66 mg, 0.171 mmol). The reaction is aborted by the addition of water. It is extracted with ethyl acetate, the combined organic phases are washed with a saturated solution of sodium chloride and dried with sodium sulfate. After removing the solvent in vacuo, the residue is purified on silica gel with hexane / ethyl acetate (0-100% ethyl acetate). 21 mg of product are obtained. XH-NMR (300 MHz, DMSO-d6): d = 1.48 (s, 3H), 1.61 (s, 3H), 2.01 (d, ÍH), 2.14 (d, ÍH), 3.88 (d, 3H), 4.70 (d, 2H), -5.40 (d, HH), 5.51 (t, HH), 6.19 (s, HH), 6.35 ( d, 1H), 6.83 (d, HH), 6.91-6.96 (m, HH), 7.04-7.11 (m, 1H), 7.21 (d, HH), 7 , 48 (t, ÍH), 7.58 (d, ÍH), 8.64 (d, 1H). EXAMPLE 110 1- [(5-Chloro-lH-indazol-4-yl) amino] -6-fluoro-5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2, 3, 4-tetrahydronaphthalene 2-ol 5-Chloro-4-nitro-lH-indazole In 100 ml of acetic acid, 2.24 g (12 mmol) of 4-chloro-2-methyl-3-nitrophenylamine, prepared as described in Example 1, are dissolved. literature (Mori et al., Chem. Pharm. Bull., 1986, 34, 4859ff, as well as Brand and Zoller, Chem. Ber. 1907, 3324ff.). At 10 ° C, 6.0 ml of a 2 molar aqueous solution of sodium nitrite are added dropwise. The suspension is then poured into the boiling acetic acid (150 ml) for 15 minutes, and the reaction mixture is refluxed for 4 hours. After removing the acetic acid in vacuo, the residue is taken up in ethyl acetate and saturated sodium bicarbonate solution. The organic phases are washed with a saturated solution of sodium chloride and dried with sodium sulfate. After removing the solvent in vacuo, the crude product is further processed (1.81 g, 76%). XH-NMR (300 MHz, DMS0-d6): d = 7.65 (d, 1H), 7.97 (d, 1H), 8.32 (s, ÍH), 13.97 (s, ÍH). 5-chloro-lH-indazol-4-ylamine A solution of 5-chloro-4-nitro-lH-indazole (872 mg, 4.41 mmol) is mixed with 150 mg of palladium on carbon (10%) and stir under a hydrogen atmosphere at room temperature. After 45 minutes, the catalyst is removed using a filter and washed with methanol. The filtrate is concentratedThe residue is taken up in 200 ml of ethyl acetate and heated. After concentrating the preparation again and concentrating the filtrate, it is purified on silica gel with hexane / ethyl acetate (100-33% hexane). 296 mg (40% of theory) of the product are obtained. XH-NMR (300 MHz, DMSO-d6): d = 5.97 (s, 2H), 6.66 (d, ÍH), 7.05 (d, 1H), 8.19 (s, ÍH), 12.83 (s, ÍH). 2- [(5-Chloro-lH-indazol-4-ylimino) -methyl] -1,11-trifluoro-4- (3-fluoro-2-methoxy-phenyl) -4-methyl-pentan-2-ol NaCl solution of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2-trifluoromethylpentanal (278 mg, 0.9 mmol) and 5-chloro-lH-indazol-4-ylamine ( 121 mg, 0.72 mmol) in 20 ml of xylol is mixed with titanium (IV) ethylate (0.42 ml, 2.0 mmol), and refluxed for 10 hours. After cooling to room temperature, the xylol is distilled off and the residue is chromatographed on silica gel with hexane / ethyl acetate (30-100% ethyl acetate) to concentrate it. 123 mg (37% of theory) of the product are obtained. XH-NMR (400 MHz, CDCl 3): d = 1.43 (s, 3H), 1.57 (s, 3H), 2.38 (d, ÍH), 3.22 (d, 1H), 3, 94 (d, 3H), 4.91 (s, 1H), 6.41-6.52 (m, 2H), 6.90 (d, 1H), 7.28 (d, ÍH), 7.38 (d, 1H), 7.56 (s, ÍH), 7.72 (s, ÍH), 10.26 (br, ÍH). 1- (5-Chloro-lH-indazol-4-ylamino) -6-fluoro-5-methoxy-4, 4-dimethyl-2-trifluoromethyl-1, 2, 3, 4-tetrahydro-naphthalen-2- In a manner analogous to Example 109, 2- [(5-chloro-lH-indazol-4-ylimino) -methyl] -1,1, 1-trifluoro-4- (3-fluo-ro-2-methoxyphenyl) is processed. ) -4-methyl-pentan-2-ol (111 mg, 0.24 mmol) with titanium tetrachloride (0.72 ml of an IM solution in dichloromethane, 0.72 mmol) in 2.0 ml of dichloromethane, and they are purified by preparative thin layer chromatography. 27 mg (24% of the theoretical result) of the product are obtained. aH-NMR (400 MHz, CDC13): d = 1.56 (s, 3H), 1.65 (s, 3H), 2.09-2.17 (2d, 2H), 3.97 (d, 3H ), 5.34-5.36 (m, 2H), 6.87-6.95 (m, 2H), 7.15 (dd, 1H), 7.32 (d, 1H), 8.05 ( s, 1H). Example 111 1- (5-methyl-lH-indazol-4-ylamino) -6-fluoro-4,4-dimethyl-2-trifluoromethyl-l / 2,3,4-tetrahydro-naphthalene-2,5-diol 5-methyl-IH-indazole-4-ylamine To a solution of 2,4-dimethylaniline (12.4 ml, 100 mmol) in 80 ml of concentrated sulfuric acid are added to 0 ° C 5.0 ml of fuming nitric acid, stirring for 20 minutes at 4 ° C, and then stirring for 30 minutes at room temperature. The reaction mixture is poured into 600 ml of ice water and is carried with 5N sodium hydroxide to pH 10. The precipitate is extracted, washed with water and dried. 15.72 g (95% of the theoretical result) of 2,4-dimethylnitrophenylamine are obtained as a mixture of regioisomers. Analogously to the preparation described for 5-chloro-4-nitro-lH-indazole, 2,4-dimethylnitrophenylamine (2.0 g, 12 mmol) is processed with 6.0 ml of a 2 molar aqueous solution of sodium nitrite in acetic acid (250 ml) to obtain 1.14 g (57% of theory) of product as a mixture of both regioisomers. MS (ES +, acetonitrile / water 1: 1 + 0.01% formic acid): m / z (%) 178 (M + 1, loo "). Analogously to the preparation described for 5-chloro-1H -indazol-4-ylamine, the mixture of regioisomers from the above reaction (1.0 g, 5.64 mmol) is processed with 100 mg of palladium on carbon in methanol under an atmosphere of hydrogen for 16 hours at room temperature. purifying on silica gel with hexane / ethyl acetate (33% hexane, then 100% ethyl acetate), 53 mg (6% of theory) of 5-methyl-lH-indazol-4-ylamine are obtained . ^? - NMR (300 MHz, DMSO-d6): d = 2.12 (s, 3H), 5.41 (s, 2H), 6.57 (d, ÍH), 6.90 (d, ÍH), 8.10 (s, 1H), 12.5 (s, 1H). 1- (5-methyl-lH-indazol-4-ylamino) -6-fluoro-4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydro-naphthalene-2,5-diol enter 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal (308 mg, 1.0 mmol) and 5-methyl-lH-indazol-4-ylamine ( 148 mg, 1.0 mmol) in 15.0 ml of xylene, and mixed with titanium (IV) ethylate (0.42 ml, 2.0 mmol). After refluxing for 3 hours, the reaction mixture is allowed to cool to room temperature. After adding ethyl acetate and saturated sodium chloride solution, stir at room temperature for 30 minutes vigorously.

The precipitate obtained is sucked off, the aqueous phase is separated and the organic phase is dried with sodium sulfate. Purify using chromatography on silica gel with hexane / ethyl acetate (30-40% ethyl acetate). 345 mg (79% of the theoretical result) of 1,1,1-trifluoro-4- (3-fluoro-2-methoxyphenyl) -4-methyl-2- [(5-methyl-lH-indazol-4-) are obtained. unlimited) methyl] -pentan-2-ol. The 1,1,1-trifluoro-4- (3-fluoro-2-methoxyphenyl) -4-methyl-2- [(5-methyl-lH-indazol-4 -limino) -methyl] -pentan-2 is mixed. -ol (150 mg, 0.34 mmol) with boron tribromide (3.40 ml of a 1M solution in dichloromethane, 3.4 mmol) at room temperature. After 4 hours at room temperature, the reaction mixture is allowed to stand overnight at -30 ° C, and then a saturated solution of sodium bicarbonate and ethyl acetate is added. It is extracted with ethyl acetate, the combined organic phases are washed with a saturated solution of sodium chloride and dried with sodium sulfate. After removing the solvent in vacuo and carrying out preparative thin-layer chromatography on silica gel with hexane / ethyl acetate (50% ethyl acetate), 56 mg (39% of theory) of product are obtained. XH-NMR (300 MHz, CDC13): d = 1.61 (s, 3H), 1.68 (s, 3H), 2.09-2.14 (m, 4H), 2.24 (d, 1H ), 4.24-4.33 (br, 1H), 5.22-5.23 (, 1H), 6, 84-6, 91 (m, 3H), 7.14 (d, 1H), 8 , 04 (s, ÍH).

MS (The +): m / z (%) = 423 (M +, 45), 147 (100). EXAMPLE 112 7-Bromo-l- [(1 H -indazol-4-yl) amino] -5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol (SL 4753-4)? -NMR (300 MHz, CD30D): d = 1.52 (3H), 1.66 (3H), 2.00-2.22 (2H), 3.88 (3H), 5.18 (ÍH), 6.35 (ÍH), 6.89 (ÍH), 7.05 (HH), 7.15-7.29 (2H), 8.13 (HH). EXAMPLE 113 5- [(2-Hydroxy-4, 4-pentamethylene-2- (trifluoromethyl) -1,2,3,4-tetrahydro-1-naphthyl) amino] -2-quinolone 5- (2-hydroxy) -4 -phenyl-, 4-pentamethylene-2-tri-fluorometylbutyl-1 -imino] -2-quinolone. Analogously to that described in example 15, 150 mg of 2-hydroxy-4-phenyl-, 4-pentamethylene-2-trifluoromethylbutyraldehyde are condensed with 88 mg of 5-aminoquinolone, in the presence of 0.21 ml of titanium tetraethylate, to obtain an imine (102 mg) . XH-NMR (300 MHz, CDC13): d = 1.40-2.05 (, 10 H), 2.40 (d, ÍH), 2.65 (d, 1H), 4.80 (br. , ÍH), 6,15 (d, ÍH), 6,80 (d, ÍH), 6,85 (t, ÍH), 7,00 (m, 2H), 7,20-7,35 (m, 4H), 8.20 (d, 1H), 12.00 (br. S, ÍH). 5- [(2-hydroxy-4,4-pentamethylene-2- (tri-fluoromethyl) -1,2,3,4-tetrahydro-1-naphyl) amino] -2-quinolone Analogously to that described in Example 15, 100 mg of imine are converted with 4 ml of a 1M solution of titanium tetrachloride-CH2Cl2 in 59 mg of product. XH-NMR (DMSO-d6): d = 1.35-1.80 (m, 11 H), 2.15 (m, 1H), 5.35 (d, 1H), 5.95 (s, 1H) ), 6.25 (d, ÍH), 6.40 (d, ÍH), 6.55 (t, 2H), 7.15 (m, 2H), 7.25 (t, 1H), 7.30 (m, ÍH), 7.55 (d, 1H), 8.20 (d, ÍH), 11.55 (br.s, ÍH). Example 114 cis-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-diol A 0.55 g (2, 7 mmol) of 1,1,1-trifluoro-4-phenyl-butan-2-one (D. Yang); M-K Wong; Z. Yan J. Org. Chem. (2000); 65; 4179-4184) in 4 ml of THF and 2 ml of water are added 200 mg (3.1 mmol) of potassium cyanide in 2 ml of water. It is cooled to 0 ° C and 1 ml of 25% sulfuric acid is added, it is allowed to warm to room temperature and is stirred for 16 hours. A saturated solution of sodium bicarbonate is added and extracted with ethyl acetate. After washing with a saturated solution of sodium chloride and drying with sodium sulfate, a crude cyanide is obtained in quantitative form, which is dissolved in 15 ml of diethyl ether and cooled to -70 ° C. For 10 minutes, 4.6 ml (5.5 mmol) of a 1.2 M solution of DIBAL in toulol are added dropwise. Allow to warm for 2 hours at room temperature, set with a 10% tartaric acid solution and then thoroughly shake. After extracting with ethyl acetate, add 5 g of silica gel and 10 ml of sulfuric acid, stir vigorously for 12 hours and filter through Celite. The phases are separated and then extracted with ethyl acetate. After chromatography on silica gel (hexane / ethyl acetate 30%), 300 mg of unpurified 2-hydroxy-4-phenyl-2- (trifluoromethyl) -butanal are obtained. To the aldehyde obtained in this way and 200 mg (1.13 mmol) of 5-amino-8-fluoro-2-methylquinazoline in 15 ml of toluene are added 0.5 ml (2.4 mmol) of titanium tetraethylate, and The mixture is heated for 2 hours at 100 ° C. After cooling, pour in water and then shake vigorously. The suspension is filtered through Celite, then thoroughly washed with ethyl acetate. The phases of the filtrate are separated and extracted once more with ethyl acetate. Dry with sodium sulfate and remove the solvent in vacuo. After chromatography on silica gel (hexane / ethyl acetate 30%), 100 mg of 1- (8-fluoro-2-methylquinazolin-5 -limino) -4-phenyl-2- (trifluoromethyl) butan is obtained. -2-ol. The imine is taken with 5 ml of dichloromethane and cooled to -70 ° C. 10 ml (1 mmol) of an ITM solution of tetrachloride in dichloromethane is added dropwise over 10 minutes and stirred for one hour. The solution is poured into a saturated solution of sodium bicarbonate and stirred vigorously for 15 minutes. It is extracted with ethyl acetate, washed with a saturated solution of sodium chloride and dried with sodium sulfate. After concentrating and chromatographing on silica gel (hexane / ethyl acetate 50%), 44 mg of the desired product are obtained. XH-NMR (300 MHz, CDC13); d = 2.25-2.32 (m, 2H), 2.91 (ddd, 1H), 2.92 (s, 3H), 3.19 (ddd, 1H), 5.09 (d, 1H) , 5.26 (d, 1H), 6.78 (dd, ÍH), 7.15-7.29 (m, 4H), 7.49 (dd, ÍH), 9.34 (s, ÍH). Example 115 cis-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2,5-diol XH-NMR (300 MHz, CDCl 3); d = 1.59 (s, 3H), 1.72 (s, 3H), 2.11 (d, ÍH), 2.21 (d, ÍH), 2.93 (s, 3H), 5.05 (d, ÍH), 5.28 (br, ÍH), 5.40 (d, ÍH), 6, 66 (d, 1H), 6.71 (dd, 1H), 6.94 (d, ÍH) , 7.03 (t, 1H), 7.47 (dd, ÍH), 9.37 (s, 1H). Example 116 cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol 5-amino-7,8-difluoro-2-methyquinazoline A 41.7 g (180 mmol) of 2,2-dimethyl-N- (3, 4, 5-tri-fluorophenyl) -propionamide in 385 ml of THF add dropwise at -70 ° C 156 ml (391 mmol) of a 2.5 M solution of butyl lithium in hexane. It is stirred for one hour and then 38.6 ml of DMF in 90 ml of THF are added dropwise, and then the solution is warmed to -60 ° C. The mixture is stirred for a further hour at -70 ° C and the cold reaction solution is poured into a mixture of 2 kg of ice and 400 ml of concentrated hydrochloric acid. It is stirred vigorously and extracted one hour later, several times with diethyl ether. The organic phases are washed with neutral water and dried with sodium sulfate. After concentrating, 49.3 g (188 mmol) of crude 4,5,6-trifluoro-2-N-piva-loylaminobenzaldehyde are obtained, which is mixed with 26 g (275 mmol) of acetamidine hydrochloride, 38, 3 g (277 mmol) of potassium carbonate and 30 g of molecular sieves (4A) in 206 ml of butyronitrile. Heat under vigorous stirring for 18 hours at 145 ° C and remove the solvent in vacuo.

After chromatographing the residue on silica gel with hexane / ethyl acetate (0-100%), 9.1 g of 7,8-difluoro-5-N-pivaloylamino-2-methylquinazoline are obtained. Dissolve 2.0 g (7.2 mmol) of 7,8-difluoro-5-N-pivaloylamino-2-methyquinazoline in 140 ml of toluene and cool to -70 ° C. 24 ml (28.8 mmol) of a 1.2 M solution of diisobutylaluminum hydride in toulol are added dropwise over 30 minutes. The reaction mixture is allowed to warm for 2 hours at -25 ° C and is stirred for 2 hours at -25 ° C. Slowly add isopropanol and then water, and stir for 12 hours at room temperature to form a precipitate, which is removed by filtration on Celite. Wash well with a mixture of methylene chloride and methanol, and concentrate. The residue is stirred vigorously in 200 ml of ethyl acetate and 50 ml of methanol, together with 100 g of silica gel and 20 g of manganese dioxide. It is filtered through Celite, washed well with a mixture of methylene chloride and methanol, and concentrated. After chromatography on silica gel with hexane-ethyl acetate (0-100%), 370 mg of product are obtained. aH-NMR (300 MHz, CD3OD); d = 2.81 (s, 3H), 6.64 (dd, 1H), 9.52 (s, 1H). cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalene-2-ol 'H-NMR (300 MHz, CDC13); d = 1, 46 (s, 3H), 1, 61 (s, 3H), 2.20 (d, 1H), 2.24 (d, 1H), 2.91 (s, 3H), 5.00 (d, ÍH), 5.86 (d, ÍH), 6.56 (dd, 1H), 6.71 (dd, ÍH), 7.18 (t, ÍH), 7.29 (d, ÍH) , 7.32 (t, ÍH), 7.43 (d, l H), 9.28 (s, 1H). Example 117 cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-6-fluoro-5-methoxy-2- (trifluoromethyl) -1,2,3 , 4-tetrahydronaphthalen-2-ol XH-NMR (300 MHz, CDC13); d = 1.59 (s, 3H), 1.70 (s, 3H), 2.12 (d, ÍH), 2.22 (d, ÍH), 2.91 (s, 3H), 3.98 (s, 3H), 4.90 (d, ÍH), 5.80 (d, 1H), 6.56 (dd, ÍH), 6.94 (dd, ÍH), 7.00 (dd, ÍH) , 9.24 (s, ÍH). Example 118 5-. { [2-hydroxy-4,4-dimethyl-2,5-bis (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (HH) -one The preparation is carried out as in example 15 (13). Cyclization of the imine is performed to obtain the product in refluxing trifluoroacetic acid, instead of TiCl in toluene. ^ - MR (300 MHz, CDC13): d = 1.55 (s, 3H), 1.65 (s, 3H), 2.05 (d, 1H), 2.30 (d, 1H), 5, 10 (d, ÍH), 5,30 (d, ÍH), 6,35 (d, ÍH), 6,60 (d, ÍH), 6,70 (d, ÍH), 7,25 (m, 1H), 7,30 (t, 1H), 7.55 (d, ÍH), 7.75 (d, ÍH), 7.95 (d, ÍH), 10.85 (br. s, ÍH). MS (ES): MW: 471. Example 119 5-. { [6-chloro-2-hydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one The synthesis is carried out as described in Example 15. a H-NMR (300 MHz, CDCl 3): d = 1.40 (s, 3H), 1.60 (s, 3H) , 2.10 (d, 1H), 2.20 (d, ÍH), 5.05 (br., ÍH), 5.70 (br., 1H), 6.50 (d, ÍH), 6, 60 (m, 2H), 7.05 (dd, 1H), 7.20 (d, 1H), 7.35 (m, 2H), 8.30 (d, 1H), 10.40 (br., ÍH). MS (ES): MW: 437/439 (3: 1). Example 120 5-. { [2-hydroxy-4,4-dimethyl-2- (trxfluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -l-methylquinolin-2 (1H) -one XH-NMR (300 MHz, CDC13): d = 1.40 (s, 3H), 1.60 (s, 3H), 2.10 (d, ÍH), 2.20 (d, ÍH), 3.60 (s, 3H), 5.15 (d, ÍH), 5.45 (d, ÍH), 6.60 (d, ÍH), 6.65 (d , HH), 6.75 (d, HH), 7.10 (t, HH), 7.30 (m, HH), 7.40 (m, 2H), 8.00 (d, HH). MS (ES): MH +: 417. Example 121 5-. { [2-hydroxy-4,4-dimethyl-2- (trifluoromethyl) -5,6-trimethylene-1, 2,3,4-tetrahydronaph-alen-1-yl] mino} -quinolin-2 (lH) -one XH-NMR (300 MHz, CDC13): d = 1.45 (s, 3H), 1.65 (s, 3H), 1.95-2.15 (m, 3H) ), 2.20 (d, ÍH), 2.80 (m, 2H), 3.15 (m, 2H), 5.10 (d, ÍH), 5.25 (d, 1H), 6.55 (m, 3H), 7.00 (d, ÍH), 7.10 (d, ÍH), 7.30 (t, ÍH), 8.00 (d, ÍH), 10.10 (br., ÍH) ). MS (ES): MH +: 443.

Separation of the enantiomers is carried out by chiral HPLC (Chiralpak AD 20, column μ with hexane-ethanol 95: 5 as eluent); the enantiomer (-) elutes at 11, 4 minutes, the (+) enantiomer elutes at 14.1 minutes. Example 122 5-. { [6-chloro-2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one XH-NMR (300 MHz, CDC13): d = 1.55 (s, 3H), 1.70 (s, 3H), 2.10 (d, ÍH), 2, 20 (d, ÍH), 3.95 (s, 3H), 5.05 (d, ÍH), 5.35 (d, ÍH), 6.55 (m, 3H), 7.00 (d, ÍH) ), 7.15 (d, ÍH), 7.35 (t, ÍH), 8.05 (d, ÍH), 9.95 (br., ÍH). MS (ES): MH +: 467/469 (3/1). Example 123 5-. { [6-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one aH-NMR (300 MHz, CDC13): d = 1.60 (s, 3H), 1.70 (s, 3H), 2.05 (d, HH), 2.20 (d, ÍH), 4.20 (br.1H), 5.05 (d, 1H), 5.40 (d, 1H), 5 , 95 (br.s, ÍH), 6.55 (m, 3H), 6.85 (d, ÍH), 7,10 (d, ÍH), 7,35 (t, ÍH), 8,10 (d, 1H), 9,75 (br., ÍH). MS (ES): MH +: 453/455 (3/1). Separation of the enantiomers is carried out by chiral HPLC (Chiralpak AD 20, column μ, with hexane-ethanol 85:15 as eluent); the (-) enantiomer elutes at 10.4 minutes, the (+) enantiomer elutes at 14.8 minutes. Enantiomer (+): XH-NMR ([D] 6-DMSO): d = 1.50 (s, 3H), 1.65 (s, 3H), 1.95 (d, ÍH), 2.10 ( d, HH), 5.30 (d, HH), 6.05 (s, HH), 6.20 (d, HH), 6.40 (d, 1H), 6.55 (m, 2H), 6.70 (d, 1H), 7.20 (m, 2H), 8.20 (d, 1H), 9.05 (s, ÍH), 11.55 (s, ÍH). Enantiomer (-): XH-NMR ([D] s-DMSO): d = 1.50 (s, 3H), 1.65 (s, 3H), 1.95 (d, 1H), 2.10 ( d, 1H), 5.30 (d, HH), 6.05 (s, HH), 6.20 (d, HH), 6.40 (d, 1H), 6.55 (m, 2H), 6.70 (d, HH), 7.20 (, 2H), 8.20 (d, HH), 9.05 (s, HH), 11.55 (s, 1H). Example 124 5-. { [5-bromo-2-hydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one The cyclization of the imine precursor is carried out to obtain the product in refluxing trifluoroacetic acid, instead of TiCl 4 in toulol. aH-NMR (300 MHz, CDC13): d = 1.70 (s, 3H), 1.85 (s, 3H), 2.10 (d, 1H), 2.25 (d, 1H), 5, 10 (d, ÍH), 5.40 (d, 1H), 6.50 (d, ÍH), 6.55 (d, 1H), 6.60 (d, ÍH), 6.90 (t, ÍH), 7.30 (d, ÍH), 7.35 (t, ÍH), 7.55 (d, ÍH), 8.05 (d, 1H), 10.40 (br. s, ÍH). MS (ES): MH +: 481/483 (l / l). Example 125 5-. { [6-chloro-2-hydroxy-5-methoxy-2- (trifluoromethyl) -4,4-trimethylene-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin- 2 (1H) -one XH-NMR (300 MHz, CDC13): d = 2.05-2.40 (m, 5H), 2.60 (d, 1H), 2.85 (m, 2H) ), 4.10 (s, 3H), 4.95 (d, ÍH), 5.05 (d, ÍH), 6.55 (m, 2H), 6.65 (d, ÍH), 6.70 (d, ÍH), 6.95 (d, ÍH), 7.15 (d, 1H), 7.35 (t, ÍH), 7.90 (d, 1H), 10.50 (br., ÍH) ). MS (ES): MH +: 478/480 (3/1). Example 126 5-. { [6-chloro-2,5-dihydroxy-2- (trifluoromethyl) -4,4-tri ethylene-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one? -NMR ([D] 6-DMSO): d = 1.80 (m, 1H), 2.05 (m 2H), 2.20 (d, ÍH), 2.30 (m, ÍH), 2.60 (d, ÍH), 2.90 (q, ÍH), 3.25 (q, ÍH), 5.30 (d, ÍH) , 5.90 (s, 1H), 6.10 (d, ÍH), 6.35 (d, ÍH), 6.55 (d, 2H), 6.70 (d, ÍH), 7.20 (d, 1H), 7.25 (t, 1H), 8.15 (d, 1H), 9.30 (s, 1H), 11.55 (b r S, IH). MS (ES): MH +: 465/467 (3/1). The separation of the enantiomers is carried out by chiral HPLC (Chiralpak AD 20, column μ with hexane-ethanol as eluent); the (-) enantiomer elutes first. XH-NMR ([D] 6-DMSO): d = 1.80 (m, 1H), 2.05 (m 2H), 2.20 (d, ÍH), 2.30 (m, ÍH), 2.60 (d, ÍH), 2.90 (q, ÍH), 3.25 (q, ÍH), 5,30 (d, ÍH), 5,90 (s, ÍH), 6,10 (d, 1H), 6,35 (d, ÍH), 6,55 (d, 2H), 6, 70 (d, ÍH), 7.20 (d, 1H), 7.25 (t, ÍH), 8.15 (d, ÍH), 9.30 (s, ÍH), 11.55 (br. , ÍH). Enantiomer (+): XH-NMR ([D] 6-DMS0): d = 1.80 (m, ÍH), 2.05 (m 2H), 2.20 (d, 1H), 2.30 (m, ÍH), 2.60 (d, 1H), 2.90 (q, ÍH), 3.25 (q, 1H), 5.30 (d, ÍH) , 5.90 (s, ÍH), 6.10 (d, ÍH), 6.35 (d, ÍH), 6.55 (d, 2H), 6.70 (d, ÍH), 7.20 (d, ÍH), 7.25 (t, ÍH), 8.15 (d, ÍH), 9.30 (s, ÍH), 11.55 (br S, ÍH). Example 127 5-. { [5-difluoromethoxy-2-hydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one The cyclization of the imine is carried out to obtain the product in refluxing trifluoroacetic acid, instead of TiCl 4 in toulol. XH-NMR ([D] 6-DMS0): d = 1.45 (s, ÍH), 1.60 (s, ÍH), 2.00 (d, ÍH), 2.15 (d, ÍH), 5.40 (d, ÍH), 6.15 (s, ÍH), 6.20 (d, 1H), 6.40 (d , ÍH), 6.55 (d, 1H), 6.60 (d, 1H), 7.05 (m, 2H), 7.20 (t, 1H), 7.30 (t, CHF2, JHF = 75 Hz), 8.20 (d, ÍH), 11.55 (s, ÍH). MS (ES): MH +: 469. Example 128 4-. { [6-chloro-2-hydroxy-4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -indazole XH-NMR (300 MHz, CDCl 3): d = 1.40 (s, 3H), 1.55 (s, 3H), 2.05 (d, 1H), 2.20 (d, ÍH), 5.15 (br., 2H), 6.40 (d, ÍH), 6.90 (d, ÍH), 7.05 (dd, ÍH), 7.25 -7.35 (, 4H), 8.55 (br., 1H). MS (ES): MH + = 410/412 (3: 1). EXAMPLE 129 5- (6-Chloro-2-hydroxy-7-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -1H-quinoline-2- ona 4- (3-chloro-4-methoxy phenyl) -2-hydroxy-methyl-2- (trifluoromethyl) -pentanal 75 ml of methylmagnesium chloride (22% in THF) in 200 ml of THF are introduced, and a solution of 9.17 g (45.7 mmol) of methyl 3-chloro-4-methoxybenzoate in 200 ml of THF is added dropwise over 1 hour. Once the conversion is complete, the reaction is terminated by adding 30 ml of concentrated ammonium chloride and the mixture is separated between ethyl ester of acetic acid and water. The aqueous phase is extracted with ethyl acetate, the combined organic phases are washed with water and a concentrated solution of sodium chloride, dried over sodium sulfate and concentrated in a rotary evaporator. 4.5 g (22.4 mmol) of crude product are introduced (with a yield of 98%) in 100 ml of dichloromethane, and 6.0 g (42.7 mmol) of 2-trimethylsilanyloxy-acrylic acid ester, then 1.85 ml of tin tetrachloride are added dropwise to the mixture. -70 ° C. After 10 minutes, pour the reaction mixture into a concentrated solution of potassium carbonate. The aqueous phase is extracted with dichloromethane, the combined organic phases are washed with a 1M solution of hydrochloric acid, water and concentrated sodium chloride solution, dried over sodium sulfate and concentrated on a rotary evaporator. After carrying out a column chromatography (silica gel, hexane / ethyl acetate 9: 1), 2.0 g (29%) of the desired intermediate product are obtained. 1.5 g (5.0 mmol) of these ketoesters are mixed in THF with 2.1 ml of trimethyltrifluoromethylsilane and 620 ml of tetrabutylammonium fluoride (ITM solution in THF) at -70 ° C. Allow to warm to room temperature, stir for 18 hours, then combine the mixture at 0 ° C with 6 ml of tetrabutylammonium fluoride (ITM solution in THF). After a further 10 minutes, the mixture is separated between ethyl acetate and an INM solution of hydrochloric acid. The aqueous phase is extracted with ethyl acetate, the combined organic phases are washed with a 1M solution of hydrochloric acid, water and concentrated sodium chloride solution, dried over sodium sulfate and concentrated on a rotary evaporator. 1.81 g of the desired intermediate product is obtained, which, dissolved in 15 ml of diethyl ether, is added dropwise at 0 ° C in a suspension of 0.40 g of aluminum hydride and lithium in diethyl ether. After 1 hour at 0 ° C and 18 hours at room temperature, the reaction is terminated by adding 25 ml of a concentrated solution of sodium bicarbonate. The precipitate produced is filtered, then the filtrate is washed with ethyl acetate and concentrated sodium chloride solution, dried over sodium sulfate, and concentrated in a rotary evaporator. After carrying out a column chromatography (silica gel, hexane / ethyl acetate 8: 2), 1.04 g (65%) of the desired diol intermediate is obtained. 109 ml (1.12 mmol) of oxalyl chloride in dichloromethane are introduced and first 190 ml (2.68 mmol) of DMSO are added dropwise and, after stirring for 15 minutes, a solution of 366 mg (1.12 mmol). mmol) of the intermediate step diol in dichloromethane at -75 ° C. Another 15 minutes later, 830 μl (5.62 mmol) of triethylamine (at -50 °) is added dropwise. Allow to slowly melt and stir for another 18 hours. The reaction is terminated by adding concentrated ammonium chloride, the phases are separated and the aqueous phase is extracted with dichloromethane. The combined organic phases are washed with an INM solution of hydrochloric acid, water and a concentrated solution of NaCl, and dried with NaSO4. Concentrate and chromatograph on silica gel with hexane / ethyl acetate (4: 1). 302 mg (84%) of the desired product are obtained, 4- (3-chloro-4-methoxy-phenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal. XH-NMR (CDC13): d = 1.34 (s, 3H), 1.40 (s, 3H), 2.30 (d, ÍH), 2.62 (d, ÍH), 3.66 (s) , ÍH), 3.90 (s, 3H), 6.84 (d, ÍH), 7.13 (dd, ÍH), 7.31 (d, ÍH), 8.90 (s, ÍH). 5- (6-Chloro-2-hydroxy-7-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-1-ylamino) -1H-quinolin-2-one enter 100 mg (0.31 mmol) of 4- (3-chloro-4-methoxy-phenyl) -2-hydroxy-4-methyl-2-trifluoromethyl-pentanal and 50 mg (0.31 mmol) of 5-amino -IH-quinolin-2-one in 30 ml of toluene, and 0.16 ml of titanium tetraethylate are added dropwise. The mixture is stirred for 1 hour in a bath at a temperature of 100 ° C. After cooling, the solution is poured onto ice, a few ml of concentrated sodium bicarbonate solution are added, filtered through diatomaceous earth and then washed with ethyl acetate and water. The phases are separated, the aqueous phase is extracted with ethyl acetate, the organic phases are combined with water and concentrated sodium chloride solution, dried over sodium sulfate and concentrated on a rotary evaporator. After purification by chromatography (silica gel, hexane / ethyl acetate, from 95: 5 to 25:75), the obtained imine is taken (30%) again in dichloromethane and mixed at -50 ° C with 3.6 ml of titanium tetrachloride (1 m in toulol). The mixture is allowed to melt and the mixture is poured into ice after stirring for 18 hours, the phases are separated, extracted with dichloromethane, washed with concentrated sodium chloride solution and dried with sodium sulfate. After concentrating in a rotary evaporator, the crude product is subjected to chromatography on silica gel (elyuent: 2% methanol in dichloromethane). The desired product is crystallized from hexane / diethylether (yield: 28%). Melting point: 182 ° C; aH-NMR (CD3OD): d = 1.28 (s, 3H), 1.42 (s, 3H), 1.95 (d, ÍH), 2.07 (d, ÍH), 3.54 (s) , 3H), 4.88 (s, ÍH), 6.42-6.48 (m, 2H), 6.58 (d, ÍH), 6.82 (s, ÍH), 7.25-7, 30 (m, 2H), 7.97 (d, 1H). EXAMPLE 130 5- (6-Chloro-2-hydroxy-7-methoxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-isoquinolin-1-one This compound is prepared using the aldehydes previously described in Example 129 and the corresponding amines. Melting point: 85 ° C, MS (ESI): 467 (M + 1). EXAMPLE 131 5- (6-Chloro-2-hydroxy-7-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-phthalazin-1- One Example 131 is prepared as in Example 129, using the corresponding substrates. XH-NMR (CD3OD): d = 1.39 (s, 3H), 1.53 (s, 3H), 2.16 (dd, 2H), 3.12 (s, 3H), 5.30 (s) , ÍH), 6.94 (s, ÍH), 7.31 (dd, ÍH), 7.42 (s, ÍH), 7.64-7.71 (m, 2H), 8.59 (s, ÍH). Example 132 6-Chloro-7-methoxy -4,4-dimethyl-1- (2-methylquinolin-5-ylamino) -2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol Example 132 is prepared as in Example 129, using the corresponding substrates. XH-NMR (CDC13): d = 1.39 (s, 3H), 1.52 (s, 3H), 2.15 (dd, 2H), 2.73 (s, 3H), 3.49 (s) ,, 3H), 4.97 (d, 1H), 5.10 (d, ÍH), 6.80-6.84 (m, 2H), 7.24 (d, ÍH), 7.36 (s) , 1H), 7.49 (d, 1H), 7.55 (dd, 1H), 8.08 (d, ÍH). Example 133 6-Chloro-l- (8-fluoro-2-methylquinazolin-5-ylamino) -7-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2 This compound is prepared using a procedure analogous to that described in example 129. XH-NMR (CDCl 3): d = 1.42 (s, 3H), 1.56 (s, 3H), 2.19 (dd, 2H ), 3.62 (s, 3H), 4.31 (s, br, 1H), 5.01 (d, ÍH), 5.56 (d, 1H), 6.70 (dd, ÍH), 6 , 90 (s, 1H), 7.39 (s, ÍH), 7.46-7.52 (, 1H), 9.39 (s, ÍH). EXAMPLE 134 5- (6-Chloro-2,7-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaf-alen-1-ylamino) -1H-quinolin-2-one 20 mg of 5- [4- (3-chloro-4-methoxyphenyl) -2,2-dihydroxy-4-methylpentylamino] -1H-quinolin-2-one (43 g mol) in dichloromethane are added, mixed with 0 , 86 mmol of boron tribromide (IM solution in dichloromethane) and stirred for 3 hours at room temperature. The reaction is terminated with concentrated sodium bicarbonate solution. It is extracted with dichloromethane, the organic phases are washed with concentrated sodium chloride solution, dried over sodium sulfate and concentrated. The crude product is crystallized from hexane / diethylether. 9 mg (40%) of the desired product are obtained. Melting point: 158 ° C; MS (ESI): 453 (M + 1). Example 135 1- (8-Fluoro-2-methylquinazolin-5-ylamino) -7-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaf-alen-2-ol 2- hydroxy -4- (4-methoxy-enyl) -4-methyl-2- (trifluoromethyl) -pentanal This aldehyde is prepared as in Example 5, from 4-methoxybenzyl cyanide. XH-NMR (CDC13): d = 1.34 (s, 3H), 1.43 (s, 3H), 2.30 (d, ÍH), 2.69 (d, 1H), 3.66 (s) , HH), 3.80 (s, 3H), 6.85 (d, 2H), 7.21 (d, 2H), 8.76 (s, HH). 1- (8-Fluoro-2-methylquinazolin-5-ylamino) -7-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-2-ol This compound is prepared using the corresponding substrates, according to the procedure described in example 129. Melting point 97 ° C; MS (ESI): 450 (M + 1). EXAMPLE 136 5- (2-Hydroxy-7-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -IH-quinolin-2 -one The preparation is performed as described in Example 129, employing 2-hydroxy-4- (4-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal and the corresponding amines. Melting point 128 ° C; MS (ESI): 433 (M + 1). EXAMPLE 137 5- (2-Hydroxy-7-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-isoquinolin-1-one The preparation is performed as described in Example 129, employing 2-hydroxy-4- (4-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal and the corresponding amines. Melting point 112 ° C; MS (ESI): 433 (M + 1). EXAMPLE 138 5- (2-Hydroxy-7-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-phthalazin-1-one The preparation performed as described in Example 129, employing 2-hydroxy-4- (4-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal and the corresponding amines. Melting point 197 ° C; MS (ESI): 434 (M + 1). Example 139 7-methoxy-4,4-dimethyl-1- (2-methyl-quinolin-5-ylamino) -2- (trifluoromethyl) -1,2,3,4-tetrahydro-naph-alen-2-ol The preparation is carried out as described in Example 129, employing 2-hydroxy-4- (4-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal and the corresponding amines. Melting point 84 ° C; MS (ESI): 431 (M + 1). The racemate is separated into the enantiomers using chiral HPLC. Analytical HPLC: Chiralpak AD lOμ, 250 x 4.6 mm, Iml / minute, hexane / ethanol 90/10, enantiomer (+): Rt = 7.0 min; melting point: 84 ° C; MS (ESI): 431 (M + 1); enantiomer (-): R = 17.8 min; melting point 85 ° C; MS (ESI): 431 (M + 1); Specific optical rotation: -5.9 (c = 0.14, CHC13). Example 140 4,4-dimethyl-1- (2-methylquinolin-5-ylamino) -2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2,7-diol The ether described in Example 139 is processed analogously to example 134, carrying out an ether separation with BBr3. Melting point 127 ° C; MS (ESI): 417 (M + l). Example 141 5- (2,7-Dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-phthalazin-1-one The ether described in Example 138 is processed analogously to example 134, carrying out an ether separation with BBr3. Melting point 116 ° C; MS (ESI): 420 (M + 1). Example 142 1- (8-Fluoro-2-methylquinazolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydro-naphthalene-2,7-diol The ether described in Example 135 it is processed analogously to Example 134, carrying out an ether separation with BBr3. ^? - NMR (CD3OD): d = 1.41 (s, 3H), 1.54 (s, 3H), 2.02 (d, ÍH), 2.17 (d, 1H), 2.82 ( s, 3H), 4.32 (s, 1H), 6.93 (dd, 1H), 7.01 (d, ÍH), 7.32-7.43 (m, 2H), 7.52-7 , 66 (m, 3H); MS (ESI): 436 (M + 1). EXAMPLE 143 5- (2,7-Dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -lH-quinolin-2-one The ether described in Example 136 is processed analogously to example 134, carrying out an ether separation with BBr3. XH-NMR (CD3OD): d = 1.38 (s, 3H), 1.52 (s, 3H), 2.13 (dd, 2H), 5.17 (s, ÍH), 6.53 (d , ÍH), 6.62 (d, 1H), 6.68-6.78 (m, 2H), 7.26 (d, 1H), 7.39 (dd, 1H), 8.26 (d, ÍH); MS (ESI): 419 (M + 1). Example 144 5- (2-Hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaph-alen-1-ylamino) -lH-quinolin-2-one Using 2-hydroxy-4- ( 2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal and the corresponding amine, the title compound is obtained as described in example 129. Melting point 228 ° C; MS (ESI): 405 (M + 1). EXAMPLE 145 1- (8-Fluoro-2-methylquinazolin-5-ylamino) -5-methoxy-2- (trifluoromethyl) -1,2,3, -tetrahydro-naphthalene-2-ol Using 2-hydroxy-4- ( 2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal and the corresponding amine, the title compound is obtained as described in example 129. Melting point 132 ° C; MS (ESI): 422 (M + 1) Example 146 7-Chloro-1- (8-fluoro-2-methylquinazolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3 , 4-tetrahydronaphthalen-2,6-diol 2-chloro-5-methylanisole 50 g (350.65 mmol) of 2-chloro-5-methylphenol are dissolved in 450 ml of acetone and mixed under nitrogen with 96.5 g (701.3 mmol) of potassium carbonate. After the addition of 43.6 ml of methyl iodide (2 equivalents), it is heated to reflux for three hours. After cooling, the reaction mixture is filtered, the filter residue is washed with acetone and the filtrate is centrifuged until dry (bath temperature 30 ° C). As the residue still contains potassium carbonate, it is taken with diethyl ether and filtered once more. After removing the solvent, 57 g (103.8%) of the desired compound is obtained, which is used in the crude in the next step. XH-NMR (300 MHz, CDC13): d = 2.35 (3H), 3.90 (3H), 6.68-6.79 (2H), 7.22 (1H). 4-Chloro-3-methoxybenzyl bromide 57 g (363.96 mmol) of 2-chloro-5-methylanisole are dissolved in 800 ml of carbon tetrachloride, and mixed at room temperature with 69.9 g (393.08 g. mmol) of N-bromsuccinimide. After the addition of 174.6 mg of benzoyl peroxide, it is heated to reflux for five hours (bath temperature: 105 ° C). The reaction mixture is suctioned through a glass fiber filter, then washed and centrifuged in a rotary evaporator. 83.6 g (97.5%) of the desired product (containing reagent moieties and dibromide) are obtained, which is used without purification in the next step. 2 H-NMR (300 MHz, CDC13): d = 3.91 (3H), 4.48 (2H), 6.90-6.98 (2H), 7.32 (1H). 4-Chloro-3-methoxybenzyl cyanide 83.6 g (354.97 mmol) of the crude bromide are mixed in 255 ml of DMF with 266 ml of water. After the addition of 34.7 g (532.45 mmol) of potassium cyanide (with heating), the mixture is stirred for three hours at room temperature. The reaction mixture is poured into one liter of ice water and extracted three times with 500 ml of diethyl ether each. The combined organic extracts are washed with water and saline. After drying with sodium sulfate, it is filtered and the solvent is removed. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 44.7 g (69.4%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 3.75 (2H), 3.94 (3H), 6.80-6.91 (2H), 7.38 (1H). 2- (4-chloro-3-methoxy phenyl) -2-methylpropanone trile 44.7 g (246.1 mmol) of the nitrile previously described are dissolved in 380 ml of DMF and mixed with 69.8 g (492.2). mmol) of methyl iodide. After cooling to 0 ° C, the reaction mixture is added for three hours in 21.5 g (492.2 mmol) of NaH (55% suspension) in portions. After 18 hours at room temperature, the preparation is poured into 600 ml of ice water and extracted three times with 500 ml of diethyl ether each. The combined organic phases are washed with water and saline. After drying with sodium sulfate, the drying media is filtered and the solvent is centrifuged in a rotary evaporator. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 42.37 g (81.1%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.75 (6 H), 3.96 (3H), 6.97 (ÍH), 7.07 (HH), 7.49 (1H). 2- ('4-chloro-3-methoxyphenyl) -2-methylpropanal 25 g (119.23 mmol) of the nitrile previously described are dissolved in 475 ml of toluene. 149 ml of a 1.2 molar solution of DIBAH in toluene are added dropwise, between -65 and -60 ° C for 60 minutes. After stirring for two hours at this temperature, 681 ml of a 20% solution of L- (+) - tartaric acid is added. After adding 200 ml, the temperature increases to -10 ° C. The remainder of the tartaric acid solution is quickly added and the preparation is stirred thoroughly for 16 hours at room temperature. The reaction mixture is stirred twice with 600 ml of diethyl ether each. The combined organic extracts are stirred with water and saline, dried and the solvent is removed. The remaining residue (25 g = 98.8%) is used raw in the next step. XH-NMR (300 MHz, CDC13): d = 1.48 (6 H), 3.90 (3 H), 6.70-6.88 (2 H), 7.37 (H), 9.49 (H) ). E-4 - (4-chloro-3-methoxyphenyl) -4-methyl-ethyl-2-enoate Ethyl 25.6 g (114.3 mmol) of triethyl phosphonoacetate are introduced into 148 ml of tetrahydrofuran. 60.8 ml of a 2M solution of LDA in THF / heptane / ethylbenzene (for quarter of an hour) is added dropwise at 0 ° C. After stirring for one hour at 0 ° C, 22.1 g (103.91 mmol) of 2- (4-chloro-3-methoxyphenyl) -2-methylpropanal, dissolved in 100 ml of tetrahydrofuran, are added dropwise. After stirring for five days at room temperature, the reaction mixture is poured into 200 ml of dilute ammonium chloride and extracted twice with 300 ml of diethyl ether each. The combined organic extracts are processed using conventional means, and the resulting residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 24.1 g (82%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.30 (3H), 1.47 (6H), 3.90 (3H), 4.20 (2H), 5.80 (ÍH), 6.80-6.88 (2H), 7.09 (1H), 7.29 (HH). Ethyl 4- (4-chloro-3-methoxy-nyl) -4-methylpentanoate 24.1 g (85.23 mmol) of E-4- (4-chloro-3-methoxyphenyl) -4-methylpent-2 are introduced. ethyl acetate in 228 ml of ethyl acetate, mixed with 2.41 g of palladium on carbon (10%), and stir overnight at room temperature under a hydrogen atmosphere. The catalyst is removed by filtration through a glass fiber filter, and the obtained concentrated residue (24.1 g = 99.1%) in the crude is used in the next step. XH-NMR (300 MHz, CDC13): d = 1.21 (3H), 1.34 (6H), 1.90-2.10 (4H), 3.92 (3H), 4.10 ( 2H), 6.82-6.90 (2H), 7.29 (1H). Ethyl 4- (-chloro-3-methoxyphenyl) -2-hydroxy-4-methylpentanoate. 24.1 g (84.63 mmol) of ethyl 4- (4-chloro-3-methoxyphenyl) -4-methylpentanoate are cooled. in 296 ml of tetrahydrofuran, and the reaction mixture is cooled between -70 ° C and -65 ° C. In the course of an hour and three quarters. 236.9 ml of a 0.5 molar solution of potassium bis- (trimethylsilylamide) are added dropwise to toulol, and then the reaction mixture is stirred for 75 minutes at -70 ° C. 30.9 g (118.48 mmol) of Davis's reagent, dissolved in water, were added dropwise. 296 ml of tetrahydrofuran, for 60 minutes. After stirring for two hours at -70 ° C, 152 ml of a saturated solution of ammonium chloride are slowly added dropwise, the cold bath is removed and stirred thoroughly for thirty minutes.

After extraction with diethyl ether, the combined organic extracts are processed using conventional means, with water and saline. After removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane) chromatography. 21.4 g (84.2%) of the desired compound (slightly contaminated) are isolated. Ethyl 4- (4-chloro-3-methoxy phenyl) -4-methyl-2-oxopentanoate 6.15 g (20.45 mmol) of 4- (4-chloro-3-methoxyphenyl) -2-hydroxy are dissolved. Ethyl 4-methyl-pentanoate in 213 ml of dichloromethane, and mixed with 71 ml of dimethyl sulfoxide. After the addition of 10.3 g (102.23 mmol) of triethylamine, the preparation is mixed in portions with 8.1 g (51.12 mmol) of S03 / pyridine complex and then stirred overnight at room temperature. The reaction mixture is combined with gentle cooling with 81 ml of saturated ammonium chloride solution, and stirred thoroughly. After extracting twice with diethyl ether, the combined organic phases are processed using conventional means. After removing the solvent, a residue is obtained which is combined with it from the subsequent steps (15.27 g), and a chromatography on silica gel is carried out (elution medium: ethyl acetate / hexane). 15.46 g (72.9%, for both steps) of the desired compound are isolated. X H-NMR (300 MHz, CDCl 3): d = 1.25 (3 H), 1.48 (6 H), 3.16 (2 H), 3.90 (3 H), 4.12 (2 H), 6, 83-6.94 (2H), 7.28 (1H). (rae.) Ethyl 4 - (4-chloro-3-methoxyphenyl) -4 -methyl-2- (trifluoromethyl) -2- (trimethylsilyloxy) -pentanoate. 15.46 g (51.75 mmol) of 4-5% are dissolved. Ethyl (4-chloro-3-methoxyphenyl) -4-methyl-2-oxopentanoate in 85 ml of tetrahydrofuran, and mixed at 0 ° C with 8.83 g (62.09 mmol) of (trifluoromethyl) -trimethylsilane. After the addition of 126.8 mg of tetrabutylammonium fluoride, it is stirred for two hours at 0 to 5 ° C. The preparation is poured into 150 ml of ice water, extracted twice with diethyl ether and the combined organic extracts are processed using conventional means. After removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). Isolate 14.11 g (61.8%) of the desired (contaminated) product, which is used as such in the next step. MS (Cl): 458 (100%). Ethyl 4- (4-chloro-3-methoxyphenyl) -methyl-2- (trifluoromethyl) -2-hydroxy-pentanoate 8.9 g (20.18 mmol) of 4- (4-chloro-3-) are dissolved. methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2- (trimethylsilyloxy) -pentanoate in 116 ml of tetrahydrofuran, it is mixed at room temperature with 6.37 g (20.18 mmol) of tetrabutylammonium fluoride trihydrate, it is stirred one hour at room temperature. The reaction mixture is combined with water and extracted twice with 250 ml of diethyl ether each. The combined organic extracts are washed with water and saline. After drying with sodium sulfate, the drying medium is filtered, the solvent is removed and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 4.03 g (54.2%) of the desired compound are isolated. Other preparations are carried out analogously. XH-NMR (300 MHz, CDC13): d = 1.19 (3H), 1.39 (3H), 1.49 (3H), 2.28 (1H), 2.49 (1H), 3.60 -3.71 (2H), 3.93 (3H), 3.98-4.10 (HH), 6.82-6.93 (2H), 7.28 (HH). 4 - (4-Chloro-3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pen tanal 5.25 g (14.24 mmol) of (rae.) 4- (4-chloro-3 - ethyl methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxy-pentanoate in 53 ml of diethyl ether, and mixed at 0 ° C with 405.2 mg (10.68 mmol) of lithium aluminum hydride for 30 minutes. The reaction mixture is stirred for one and a quarter hours at 0 ° C. For hydrolysis, it is mixed by drops in an ice bath with 12.5 ml of saturated sodium bicarbonate solution. It is thoroughly stirred for 30 minutes in an ice bath and 60 minutes at room temperature. The precipitate is extracted and washed with diethyl ether. The filtrate is concentrated on a rotary evaporator and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 3.29 g (71.2%) of the desired aldehyde are isolated, which contain some of the initial ester and 54.7 mg of the corresponding diol. XH-NMR (300 MHz, CDC13): d = 1.39 (3H), 1.48 (3H), 2.34 (1H), 2.69 (1H), 3.69 (1H), 3.92. (3H), 6.80-6.93 (2H), 7.30 (1H), 8.90 (1H). 4- (4-chloro-3-methoxy-phenyl) -1,1-trifluoro-2 -. { [(E) -8-fluoro-2-methyl -quinazolin-5 -limino] -methyl} -4-methyl-pentane-2-ol 350 mg (1.08 mmol) of (rae.) -4- (4-chloro-3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pentanal in 5.8 ml of O-xylol with 190.9 mg (1.08 mmol) of 5-amino-8-fluoro-2-methylquinazolin. After the addition of 0.64 ml (2.16) of titanium-IV isopropylate, it is heated to reflux for three hours (bath temperature: 120 ° C). After cooling, the preparation is poured into saturated sodium chloride solution and stirred thoroughly for 20 minutes. After extracting twice with ethyl acetate, the combined organic extracts are washed with saline. After drying with sodium sulfate, sucking the drying media and removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 327.5 mg (62.8%) of the desired imine are isolated. XH-NMR (300 MHz, CDC13): d = 1.38 (3H), 1.58 (3H), 2.45 (1H), 2.71 (1H), 2.99 (3H), 3.69 (3H), 4.75 (1H), 6.28 (1H), 6.79-6.90 (2H), 7.08 (1H), 7.37-7.49 (2H), 9.63 (ÍH). 7-chloro-1 - (8-fluoro-2-methyl-tyzolin-5-ylamino) -6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalene-2-ol Dissolve 80 mg (0.165 mmol) of imine in 1.2 ml of dichloromethane, mix at 0 ° C dropwise with 0.5 ml of titanium tetrachloride, and stir for one hour and three quarters at this temperature. The reaction mixture is combined at 0 ° C by dropwise with a saturated solution of sodium bicarbonate and with ethyl acetate. The cold bath is removed and the preparation is stirred thoroughly for 20 minutes. After extracting with ethyl acetate, the combined organic extracts are processed using conventional means. After chromatography on silica gel (elution medium: methanol / dichloromethane), 60.7 mg (75.8%) of the desired compound, XH-NMR (300 MHz, DMSO-ds) are obtained: d = 1 , 40 (3H), 1.56 (3H), 1.99-2.15 (2H), 2.78 (3H), 3.90 (3H), 5.40 (1H), 6.18 (1H) ), 6.72-6.90 (2H), 7.10-7.20 (2H), 7.60 (1H), 9.79 (1H). 7-chloro-1 - (8-fluoro-2-methyl-tyzolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2,6-diol are mixed 35 mg (0.072 mmol) of the compound previously described with 0.7 ml of a 1 molar solution of boron tribromide in dichloromethane in an ice bath, and stirred for two hours in an ice bath. The reaction mixture is combined dropwise at -30 ° C with a saturated solution of sodium bicarbonate, and brought to pH 8. The cold bath is removed and the preparation is stirred thoroughly for 15 minutes at room temperature. After extracting twice with ethyl acetate, the organic extracts are processed using conventional means. After chromatography on silica gel (elution medium: methanol / dichloromethane), 17.7 mg (52.2 mg) of the desired compound are finally obtained. XH-NMR (300 MHz, CD30D): d = 1.40 (3H), 1.56 (3H), 2.07-2.20 (2H), 2.89 (3H), 5.23 (1H) , 6.83 (ÍH), 6.99 (1H), 7.20 (1H), 7.59 (1H), 9.69 (HH). EXAMPLE 147 5- (7-Chloro-2,6-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino-2H-isoquinolin-1-one 5- [4 - (4-chloro-3-methoxy phenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pent-ylidenamino) -2H-isoquinolin-l -one They are converted to imine 400 mg (1.232 mmol) of 4- (4-chloro-3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pentanal deseripto in the previous example with 197.3 mg (1.232 mmol) of 5-amino-2H-isoquinolin-1-one . After the reaction, it is processed using conventional means and chromatography is performed to obtain 332.9 mg (57.9%) of the desired imine. XH-NMR (300 MHz, CDC13): d = 1.38 (3H), 1.56 (3H), 2.43 (1H), 2.72 (1H), 3.70 (3H), 4.95. (1H), 6.41 (1H), 6.75-6.98 (3H), 7.08-7.31 (2H), 7.31-7.48 (2H), 11.2 (1H) . 5- (7-chloro-2-hydroxy-6-methoxy -4,4-dimethyl-2- (tri-fluoromethyl) -1,2,4,4-tetrahydrone-f-talen-1-ylamino-2H-isoquinoline-1 -one 100 mg (0.214 mmol) of imine are processed with titanium tetrachloride as described in example 146. 36.9 mg (36.9%) of the desired cyclic compound are isolated, in the form of a mixture of diastereomers at a ratio of 65:35. MS (ES +): 467 (100%) 5- (7-chloro-2,6-dihydroxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-1-ylamino-2H Isoquinolin-1 -one 27 mg (0.058 mmol) of the ether previously described with boron tribromide are processed, as described in example 146. After continuing the reaction and processing the product using conventional means, 19.9 mg are obtained. (75.9%) of the desired compound in the form of a uniform diastereomer. XH-NMR (300 MHz, CD30D): 5 = 1.29 (3H), 1.43 (3H), 1.98-2.09 (2H), 5.00 (1H), 6.75 (1H) , 6.86 (ÍH), 6.93 (1H), 7.00-7.10 (2H), 7.29 (1H), 7.59 (1H). Example 148 5- (7-Chloro-2,6-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-etrahydronaphthalen-1-ylamino-2-methyl-2H-phthalazine- 1-ona 5- [4 - (4-chloro-3-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentylideneamino] -2-methyl-2H-phthalazin-1 -one They are converted to imine 350 mg (1.078 mmol) of 4- (4-chloro-3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pentanal previously described with 251.8 mg (1.078 mmol) of 5-amino-2-methyl-2H -ftalazin-1-one After the reaction, it is processed using conventional means and chromatography is performed to obtain 328.4 mg (63.2%) of the desired imine XH-NMR (300 MHz, CDC13): d = 1.38 (3H), 1.58 (3H), 2.43 (1H), 2.72 (1H), 3.70 (3H), 3.89 (3H), 4.70 (ÍH), 6.51 (ÍH), 6.80-6.89 (2H), 7.10 (ÍH), 7.40 (1H), 7.63 (ÍH), 8.33 (ÍH), 8.42 (ÍH). ÍH). 5- (7-chloro-2-hydroxy-6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-1-amino-1, 2-methyl-2-heptalazine l -one 100 mg (0, 207 mmol) of imine with titanium tetrachloride in dichloromethane as described in Example 146. 30.5 mg (30.5%) of the desired compound are isolated, in the form of a mixture of diastereomers. MS (ES +): 482 (100%) 5- (7-chloro-2,6-dihydroxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3-tetrahydronaphthalene-1-ylamino-2 methyl 2H phthalazin-1 -one 24 mg (0.049 mmol) of the ether previously described with boron tribromide are processed, as described in example 146. After continuing the reaction and processing the product using conventional means, 18 are obtained. , 7 mg (75.9%) of the desired compound, in the form of a mixture of diastereomers MS (ES +): 468 (100%) Example 149 5- (7-chloro-2,6-dihydroxy-4.4 -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino-1H-quinolin-2-one 5- (4- (4-chloro-3-methoxyphenyl) -2-hydroxy-4 -methyl -2- (tri-fluoromethyl) -pentylidene) -lH-quinolin-2 -one 350 mg (1.078 mmol) of 4- (4-chloro-3-methoxyphenyl) -2-hydroxy-2 are converted to imine - (trifluoromethyl) -pentanal described previously with 172.6 mg (1.078 mmol) of 5-amino-lH-quinolin-2-one After the reaction, it is processed using means c and a chromatography is performed to obtain 319.4 mg (6349%) of the desired imine. XH-NMR (300 MHz, CDCl 3): d = 1.34 (3H), 1.55 (3H), 2.43 (1H), 2.70 (1H), 3.70 (3H), 4.85. (ÍH), 6.00 (1H), 6.70-6.90 (3H), 7.13 (ÍH), 7.29-7.45 (3H), 8.17 (1H), 12.30 (ÍH). 5- (7-chloro-2,6-dihydroxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-1-ylamino-1H-quinolin-2 -one are mixed 106 mg (0.227 mmol) of imine at -20 ° C with 2.3 ml of a 1M solution of boron tribromide in dichloromethane, and stirring between -20 and 0 ° C. The reaction mixture is brought to pH 8 with a saturated solution of sodium bicarbonate and processed using conventional means After chromatography on silica gel (elution medium: methanol / dichloromethane), 55.1 mg (53.5%) of the desired cyclic compound are obtained as free phenol XH-NMR (300 MHz, CD30D): d = 1.41 (3H), 1.55 (3H), 2.05-2.20 (2H), 5.12 (ÍH), 6.49-6.64 (2H), 6.73 (1H), 6.98 (ÍH), 7.16 (1H), 7.40 (1H), 8.25 (1H). Example 150 7-Chloro-l- (2-methylquinazolin-5-ylamino) -4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2,6-diol 4 - (4-chloro-3-methoxy phenyl) -1, 1-tri-fluoro-2 - 1 (2-methylquinazolin-5 -limino) -methyl] -4-methyl-pentan-2-ol They are converted to imine 200 mg (0.616 mmol) of (rae.) -4- (4-chloro-3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pentanal with 98.1 mg (0.616 mmol) of 5-amino-2-methylquinazoline as described in example 146. After carrying out a processing and purification using conventional means, they are isolated 184.3 mg (64.2%) of the desired imine. XH-NMR (300 MHz, CDC13): d = 1.36 (3H), 1.59 (3H), 2.45 (1H), 2.73 (1H), 2.93 (3H), 3.68 (3H), 4.82 (ÍH), 6.30 (1H), 6.78-6.90 (2H), 7.08 (HH), 7.48 (ÍH), 7.71 (1H), 7.84 (1H), 9.60 (1H). 7-Chloro-1 - (2-methyl-tyzolin-5-ylamino) -6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol 180 mg are cyclized (0.386 mmol) of imine with the aid of titanium tetrachloride, as previously described. 165.6 mg (92%) of the desired cyclic compound are isolated. aH-NMR (300 MHz, CD3OD): d = 1.49 (3H), 1.61 (3H), 2.10-2.25 (2H), 2.84 (3H), 3.93 (3H) , 5.31 (ÍH), 6.95 (ÍH), 7.10 (ÍH), 7.19-7.27 (2H), 7.81 (ÍH), 9.65 (HH). 7-Chloro-l- (2-methylquinzolin-5-ylamino) -4,4-dimethyl-2- (tri-fluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2,6-diol Convert 50 mg (0.107 mmol) of the derivative previously described, with the help of boron tribromide, in the corresponding phenol. 30.2 mg (66.1%) of the desired compound are isolated. XH-NMR (300 MHz, DMSO-ds): d = 1.33 (3H), 1.48 (3H), 1.95-2.13 (2H), 2.72 (3H), 5.39 (HI), 6.15 (1H), 6.80-6.95 (2H), 6.95-7.13 (3H), 7.69 (1H), 9.72 (HH), 10.03 (HH). Example 151 7-Chloro-l- (7-fluoro-2-methylquinazolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2,6-diol 4 - (4-chloro-3-methoxyphenyl) -1, 1, 1-tri-fluoro -2- [(7-fluoro-2-methyl-tyzolin-5-ylimino) -methyl] -4-methyl-pentan-2-ol they process 200 mg (0.616 mmol) of aldehyde with 109.1 mg (0.616) of 5-amino-7-fluoro-2-methylquinazoline, as has already been described on several occasions. 173 mg (58.1%) of the desired imine are isolated. XH-NMR (300 MHz, CDC13): d = 1.39 (3H), 1.58 (3H), 2.47 (1H), 2.73 (1H), 2.90 (3H), 3.72. (3H), 4.64 (ÍH), 6.17 (1H), 6.80-6.90 (2H), 7.09 (HH), 7.40-7.50 (2H), 9.49 (1 HOUR) . 7-chloro-1 - ('-fluoro-2-methyl-tyzolin-5-ylamino) -6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2-ol cyclized 170 mg (0.351 mmol) of the above-described amine with 1.05 ml (1.053 mmol) of titanium tetrachloride in dichloromethane. After performing the usual processing using conventional means and then performing chromatography, 168.4 mg (99%) of the desired cyclic compound is isolated as an ether. XH-NMR (300 MHz, CD30D): d = 1.49 (3H), 1.61 (3H), 2.20 (2H), 2.80 (3H), 3.93 (3H), 5.33. (1H), 6.70-6.85 (2H), 7.10 (1H), 7.20 (1H), 9.57 (1H). 7-chloro-1 - (7'-fluoro-2-methyl-tyzolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2,6-diol submit 50 mg (0.103 mmol) of the ether previously described to an ether separation with boron tribromide using conventional means. After processing and chromatography on silica gel using conventional means (elution medium: methanol / dichloromethane), 32.2 mg (66.4%) of the desired compound are isolated. XH-NMR (300 MHz, DMS0-d6): d = 1.32 (3H), 1.49 (3H), 1.95-2.13 (2H), 2.70 (3H), 5.48 ( 1H), 6.15 (1H), 6.79 (1H), 6.88 (ÍH), 6.95-7.16 (2H), 9.68 (HH), 10.03 (1H). Example 152 7-Chloro-l- (7,8-difluoro-2-methylquinazolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2,6 -diol 4- (4-chloro-3-methoxy phenyl) -1, 1, l -trifluoro-2- [(7,8-difluoro-2-methylquinazolin-5 -limino) -methyl] -4-methyl-pentan -2-ol 200 mg (0.616 mmol) of aldehyde are processed with 120 mg (0.616) of 5-amino-7,8-difluoro-2-methylquinazoline, as has already been described on several occasions. 201.3 mg (65.1%) of the desired imine are isolated. XH-NMR (300 MHz, CDC13): d = 1.38 (3H), 1.58 (3H), 2.46 (1H), 2.72 (1H), 2.96 (3H), 3.72. (3H), 4.59 (ÍH), 6.28 (ÍH), 6.80-6.90 (2H), 7.10 (1H), 7.46 (HH), 9.53 (HH). 7-chloro-1- (7,8-difluoro-2-methylquinazolin-5-ylamino) -6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2- 200 mg (0.398 mmol) of the imine previously described are cyclized with 1.19 ml (1.194 mmol) of titanium tetrachloride in dichloromethane. After carrying out the usual work-up and chromatography using conventional means, 163.6 mg (81.8%) of the desired cyclic compound are isolated. XH-NMR (300 MHz, CD30D): d = 1.48 (3H), 1.61 (3H), 2.19 (2H), 2.86 (3H), 3.93 (3H), 5.30 (1H), 6.88 (ÍH), 7.09 (HH), 7.21 (1H), 9.62 ( 1 HOUR) . 7-chloro-l- (7,8-difluoro-2-methyl-tyzolin-5-ylamino) -, 4-dimethyl-2- (trifluoromethyl) -1,2, -tetrahydronaphthalene-2,6-diol 50 mg ( 0.099 mmol) of the ether described previously to an ether separation with boron tribromide using conventional means. After processing and purification by flash chromatography (elution medium: methanol / dichloromethane), 29.5 mg (60.7%) of the desired compound are isolated.

XH-NMR (300 MHz, DMSO-ds): d = 1.32 (3H), 1.47 (3H), 1.95-2.12 (2H), 2.78 (3H), 5.45 ( ÍH), 6,13 (ÍH), 6,92-7,18 (4 H), 9,73 (ÍH), 10,02 (ÍH). EXAMPLE 153 4- (7-Chloro-2,6-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -1, 3-dihydroindol-2-one 4- [4- (4-chloro-3-methoxyphenyl) -2-hydroxy-4-methyl-2- (tri-fluoromethyl) -pentylidene] -1,3-dihydro-indole 2 -one 150 mg (0.462 mmol) of aldehyde are heated with 102.7 mg (0.693 mmol) of 4-amino-1,3-dihydroindol-2-one in xylene, as already described in the previous examples, after of adding titanium tetraisopropylate in a water separator. After carrying out the usual processing using conventional means and chromatography, 119.3 mg (56.7%) of the desired imine are isolated. XH-NMR (300 MHz, CDC13): d = 1.35 (3H), 1.50 (3H), 2.49 (HH), 2.66 (ÍH), 3.35-3.59 (2H) , 3.75 (3H), 4.89 (ÍH), 5.98 (ÍH), 6.70-6.90 (3H), 7.09-7.22 (2H), 7.33 (HH) , 8.22 (ÍH). 4- (7-chloro-2-hydroxy-6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -1,3-dihydrohydrin 2- Ona 119 mg (0.261 mmol) of the imine described above are cyclized in dichloromethane, with 0.78 ml of titanium tetrachloride, using conventional means. After processing and carrying out chromatography, 78.1 mg (65.6%) of the desired compound are obtained. XH-NMR (300 MHz, CD3OD): d = 1.42 (3H), 1.59 (3H), 2.00-2.20 (2H), 3.23-3.49 (2H), 3, 91 (3H), 5.03 (ÍH), 6.37 (ÍH), 6.48 (1H), 7.03 (HH), 7.10 (1H), 7.29 (1H). 4 - (7-chloro-2,6-dihydroxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -1, 3-dihydro-2-hydroxy One 65 mg (0.143 mmol) of the ether previously described is mixed with 1.4 boron tribromide in dichloromethane. After processing and carrying out chromatography, 45.4 mg (72.1%) of the desired phenol are obtained. XH-NMR (300 MHz, CD3OD): d = 1.39 (3H), 1.51 (3H), 1.98-2.20 (2H), 3.25-3.50 (2H), 5, 00 (ÍH), 6.37 (1H), 6.46 (ÍH), 6.93 (1H), 7.10 (ÍH), 7.21 (1H). EXAMPLE 154 8,8-dimethyl-5- (naph-alen-1-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 1,1,1-tri-fluoro-4 - (2-methoxyphenyl) -4-methyl -2- (naphthalen-1-yliminomethyl) -pentan-2-ol 150 mg (0.517 mmol) of 2-hydroxy-4- (2-methoxyphenyl) -4 are converted to imine -methyl-2- (trifluoromethyl) -pentanal with 74 mg (0.517 mmol) of 1-naphthylamine in toulol, with the aid of titanium tetraisopropylate. After usual processing and chromatography, 166.7 mg (77.7%) of the desired imine are isolated.

XH-NMR (300 MHz, CDC13): d = 1.42 (3H), 1.59 (3H), 2.29 (1H), 3.57 (1H), 3.88 (3H), 5.09 (1H), 6.10 (1H), 6.48 (ÍH), 6.79 (1H), 7.00 (ÍH), 7.10 (1H), 7.22 (ÍH), 7.40 ( HH), 7.47-7.58 (2H), 7.69 (ÍH), 7.80 (ÍH), 8.05 (1H). 8, 8-dimethyl -5- (naph 'talen-1-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronafat? -1,6-diol 160.9 mg (0.387 mmol) are processed ) of the imine previously described with boron tribromide at 0 ° C using conventional means, and after carrying out the usual processing and flash chromatography according to conventional procedures, 100.9 mg (62.7%) of the phenol are obtained desired cyclic. XH-NMR (300 MHz, CDC13): d = 1.60 (3H), 1.73 (3H), 2.00-2.28 (2H), 3.09 (1H), 4.79 (1H) , 5.02 (ÍH), 5.20 (1H), 6.62 (1H), 6.85-7.02 (3H), 7.30-7.58 (4H), 7.73-7 90 (3H). EXAMPLE 155 8,8-dimethyl-5- (naphthalen-2-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaf-alen-1,6-diol 1,1-trifluoro-4-diol (2-methoxy phenyl) -4-methyl-2- (naphthalene-2-triminomethyl) -pentan-2-ol 150 mg (0.517 mmol) of 2-hydroxy-4- (2-methoxyphenyl) -4- are converted to imine methyl-2- (trifluoromethyl) -pentanal with 74 mg (0.517 mmol) of 2-naphthylamine in toulol, with the aid of titanium tetraisopropylate. After usual processing and chromatography, 192.8 mg (89.8%) of the desired imine are isolated.

XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.58 (3H), 2.20 (1H), 3.58 (1H), 3.89 (3H), 5.09 (1H), 6.69 (ÍH), 6.80-6.90 (2H), 6.95 (HH), 7.05-7.18 (2H), 7.38-7.53 (3H) 7.63-7.85 (3H). 8, 8-dimethyl-5- (naphthalen-2-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol. 173.0 mg (0.416 mmol) are processed. the imine previously described with boron tribromide at 0 ° C, using conventional means, and after processing in a normal manner and carrying out an instantaneous chromatography, 132.6 mg are obtained (76.6%) of the desired cyclic phenol. XH-NMR (300 MHz, CDC13): d = 1.60 (3H), 1.66 (3H), 2.00-2.24 (2H), 3.04 (1H), 5.00 (1H) , 5.09 (1H), 6.62 (ÍH), 6.92-7.10 (4H), 7.28 (ÍH), 7.40 (1H), 7 7.60-7.78 ( 3H). Example 156 2-Chloro-5- (6-hydroxynaphthalen-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1,6-diol 5- ( 4- (3-Chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentylidene-1-ene] -naphthalen-2-ol. They become imine 200 mg (0.616 mmol) of 2-hydroxy -4- (3-chloro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal with 98.1 mg (0.616 mmol) of 5-amino-2-naphthol using conventional means. mg (64.5%) of the desired compound XH-NMR (300 MHz, CDC13): d = 1.47 (3H), 1.62 (3H); "2; 40 (1H), 3.23 (1H ), 4.00 (3H), 4.99 (1H), 5.15 (ÍH), 6.39 (1H), 6.49 (1H), 6.83 (ÍH), 7.00 (ÍH) 7.05-7.20 (2H), 7.23-7.32 (2H), 7.52-7.63 (2H), 7.95 (1H) 2-chloro-5- (6 ') -hydroxynaph talen-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1,6-diol 185.1 mg (0.397 mmol) of imine are cyclized With boron tribromide, as has been described on several occasions, 146.9 mg (81.8%) of phenol is isolated from eseado. XH-NMR (300 MHz, CDC13): d = 1.59 (3H), 1.70 (3H), 2.02-2.28 (2H), 3.00 (1H), 4.75 (1H) , 5.10-5.19 (2H), 5.95 (HH), 6.73 (ÍH), 6.88 (1H), 7.00-7.12 (2H), 7.12-7, 22 (2H), 7.34 (IH), 7.70 (1H). Example 157 2-Chloro-5- (5-hydroxynaphthalen-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1,6-diol 5- ( 4- (3-Chloro-2-methoxy phenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentylideneamino] -naphthalen-ol They are converted to imine 200 mg (0.616 mmol) of 2-hydroxy -4- (3-Chloro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal with 98.1 mg (0.616 mmol) of 5-amino-1-naphthol using conventional means. mg (50.5%) of the desired compound XH-NMR (300 MHz, CDC13): d = 1.45 (3H), 1.62 (3H), 2.40 (1H), 3.25 (1H) , 4.01 (3H), 5.01 (1H), 5.39 (IH), 6.46 (IH), 6.53 (1H), 6.80-6.91 (2H), 7.02 (HH), 7.30-7.40 (2H), 7.59 (HH), 7.64 (1H), 8.10 (HH). 2-Chloro-5- (5-hydroxynaphthalene-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1,6-diol Cyclized 145.0 mg (0.311 mmol) of imine with boron tribromide, as has already been described on several occasions. 87.6 mg (62.3%) of the desired phenol are isolated. XH-NMR (300 MHz, CDC13): d = 1.58 (3H), 1.70 (3H), 2.05-2.28 (2H), 3.00 (1H), 4.78 (1H) , 5,15 (1H), 5,49 (ÍH), 5,95 (1H), 6,80-6,93 (3H), 7,10 (ÍH), 7,29 (ÍH), 7,32 -7.45 (2H), 7.68 (ÍH). Example 158 3-Chloro-5- (6-hydroxynaphthalen-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1,6-diol 5- ( 4 - (4-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (tri-fluoromethyl) -pentylideneamino] -naphthalene-2-ol They are converted to imine 200 mg (0.616 mmol) of 2-hydroxy -4- (4-chloro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal with 98.1 mg (0.616 mmol) of 5-amino-2-naphthol using conventional means. mg (39.4%) of the desired compound XH-NMR (300 MHz, CDC13): d = 1.38 (3H), 1.58 (3H), 2.30 (1H), 3.40 (1H) , 3.85 (3H), 5.00 (1H), 5.15 (HH), 6.06 (1H), 6.50 (ÍH), 6.75 (ÍH), 6.99 (1H), 7.05-7.20 (2H), 7.28 (1H), 7.45 (1H), 7.58 (IH), 7.93 (1H), 3-chloro-5- (6-hydroxynaphtalene) 1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalen-1,6-diol 113.0 mg (0.243 mmol) of imine are cyclized with tribromide of boron, as already described on several occasions, 85.7 mg are isolated (78.2% ) of the desired compound. XH-NMR (300 MHz, CDC13): d = 1.55 (3H), 1.65 (3H), 2.01-2.23 (2H), 2.95 (HH), 4.80 (HH) , 5.10 (1H), 5.20 (HH), 5.48 (1H), 6.60-6.75 (2H), 6.93 (1H), 7.09 (HH), 7.10 -7.23 (2H), 7.35 (1H), 7.74 (1H). Example 159 2-Chloro-8,8-dimethyl-5- (pyridin-3-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-1,6-diol 4 - (3-chloro- 2-methoxy phenyl) -1,1,1- (trifluoromethyl) -4 -methyl- (pyridin-3-yliminomethyl) -pentan-2-ol They are converted to imine 200 mg (0.616 mmol) of 2-hydroxy-4- (3-chloro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal with 57.9 mg (0.616 mmol) of 3-aminopyridine using conventional means. 197.2 mg (79.9%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.43 (3H), 1.60 (3H), 2.28 (1H), 3.25 (1H), 3.98 (3H), 4.70 (ÍH), 6.75 (ÍH), 6.95 (ÍH), 7,00-7,15 (2H), 7,23 (ÍH), 7,58 (1H), 8,12 (ÍH), 8.49 (ÍH). 6-chloro-5-methoxy -4,4-dimethyl-1- (pyridin-3-ylamino) -2- (trifluoromethyl) -1,2,3,4-tetrahydro-naphthalene-2-ol 190.0 cyclized mg (0.474 mmol) of imine, with titanium tetrachloride, as has already been described on several occasions. 184.0 mg (96.8%) of the desired desired cyclic compound is isolated as an ether.

XH-NMR (300 MHz, CD3OD): d = 1.54 (3H), 1.62 (3H), 2.11 (2H), 3.95 (3H), 5.05 (1H), 7.11 (1H), 7.15-7.28 (3H), 7.83 (HH), 8.09 (HH). 2-Chloro-8,8-dimethyl-5- (pyridin-3-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydrona-talen-1,6-diol 100 mg (0.249 mmol) are processed of the ether previously described with boron tribromide, using conventional means. After performing the usual work-up using conventional means and chromatography, 85.8 mg (88.9%) of the desired compound are isolated. XH-NMR (300 MHz, CD30D): d = 1.58 (3H), 1.69 (3H), 2.00-2.20 (2H), 5.00 (1H), 6.89 (1H) , 7.10-7.30 (3H), 7.81 (1H), 8, 06 (1H). Use 160 1, 6-dihydroxy-8, 8-dimethyl-5- (pyridin-3-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-2-carbonitrile 50 mg are dissolved of 2-chloro-8,8-dimethyl-5- (pyridin-3-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol described in Example 159 in 0 12 ml of l-methyl-2-pyrrolidinone, and it is mixed with 12.6 mg (0.258 mmol) of sodium cyanide and 28.2 mg (0.129 mmol) of nickel-II bromide. The reaction mixture is reacted in a microwave oven as described in the literature (J. Org. Chem.68, 9122 (2003) (200 ° C, 20 bar) After cooling, the reaction mixture is diluted with ethyl acetate and then a small amount of water is added The mixture is filtered by Extrelute (elution medium: ethyl acetate) The solvent is centrifuged and the residue is chromatographed on silica gel (elution medium: methanol / dichloromethane) 9.4 mg (19.2%) of the desired nitrile are isolated MS (Cl): 378 (100%); IR (KBr): 2228. EXAMPLE 161 2-Chloro-8,8-dimethyl-5- (pyridin-4-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 4- (3-chloro-2-methoxyphenyl) -1,1,1- (trifluoromethyl) -4-methyl- (pyridin-4-yliminomethyl) -pentan-2-ol They are converted to imine 200 mg (0.616 mmol) of 2-Hydroxy-4- (3-chloro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal with 57.9 mg (0.616 mmol) of 4-aminopyridine using conventional means. 167.9 mg (68.0%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.43 (3H), 1.60 (3H), 2.29 (1H), 3.26 (1H), 4.00 (3H), 4.55 (HH), 6.59-6.65 (2H), 6.80 (1H), 7.01 (HH), 7.11 (1H), 7.55 (HH), 8.46-8.55 (2H). 6-chloro-5-methoxy -4,4-dimethyl-1- (pyridin-4-ylamino) -2- (trifluoromethyl) -1,2,3,4-tetrahydro-naphthalene-2-ol Cycle 160.0 mg (0.399 mmol) of imine with titanium tetrachloride, as has already been described on several occasions. 45.2 mg (28.2%) of the desired cyclic compound is isolated as an ether. XH-NMR (300 MHz, CD30D): d = 1.55 (3H), 1.69 (3H), 2.12 (2H), 3.98 (3H), 5.28 (HH), 6.80-6.93 (2H), 6.99 (1H), 7.28 (HH), 7.98-8.20 (2H). 2-Chloro-8,8-dimethyl-5- (pyridin--ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaf talen-1,6-diol 37 mg (0.092 mmol) are processed of the ester described previously with boron tribromide, using conventional means. After performing the usual workup and chromatography using conventional means, 13.8 mg (38.6%) of the desired compound are isolated. XH-NMR (300 MHz, CD3OD): d = 1.58 (3H), 1.70 (3H), 2.00-2.20 (2H), 5.19 (1H), 6.70-6, 89 (3H), 7.19 (1H), 7.90- 8.20 (2H). EXAMPLE 162 5- (2,5-Dihydroxy-6-isopropyl-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-isoquinolin-1-one 3 Methyl-isopropyl-2-methoxybenzoate 28 g (156.25 mmol) of 2-hydroxy-3-isopropylbenzoic acid are dissolved in 280 ml of DMF and added dropwise to a mixture of 47.5 g of potassium carbonate in 274 ml of DMF. After stirring for one hour at room temperature, 21.4 ml (343.76 mmol) of iodomethane are added dropwise and the mixture is stirred for one day at room temperature.

After acidifying with 10% sulfuric acid until pH 3-4 (with cooling in an ice bath), the reaction mixture is extracted four times with 500 ml of ethyl-ter-each.

The combined organic extracts are washed with water and saline, and dried with sodium sulfate. After filtering the drying media, the solvent is removed and the residue is chromatographed several times on silica gel (elution medium: methyl-tert-butyl ether / hexane). 25.59 g (79.02%) of the desired compound are isolated. X H-NMR (300 MHz, CDCl 3): d = 1.26 (6 H), 3.42 (1 H), 3.85 (3 H), 3.96 (3 H), 7.15 (1 H), 7, 43 (1H), 7.65 (1H). 2- (3-Isopropyl-2-methoxyphenyl) -propan-2-ol 25.59 g (142.81 mmol) of methyl 3-isopropyl-2-methoxybenzoate are dissolved in 250 ml of tetrahydrofuran and added dropwise. to 114.25 ml (342.74 mmol) of methylmagnesium bromide (3M in diethyl ether). Then the temperature is increased to 46 ° C. After stirring for three hours at room temperature, 625 ml of a saturated solution of ammonium chloride are added dropwise to the reaction mixture. After extracting twice with methyl tert-butyl ether, the combined organic extracts are washed with water and saline, and dried (sodium sulfate). The drying media is filtered, the solvent is removed and the crude residue (28.16 g = 95.15%) is used in the next step. XH-NMR (300 MHz, CDC13): d = 1.25 (6 H), 1.63 (6 H), 3.31 (1 H), 3.90 (3 H), 4.78 (1 H), 7 , 00-7.23 (3H). Ethyl 4 - (3-isopropyl-2-methoxyphenyl) -4-methyl-2-oxo-pentanoate 15.3 ml (129.71 mmol) of tin tetrachloride are added dropwise to a mixture cooled to -72 ° C. of 28.16 g (135.19 mmol) of 2- (3-isopropyl-2-methoxyphenyl) -propan-2-ol and 50.9 g (270.38 mmol) of ethyl ester of 2-trimethylsilanyloxy-acrylic acid in 420 ml of dichloromethane. Then the temperature increases to -65 ° C. After stirring for 30 minutes in this temperature range, the reaction mixture is poured into a mixture of a saturated solution of sodium carbonate and dichloromethane (250 ml of each). After stirring for 30 minutes at room temperature, the preparation is transferred to a separating funnel and a 1: 1 mixture of water and dichloromethane is added in order to separate the phases. After stirring the organic phase with sodium carbonate, 1N HCl and water, it is dried with sodium sulfate. Using conventional procedures, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 20.44 g (48.35%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.15-1.34 (9 H), 3.28 (HH), 3.38 (2H), 3.78 (3H), 4.09-4 , 21 (2H), 7.05 (1H), 7.10-7.19 (2H). Ethyl 2-hydroxy-4- (3-isopropyl-2-methoxy-3-enyl) -4-methyl-ethyl- (trifluoromethyl) pentanoate 11.82 g (38.58 mmol) of 4- (3-isopropyl-2) are dissolved. -methoxyphenyl) -4-methyl-2-oxopentanoate and, 58 g (46.29 mmol) of (trifluoromethyl) -trimethylsilane in 70 ml of tetrahydrofuran, and mixed with 50 mg of tetrabutylammonium fluoride trihydrate (with a slight increase in temperature). Since the transformation is not complete after three hours, it is combined with a similar amount of tetrabutylammonium fluoride trihydrate. After stirring overnight, 12.17 g of tetrabutylammonium fluoride trihydrate are added, the remaining silyl ether is removed and the free hydroxyl compound is obtained directly. The reaction mixture is diluted with methyl tert-butyl ether and the organic extract is washed with water and saline. After drying (sodium sulfate), filtering the drying media and removing the solvent by filtration, the residue is subjected several times to a chromatography on silica gel (elution medium: ethyl acetate / hexane). 11.04 g (76%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.13-1.32 (9 H), 1.40-1.48 (6 H), 2.48 (HH), 2.72 (ÍH), 3.32 (ÍH), 3.57 (1H), 3.65-3.78 (ÍH), 3.85 (3H), 4.08-4.20 (1H), 6.96-7.09 (2H), 7.18 (1H). 4- (3-Isopropyl-2-methyl-phenyl) -4-methyl-2- (trifluoromethyl) pentan-1,2-diol. 11.04 g (29.33 mmol) of the ether previously described are dissolved in 90 ml. diethyl ether, and mixed at 2.degree. C. in portions with 2.23 g (58.66 mmol) of lithium aluminum hydride. After stirring overnight at room temperature, 50 ml of saturated sodium bicarbonate solution are carefully added in an ice bath. After thorough stirring for one hour at room temperature, it is extracted three times with methyl-tert-butyl ether. The combined organic extracts are processed using conventional means, and, after removing the solvent, the residue is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 7.15 g (72.9%) of the desired diol are isolated. XH-NMR (300 MHz, CDCl 3): d = 1.25 (3H), 1.29 (3H), 1.50 (3H), 1.58 (3H), 1.80 (1H), 2.23. (1H), 2.61 (1H), 2.83 (1H), 3.23-3.49 (3H), 3.89 (3H), 7.09 (1H), 7.17-7.26 (2H). 2-hydroxy-4- (3-isopropyl-2-methoxy-enyl) -4-methyl-2- (trifluoromethyl) -pentanal 3.17 g (25.04 mmol) of oxalyl chloride are introduced 83 ml of dichloromethane and cooled to -78 ° C. At this temperature, 3.9 g (50.08 mmol) of dimethyl sulfoxide, dissolved in 10 ml of dichloromethane, are added dropwise. After stirring for five minutes, 7.15 g (21.38 mmol) of 4- (3-isopropyl-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentan-1,2-diol are added, dissolved in 21.4 ml of dichloromethane. The reaction mixture is then stirred for two hours at this temperature. 10.8 g (106.9 mmol) of triethylamine are carefully added dropwise, and then the preparation is stirred thoroughly for one hour at room temperature. After adding water and stirring for another ten minutes, it is extracted twice with dichloromethane. The combined organic extracts are washed with 1% sulfuric acid, saturated sodium bicarbonate solution and saline solution.

After drying and removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). Finally, 5.93 g (83.44%) of the desired aldehyde are obtained. XH-NMR (300 MHz, CDC13): = = 1.20 (3H), 1.32 (3H), 1.40-1.54 (6H), 2.22 (HH), 3.30 (1H) ), 3.40 (ÍH), 3.59 (ÍH), 3.83 (3H), 6.95-7.07 (2H), 7.20 (1H), 8.91 (ÍH). 5- [2-hydroxy-4- (3-isopropyl-2-methoxy-phenyl) -4-methyl-2- (tri-fluoromethyl) -pentylideneamino] -2H-isoquinoline-1-one. They are stirred overnight 147.3 mg (0.443 mmol) of the aldehyde previously described with 71 mg (0.443 mmol) of 5-amino-2H-isoquinolin-1-one in 1.3 ml of ethyl acetate at room temperature. The reaction mixture is combined three times with toluene and the residue is subjected to flash chromatography. 157 mg (75%) of the desired imine are isolated. XH-NMR (300 MHz, DMS0-d6): d = 0.93 (3H), 1.19 (3H), 1.43 (3H), 1.55 (3H), 2.18 (1H), 3 , 18 (ÍH), 3,29 (1 H, half under water of DMSO), 3,75 (3H), 6,19 (ÍH), 6,33 (ÍH), 6,63 (1H), 6.77 (ÍH), 6.89-6.99 (2H), 7.16-7.32 (3H), 8.03 (HH), 11.33 (1H). 5- (2-Hydroxy-6-isopropyl-5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-isoquinoline-1 - One 157 mg of imine (0.331 mmol) is dissolved in 2.5 ml of dichloromethane and mixed at 0 ° C by dropwise with 0.95 ml (0.993 mmol) of titanium-IV chloride. After stirring for one hour at 0CC, the reaction mixture is combined dropwise with a saturated solution of sodium bicarbonate, and diluted with ethyl acetate. The cold bath is removed and the preparation is thoroughly stirred for 30 minutes at room temperature. After extracting twice with ethyl acetate, the organic extract is processed using conventional means. After flash chromatography of the residue, 108 mg (68.98%) of the desired cyclic compound is obtained as racemate. XH-NMR (300 MHz, CD30D): d = 1.10-1.30 (6 H), 1.55 (3H), 1.70 (3H), 2.13 (2H), 3.39 (1 H, under the CH 3 OH signal), 3.80 (3H), 5.19 (H), 6.86 (1H), 6.99-7.20 (4 H), 7.39 (H), 7 , 70 (ÍH). 5- (2,? -dihydroxy-6-isopropyl-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-isoquinolin-1 -one They are dissolved 70 mg (0.147 mmol) of the cyclic ether previously described at room temperature with 1.5 ml of a 1M solution of boron tribromide in dichloromethane, and stirring five hours at room temperature. The reaction mixture is combined with pieces of iron. A saturated solution of sodium bicarbonate is carefully added dropwise and brought to pH 8. After diluting the mixture with ethyl acetate, it is thoroughly stirred. After extracting twice with ethyl acetate, the combined organic extracts are washed with water and saline, and dried (sodium sulfate). After filtering and removing the solvent, the residue is chromatographed on silica gel (elution medium: methanol / dichloromethane). 43.2 mg (63.6%) of the desired compound are isolated. XH-NMR (300 MHz, DMSO-ds): d = 0.96-1.20 (6H), 1.52 (3H), 1.68 (3H), 1.90-2.11 (2H) , 3.30 (1 H, half under the water signal), 5.29 (1H), 5.91 (1H), 6.00 (1H), 6.70 (1H), 6.81 (1H), 6.97 (1H), 7.05 (1H), 7.17 (1H), 7.25 (1H), 7.49 (1H), 8, 09 (1H), 11.20 (1H). Example 163 5- (2,5-Dihydroxy-6-isopropyl-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -1H-quinolin-2-one - [2-Hydroxy -4 - (3-isopropyl-2-methoxy phenyl) -4-methyl- (tri-foromethyl) -pentylideneamino] -1H-quinolin-2 -one. 300 mg (0.903 mmol) of the 2-hydroxy-4- (3-isopropyl-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal described in Example 102 with 5-amino-1H-quinolin-2-one, as described in Previous example. After carrying out flash chromatography, 372 mg (86.91%) of the desired imine are isolated. XH-NMR (300 MHz, DMS0-d6): d = 0.90 (3H), 1.18 (3H), 1.40 (3H), 1.54 (3H), 2.15 (ÍH), 3.15 (ÍH), 3.29 (1H, half underwater DMSO), 3.75 (3H) 5.90 (IN), 6.20 (ÍH), 6,53 (ÍH), 6,64 (ÍH), 6,85-6,98 (2H), 7,13 (ÍH), 7,22-7,36 (2H), 8,09 (ÍH), 11.77 (1H). 5- (2-Hydroxy-6-isopropyl-5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydro-naphthalene-1-ylamino) -1H-quinolin-2- One 120 mg (0.253 mmol) of the imine previously described is cyclized as in example 162, with titanium-IV chloride in dichloromethane. After processing and carrying out chromatography, 64.3 mg (53.6%) of the desired cyclic compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.10-1.30 (6 H), 1.58 (3H), 1.71 (3H), 2.00-2.20 (2H), 3 , 31 (1H), 3.80 (3H), 4.01 (ÍH), 5.09 (1H), 5.25 (1H), 6.50-6.70 (3H), 7.00-7 , 12 (2H), 7.35 (1H), 8.01 (1H), 10.78 (1H). 5- (2,5-dihydroxy -6-isopropyl-, 4-dimethyl-2- (tri-fluoromethyl) -1, 2, 3, 4-tetrahydronaphthalene-1-ylamino) -1H-quinolin-2-one Cooled 114 mg (0.240 mmol) of the imine previously described at -20 ° C, and mixed with 2.4 ml of a solution 1M boron tribromide in dichloromethane. Then it is stirred for two hours between -20 ° C and 0 ° C, and then for 30 minutes at room temperature. The reaction mixture is mixed at -20 ° C by dripping with a saturated solution of sodium bicarbonate until reaching pH 8. The cold bath is removed and the preparation is stirred thoroughly at room temperature for 10 minutes. After extracting with ethyl acetate, the combined organic extracts are stirred using conventional means. After removing the solvent, 48 mg of a mixture of cyclic ester and cyclic phenol are obtained. To obtain the corresponding uniform compound, the mixture is processed once more with 1.2 ml of a boron tribromide solution, this time at room temperature (stirring for three and a half hours). After continuing the work up using conventional means and carrying out chromatography on silica gel, 52.6 mg (92.9%) of the desired compound are obtained. XH-NMR (300 MHz, CD3OD): d = 1.10-1.30 (6 H), 1.60 (3H), 1.72 (3H), 2.00-2.20 (2H), 3 , 25 (1H), 5,15 (ÍH), 6,51 (1H), 6,63 (1H), 6,70 (ÍH), 6,88 (ÍH), 7,01 (1H), 7, 39 (ÍH), 8.24 (1H). Example 164 5- (7-Fluoro-2-methylquinazolin-5-ylamino) -2-isopropyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydr-onaftalen-1,6- Diol 1,1,1-trifluoro-2- [(7-fluoro-2-methylquinazolin-5-ylimino) -methyl] -4- (3-isopropyl-2-methoxy-phenyl) -4-methyl-pentan-2 -ol 150 mg (0.451 mmol) of the aldehyde described in example 162 are converted to imine with 79.9 mg (0.451 mmol) of 7-fluoro-2-methylquinazolin-5-ylamine in xylene, with the aid of titanium isopropylate. -IV. After carrying out the usual processing using conventional means, 207.8 mg (93.6%) of the desired compound, XH-NMR (300 MHz, CDCl3), d = 0.83 (3H), 1.20 (3H) are obtained. ), 1.41 (3H), 1.62 (3H), 2.25 (ÍH), 2.90 (3H), 3.20 (HH), 3.68 (ÍH), 3.83 (3H), 4.61 (ÍH), 5.95 (1H), 6.54 (ÍH), 6.80 (ÍH), 6.99 (ÍH), 7.30-7.42 ( 2H), 9.30 (1H). 1- (7-Fluoro-2-methylquinazolin-5-ylamino) -6-isopropyl-5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2-ol cyan 207.8 mg (0.422 mmol) of the imine described previously with 1.26 ml of titanium-IV chloride in dichloromethane. After proceeding as described in Example 162, 194.4 mg (93.5%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.10-1.30 (6 H), 1.60 (3H), 1.75 (3H), 2.10-2.28 (2H), 2.87 (3H), 3.33 (IH), 3.80 (3H), 4.99 (1H), 6.09 (1H), 6.20 (1H), 6.54 (ÍH), 6.90 (1H), 7.06-7.19 (2H), 9.20 (HH). (-) 1 - (7'-Fluoro-2-methyl-tyzolin-5-ylamino) -6-isopropyl-5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalene- 2 -ol (+) -1- (7'-fluoro-2-methyl-tyzolin-5-ylamino) -6-isopropyl-5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4 -tetrahydronaphthalen-2-ol 94 mg of the pharamamic mixture are separated using ether separation on a chiral column, in order to obtain both enantiomers. 36 mg of the (-) enantiomer and 32 mg of (+) enantiomer are isolated. enantiomer (-): [a] D = -34.4 ° (c = 1, CH30H), • enantiomer (+): MD = + 31.77 ° (c = 1, CH30H) 5- (7 -fluoro- 2-methylquinazolin-5-ylamino) -2- isopropyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaph 'talen-1,6-diol 100 mg (0.203 mmol) are processed of 1- (7-fluoro-2-methylquinazolin-5-ylamino) -6-isopropyl-5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2-diol with BBr3 in dichloromethane, as has already been described several times. After processing and carrying out a chromatography, 18.5 mg (19.1%) of the desired phenol are obtained. XH-NMR (300 MHz, CD30D): d = 1.05-1.30 (6 H), 1.65 (3 H), 1.74 (3 H), 2.28 (2 H), 2.79 (3 H) ), 3.27 (1H), 5.30 (ÍH), 6.65-6.90 (2H), 6, 93-7, 17 (2H), 9.55 (HH). (-) -5- (7'-Fluoro-2-methyl-tyzolin-5-ylamino) -2-iso-propyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaf-talen -1,6-diol (+) - 5 - (7'-fluoro-2-methyl-tyzolin-5-ylamino) -2-isopropyl-8,8-dimethyl-6- (triforuilne-useful) -5,6,7 , 8-tetrahydronaphthalen-1,6-diol The pure ether of enantiomer previously described is converted into pure enantiomer phenol, as described for the racemate. From 24.7 mg of ether (enantiomer (-), 10.4 mg (43.5) of phenol are obtained.) From ether (26.7 mg) (enantiomer (+)), 5.1 mg (19.6%) of phenol are obtained. EXAMPLE 165 5- (7,8-difluoro-2-methylquinazolin-5-ylamino) -2-isopropyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene- 1,6 -diol 1, 1, 1-tri-fluoro-2- [(7,8-difluoro-2-methyl-tyzolin-5-ylimino) -methyl] -4 - (3-isopropyl-2-methoxy-phenyl) -4-methyl -pentan-2 -ol 150 mg (0.451 mmol) of the aldehyde described in example 162 are converted to imine with 88 mg (0.451 mmol) of 7,8-difluoro-2-methylquinazolin-5-ylamine in xylene, with the aid of titanium-IV isopropylate After carrying out the usual processing using conventional means, 208.6 mg (90.7%) of the desired compound are obtained XH-NMR (300 MHz, CDC13): d = 0.90 (3H ), 1.23 (3H), 1.43 (3H), 1.63 (3H), 2.23 (1H), 2.98 (3H), 3.22 (1H), 3.69 (1H) , 3.83 (3H), 4.58 (1H), 5.99 (HH), 6.58 (1H), 6.88 (1H), 6.99 (HH), 7.39 (ÍH), 9.39 (ÍH). 1- (7, 8-difluoro-2-methyl-tyzolin-5-ylamino) -6-isopropyl-5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4 -te trahi dronaftal en-2-ol 208.6 mg (0.409 mmol) of the imine described above are cyclized with 1.23 ml of titanium-IV chloride in dichloromethane. After proceeding as described in Example 162, 198 mg (95.9%) of the desired compound are isolated. aH-NMR (300 MHz, CDC13): d = 1.10-1.30 (6 H), 1.63 (3H), 1.76 (3H), 2.09-2.25 (2H), 2 , 91 (311), 3.32 (ÍH), 3.80 (311), 4.94 (1H), 5.40 (1H), 5.82 (1H), 6.58 (HH), 7, 03-7.19 (211), 9.27 (1H). (-) 1 - (7,8-dif luoro-2-methylquinazolin-5-ylamino) -6-isopropyl-5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4 - trahi dronaftal en-2-ol (+) -1- (7, 8-difluoro-2-methylquinazolin-5-ylamino) -6-isopropyl-5-methoxy -4, -dimethyl-2- (trifluoromethyl) - 1, 2, 3, 4-tetrahydronaphthalen-2-ol. 80 mg of the racemic compound are separated by ether separation on a chiral column, in order to obtain both enantiomers. 38.1 mg of the (-) enantiomer and 35.5 mg of (+) enantiomer are obtained. enantiomer (-): [a] D = -38.5 ° (c = 1, CH30H); enantiomer (+): [a] D = + 37 ° (c = 1, CH30H) 5- (7, 8 -difluoro-2-methyl-tyzolin-5-ylamino) -2-isopropyl -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 100 mg (0.196 mmol) of 1- (7,8-difluoro-2-methylquinazolin-5-ylamino) -6-isopropyl- are processed. 5-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaf-alen-2-ol with BBr 3 in dichloromethane, as has already been described on several occasions. After processing and carrying out chromatography, 33 mg (33.9%) of the desired phenol are obtained. XH-NMR (300 MHz, CD30D): d = 1.05-1.30 (6 H), 1.63 (3H), 1.74 (3H), 2.12 (2H), 2.83 (3H) ), 3.26 (ÍH), 5.38 (1H), 6.73-6.90 (2H), 7.03 (1H), 9.59 (HH). (-) -5- (7,8-difluoro-2-methyl-quinazolin-5-ylamino) -2-isopropyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen 1,6-diol (+) - 5 - (7,8-difluoro-2-methylquinzol-5-ylamino) -2-, isopropyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7 , 8-te trahidronaf "talen-1, 6-diol The pure ether of enantiomers previously described in the pure phenol of enantiomers is converted, as described for the racemate, from 29.7 mg of ether (enantiomer (-) ), 6.6 mg (22.9%) of phenol are obtained.From 27.1 mg of ether (enantiomer (+)), 10.7 mg (40.6%) of phenol are isolated. 5- (8-Fluoro-2-methylquinazolin-5-ylamino) -2-isopropyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaf-alen-1,6-diol 1, 1, 1-tri-fluoro-2- [(8-fluoro-2-methyl-tyzolin-5-ylimino) -methyl] -4 - (3-isopropyl-2-methoxy-phenyl) -4-methyl-pentan-2-ol 150 mg (0.451 mmol) of the aldehyde described in Example 162 are converted to 79.9 mg (0.451 mmol) of 8-fluoro-2-methylquinazolin-5-ylamine in xylene, with the aid of titanium-IV isopropylate. After carrying out the usual processing using conventional means, 176 mg (79.3%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 0.82 (3H), 1.20 (3H), 1.45 (3H), 1.62 (3H), 2.25 (1H), 3.00 (3H), 3.20 (ÍH), 3.63 (1H), 3.83 (3H), 4.69 (ÍH), 6.20 (1H), 6.47 (ÍH), 6.70 (ÍH), 6.98 (ÍH), 7.28-7.40 ( 2H), 9.48 (ÍH). 1- (8-Fluoro-2-methyl-tyzolin-5-ylamino) -6-isopropyl-5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2-ol cyclan 176 mg (0.358 mmol) of the imine described above with 1.1 ml of titanium-IV chloride in dichloromethane. After proceeding as described in example 162 and carrying out chromatography, 147.3 mg (83.6%) of the desired compound are isolated. aH-NMR (300 MHz, CDC13): d = 1.10-1.35 (6 H), 1.60 (3H), 1.75 (3H), 2.05-2.25 (2H), 2.93 (3H), 3.33 (1H), 3.80 (3H), 4.88 (ÍH), 5.02 (HH), 5.52 (ÍH), 6.70 (1H), 7.00-7.18 (2H), 7.49 (1H), 9.35 (HH). 5- (8-f luoro-2-methylquinazolin-5-ylamino) -2-isopropyl-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-1,6-diol 50 mg (0.102 mmol) of 1- (8-fluoro-2-methylquinazolin-5-ylamino) -6-isopropyl-5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1, 2, 3 are processed. , 4-tetrahydronaphthalen-2-ol with BBr3 in dichloromethane, as has already been described on several occasions. After continuing the process and carrying out a chromatography, 13.7 mg (28.2%) of the desired phenol are obtained. XH-NMR (300 MHz, CD3OD): d = 1.05-1.30 (6 H), 1.65 (3H), 1.76 (3H), 2.00-2.20 (2H), 2 , 88 (3H), 3.27 (ÍH), 5.25 (ÍH), 6.77-6.94 (2H), 7.00 (ÍH), 7.59 (ÍH), 9.68 (ÍH) ). Example 167 4- (2,5-dihydroxy-6-isopropyl-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydro-naphthalene-1-ylamino) -1, 3-dihydro- indole -2 -one 4 - [2-hydroxy-4- (3-isopropyl-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentylideneamino] -1,3-dihydro-indole-2 -one and processing 250 mg (0.903 mmol) of the 2-hydroxy-4- (3-isopropyl-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -pentanal described in Example 162 with 4-amino-1, 3- dihydro-indole-2-one, as described in the previous example. After chromatography, 334.9 mg (92.2%) of the desired imine are isolated. ? -NMR (300 MHz, CDC13): d = 0.99 (3H), 1.25 (3H), 1.46 (3H), 1.54 (3H), 2.20 (1H), 3.27 (ÍH), 3.42 (2H), 3.49 (ÍH), 3.84 (3H), 4.79 (1H), 5.90 (HH), 6.68-6.82 (2H), 6.90-7.09 (3H), 8.28 (1H). 4- (2-Hydroxy-6-isopropyl-5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydro-naphthalen-1-ylamino) -1,3-dihydroxy- indol-2-one 230 mg (0.497 mmol) of the described imine are cyclized with titanium-IV chloride in dichloromethane, as described in example 162. After processing and chromatography, 208.3 mg (90 mg) are obtained. , 5%) of the desired cyclic compound. XH-NMR (300 MHz, CD30D): d = 1.10-1.30 (6 H), 1.51 (3H), 1.66 (3H), 1.96-2.16 (2H), 3 , 38 (3H, under the methanol signal), 3.79 (3H), 5.03 (HH), 6.33 (ÍH), 6.49 (ÍH), 7.00-7.20 (3H) . 4- (2,5-dihydroxy-6-isopropyl-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-1-ylamino) -1,3-dihydro-indol-2-one 50 mg (0.108 mmol) of the ether previously described are processed with a solution of BBr3 in dichloromethane. After processing as previously described and performing a chromatography, 35.6 mg (73.4%) of the desired compound are obtained. XH-NMR (300 MHz, CD3OD): d = 1.10-1.30 (6 H), 1.61 (3H), 1.70 (3H), 1.95-2.18 (2H), 3.27 (ÍH), 3.38 (2H, liegen unter dem Metanolsignal), 5.01 (1H), 6, 33 (1H), 6.49 (ÍH), 6.89 (ÍH), 6.95-7.15 (2H). The following compounds are synthesized analogously to the corresponding aldehydes and amines. Example 168 cis-6-chloro-l- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-5-methoxy-2- (trifluoromethyl) -1,2,3 , 4-tetrahydronaphthalen-2-ol XH-NMR (300 MHz, CDC13); d = 1.58 (s, 3H), 1.72 (s, 3H), 2.14 (d, ÍH), 2.22 (d, ÍH), 2.92 (s, 3H), 3.97 (s, 3H), 4.91 (d, ÍH), 5.83 (d, ÍH), 6.55 (dd, ÍH), 7.03 (d, ÍH), 7.23 (d, ÍH) , 9.24 (s, ÍH). Example 169 cis-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -7-ethoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol XH-NMR ( 300 MHz, CDC13); d = 2.24-2.34 (m, 2H), 2.86 (ddd, 1H), 2.91 (s, 3H), 3.12 (ddd, 1H), 3.63 (s, 3H) , 5.00 (d, 1H), 5.47 (d, 1H), 6.75 (dd, ÍH), 6.79 (d, 1H), 6.84 (s, ÍH), 7.11 ( d, 1H), 7.49 (dd, 1H), 9.35 (s, ÍH). Example 170 cis-6-chloro-l- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4- tetrahydronaf talen-2,5-diol XH-NMR (300 MHz, CD3OD); d = 1.60 (s, 3H), 1.72 (s, 3H), 2.16 (s, 2H), 2.84 (s, 3H), 5.30 (s, ÍH), 6.84 (d, 1H), 6.86 (dd, ÍH), 7.17 (d, ÍH), 9.60 (s, ÍH). Example 171 cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -6-f luoro-4,4-dimethyl-2- (trifluoromethyl) "1, 2,3,4 -tetrahydronaf talen- 2, 5 -diol XH-NMR (300 MHz, CD3OD), d = 1.61 (s, 3H), 1.72 (s, 3H), 2.14 (s, 2H), 2, 84 (s, 3H), 3.98 (s, 3H), 5.27 (s, ÍH), 6.76-6.94 (m, 3H), 9.59 (s, ÍH) Example 172 cis -1- [(8-f-luoro-2-methylquinazolin-5-yl) amino] -2- (trifluoromethyl) -1,2,3,4-tetrahydro-tahlen-2-diol XH-NMR (300 MHz, CD3OD); d = 2.16-2.35 (m, 2H), 2.81 (ddd, 1H), 2.85 (s, 3H), 3.08 (ddd, 1H), 5.24 (s, 1H) , 6.67 (dd, ÍH), 6.78 (d, 1H), 6.89 (dd, ÍH), 7.02 (d, 1H), 7.59 (dd, ÍH), 9.67 ( Yes H) .

Example 173 2-Hydroxy-3- (1-phenvlcyclohexyl) -2- (trifluoromethyl) propanal 12.6 g (45.9 mmol) of ethyl 2-oxo-3- (l-phenylcyclohexyl) -propionate are cooled (WO. 9854159) and 19.9 ml (138 mmol) of (trifluoromethyl) -trimethylsilane in 215 ml of THF at -70 ° C is mixed with 8.6 ml of a 1 molar solution of tetrabutylammonium fluoride in THF. The reaction mixture is allowed to warm for 18 hours at room temperature and then poured into a saturated solution of sodium chloride. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 20%), 13.1 g of ethyl 2-hydroxy-3- (1-phenylcyclohexyl) -2- (trifluoromethyl) -propionate are obtained as an oil yellow.

To 13.1 g (38.1 mmol) of ester in 174 ml of THF, a solution of 3.33 g (87.7 mmol) of lithium aluminum hydride in 173 ml of sodium chloride is added dropwise at 0 ° C. THF, and stirred for 16 hours at room temperature. Carefully add 20 ml of saturated ammonium chloride solution to the preparation at 0 ° C, and stir thoroughly for 15 minutes. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 0% -33%), 6.1 g of 3- (1-phenyl) -cyclohexyl) -2- (trifluoromethyl) -propan-1 are obtained, 2-diol. To 6.1 g (20.2 mmol) of diol in 245 ml of dichloromethane and 79 ml of DMSO, 15.7 ml (113 mmol) of triethylamine and 13.8 g (87 mmol) of pyridine complex are added and S03, in portions for 10 minutes. It is stirred for 3 hours and a saturated solution of ammonium chloride is added. The mixture is stirred for another 15 minutes, the phases are separated and extracted with dichloromethane. It is washed with water and dried with sodium sulfate. The solvent is removed in vacuo and, after purification by chromatography on silica gel (hexane / ethyl acetate, 0-33%), the desired product is obtained quantitatively. 2H-NMR (CDC13): d = 1.17-1.78 (m, 9H), 1.98-2.05 (m, HH), 2.41 (d, 1H), 3.46 (d, ÍH), 3.66 (s, 1H), 7.18 (d, 2H), 7.24 (t, 2H), 7.31 (d, ÍH), 8.55 (s, 1H). cis-4 '- [(8-fluoro-2-methylquinazolin-5-yl) amino] -3', 4 '-dihydro-3' - (trifluoromethyl) -spiro [cyclohexane-1,1 '(2'H) -naphthalene] -3 '-ol XH-NMR (300 MHz, CDC13); d = 1.25-1.85 (m, 9H), 1.97 (d, HH), 2.11 (d, 1H), 2.68 (d, HH), 2.91 (s, 3H) , 5.08 (d, ÍH), 5.38 (d, 1H), 6.69 (dd, 1H), 7.18 (t, 1H), 7.34 (d, 1H), 7.35 ( t, 1H), 7.47 (dd, ÍH), 7.56 (d, ÍH), 9.36 (s, ÍH). Example 174 cis-4 '- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -3,4'-dihydro-3' - (trifluoromethyl) -spiro [cyclohexane-1,1 '(2 'H) -naphthalene] -3' -ol XH-NMR (300 MHz, CDC13); d = 1.25-1.90 (m, 9H), 1.93 (d, HH), 2.02 (d, 1H), 2.64 (d, HH), 2.89 (s, 3H) , 4.99 (d, ÍH), 5.66 (d, 1H), 6.54 (dd, 1H), 7.18 (t, ÍH), 7.29 (d, ÍH), 7.36 ( t, 1H), 7.54 (d, ÍH), 9.25 (s, 1H). Example 175 cis-1- (1,8-difluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2, 5-diol XH-NMR (300 MHz, CD30D); d = 1.58 (s, 3H), 1.70 (s, 3H), 2.13 (s, 2H), 2.84 (s, 3H), 5.28 (s, ÍH), 6.71 -6.87 (m, 3H), 6.99 (t, ÍH), 9.59 (s, ÍH). Example 176 trans-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -6-f luoro-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4 -tetrahydronaf talen-2, 5-diol XH-NMR (300 MHz, CDC13); d = 1.40 (s, 3H), 1.54 (s, 3H), 2.05 (d, ÍH), 2.19 (d, ÍH), 2.76 (s, 3H), 3.57 (br, 1H), 4.62 (d, 1H), 5.27 (d, ÍH), 6.54 (br, ÍH), 6.90-6.97 (, 2H), 7.07 (dd) , 1H), 9.10 (s, ÍH). Example 177 cis-5-. { 3 ', 4' -dihydro-3 '-hydroxy-3' - (trifluoromethyl) -spiro [cyclohexan-1, 1 '(2'H) -naph talen-4'-yl] amino} - quinolin -2 (ÍH) -one? -NMR (300 MHz, CD3OD); d = 0.91 (m, HH), 1.12 (m, 3H), 1.89 (d, HH), 2.44 (d, 1H), 5.29 (s, HH), 6.51 (d, HH), 6.67 (d, 1H), 6.71 (d, HH), 6.79 (d, HH), 7.09 (t, HH), 7.21 (t, HH) , 7.24 (d, ÍH), 7.39 (t, ÍH), 8.24 (d, 1H). Example 178 cis-4 '- [(8-fluoro-2-methylquinazolin-5-yl) amino] -3,4'-dihydro-3'- (trifluoromethyl) -spiro [cyclopropan-1,1' (2'H ) -naphthalene] -3 '-ol XH-NMR (300 MHz, CD30D); d = 0.92-0.98 (m, 1H), 1.13-1.19 (m, 3H), 1.98 (d, HH), 2.40 (d, HH), 2.85 ( s, 3H), 5.36 (s, ÍH), 6.81 (d, ÍH), 6.91 (dd, ÍH), 7.10 (t, 1H), 7.23 (t, ÍH), 7.28 (d, ÍH), 7.59 (dd, ÍH), 9.68 (s, 1H). Example 179 cis-6-chloro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (pentafluoroethyl) -1,2,3,4-tetrahydronaphthalene-2 , 5-diol 4 - (3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (tri-f-luoethyl) -pentanal 1.0 g (3.35 mmol) of 4- (3 ethyl-2-chloro-2-methoxyphenyl) -4-methyl-2-oxovalelate and 0.96 (5.0 mmol) of (pentafluoroethyl) -trimethylsilane in 7 ml of THF with 62 mg (0.67 mmol) of tetramethylammonium at -40 ° C. It is stirred for 2 hours at -25 ° C, then 1 ml of IN hydrochloric acid is added to the reaction mixture and after 10 minutes it is poured into water. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. 1.44 g of 4- (3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) -valerate are obtained from ethyl, which are mixed in 14.5 ml of diethyl ether at 0 °. C with 0.22 g (5.9 mmol) of lithium aluminum hydride, and stir for 2 hours at room temperature. The preparation is poured into ice water and stirred thoroughly for 15 minutes. It is filtered through Celite, extracted several times with diethyl ether, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 0% -20%), 0.77 g of 4- (3-chloro-2-methoxyphenyl) -2- (pentafluoroethyl) -4-methyl are obtained -propan-1,2-diol. To 0.46 g (1.22 mmol) of diol in 9.5 ml of dichloromethane and 2.5 ml of DMSO, 0.84 ml (6.1 mmol) of triethylamine and 388 mg (2.44 mmol) are added. ) of pyridine complex and S03. It is stirred for 2 hours and another 388 mg (2.44 mmol) of pyridine complex and S03 are metered in. After stirring for 1 hour, a saturated solution of ammonium chloride is added. The mixture is stirred for another 15 minutes, the phases are separated and extracted with diethyl ether. It is washed with a saturated solution of ammonium chloride and dried with sodium sulfate. The solvent is removed under vacuum and. After purification by chromatography on silica gel (hexane / ethyl acetate, 30%), 357 g of product are obtained. XH-NMR (CDC13), d = 1.43 (s, 3H), 1.48 (s, 3H), 2.34 (d, ÍH), 3.29 (d, ÍH), 3.58 (s) , ÍH), 4.01 (s, 3H), 6.95 (t, HH), 7.05 (dd, 1H), 7.30 (dd, 1H), 9.10 (s, HH). cis-6-chloro-l - [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -4,4-dimethyl-2- (pentaf-luoroethyl) -1, 2, 3, 4-tetrahydronaf-talen-2 , 5-XH-NMR -diol (300 MHZ, CD3OD); d = 1.61 (s, 3H), 1.74 (s, 3H), 2.14 (d, 1H), 2.20 (d, ÍH), 2.86 (s, 3H), 5.34 (s, 1H), 6.84. (d, 1H), 6.86 (dd, ÍH), 7.12 (d, ÍH), 7.57 (dd, 1H), 9.65 (s, ÍH). Example 180 cis-6-chloro-l- [(7-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (pentafluoroethyl) -1, 2, 3, 4-tetrahydronaf ale 2,5-diol XH-NMR (300 MHz, CDC13); d = 1.58 (s, 3H), 1.72 (s, 3H), 2.17 (d, ÍH), 2.26 (d, 1H), 2.84 (s, 3H), 3.95 (s, 3H), 5.05 (d, ÍH), 6.07 (d, ÍH), 6.51 (dd, 1H), 6.91 (dd, 1H), 7.04 (d, ÍH) , 7.18 (d, 1H), 9.17 (s, ÍH). EXAMPLE 181 trans -6-chloro-1- [(7-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (pentafluoroethyl) -1,2,3,4-tetrahydronaphthalene-2 , 5-diol XH-NMR (300 MHz, CD3OD); d = 1.45 (s, 3H), 1.61 (s, 3H), 2.29 (d, ÍH), 2.37 (d, ÍH), 2.74 (s, 3H), 3.65 (s, 3H), 5.58 (s, ÍH), 6, 83 (dd, ÍH), 6.98 (dd, ÍH), 7.30 (dd, 1H), 7.42 (d, ÍH), 9.52 (s, 1H). Example 182 cis-5-. { [6-chloro-2-hydroxy-5-methoxy-4,4-dimethyl-2- (pentafluoroethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} - quinolin-2 (1H) -one XH-NMR (300 MHz, CDC13); d = 1.55 (s, 3H), 1.72 (s, 3H), 2.07 (d, ÍH), 2.20 (d, 1H), 3.96 (s, 3H), 5.12 (d, ÍH), 5.46 (br, ÍH), 5.81 (d, ÍH), 6.44-6.53 (m, 3H), 6.95 (d, ÍH), 7.06 ( d, HH), 7.32 (t, 1H), 8.28 (d, HH), 9.92 (s, 1H). Example 183 cis-5-. { [2,5-dihydroxy-4,4-dimethyl-2- (pentafluoroethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one XH-NMR (300 MHz, CDC13); d = 1.58 (s, 3H), 1.76 (s, 3H), 2.08 (d, 1H), 2.24 (d, ÍH), 2.63 (s, ÍH), 5.11 (d, ÍH), 5.54 (s, ÍH), 5.85 (d, 1H), 5.97 (s, 1H), 6.42 (d, ÍH), 6.49 (d, 1H) , 6.49 (d, ÍH), 6.52 (d, ÍH), 7.00 (dd, ÍH), 7.31 (t, ÍH), 8.31 (d, 1H), 9.77 ( s, 1H). EXAMPLE 184 cis-7 '-fluoro-4' - [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -3 ', 4' -dihydro-8 '-methoxy-3' - (trifluoromethyl) -spiro [cyclohexan-1, 1 '(2'H) -naphthalene] -3' -ol 3 - [1 - (3-f luoro-2-methyl-phenyl) -cyclohexyl] -2-hydroxy-2- (trifluoromethyl) 1) 26.5 g (184 mmol) of 2,6-difluoroanisole and 24 ml (198 mmol) of cyclohexyl cyanide in 500 ml of toluene are added dropwise to 385 ml of a 0.5 molar solution (182 g). mmol) of potassium bis- (trimethylsilyl) -amide in toluene, at 0 ° C for 40 minutes. Stir 18 hours at room temperature, mix in an ice bath with water and bring the solution with 4 N hydrochloric acid until pH. The organic phase is separated and the aqueous phase is extracted several times with diethyl ether. Wash with saline, dry with sodium sulfate and concentrate in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 5% -10%), 28.5 g of 1- (3-fluoro-2-methoxyphenyl) -cyclohexyl nitrile are obtained. 27.5 g (118 mmol) of nitrile are slowly mixed in 430 ml of toluene at -78 ° C with 147 ml (176 mmol) of a solution of diisobutylaluminum hydride (20% in toulol), and added dropwise. ml of isopropanol, after 3 hours at -78 ° C. Allow to warm to -5 ° C and add 600 ml of a 10% aqueous solution of tartaric acid. After diluting with ether, stirring thoroughly, the organic phase is separated and the aqueous phase is extracted several times with ethyl acetate. Wash with saline, dry with sodium sulfate and concentrate in vacuo. 27.5 g of aldehyde are obtained as a yellow oil. A solution of 5.7 g (21.2 mmol) of 2-diethylphosphono-2-ethoxyacetic acid ethyl ester in 25 ml of tetrahydrofuran is mixed in an ice bath with 13.6 ml (27.2 mmol) of a 2 M solution of lithium diisopropylamide in tetrahydrofuran-heptane-toluene for 15 minutes, and stir 20 minutes at 0 ° C. For 30 minutes, a solution of 5 g (21.2 mmol) of 1- (3-fluoro-2-methoxyphenyl) -cyclohexylformanal in 5 ml of tetrahydrofuran at 0 ° C is added dropwise. After 16 hours at room temperature, ice water is added and extracted several times with ether. It is washed with a saturated solution of ammonium chloride, dried over sodium sulfate and concentrated. The crude product is saponified with 6 g of sodium hydroxide in 100 ml of ethanol and 50 ml of water for 4 days at room temperature. 1.7 g of acid are obtained, which is stirred with 35 ml of 2 N sulfuric acid and 7 ml of acetic acid at 90 ° C for 30 hours. After cooling, basify with potassium carbonate, wash with ether and acidify with hydrochloric acid. After extracting with ethyl acetate, washing with a saturated solution of sodium chloride and removing the solvent, 1.09 g of the crude keto acid are obtained. 1.09 g (3.7 mmol) of 3- [1- (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2-oxopropionic acid and 0.45 ml of sulfuric acid (96% strength) are heated to reflux. in 40 ml of ethanol for 2 hours. The preparation is concentrated in vacuo, the residue is placed in ice water and basified with a saturated solution of sodium bicarbonate. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried (sodium sulfate) and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 20%), 1.05 g of ethyl 3- [1- (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2-oxopropionate are obtained. 1.05 g (3.3 mmol) of ethyl 3- [1- (3-fluoro-2-methoxyphenyl) -cyclohexyl] -2-oxopropionate and 0.74 ml (5 mmol) of (trifluoromethyl) - are mixed. trimethylsilane in 7 ml of THF with 62 mg tetramethylammonium fluoride at -40 ° C. Stir 2 hours at -25 aC and add another 0.35 ml (2.4 mmol) of (trifluoromethyl) -trimethylsilane and 62 mg of tetramethylammonium fluoride. After another 2 hours, add 1 ml of 2 N hydrochloric acid and pour the reaction mixture into water. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 10% -40%), 800 mg of 3- [1- (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2-hydroxy- are obtained. 2- (trifluoromethyl) -propionate ethyl as a yellow oil. This oil is mixed in 40 ml of diethyl ether at 0 ° C with 150 g (4 mmol) of lithium aluminum hydride and stirred for another 2.5 hours at room temperature. 20 ml of saturated ammonium chloride solution is carefully added to the preparation at 0 ° C, and then thoroughly stirred for 15 minutes. It is extracted several times with diethyl ether, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 10% -15%), 630 g of 3- [1- (3-fluoro-2-methoxy-phenyl) -cyclopropyl] -2- (trifluoromethyl) are obtained ) -propan-1,2-diol. XH-NMR (CDC13): d = 1.44-1.87 (m, 10H), 2.19-2.38 (m, 4H), 3.15-3.42 (br, 2H), 3, 96 (s, 3H), 6.9 (ddd, ÍH), 7.01 (d, 1H), 7.16 (ddd, ÍH).

To 700 mg (2 mmol) of diol in 20 ml of dichloromethane and 7.8 ml of DMSO, 1.6 ml (11 mmol) of triethylamine and 1.4 g (70 mmol) of pyridine complex and S03 are added, in portions for 10 minutes. It is stirred for 3 hours and a saturated solution of ammonium chloride is added. The mixture is stirred for another 15 minutes, the phases are separated and extracted with dichloromethane. It is washed with water and dried with sodium sulfate. The solvent is removed in vacuo and the desired aldehyde is obtained quantitatively. cis -7'-fluoro-4- [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -3,4-dihydro-8-methoxy-3 - (trifluoromethyl) -spiro [cyclohexan-1, 1 ' (2 'H) -naphthalene] -3-ol XH-NMR (300 MHz, CDC13); d = 1.25-1.85 (m, 8H), 2.00 (d, HH), 2.44 (ddd, HH), 2.64 (ddd, 1H), 2.91 (s, 3H), 2.92 (d, HH), 4.00 (s, 3H) , 4.96 (d, ÍH), 5.41 (d, ÍH), 6.66 (dd, ÍH), 6,93 (dd, ÍH), 7,04 (dd, ÍH), 7,47 (dd, ÍH), 9,34 (s, 1 HOUR) . Example 185 cis-7 '-fluoro-4' - [(8-fluoro-2-methylquinazolxn-5-yl) amino] -3 ', 4' -dihydro-3 '- (trifluoromethyl) -spiro [cyclohexan-1, 1 '(2'H) -naphthalene] -3', 8'-diol XH-NMR (300 MHz, CD30D); d = 1.22-1.85 (m, 8H), 2.03 (d, 1H), 2.82 (ddd, 1H), 2.85 (s, 3H), 2.91 (d, 1H) , 3.05 (ddd, ÍH), 5.22 (s, ÍH), 680-6.95 (m, 3H), 7.56 (dd, ÍH), 9.65 (s, ÍH). Example 186 cis-7 '-fluoro-4' - [(7-fluoro-2-methylquinazolin-5-yl) amino] -3 ', 4' -dihydro-8 '-methoxy-3' - (trifluoromethyl) -spiro [cyclohexan-1, 1 '(2'H) -naph alen] -3' -ol XH-NMR (300 MHz, CDC13); d = 1.25-1.90 (m, 10H), 2.17 (d, 1H), 2.34 (d, 1H), 2.80 (s, 3H), 3.56 (s, 3H) , 4.59 (d, 1H), 5.33 (d, 1H), 6.91 (dd, 1H), 7.00 (dd, ÍH), 7.10 (dd, ÍH), 7.17 (d, dd, 1H), 9.03 (s, ÍH). Example 187 cis-5- [7'-Fluoro-3 ', 4'-dihydro-3'-hydroxy-8' -methoxy-3 '- (trifluoromethyl) -spiro [cyclohexane-1, 1? (2'H) -naphthalen-4 '-yl] amino] -quinolin-2 (1H) -one XH-NMR (300 MHz, CDC13); d = 1.25-1.90 (m, 8H), 2.09 (d, ÍH), 2.41 (ddd, ÍH), 2.60 (ddd, ÍH), 2.90 (d, ÍH), 3.99 (S, 3H), 4.85 (s, ÍH), 5.00 (d, ÍH), 5.67 (d, ÍH), 6.48-6.55 (m, 3H), 6.83 ( dd, ÍH), 6.96 (dd, ÍH), 7.31 (t, 1H), 8.22 (d, l H), 9.79 (s, ÍH). Example 188 cis-6-chloro-l- [(7-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (pentafluoroethyl) -1,2,3,4-tetrahydronaphthalene-2 , 5-diol XH-NMR (300 MHz, CD3OD); d = 1.61 (s, 3H), 1.74 (s, 3H), 2.18 (s, 2H), 2.79 (s, 3H), 5.42 (s, 1H), 6.76 -6.82 (m, 3H), 7.15 (d, ÍH), 9.54 (s, ÍH). Example 189 cis-6-chloro-l- [(2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (pentafluoroethyl) -1, 2, 3, 4-tetrahydronaf-alen-2, 5- diol XH-NMR (300 MHz, CD3OD); d = 1.61 (s, 3H), 1.74 (s, 3H), 2.18 (s, 2H), 2.82 (s, 3H), 5.40 (s, ÍH), 6.84 (d, ÍH), 6.95 (d, ÍH), 7.10 (d, ÍH), 7.20 (d, ÍH), 7.79 (t, ÍH), 9.62 (s, ÍH) . Example 190 cis-5-. { 7'-chloro-3,4'-dihydro-3 ', 8'-dihydroxy-3' - (trifluoromethyl) -spiro [cyclohexan-1, l? (2'H) -naphthalen-4 '-yl] -amino} -quinolin-2 (1H) -one XH-NMR (300 MHz, CD3OD); d = 1.25-1.90 (m, 8H), 2.02 (d, HH), 2.80 (ddd, HH), 2.91 (d, HH), 3.05 (ddd, 1H) , 5.12 (d, ÍH), 5.51 (d, ÍH), 6.59 (d, 1H), 6.69 (d, 1H), 6.81 (dd, ÍH), 6.986 (dd, ÍH), 7.37 (t, 1H), 8.23 (d, 1 H). Example 191 cis-6-fluoro-1- [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -5-methoxy-, 4-dimethyl-2- (pentafluoroethyl) -1,2,3,4- tetrahydronaphthalen-2-ol 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (pentaf luoroethyl) pentanal 1.0 g (3.54 mmol) of 4- (3-) are mixed. fluoro-2-methoxyphenyl) -2-oxo-4-methyl-valeriato of ethyl and 0.98 g (5.1 mmol) of (pentafluoroethyl) -trimethylsilane in 7 ml of THF with 65 mg (0.7 mmol) of tetramethylammonium fluoride at -40 ° C. The reaction mixture is warmed to -25 ° C and stirred at this temperature. After 4.5 hours, add 1 ml of 2N hydrochloric acid and pour the reaction mixture into water. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. 1.65 g of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) valerate of ethyl are obtained as crude product. The ester is mixed in 80 ml of diethyl ether at 0 ° C with 300 mg (8 mmol) of lithium aluminum hydride and stirred for another 3.5 hours at room temperature. Carefully add a small amount of water at 0 ° C to the preparation, stirring thoroughly for 15 minutes. Filter through Celite and exhaust the precipitate thoroughly with ethyl acetate. The filtrate is dried with sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / 10% ethyl acetate -15%), 800 mg of 4- (3-fluoro-2-methoxyphenyl) -4-methyl-2- (pentafluoroethyl) pentan are obtained. -1, 2-diol. To 800 mg (2.2 mmol) of diol in 25 ml of dichloromethane and 8.9 ml of DMSO, 1.8 ml (13 mmol) of triethylamine and 1.6 g (10 mmol) of pyridine complex are added and S03, in portions for 10 minutes. The mixture is stirred for 2.5 hours and saturated ammonium chloride solution is added. The mixture is stirred for another 15 minutes, the phases are separated and extracted with dichloromethane. It is washed with water and dried with sodium sulfate. The solvent is removed in vacuo and the desired aldehyde is obtained quantitatively. XH-NMR (CDC13): d = 1.40 (s, 3H), 1.46 (s, 3H), 2.35 (d, 1H), 3.28 (d, 1H), 3.60 (s) , 1H), 4.02 (s, 3H), 6.86 (dd, ÍH), 6.91 (ddd, ÍH), 7.01 (ddd, ÍH), 9.14 (s, 1H). cis -6-fluoro-1 [(8-fluoro-2-methylquinazolin-5-yl) amino] -5-methoxy -4,4-dimethyl-2- (pentaf luoroethyl) -1, 2, 3, 4-tetrahydronaf talen-2-ol XH-NMR (300 MHz, CDC13); d = 1.55 (s, 3H), 1.69 (s, 3H), 2.13 (d, 1H), 2.20 (d, ÍH), 2.92 (s, 3H), 3.97 (s, 3H), 5.08 (d, 1H), 5.41 (d, 1H), 6.70 (dd, ÍH), 6.90 (dd, ÍH), 7.00 (dd, 1H) , 7.48 (dd, ÍH), 9.33 (s, 1H). Example 192 cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -6-fluoro-5-methoxy-4, 4-dimethyl-2 - (pentafluoroethyl) -1,2,3 , 4-tetrahydronaphthalen-2-ol XH-NMR (300 MHz, CD3OD); d = 1.55 (s, 3H), 1.68 (s, 3H), 2.14 (d, ÍH), 2.21 (d, 1H), 2.84 (s, 3H), 3.97 (s, 3H), 5.39 (s, ÍH), 6.88 (dd, 1H), 6.98 (dd, ÍH), 7.03 (dd, ÍH), 9.59 (s, ÍH) . Example 193 cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-6-fluoro-2- (pentafluoroethyl) -1,2,3,4-tetrahydronaphthalene -2, 5 -diol XH-NMR (300 MHz, CDC13); d = 1.61 (s, 3H), 1.72 (s, 3H), 2.15 (d, ÍH), 2.22 (d, ÍH), 2.91 (s, 3H), 5.00 (d, ÍH), 5.61 (br, ÍH), 5.71 (d, 1H), 6.56 (dd, ÍH), 6.83 (dd, 1H), 6.92 (dd, 1H) , 9.24 (s, ÍH).

Example 194 cis-5-. { [6-fluoro-2-hydroxy-5-methoxy-4,4-dimethyl-2- (pe tafluoroethyl) -1, 2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one XH-NMR (300 MHz, CDC13); d = 1.54 (s, 3H), 1.69 (s, 3H), 2.07 (d, ÍH), 2.17 (d, ÍH), 3.97 (s, 3H), 4.58 (br, ÍH), 5.10 (d, ÍH), 5.45 (d, 1H), 6.52-6.56 (m, 3H), 6.83 (dd, ÍH), 6.94 ( dd, I H), 7.34 (t, 1H), 8.12 (d, IH), 10.11 (s, IH). Example 195 cis-6-fluoro-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (pentafluoroethyl) -1,2,3,4-tetrahydronaphthalene-2 , 5-diol XH-NMR (300 MHz, CDCl 3); d = 1.61 (s, 3H), 1.72 (s, 3H), 2.15 (d, ÍH), 2.23 (d, ÍH), 2.92 (s, 3H), 5.08 (d, 1H), 5.38 (d, 1H), 5.64 (br, ÍH), 6.70 (dd, ÍH), 6.85 (dd, 1H), 6.90 (dd, ÍH) , 7.48 (dd, 1H), 9.33 (s, ÍH). Example 196 cis-4 '- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -7' -fluoro-3 ', 4'-dihydro-8' -methoxy-3 '- (trifluoromethyl) -spiro [cyclopropan-1, 11 (2'H) -naphthalene] -3 '-ol 3 - [1 - (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2-oxopropy on to ethyl To 26 g ( 180 mmol) of 2,6-difluoroanisole and 14.6 ml (198 mmol) of cyclopropyl cyanide in 500 ml of toluene are added 396 ml of a 0.5 molar solution (198 mmol) of bis- (trimethylsilyl) -amide of potassium in toluene, at 0 ° C for 40 minutes. Stir for 18 hours at room temperature and mix in an ice bath with water and sulfuric acid. The organic phase is separated and the aqueous phase is extracted several times with ethyl acetate. Wash with saline, dry with sodium sulfate and concentrate in vacuo. After purification by chromatography on silica gel (Hexane / 10% -20% ethyl acetate), 12.7 g of 1- (3-fluoro-2-methoxyphenyl) -cyclopropylnitrile are obtained. 12.7 g (66.1 mmol) of nitrile are slowly mixed at -78 ° C with 82.7 ml (99.2 mmol) of a solution of diisobutylaluminum hydride (20% in toulol), and, after 3 hours at -78 ° C, 11.1 ml of isopropanol are added dropwise. Allow to warm to -5 ° C and add 150 ml of a 10% aqueous solution of tartaric acid. After diluting with ether, stirring thoroughly, the organic phase is separated and the aqueous phase is extracted several times with ethyl acetate. Wash with saline, dry with sodium sulfate and concentrate in vacuo. 11.8 g of aldehyde are obtained as a yellow oil. A solution of 16.3 g (60.7 mmol) of 2-diethylphosphono-2-ethoxyacetic acid ethyl ester in 60 ml of tetrahydrofuran is mixed with 33.4 ml (66.8 mmol) of a 2M solution of diisopropylamide. lithium in tetrahydrofuran-heptane-toluene, in an ice bath for 20 minutes, and stirred for 30 minutes at 0 ° C. A solution of 11.8 g (60.7 mmol) of I in 61 ml of tetrahydrofuran is added dropwise at 0 ° C for 30 minutes. After 20 hours at room temperature, ice water is added and extracted several times with ether and ethyl acetate. It is washed with a saturated solution of ammonium chloride, dried over sodium sulfate and concentrated. The crude product is saponified with 170 ml of 2N sodium hydroxide in 170 ml of ethanol, for 15 hours at room temperature. 13.9 g of acid are obtained, which is stirred with 87 ml of 2N sulfuric acid at 90 ° C for 16 hours. After cooling, basify with potassium carbonate, wash with ether and acidify with hydrochloric acid. After extracting with ethyl acetate, washing with a saturated solution of sodium chloride and removing the solvent, 10.2 g of the crude keto acid are isolated. 10.2 g (40.6 mmol) of 3- [1- (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2-oxopropionic acid and 4.5 ml (85.3 mmol) of acid are heated to reflux. sulfuric (96%) in 200 ml of ethanol for 1 hour. The preparation is concentrated in vacuo, the residue is poured into ice water and basified with a saturated solution of sodium bicarbonate. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried (sodium sulfate) and concentrated in vacuo. After purification by chromatography on silica gel (hexane / ethyl acetate 20%), 9.6 g of ethyl 3- [1- (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2-oxopropionate are obtained. XH-NMR (CDC13): d = 0.90 (m, 4H), 1.29 (t, 3H), 3.09 (s, 2H), 3.99 (d, 3H), 4.20 (q, 2H), 6.87 (ddd, 1H), 6.95 (ddd, ÍH), 7.07 (d, ÍH) , 9.26. 3 - [1 - (3-f uoro -2-methoxyphenyl) -cyclopropyl] -2-hydroxy-2- (trifluoromethyl) propanal 9.6 g (34.3 mmol) of 3- [1- (3 ethyl fluoride-2-methoxyphenyl) -cyclopropyl] -2-oxopropionate and 34.5 ml (233 mmol) of (trifluoromethyl) -trimethylsilane in 343 ml of DMF with 46.9 g of cesium carbonate at 0 ° C. It is stirred for 2 hours at 0 ° C and then the reaction mixture is poured into water. It is extracted several times with ethyl acetate, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / 10% -40% ethyl acetate), 10.4 g of 3- [1- (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2- are obtained. ethyl hydroxy-2- (trifluoromethyl) -propionate as a yellow oil. This oil is mixed in 297 ml of diethyl ether at 0 ° C with 2.25 g (59.4 mmol) of lithium aluminum hydride and stirred at room temperature for a further 1 hour. 20 ml of saturated ammonium chloride solution at 0 ° C are carefully added to the preparation and stirred thoroughly for 15 minutes. It is extracted several times with diethyl ether, washed with a saturated solution of sodium chloride, dried over sodium sulfate and concentrated in vacuo. After purification by chromatography on silica gel (hexane / 10% -50% ethyl acetate), 5.6 g of 3- [1- (3-fluoro-2-methoxyphenyl) -cyclopropyl] -2- are obtained. (trifluoromethyl) -propan-1,2-diol. To 5.6 g (18.1 mmol) of diol in 100 ml of dichloromethane and 61 ml of DMSO, 12.4 ml (89 mmol) of triethylamine and 11 g (70 mmol ') of pyridine complex / S03 are added. , in portions for 10 minutes. Stir for 3 hours and add saturated ammonium chloride solution. The mixture is stirred for another 15 minutes, the phases are separated and extracted with dichloromethane. It is washed with water and dried with sodium sulfite. The solvent is removed in vacuo and, after purification by chromatography on silica gel (hexane / ethyl acetate, 0-50%), 5.9 g of product are obtained. XH-NMR (CDC13): d = 0.68-0.76 (m, 2H), 0.90-1.02 (m, 2H), 2.03 (d, ÍH), 2.91 (d, 1H), 3.85 (s, 1H), 4.03 (s, 3H), 6.80 (d, ÍH), 6.87 (ddd, ÍH), 6.98 (dd, 1H), 9, 26 (s, 1H). cis-4- [(7,8-dif'-luoro-2-methyl-tyzolin-5-yl) amino] -7'-fluoro-3,4-dihydro-8-methoxy-3 '- (trifluoromethyl) -spiro [cyclopropan] -1, 1 x (2?) -naphthalen] -3 '-ol XH-NMR (300 MHz, CD3OD); d = 0.83 (ddd, HH), 0.99 (ddd, HH), 1.42 (ddd, HH), 1.89 (ddd, HH), 2.01 (d, HH), 2.15 (d, ÍH), 2.84 (s, 3H), 3.85 (s, 3H), 5.19 (s, 1H), 6.65 (dd, 1H), 6.96 (dd, 1H) , 7.04 (dd, 1H), 9.63 (s, ÍH). Example 197 cis-7 '-fluoro-3', 4 '-dihydro-8' -methoxy-4 '- [(2-methylquinazolin-5-yl) amino] -3' - (trifluoromethyl) -spiro [ciciopropan-1 , 1 ? (2'H) -naphthalene] -3 '-ol a H-NMR (300 MHz, CDCl 3); d = 0.82 (ddd, HH), 1.00 (ddd, 1H), 1.54 (ddd, HH), 1.86 (ddd, HH), 1.91 (d, 1H), 2.32 (d, 1H), 2.84 (s, 3H), 3.87 (s, 3H), 5.08 (d, ÍH), 5.78 (d, ÍH), 6.67 (d, ÍH) , 6.88 (dd, ÍH), 7.05 (dd, 1H), 7.28 (d, ÍH), 7.70 (t, ÍH), 9.36 (s, ÍH). Example 198 cis-7 '-fluoro-3', 4 '-dihydro-4' - [(2-methylquinazolin-5-yl) amino] -3 '- (trifluoromethyl) -spiro [cyclopropan-1,1' (2 'H) -naphthalene] -3', 8 '-diol XH-NMR (300 MHz, CD3OD); d = 0.67 (ddd, HH), 0.90 (ddd, HH), 1.77 (ddd, HH), 1.93 (d, HH), 2.12 (ddd, HH), 2.21 (d, ÍH), 2.81 (s, 3H), 5.28 (s, ÍH), 6.75-6.88 (m, 3H), 7.18 (d, ÍH), 7.78 ( t, ÍH), 9.65 (s, 1H). Example 199 cis-4 '- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -7' -fluoro-3 ', 4' -dihydro-3 '- (trifluoromethyl) -spiro [cyclopropan] -1,1 '(2'H) -naphthalene] -3', 8'-diol XH-NMR (300 MHz, CDC13); d = 0.71 (ddd, 1H), 0.91 (ddd, 1H), 1.81 (d, 1H), 1.83-2.00 (m, 2H), 2.39 (d, 1H) , 2.87 (s, 3H), 4.98 (d, 1H), 5.75 (d, 1H), 6.49 (dd, ÍH), 6.78-6.89 (m, 2H), 9.28 (s, ÍH). Example 200 cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -5-fluoro-6-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3 , 4-tetrahydronaphthalen-2-ol XH-NMR (300 MHz, CD3OD); d = 1.53 (s, 3H), 1.65 (s, 3H), 2.17 (s, 2H), 2.84 (s, 3H), 3.85 (s, 3H), 5.32 (s, ÍH), 6.87 (dd, ÍH), 6.95 (dd, ÍH), 7.07 (d, 1H), 9.61 (s, ÍH). Example 201 cis-1- [(7,8-difluoro-2-methylquinazolin-5-yl) amino] -5-fluoro-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene- 2,6-diol XH-NMR (300 MHz, CD3OD); d = 1.54 (s, 3H), 1.66 (s, 3H), 2.16 (S, 2H), 2.84 (s, 3H), 3.98 (s, 3H), 5.29 (s, 1H), 6.78 (dd, ÍH), 6.86 (dd, ÍH), 6.94 (dd, ÍH), 9.60 (s, 1H). Example 202 cis-7 '-fluoro-4' - [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -3 ', 4' -dihydro-3 '- (trifluoromethyl) -espiro [cyclopropan-1, 1 '(2'H) -naphthalene] -3', 8'-diol XH-NMR (300 MHz, CDC13); d = 0.71 (ddd, HH), 0.93 (ddd, 1H), 1.79 (d, HH), 1.90-2.06 (m, 2H), 2.39 (d, HH) , 2.91 (s, 3H), 3.80 (br, 1H), 5.05 (d, ÍH), 5.39 (d, ÍH), 5.48 (br, ÍH), 6.65 ( dd, 1H), 6.80-6.90 (m, 2H), 7.46 (dd, 1H), 9.35 (s, 1H). Example 203 cis-7 '-f luoro-4' - [(7-f luoro-2-methylquinazolin-5-yl) amino] -3 ', 4' -dihydro-3 '(trifluoromethyl) -spiro [cyclohexan-1] , 1 '- (2'H) -naphthalene] -3', 8'-diol XH-NMR (300 MHz, CDC13); d = 1.20-2.10 (m, 10H), 2.10 (d, 1H), 2.47 (d, 1H), 2.68 (s, 3H), 4.66 (d, ÍH), 5.33 (d, ÍH), 6.91 (d, 2H) , 7.03 (dd, 1H), 7.10 (dd, 1H), 9.01 (s, 1H). EXAMPLE 204 cis-6-chloro-5-methoxy-l- [(2-methylquinolin-5-yl) amino] -4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-te rahydronaphthalen-2 -ol XH-NMR (300 MHz, CD3OD); d = 1.56 (s, 3H), 1.69 (s, 3H), 2.16 (s, 2H), 2.72 (s, 3H), 3.97 (s, 3H), 5.25 (s, ÍH); 6.82 (d, ÍH), 7,11 (d, ÍH), 7,20 (d, ÍH), 7,32 (d, ÍH), 7,36 (d, ÍH), 7,55 (t , ÍH), 8.45 (d, 1H). EXAMPLE 205 cis-6-chloro-l- [(2-methylquinolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2,5-diol XH-NMR (300 MHz, CD3OD); d = 1.61 (s, 3H), 1.73 (s, 3H), 2.12 (d, ÍH), 2.18 (d, 1H), 2.72 (s, 3H), 5.23 (s, ÍH), 6.82 (d, ÍH), 6.87 (d, 1H), 7,11 (d, ÍH), 7,31 (d, ÍH), 7,35 (d, ÍH) , 7.55 (t, ÍH), 8.45 (d, ÍH). EXAMPLE 206 N-oxide cis-1- [(2-methyl-l-quinolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2- ol XH-NMR (300 MHz, CD3OD); d = 1.44 (s, 3H), 1.58 (s, 3H), 2.19 (s, 2H), 2.76 (s, 3H), 5.35 (s, ÍH), 7.00 (dd, 1H), 7.12 (t, ÍH), 7.27-7.34 (m, 2H), 7.45-7.52 (m, 2H), 7.71 (t, ÍH), 7.96 (d, ÍH), 8.29 (d, ÍH). Example 207 N-oxide cis-6-chloro-l- [(2-methylquinolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2, 5 -diol To 84 mg (0.19 mmol). cis-6-chloro-l- [(2-methylquinolin-5-yl) amino] -4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2,5-diol in 8 ml of dichloromethane are added 75 mg 70% meta-chloroperbenzoic acid and the solution is stirred for two hours. 50 mg solid sodium bicarbonate are added and after 30 minutes it is poured into water. It is extracted with dichloromethane, washed with a saturated solution of sodium chloride and dried with sodium sulfate. After concentration and chromatography on silica gel (hexane / ethyl acetate 0-100%), 58 mg of the title compound are obtained. XH-NMR (300 MHz, CD3OD); d = 1.61 (s, 3H), 1.73 (s, 3H), 2.13 (d, 1H), 2.18 (d, 1H), 2.75 (s, 3H), 5.30 (s, ÍH), 6,85 (d, ÍH), 7,01 (d, ÍH), 7,13 (d, ÍH), 7,48 (d, ÍH), 7,70 (t, ÍH) , 7.96 (d, ÍH), 8.27 (d, ÍH). Example 208 N-oxide cis-6- [(2-methyl-quinolin-5-yl) amino] -9,9-dimethyl-7- (trifluoromethyl) -6,7,8,9-tetrahydro-naphyl-1 , 2-dH, 3-dioxol-7-ol XH-NMR (300 MHz, CDC13); d = 1.49 (s, 3H), 1.58 (s, 3H), 2.06 (d, ÍH), 2.20 (d, ÍH), 2.61 (s, 3H), 5.08 (d, 1H), 5.62 (d, 1H), 5.99 (s, 2H), 6.64 (d, 1H), 6.83 (d, 1H), 6.85 (d, 1H) , 7.13 (d, ÍH), 7.55 (t, ÍH), 7.96 (d, ÍH), 8.03 (d, 1H). Example 209 cis-7 '-fluoro-4' - [(7-fluoro-2-methylquinazolin-5-yl) amino] -3 ', 4' -dihydro-3 '- (trifluoromethyl) -spiro [cyclopropan-1, 1"(2?) -naphthalene] -3 *, 8 '-diol XH-NMR (300 MHz, CD30D), d = 0.66 (ddd, 1H), 0.89 (ddd, 1H), 1.86 (ddd, 1H), 1.93 (d, 1H), 2.10 (ddd, ÍH), 2.22 (d, 2H), 2.78 (s, 3H), 5.26 (s, ÍH) 6.67 (dd, ÍH), 6.75-6.82 (m, 2H), 6.87 (dd, ÍH), 9.58 (s, ÍH) Example 210 cis-5-. 7 '-fluoro-3' 4 '-dihydro-3', 8 '-dihydroxy-3' - (trifluoromethyl) -spiro [cyclopropan-1, 1 '(2'H) -naf talen-4' -yl] - amino.).-.quinoline-2 (1H) -one XH-NMR (300 MHz, CD3OD), d = 0.66 (ddd, 1H), 0.90 (ddd, 1H), 1.71 (ddd, 1H) ), 1.88 (d, HH), 2.09 (ddd, HH), 2.20 (d, 2H), 5.15 (s, 1H), 6.51-6.54 (m, 2H) 6.70 (d, ÍH), 6.79 (dd, ÍH), 6.85 (dd, ÍH), 7.36 (t, 1H), 8.25 (d, ÍH) Example 211 cis- 7 '-chloro-4' - [(7-f-luoro-2-methylquinazolin-5-yl) amino] -3 ', 4' -dihydro-3 '- (trifluoromethyl) -spiro [cyclopropan-1, 1' ( 2'H) -naftalen] -3 ' , 8 '-diol XH-NMR (300 MHz, CDC13); d = 0.70 (ddd, ÍH), 0.91 (ddd, ÍH), 1.70 (ddd, ÍH), 1.77 (d, ÍH), 2.08 (ddd, 1H), 2.44 (d, lH), 2.82 (s, 3H), 5, 06 (d; 1H) 5.77 (s, ÍH), 5.88 (d, lH), 6.44 (dd, ÍH), 6.88 (d, 1H), 6.91 (dd, ÍH) , 7.13 (d, ÍH), 9.23 (s, 1H). Example 212 cis-7'-chloro-3 '4' -dihydro-4 '- [(2-methylquinolin-5-yl) amino] -3' - (trifluoromethyl) -spiro [cyclopropan-1, 1"(2 ' H) -naphthalene] -3 ', 8' -diol XH-NMR (300 MHz, CD30D), d = 0.68 (ddd, 1H), 0.91 (ddd, 1H), 1.69 (ddd, 1H) ), 1.91 (d, 1H), 2.11 (ddd, HH), 2.22 (d, HH), 2.72 (s, 3H), 5.20 (s, HH), 6.70 (d, ÍH), 6.78-6.85 (m, 2H), 7.30 (d, ÍH), 7.36 (d, ÍH), 7.53 (t, ÍH), 8.47 ( d, 1H) Example 213 N-oxide cis-7'-chloro-3 ', 4'-dihydro-4' - [(2-methyl-quinolin-5-yl) amino] -3 '- (trifluoromethyl) - spiro [cyclopropan-1,1"(2 'H) -naphthalene] -3 •, 8' -diol XH-NMR (300 MHz, CD30D); d = 0.67 (ddd, HH), 0.91 (ddd, 1H), 1.74 (ddd, HH), 1.91 (d, 1H), 2.10 (ddd, HH), 2.23 (d, ÍH), 2.75 (s, 3H), 5.25 (s, ÍH), 6.78 (dd, ÍH), 6.84 (dd, 1H), 6.90 (d, 1H) , 7.49 (d, ÍH), 7.69 (t, ÍH), 7.95 (d, ÍH), 8.30 (d, ÍH). Example 214 cis-7'-chloro-4 '- [(7-fluoro-2-methylquinazolin-5-yl) amino] -3,4'-dihydro-8' -methoxy-3 '- (trifluoromethyl) -spiro [ cyclohexane-1, 1 '(2'H) -naphthalene] -3' -ol XH-NMR (300 MHz, CDC13); d = 1.20-1.85 (m, 8H), 2.05 (d, 1H), 2.44 (ddd, 1H), 2.63 (ddd, 1H), 2.82 (s, 3H), 2.97 (d, 1H), 4.00 (s, 3H),. 4.95 (d, ÍH), 5.92 (d, ÍH), 6.49 (dd, ÍH), 6.91 (dd, ÍH), 7.04 (d, ÍH), 7.22 (d, ÍH), 9.16 (s, 1H). EXAMPLE 215 cis-7'-chloro-4 '- [(7-fluoro-2-methyl-tyzolin-5-yl) amino] -3,4'-dihydro-3' - (trifluoromethyl) -spiro [cyclohexane-1, 1 '(2'H) -naphthalene] -3', 8'-diol XH-NMR (300 MHz, CDC13); d = 1.25-1.85 (m, 8H), 1.86 (d, HH), 2.79 (ddd, 1H), 2.82 (s, 3H), 2.93 (ddd, HH) , 2.97 (d, ÍH), 4.95 (d, 1H), 5.85 (d, ÍH), 6.14 (s, ÍH), 6.48 (dd, ÍH), 6.89- 6.93 (m, 2H), 7.19 (d, ÍH), 9.19 (s, ÍH). Example 216 cis-7'-chloro-3 ', 4'-dihydro-4' - [(2-methylquinazolin-5-yl) amino] -3 '- (trifluoromethyl) -spiro [cyclopropan-1, 11 (2' H) -naf alen] -3 ', 8' -diol XH-NMR (300 MHz, CD30D); 8 = 0.69 (ddd, ÍH), 0.92 (ddd, ÍH), 1.71 (ddd, ÍH), 1.95 (d, ÍH), 2.13 (ddd, ÍH), 2.20 (d, ÍH), 2.81 (s, 3H), 5.29 (s, ÍH), 6.85 (d, 2H), 7.10 (d, 1H), 7.19 (d, ÍH) , 7.78 (t, ÍH), 9.65 (d, ÍH). Example 217 (-) -2-chloro-5- (lH-indazol-4-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1,6 -diol and (+) -2-chloro-5- (lH-indazol-4-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1, 6 -diol (-) -6-chloro-l- (IB.- indazol-4-ylamino) -5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen 2-ol and (+) -6-chloro-l - (IH-indazol-4-ylamino) -5-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaf talen-2-ol The compound racemic prepared as described in the previous examples (324.2 mg) is separated in the ether stage from a chiral column (Chiralpak AD 20μ, elution medium hexane / ethanol) to obtain its enantiomers. 122.8 mg of the (-) enantiomer and 147.1 mg of the (+) enantiomer are obtained. Enantiomer (-): [ce] D = -0.8 (c = 1, MeOH) Enantiomer (+): [o] D = +1, 0 (c = 1, MeOH) (-) -2 ~ chlorine -5- (IR-indazol-4-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalene-1,6-diol and (+) -2 ~ Chloro-5- (IH-indazol-4-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydro-naphthalen-1,6-diol From 115,8 mg of the enantiomeric ether (-) are obtained, by ether separation with BBr3, 24 mg (21.4%) of the phenol. Of 141.2 mg of the enantiomeric ether (+), 91.5 mg (66.9%) of the phenol are obtained by separation in ether with BBr3. Example 218 5-. { [4, 4-dimethyl-2-hydroxy-5-methoxy-2- (pentafluoroethyl) -1,2,3, -te-rahydronaphthalen-1-yl] amino} -quinolin-2 (1 H) -one 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) pentanal. Analogously to the one described in Example 7, 687 mg ethyl-4- (2-methoxyphenyl) -4-methyl-2-oxopen-tannate (WO 00/32584) was converted with 1 g pentafluoroethyl) trimethylsilane and 0.5 ml of tetrabutylammonium fluoride solution (IM in THF)) in 18 ml of THF to obtain ethyl-4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) -pentanatoate. 450 mg of the ester obtained in 12 ml of diethyl ether are mixed in portions at 0 ° C with 66 mg of lithium aluminum hydride.

After stirring for 11 h, it is flushed with saturated bicarbonate solution and filtered through diatomaceous earth. The phases are separated and the aqueous phase is extracted with ethyl acetate. The organic phases are washed with water and saline, dried (NaS04) and evaporated. 420 mg of diol are obtained as a yellow oil. 400 mg of the diol is oxidized with 0.11 ml of oxalyl chloride, 0.21 ml of DMSO and 1 ml of triethylamine to obtain the corresponding aldehyde. Wash with water and saline, dry with sodium sulfate and concentrate in vacuo. After chromatography on silica gel (hexane / ethyl acetate 0-> 5%), 268 mg of the title compound are obtained as a yellow oil. XH-NMR (CDC13), d (ppm) = 1.39 (s, 3H), 1.46 (s, 3H), 2.26 (d, ÍH), 3.46 (d, ÍH), 3.88 (s, 3H) , 6.77-6.95 (m, 2H), 7.11 (dd, 1H), 7.13-7.28 (m, ÍH), 8.95 (s, ÍH) 5-. { [4, 4-dimethyl-2-hydroxy-5-methoxy-2- (pentafluoroethyl) -1,2,3-tetrahydronaphthalen-1-yl] mino] -quinolin-2 (1H) -one Using an analogous procedure to that described in example 10, starting with 180 mg of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) pentanal and 83 mg of 5-aminoquinolin-2 (1H) -one, get the corresponding imine. In a reaction of 70 mg of imine with 58 mg aluminum trichloride in 1.5 ml of dichloromethane, 7 mg of the title compound are obtained.

XH-NMR (CD3OD): d = 1.52 (s, 3H), 1.66 (s, 3H), 2.09 (d, ÍH), 2.15 (d, ÍH), 3.85 (s) , 3H), 5.27 (s, 1H), 6.51 (d, ÍH), 6.62 (d, 1H), 6.70 (d, ÍH), 6.92 (d, 2H), 7 , 11 (dd, 1H), 7.38 (t, 1H), 8.23 (d, 1H) Example 219; 5-. { [6-chloro-4,4-dimethyl-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} 6-methylquinolin-2 (1H) -one 5 Amino-6-methylquinolin-2 (1H) -one: 4.12 g 2-chloro-6-methylquinoline are added (J. Med. Chem. 1992, pp. 2761 -2768) at 0 ° C, to a solution of 15 ml of 100% fuming nitric acid and 2 ml of 96% sulfuric acid. After 4 hours at 0 ° C, it is poured into water and the product is removed by filtration. 4.66 g 2-chloro-6-methyl-5-nitroquinoline are obtained as a beige solid. This is converted 80 hours at 100 ° C into 46 ml of ethyl acetate and 26 ml of water. The 6-methyl-5-nitroquinolin-2 (1H) -one thus obtained is removed by filtration from the reaction solution. The 3.45 g of product obtained is converted with hydrogen at normal pressure into methanol with palladium on active carbon to obtain aniline. 2.89 g of the title compound are obtained as a beige solid. XH-NMR (DMSO): d = 2.08 (s, 3H), 5.56 (s, 2H), 6.25 (d, ÍH), 6.42 (d, ÍH), 7.06 (d , 1H =, 8.18 (d, HH), 11.32 (s, HH) 5- { [6-Chloro-4, 4-dimethyl-2-hydroxy-5-methyl-2- (trifluoromethyl) ) -1, 2, 3, 4-tetrahydronaphthalen-1-yl] amino.} - 6-methylquinolin-2 (1H) -one Using a procedure analogous to that described in Example 10, starting with 500 mg of 4- ( 3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 300 mg of 5-amino-6-methylquinolin-2 (1H) -one the corresponding imine is prepared. reaction of 80 mg of imine with 2.5 ml of titanium tetrachloride solution (1M in dichloromethane) in 4.3 ml of dichloromethane, 10 mg of the title compound XH-NMR (DMSO): d = 1.57 ( s, 3H), 1.68 (s, 3H), 1.87 (d, ÍH), 2.12 (d, ÍH), 2.38 (s, 3H), 3.88 (s, 3H), 4.87 (d, 1H), 5.85 (d, ÍH), 5, 96 (d, ÍH), 6,62 (d, ÍH), 6,81 (d, ÍH), 7,11 (d, ÍH), 7,44 (d, 1H), 8,42 (s, 1H ), 11.57 (s, 1H) Example 220 5-. { [2,5-dihydroxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (HH) -one Using a procedure analogous to that described in Example 3, starting with 74 mg of the compound of Example 41 with 0.48 ml of BBr3 solution (MM in dichloromethane) at 40 ° C, mg of the title compound XH-NMR (CD3OD): d = 1.53 (s, 3H), 1.65 (s, 3H), 2.01 (d, 1H), 2.10 (s, 3H), 2.12 (d, HH), 5.10 (s, HH), 6.47-6.56 (m, 2H), 6.58-6.65 (m, 2H), 6.69 (d, ÍH), 7.39 (t, ÍH), 8.22 (d, lH) Example 221 5-. { [2-hydroxy-5-methoxy-2- (pentafluoroethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaph alen-1-yl] amino} -quinolin- 2 (ÍH) -one 4 - (2-methoxy-4-methyl-phenyl) -2-hydroxy-4-methyl-2- (pentaf-luoroethyl) pentanal. Analogous to the synthesis of 4- (2- methoxyphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) -pentanal 1.05 g of the title compound are obtained starting from 1.7 g ethyl-4- (2-methoxy-4-methylphenyl) -4- methyl-2-oxopentanoate (Example 41) with 1.4 g (pentafluoroethyl) trimethylsilane, following reduction with 344 mg of lithium aluminum hydride and then oxidation under Swern conditions. XH-NMR (CDC13): d = 1.36 (s, 3H), 1.42 (s, 3H), 2.23 (d, ÍH), 2.32 (s, 3H), 3.48 (d , 1H), 3.64 (s, ÍH), 3.87 (s, 3H), 6.67 (s, ÍH), 6.71 (d, ÍH), 6.97 (d, ÍH), 8 , 93 (s, 1H) 5-. { [2-hydroxy-5-methoxy-2- (pentafluoroethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalene-1-yl] amino} -quinolin-2 (1H) -one Using a procedure analogous to that described in example 10, starting with 200 mg of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) pentanal and 93 mg of 5-aminoquinolin-2 (1H) -one, the corresponding imine is obtained. By reaction of 80 mg of imine with 1.6 ml of titanium tetrachloride solution (IM in dichloromethane) in 5 ml of dichloromethane, 2 mg of the title compound are obtained.

XH-NMR (CD3OD): d = 1.48 (s), 3H), 1.62 (s, 3H), 2.05 (d, 1H), 2.12 d, 1H), 2.16 (s, 3H), 3.83 (s, 3H), 5, 21 (s, ÍH), 6,52 (d, ÍH), 6,62 (d, ÍH), 6,71 (d, ÍH), 6,75 (s, 2H), 7,40 (t, ÍH) ), 8.23 (d, 1H) Example 222 5-. { [2-hydroxy-5-methoxy-2- (trifluoromethyl) -4,4,6-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one Ethyl -4- (2-methoxy -3-methyl-phenyl) -4-methyl-2-oxopentanoate. Analogously to the one described in example 7, methyl-2-methoxy is prepared. 3-methylbenzoate from 30 g 3-methylsalicynic acid and 60 ml methyl iodide with 125 g potassium carbonate in 640 ml DMF. The ester is transformed by reaction with 129 ml methylmagnesium chloride (3M in THF) in 435 ml of THF to obtain 1- (2-methoxy-4-methylphenyl) -1-methylethanol. 20.8 g of the product obtained are converted with 27.1 g 2- (trimethylsilyloxy) -acrylic acid ethyl ester in 410 ml of dichloromethane at 0 ° C with 10.4 ml tin tetrachloride to obtain 12.63 g of the compound of the title. XH-NMR (300 MHz, CDC13): d = 1.28 (t, 3H), 1.48 (s, 6H), 2.29 (s, 3H), 3.37 (s, 2H), 3.76 (s, 3H), 4.14 (q, 2H), 6.95 (t, ÍH), 7.05 (d , HH), 7,13 (d, 1H) -4 - (2-methoxy-4-methylphyl) -2-hydroxy-4-methyl-2-tri-fluoromethyl) pentanal. Analogously to that described in Example 7 14.68 g ethyl-4- (2-methoxy-4-methylphenyl) -4-methyl-2-oxopentanoate are converted to 21.6 ml (trifluoromethyl) trimethylsilane and 9.7 ml tetrabutylammonium fluoride solution (1M in THF) ) in 195 ml of THF to obtain 13.73 g ethyl-4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanoate. The product is reduced with 2.84 g of lithium aluminum hydride in 560 ml of diethyl ether to give 11.62 g 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanol. The oxidation of the diol is carried out analogously to that described in example 7 under Swern conditions with 3.8 ml of oxalyl chloride, 7.1 ml of DMSO and 26.5 ml of triethylamine to obtain 5.91 g of the compound of the title. XH-NMR (CDC13): d = 1.44 (s, 3H), 1.48 (s, 3H), 2.22 (d, ÍH), 3.36 (d, ÍH), 3.83 (s) , 3H), 6.90-7.12 (m, 3H), 8.93 (s, ÍH) 5-. { [2-hydroxy-5-methoxy-2- (trifluoromethyl) -4,4,6-trimethyl-1,4-, 3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one Using a procedure analogous to that described in Example 10, starting with 600 mg of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 315 mg of 5-aminoquinolin-2 (HH) -one, the corresponding imine is obtained. By reaction of 370 mg of imine with 8.3 ml of titanium tetrachloride (1M in dichloromethane) in 20 ml of dichloromethane, 12 mg of the title compound are obtained.

XH-NMR (CD3OD): d = 1.52 (s, 3H), 1.67 (s, 3H), 2.10 (s, 2H), -2.30 (s, 3H), 3.79 ( s, 3 H), 5,16 (s, ÍH), 6,51 (d, ÍH), 6,61 (d, ÍH), 6,70 (d, ÍH), 7,00 (s, 2H), 7.38 (t, 1H), 8.21 (d, 1H) Examples 223 and 224 4-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -fatty and 4-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} - phthalide By a procedure analogous to that described in Example 10, starting with 600 mg of 4- (2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 308 mg of 4-aminophthalide, the corresponding imine. Reaction of 640 mg of imine with 7.7 ml of bromine bromide solution (IM in dichloromethane) gives 165 mg of 4-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -fatty as fraction 1 and 115 mg of 4-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-1-yl] amino} -fatty as fraction 2. Fraction l: aH-NMR (CDC13): d = 1.40 (s, 3H), 1.49 (s, 3H), 2.03 (d, ÍH), 2.13 (d, ÍH), 3.17 (d, ÍH), 3.32 (s, ÍH), 3.90 (s, 3H), 5.01 (d, 1H), 5.11-5.24 (m, 2H), 6.66 (d, ÍH), 7.03 (d, ÍH), 7.21-7.32 (m, 2H), 7.39-7.50 (m, 2H) Fraction 2: XH-NMR (CD30D): d = 1.55 ( s, 3H), 1.67 (s, 3H), 2.04 (d, 1H), 2.12 (d, ÍH), 5.15 (s, ÍH), 5.21 (d, 1H), 5,32 (d, ÍH), 6,70 (d, ÍH), 6,84 (d, ÍH), 6, 96 (t, ÍH), 7,07 (d, ÍH), 7,18 (d , HH), 7.42 (t, HH) Examples 225 and 226 (-) -4-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -fatty and (+) -4-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -fatty Separation from (+/-) -4-. { [4,4-dimethyl-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -fature The mixture of enantiomers is separated by chromatography on chiral substrate (CHIRALPAK AD®, Fa DAICEL) with hexane / ethanol (95: 5, vw). In this way the (-) enantiomer is obtained: MS (El): M + = 421, [a] D-79.3 ° (c = 0.9, CHC13) and the enantiomer (+): MS (El): M + = 421 Examples 227 and 228 (-) -4-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -, 2, 3, 4-tetrahydronaphthalen-1-yl] amino} -fatty and (+) -4-. { [2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -, 2,3,4-tetrahydronaphthalen-1-yl] amino} -fatty Separation from (+/-) -4-. { [2, 5-dihydroxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -fature The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, Fa DAICEL) with hexane / ethanol (90: 10, vw). In this way the (-) enantiomer is obtained: MS (El): M + = 407, [a] D-66.0 ° (c = 1.0, CHC13) and the enantiomer (+): - MS (El) : M + = 407 Example 229 5-. { [5-methoxy-2-hydroxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Using a procedure analogous to that described in Example 10, starting with 500 mg of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 288 mg of 5-amino-2-methylphthalazin-1-one, the corresponding imine is obtained. As in Example 3, 90 mg of imine is converted by reaction with 0.4 ml of titanium tetrachloride (IM in dichloromethane) in 5 ml of dichloromethane and 25 mg of the title compound are obtained. XH-NMR (DMSO): d = 1.42 (s, 3H), 1.57 (s, 3H), 1.95 (d, ÍH), 2.05 (d, ÍH), 2.14 (s, 3H), 3.70 (s, 3H), 3.80 (s, 3H), .38 (d, ÍH), 5.98 (s, ÍH), 6.57 (d, ÍH), 6.66 (s, ÍH), 6.80 (s, ÍH), 7.25 (d, 1H), 7.47 (d, ÍH), 7.58 (t, ÍH), 8.63 (s, ÍH) Examples 230 and 231 (-) -5 -. { [5-methoxy-2-hydroxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one and (+) - 5 - ([5-methoxy-2-hydroxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,4-tetrahydronaohthalin-1 -yl] amino.} -2-methylphthalazin-1-one Separation of - (+/-) - 5- { [5-methoxy-2-hydroxy-2- (trifluoromethyl) -4,4,7- trimethyl-l, 2,3,4-tetrahydronaphthalen-1-yl] amino.} -2-methylphthalazin-1-one The mixture of enantiomers is separated by chromatography on chiral substrate (CHIRALPAK AD®, Fa DAICEL) with ethanol as Eluent: In this way the (-) enantiomer is obtained: MS (El): M + = 461 and the enantiomer (+): MS (El): M + = 461, [a] D + 4.9 ° (c = 0.7, CHC13) Example 232 5- { [6-Chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1- il] amino.} -2-methylphthalazin-1-one Using a procedure analogous to that described in example 10, starting with 1.0 g 4- (3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl -2- (trifluoromethyl) pentanal and 542 mg of 5-amino-2-methyl-phthalazin-1-one the corresponding imine is obtained. in Example 3, 840 mg of imine are converted in a reaction with 43.6 ml of titanium tetrachloride (IM in dichloromethane) in 40 ml of dichloromethane and 114 mg of the title compound are obtained. XH-NMR (DMSO): d = 1.47 (s, 3H), 1.61 (s, 3H), 2.00 (d, ÍH), 2.14 (d, ÍH), 3.71 (s) , 3H), 3.88 (s, 3H), 5.46 (d, ÍH), 6.17 (s, ÍH), 6.61 (d, ÍH), 7.00 (d, ÍH), 7 , 27 (d, 1H), 7.33 (d, ÍH), 7.49 (d, ÍH), 7.60 (t, ÍH), 8.64 (s, ÍH) Examples 233 and 234 (-) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one and (+) - 5 -. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Separation of (+/-) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one The mixture of enantiomers is separated by chromatography on chiral substrate (CHIRALPAK ADO, Fa DAICEL) with hexane / ethanol (90: 10, vw). In this way the (-) enantiomer is obtained: MS (El): M + = 481/483 and the (+) enantiomer: MS (El): M + = 481/483, [a] D + 10.6 ° (c = 0.8, CHC13) Example 235 5-. { [6-chloro-2,5-dihydroxy-4,4-dimethyl-2 - (trifluoromethyl) -1,2,3,4-etrahydronaphthalen-1-yl] amino} -amino) -2-methylphthalazin-1-one Using a procedure analogous to that described in example 3, starting with 20 mg of 5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one with 0.13 ml of BBr3 solution (IM in dichloromethane) at 40 ° C, gives 19 mg of the title compound. XH-NMR (DMSO): d = 1.52 (s, 3H), 1.65 (s, 3H), 2.00 (d, ÍH), 2.11 (d, 1H), 3.70 (s) , 3 H), 5,42 (d, ÍH), 6,07 (s, ÍH), 6,58 (d, ÍH), 6,74 (d, ÍH), 7,20 (d, 1H), 7 , 26 (d, ÍH), 7,47 (d, ÍH), 7,58 (t, ÍH), 8,63 (s, ÍH), 9,09 (s, ÍH) Example 236 (-) -5 -. { [6-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifiuoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -amino) -2-methylphthalazin-1-one By a procedure analogous to that described in example 3 are obtained, starting from 26 mg (-) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one with 0.5 ml of BBr3 solution (IM in dichloromethane) in 0.25 ml of dichloromethane at 40 ° C, 23 mg of the title compound. XH-NMR (DMSO): d = 1.52 (s, 3H), 1.65 (s, 3H), 2.00 (d, 1H), 2.11 (d, ÍH), 3.70 (s) , 3 H), 5,42 (d, ÍH), 6,07 (s, ÍH), 6,58 (d, ÍH), 6,74 (d, ÍH), 7,20 (d, ÍH), 7 , 26 (d, 1H), 7.47 (d, ÍH), 7.58 (t, 1H), 8.63 (s, 1H), 9.09 (s, ÍH) Example 237 (+) -5 -. { [6-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-etrahydronaphthalen-1-yl] amino} - Not me} -2-methylphthalazin-1-one By a procedure analogous to that described in example 3, they are obtained, starting from 20 mg (+) -5-. { [6-Chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] mino} -2-methylphthalazin-1-one, with 0.4 ml of BBr3 solution (IM in dichloromethane) in 0.25 ml of dichloromethane at 40 ° C, 12 mg of the title compound. XH-NMR (DMSO): d = 1.52 (s, 3H), 1.65 (s, 3H), 2.00 (d, ÍH), 2,11 (d, ÍH), 3,70 (s, 3H), 5,42 (d, 1H), 6,07 (s, ÍH), 6,58 (d, 1H), 6, 74 (d, ÍH), 7,20 (d, ÍH), 7,26 (d, 1H), 7,47 (d, ÍH), 7,58 (t, ÍH), 8,63 (s, ÍH) ), 9.09 (s, ÍH) Example 238 (+) -5-. { [2,5-dihydroxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino] -amino} -2-methylphthalazin-1-one Using a procedure analogous to that described in Example 3, starting with 20 mg of 5-. { [5-methoxy-2-hydroxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2, 3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, with 0.13 ml of BBr3 solution (IM in dichloromethane) at 40 ° C, 19 mg of the title compound. XH-NMR (DMSO): d = 1.46 (s, 3H), 1.60 (s, 3H), 1.94 (d, 1H), 2.01 (d, 1H), 2.06 (s) , 3H), 3.70 (s, 3H), 5.35 (d, 1H), 5.92 (s, ÍH), 6.51 (s, 1H), 6.53-6.63 (m, 2H), 7.26 (d, ÍH), 7.46 (d, 1H), 7.57 (t, ÍH), 8.63 (s, ÍH), 9.31 (s, ÍH) Example 239 5 -. { [5-methoxy-2-hydroxy-2- (trifluoromethyl) -4,4,6-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Using a procedure analogous to that described in Example 10, starting with 600 mg of 4- (3-methyl-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 316 mg of 5-amino-2-methylphthalazin-1-one, the corresponding imine is obtained. As in Example 3, 460 mg of imine are converted by reaction with 5.2 ml of titanium tetrachloride (MMI in dichloromethane) in 23 ml of dichloromethane and 36 mg of the title compound are obtained. XH-NMR (DMSO): d = 1.45 (s, 3H), 1.60 (s, 3H), 1.96 (d, ÍH), 2,10 (d, ÍH), 2,24 (s, 3H), 3,70 (s, 3H), 3,72 (s, 3H), 5,40 (d, ÍH), 6, 03 (s, ÍH), 6.57 (d, 1H), 6.87 (d, ÍH), 7.03 (d, 1H), 7.25 (d, ÍH), 7.46 (d, ÍH) ), 7.58 (t, ÍH), 8.63 (s, ÍH) Example 240 5 -. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2 - (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -ftalazin-1-one Using a procedure analogous to that described in example 10, the corresponding imine is prepared starting from 1.0 g 4- (3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 494 mg of 5-amino-phthalazin-1-one. As in Example 3, 775 mg of imine are converted by reaction with 24.9 ml of titanium tetrachloride (MMI in dichloromethane) in 46 ml of dichloromethane and 483 mg of the title compound are obtained. XH-NMR (DMSO): d = 1.47 (s, 3H), 1.61 (s, 3H), 1.99 (d, ÍH), 2.13 (d, ÍH), 3.88 (s) , 3H), 5,45 (d, ÍH), 6,17 (s, ÍH), 6,57 (d, ÍH), 7,00 (d, ÍH), 7,28 (d, ÍH), 7 , 33 (d, 1H), 7.46 (d, 1H), 7.57 (t, ÍH), 8.61 (s, ÍH), 12.56 (s, 1H) Examples 241 and 242 (-) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -ftalazin-1-one and (+) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -ftalazin-1-ona Separation of (+/-) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -ftalazin-1-one The mixture of enantiomers is separated by chromatography on chiral substrate (CH IRALPAK AD®, Fa DAICEL) with hexane / ethanol (90:10, v / v). In this way, the (-) enantiomer: Fp. = 267-270 ° C and the enantiomer (+): Fp. = 263-265 ° C, [] D + 6.5 ° (c = 1.2, CHC13) Example 243 5-. { [6-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -amino] -phthalazin-1-one Using a procedure analogous to that described in example 3, starting with 20 mg of 5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-l-yl] amino} phthalazin-1-one with 0.13 ml of BBr3 solution (IM in dichloromethane) at 40 ° C, gives 19 mg of the title compound. XH-NMR (DMSO): d = 1.43 (s, ÍH), 1.56 (s, 3H), 1.91 (d, 1H), 2.01 (d, ÍH), 5.33 (d, 1H), 6.00 (s, ÍH), 6.44 (d, ÍH), 6.65 (d, 1H), 7, 12 (d, 1H), 7.18 (d, 1H), 7.36 (d, 1H), 7.49 (t, 1H), 8.52 (S, 1H), 9.02 (s, 1H) ), 12.46 (s, ÍH) Example 244 (-) -5-. { [6-chloro-2, 5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2, 3,4-tetrahydronaphthalen-1-yl] amino} -amino] -2-methylphthalazin-1-one By a procedure analogous to that described in example 3, starting with 100 mg (-) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} Phthalazin-1-one with 2.1 ml of BBr3 solution (IM in dichloromethane) in 1 ml of dichloromethane at 40 ° C gives 94 mg of the title compound. XH-NMR (DMSO): d = 1.43 (s, ÍH), 1.56 (s, 3H), 1.91 (d, 1H), 2.01 (d, ÍH), 5.33 (d , 1H), 6.00 (s, ÍH), 6.44 (d, 1H), 6,65 (d, ÍH), 7,12 (d, ÍH), 7,18 (d, ÍH), 7,36 (d, ÍH), 7,49 (t, 1H), 8,52 (s) , ÍH), 9.02 (s, ÍH), 19.46 (s, ÍH) Example 245 (+) -5-. { [6-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] ao} -amino] -ftalazin-1-one Using a procedure analogous to that described in example 3, starting with 100 mg (+) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3,4-tetrahi-dronaphthalen-1-yl] amino} Phthalazin-1-one with 2.1 ml of BBr3 solution (IM in dichloromethane) in 1 ml of dichloromethane at 40 ° C gives 82 mg of the title compound. XH-NMR (DMSO): d = 1.43 (s, ÍH), 1.56 (s, 3H), 1.91 (d, ÍH), 2.01 (d, ÍH), 5.33 (d , ÍH), 6.00 (s, ÍH), 6.44 (d, 1H), 6.65 (d, 1H), 7.12 (d, HH), 7.18 (d, HH), 7 , 36 (d, ÍH), 7.49 (t, 1H), 8.52 (s, ÍH), 9.02 (s, 1H), 12.46 (s, ÍH) Example 246 5-. { [2-hydroxy-5-methoxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] min} -ftalazin-1-one Using a procedure analogous to that described in example 10, starting with 500 mg of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 287 mg of 5-amino-phthalazin-1-one, the corresponding imine is obtained. As in Example 3, 320 mg of imine are converted by reaction with 7.2 ml of titanium tetrachloride (MMI in dichloromethane) in 20 ml of dichloromethane and 80 mg of the title compound are obtained. XH-NMR (DMSO): d = 1.43 (s, ÍH), 1.57 (s, 3H), 1.95 (d, ÍH), 2.06 (d, ÍH), 2.15 (s, 3H), 3.80 (s, 3H), 5.38 (d, ÍH), .99 (s, 1H), 6.53 (d, ÍH), 6.66 (s, ÍH), 6.79 (s, 1H), 7.25 (d, 1H), 7.44 (d) , ÍH), 7.57 (t, 1H), 8.61 (s, ÍH), 12.54 (s, ÍH) Examples 247 and 248 (-) -5-. { [2-hydroxy-5-methoxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] mino} -ftalazin-1-one and (+) -5-. { [2-hydroxy-5-methoxy-2- (trifluoromethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Separation of (+/-) -5-. { [6-chloro-4,4-dimethyl-5-methoxy-2-hydroxy-2- (trifluoromethyl) -1,2,3, -tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one The mixture of enantiomers is separated by chromatography on chiral substrate (CHIRALPAK AD®, Fa DAICEL) with ethanol as eluent. In this way the (-) eantiomer is obtained: MS (El): M + = 447, [a] D -3.4 ° (c = 0.7, CHC13) and the enantiomer (+): MS (El): M + = 447, [] D + 3.7 ° (c = 1.1, CHCl3) Example 249 5-. { [2-Hydroxy-5-methoxy-2- (pentafluoroethyl) -4,4,7-trimethyl-1,2,3,4-tetrahydronaphthalen-1-yl] amino} -f alazin-1-one Using a procedure analogous to that described in Example 10, starting with 250 mg of 4- (2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (pentafluoroethyl) pentanal and 118 mg of 5- amino-phthalazin-1-one, the corresponding imine is obtained. As in Example 3, 65 mg of imine is converted by reaction with 0.38 ml of titanium tetrachloride (IM in dichloromethane) in 6 ml of dichloromethane and 8 mg of the title compound are obtained. XH-NMR (CD30D): d = 1.40 (s, ÍH), 1.55 (s, 3H), 2.19 (d, ÍH), 2.29 (d, ÍH), 2.33 (s) , 3H), 3.47 (s, 3H), 5.46 (s, ÍH), 6.61 (s, 1H), 6.90 (s, ÍH), 7.54-7.63 (m, 2H), 7.63-7.73 (m, 2H), 8.43 (s, 1H) Example 250 5-. { [6-chloro-, 4-dimethyl-2-hydroxy-5-methoxy-2 - (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -8-fluoroquinoline-2 (1H) -one 5-amino-8-fluoroquinoline-2 (1H) -one 10 g 2,5-difluoroaniline and 6 g pyridine in 350 ml of dichloromethane are mixed by dripping at 0 ° C with 12.9 g cinnamic acid chloride and stir at 0 ° C until it has completely transformed. The preparation is poured onto 2N hydrochloric acid and extracted with dichloromethane. It is washed with water, dried with sodium sulfate and concentrated in vacuo. The solid obtained is mixed with 11.1 g aluminum chloride and heated for 8 hours at 150 ° C. After chromatography on silica gel, 2.9 g of 5,8-difluoroquinolin-2 (1H) -one are obtained. This is transformed into 100 ml ethylene glycol in the presence of 780 mg copper (II) oxide for 20 hours at 200 ° C in an ammonia atmosphere at 60 bar. After chromatography on silica gel, 5-amino-8-fluoroquinoline-2 (1H) -one is obtained as fraction A and 2, 5-diamino-8-fluoroquinoline as fraction B. Fraction A: XH-NMR (DMSO): d = 5.73 (s, 2H), 6.28 (dd, 1H), 6.35 (d, 1H ), 7.07 (dd, ÍH), 8.08 (dd, 1H), 11.31 (s, ÍH). Fraction B: XH-NMR (DMSO): d = 5.36 (s, 2H), 6.23 (dd, 1H), 6.47 (s, 2H), 6.63 (d, ÍH), 6, 96 (dd, ÍH), 8.07 (dd, 1H). 5- . { [6-chloro-4, 4-dimethyl-2-hydroxy-5-methyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -8-f luoro -quinolin 2 (ÍH) -one Using a procedure analogous to that described in example 10, starting with 250 g 4- (3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 137 mg of 5-amino-8-fluoroquinolin-2 (HH) -one, the corresponding imine is obtained. The title compound is obtained by a procedure analogous to that described in Example 3 by transformation of the amine formed with 1.4 ml of titanium tetrachloride solution (IM in dichloromethane). aH-NMR (CD3OD): d = 1.53 (s, 3H), 1.67 (s, 3H), 2.22 (s, 2H), 3.96 (s, 3H), 5.14 (s) , 1H), 6.51-6.61 (m, 2H), 7.09 (d, 1H), 7.20 (d, 1H), 7.24 (dd, 1H), 8.21 (dd, 1 HOUR) . Example 251 2-amino-5-. { [6-chloro-4,4-dimethyl-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -8-fluoro-quinolin Using a procedure analogous to that described in example 10, starting with 250 g 4- (3-chloro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 137 mg 2,5-diamino-8-fluoroquinoline, the corresponding imine is obtained. The title compound is obtained by a procedure analogous to that described in Example 3 by transformation of the imine formed with 1.0 ml solution of titanium tetrachloride (IM in dichloromethane). XH-NMR (CD3OD): d = 1.54 (s, 3H), 1.67 (s, 3H), 2.20 (s, 2H), 3.94 (s, 3H), 5.11 (s) , 1H), 6.43 (dd, ÍH), 6.81 (d, ÍH), 7,11 (d, ÍH), 7,15 (d, ÍH), 7,20 (d, ÍH), 8 , 18 (dd, ÍH). Examples 252 and 253 5-. { [4,4-dimethyl-6-fluoro-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} - 8-fluoro-quinolin-2 (ÍH) -one and 2-amino-5. { [4,4-dimethyl-1-6-fluoro-2-hydroxy-5-methoxy-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -8-Fluoro-quinolin Using a procedure analogous to that described in Example 10, starting with 237 g 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 137 mg of a mixture of 5-amino-8-fluoroquinoline-2 (1H) -one and 2,5-diamino-8-fluoroquinoline, a mixture of the corresponding imines is prepared. Analogously to that described in Example 3, the mixture of imines was transformed with 2.5 ml of titanium tetrachloride solution (1M in dichloromethane) and the two title compounds were obtained after chromatography on silica gel. Fraction A. XH-NMR (CD3OD): d = 1.53 (s, 3H), 1.65 (s, 3H), 2.08 (d, ÍH), 2.23 (d, 1H), 3, 95 (d, 3H), 5.11 (s, ÍH), 6.50-6.61 (m, 2H), 6.98 (dd, ÍH), 7.06 (dd, 1H), 7.23 (dd, 1H), 8.22 (dd, ÍH). Fraction B: XH-NMR (CD30D): d = 1.52 (s, 3H), 1.66 (s, 3H), 2.08 (d, ÍH), 2.15 (d, 1H), 3, 95 (d, ÍH), 5.09 (s, ÍH), 6.40-6.57 (m, 2H), 6.82 (d, ÍH), 6.94 (dd, ÍH), 7.02 -7.20 (m, 2H), 8.18 (t, ÍH). Example 254 5-. { [7-fluoro-3-hydroxy-8-methoxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclobutan-1, 1'-naphthalen-4-yl] amino.} - -quinolin-2 (ÍH) -one 3 - { (3-f uoro-2-methoxy phenyl) -cyclobutyl) -2-hydroxy -2- (tri-fluoromethyl) -pentanal Analogous to the synthesis of 4 (3-fluoro) -2- methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal in Example 3 gives 3-. { [3-fluoro-2-methoxyphenyl) -cyclobutyl} -2-hydroxy-2- (trifluoromethyl) -pentanal starting from 2,6-difluoranisole and cyclobutanecarbonitrile. XH-NMR (CDC13): d = 1.75-1.90 (m, HH), 2.10-2.40 (m, 3H), 2.46-2.57 (m, 2H), 2.83 (d, 1H), 3.00 (d, ÍH), 3.94 (d, 3H), 6.75 (dt, ÍH) ), 6.83-7.02 (m, 2H), 8.94 (s, ÍH). 5 - . { [7-Fluoro-3-hydroxy-8-methoxy -3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclobutan-1, 1-naphthalen-4yl] amino.}. -quinolin-2 (1H ) -one using a procedure analogous to that described in example 10, starting with 350 g 3- ({3-fluoro-2-methoxyphenyl) cyclobutyl] -2-hydroxy-2- (trifluoromethyl) pentanal and 200 mg of 5 -amino-quinolin-2 (HH) -one, the corresponding imine is obtained.An example analogous to that described in Example 3, the imine is transformed with 1.6 ml of titanium tetrachloride solution (ΔM in dichloromethane) and obtained 35 mg of the title compound.XH-NMR (CD3OD): d = 2.10-2.29 (m, 4H), 2.40-2.56 (m, 1H), 2.65-2.80 (m. m, 2H), 2.93-3.06 (m, HH), 4.09 (d, 3H), 5.14 (s, HH), 6.49 (d, HH), 6.63 (d , HH), 6.70 (d, HH), 6.97 (d, 2H), 8.20 (d, 1H) Example 255 5- { [3, 8-dihydroxy-7-fluoro-3 - (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclobutan-1, 1'-naphthalen-4-yl] amino.} - quinolin-2 (1H) -one Using an analogous procedure to the described in Example 3, starting with 20 mg of 5-. { [7-fluoro-3-hydroxy-8-methoxy-3- (trifluoromethyl) -3, 4-dihydro-2H-spiro (cyclobutan-1,1'-naphthalen-4-yl] amino.}. -quinolin-2 (HH) -one with 0.22 ml of BBr3 solution (MM in dichloromethane) at room temperature At room temperature, 12 mg of the title compound is obtained.XH-NMR (CD30D): d = 1.8H, 94 (m, 1H), 2.08-2.27 (m, 3H), 2.28-2, 41 (m, ÍH), 2.75 (d, ÍH), 3.08 (q, ÍH), 3.44 (q, ÍH), 5.13 (s, ÍH), 6.48 (d, 1H ), 6.63 (d, 1H), 6.68 (d, ÍH), 6.73 (dd, ÍH), 6.90 (dd, ÍH), 7.37 (t, 1H), 8.20 (d, ÍH) Example 256 5- { [7-Fluoro-3-hydroxy-8-methoxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclopentan-1, 1'-naphthalene -4-yl] amino.}. -quinolin-2 (1H) -one 3 -. {(3-f luoro-2-methoxyphenyl) -cyclopentyl) -2-hydroxy-2- (trifluoromethyl) pentanal - Analogous to the synthesis of 4- (3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) -pentanal in Example 3, 3- (3-fluoro-2 is obtained. -methoxyphenyl) -cyclopentyl) -2-hydroxy-2-trifluoromethyl-pentanal starting from 2,6-difluoroanisole and cyclopentanecarbonitrile. XH-NMR (CD3OD): d = 1.15-2.26 (m, 8H), 2.33 (d, HH), 3.11 (d, HH), 3.57 (s, HH), 3 , 98 (d, 3H), 6.82-6.93 (m, 2H), 6.94-7.05 (m, ÍH), 8.98 (s, 1H). -. { [7-fluoro-3-hydroxy-8-methoxy -3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclopentan-1,1-naphthalen-4-yl] amino.} - quinoline 2 ( ÍH) -one Using a procedure analogous to that described in example 10, starting with 350 g 3- ({3-fluoro-2-methoxy-phenyl) cyclobutyl} -2-hydroxy-2- (trifluoromethyl) pentanal and 190 mg of 5-amino-quinolin-2 (HH) -one, the corresponding imine is obtained.An analogous manner to that described in example 3, the imine is transformed with 5.25 ml of titanium tetrachloride solution (ΔM). in dichloromethane) and 193 mg of the title compound are obtained.XH-NMR (CDC13): d = 1.53-1.67 (m, 1H), 1.73-2.15 (m, 6H), 2, 28-2.48 (m, 3H), 3.95 (d, 3H), 4.81 (bs, ÍH), 5.06 (d, ÍH), 5.55 (d, ÍH), 6.47 -6.58 (m, 3H), 6.82 (dd, ÍH), 6.93 (dd, ÍH), 7.32 (t, ÍH), 8.18 (d, ÍH) Example 257 5- { [3,8-Dihydroxy-7-fluoro-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclopentan-1, 1'-naphthalen-4-yl] amino.}. -quinolin- 2 (1H) -one Employ A procedure analogous to that described in example 3, starting with 60 mg of 5-. { [7-fluoro-3-hydroxy-8-methoxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclopentan-1,1'-naphthalen-4-yl] amino.} - -quinolin-2 (1H) -one with 0.25 ml of BBr3 solution (IM in dichloromethane) at room temperature gives 17 mg of the title compound.

XH-NMR (CD3OD): d = 1.45-1.57 (m, ÍH), 1.72-1.88 (m, 2H), 1.90-2.12 (m, 3H), 2, 18-2.43 (m, 3H), 2.70-2.85 (m, ÍH), 5.18 (s, ÍH), 6.51 (d, ÍH), 6.63 (d, ÍH) , 6.70 (d, 1H), 6.78 (dd, ÍH), 6.87 (dd, ÍH), 7.38 (t, ÍH), 8.22 (d, 1H). Example 258 5-. { [2,5-dihydroxy-4,4-dimethyl-7-fluoro-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Using a procedure analogous to that described in Example 10, starting with 1.0 g 4- (4-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 560 mg of 5-amino-2-methylphthalazin-1-one, the corresponding imine is obtained. As in Example 3, the imine formed is converted by reaction with 10 ml of boron tribromide solution (1M in dichloromethane) and 45 mg of the title compound are obtained. XH-NMR (DMSO): d = 1.47 (s, 3H), 1.59 (s, 3H), 1.97 (d, 1H), 2.07 (d, ÍH), 3.70 (s) , 3H), 5.41 (s, ÍH), 6.11 (s, ÍH), 6.41 (dd, ÍH), 6.56 (dd, 1H), 7.27 (d, ÍH), 7 , 48 (d, ÍH), 7,59 (t, ÍH), 8,63 (s, ÍH), 10,00 (s, ÍH). Examples 259 and 260 (-) -5-. { [2,5-Dihydroxy-4,4-dimethyl-7-fluoro-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one and (+) -5-. { [2,5-dihydroxy-4,4-dimethyl-7-fluoro-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Separation of (+/-) -5-. { [2,5-dihydroxy-4,4-dimethyl-7-fluoro-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one: The mixture of enantiomers is separated by chromatography on chiral substrate (CHIRALPAK ADO, Fa DAICEL) with hexane / ethanol (90: 10, vw). In this way the (-) enantiomer is obtained: MS (El): M + = 451, [a] d -34.6 ° (c = 1.3, CHC13) and the enantiomer (+): MS (El): M + = 451, [a] D + 35.4 ° (c = 1.3, CHC13). Examples 261 and 262 5-. { [7-Bromo-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, Diastereomer B and 5-. { [7-Bromo-2,5-dihydroxy-4,4-dimethyl-2 - (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one. Diastereomer A Using a procedure analogous to that described in example 10, starting with 800 mg of 4- (4-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 380 mg of 5- amino-2-methylphthalazin-1-one, the corresponding imine is obtained. As in Example 3, the imine formed by reaction is converted with 9.4 ml boron tribromide solution (IM in dichloromethane) and 37 mg of diastereomer B of 5 are obtained. { [7-bromo-2, 5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3, -tetrahydronaphthalen-1-yl] amino} -2- ethylftalazin-1-one as fraction A and 11 mg of diastereomer A of 5-. { [7-bromo-2,5-dihydroxy-, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one as fraction B. Fraction A: XH-NMR (CD3OD): d = 1.40 (s, 3H), 1.55 (s, 3H), 1.92 (d, 1H ), 2.25 (d, ÍH), 3.84 (s, 3H), 5.27 (s, ÍH), 6.70 (d, ÍH), 7.19-7.29 (m, 2H) , 7.51 (t, ÍH), 7.60 (d, ÍH), 8.52 (s, ÍH). Fraction B: XH-NMR (CD3OD): d = 1.55 (s, 3H), 1.66 (s, 3H), 2.07 (d, ÍH), 2.15 (d, ÍH), 3, 83 (s, 3H), 5.24 (s, ÍH), 6.88 (d, 1H), 6.94 (d, 1H), 7.18-7.28 (m, ÍH), 7.62 -7.70 (m, 2H), 8.56 (s, 1H). Example 263 5-. { [7-chloro-3,8-dihydroxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclohexane-1, 1'-naphthalen-4-yl] amino.}. -quinolin-2 (1H) ) -one 3- [1- (3-chloro-2-methoxyphenyl) -cyclohexyl] -2-hydroxy-2- (tri-trifluoromethyl) propanal 9.57 g (30.79 mmol) of 3- [1- (3-chloro-2-methoxyphenyl) -cyclohexyl] -2-oxopropionic acid (this compound was prepared, starting from the corresponding starting materials, analogously to that described in WO 98/54159) with 191 ml of ethanol and 3.4 ml of concentrated sulfuric acid After cooking at reflux for five hours, the preparation is centrifuged to dryness and the residue is mixed with 500 ml of saturated sodium bicarbonate solution, the aqueous phase is extracted three times with acetate The ethyl acetate and the combined organic extracts are washed with saline solution, and after drying and removal of the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane) to obtain 7.07 g (67%). , 8%) of the desired ester. 7.7 g (20.87 mmol) ethyl-3- [1- (3-chloro-2-methoxyphenyl) -cyclohexyl] -2-oxopropionate are dissolved in 33 ml of tetrahydrofuran and mixed with 3.56 g (25 g). , 04 mmol) (trifluoromethyl) -trimethylsilane. After the addition of 51.1 mg of tetrabutylammonium fluoride, the preparation is stirred overnight. The reaction mixture is diluted with methyl tert-butyl ether, washed once with water and then with saline. After working up in a conventional manner, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). The 5.71 g (60.4%) of the isolated product are mixed in 70 ml of tetrahydrofuran with 3.98 g (12.61 mmol) of tetrabutylammonium fluoride and stirred one hour at room temperature. After mixing the reaction mixture with water, it is extracted with methyl tert-butyl ether. After carrying out a processing using conventional means, the residue is subjected to flash chromatography. 2.63 g (51.1%) of the desired compound are isolated: ethyl-2- [1- (3-chloro-2-methoxyphenyl) -cyclohexylmethyl] -3,3,3-trifluoro-2-hydroxypropionate. 1.59 g (3.89 mmol) of the ester described above are dissolved in 14 ml of diethyl ether and mixed at 0 ° C in portions with 110.7 mg (2.92 mmol) of lithium aluminum hydride. After stirring two hours at 0-5 ° C, 3.4 ml of saturated sodium bicarbonate solution are carefully added dropwise. Stir vigorously for ten minutes at room temperature. After extracting the aqueous phase several times with methyl tert-butyl ether, the combined organic extracts are treated using conventional means. After flash chromatography, 750 mg (52.8%) of a mixture consisting of two thirds of the desired aldehyde and one third of the ester are obtained. At the same time 201.4 mg of the respective alcohol (not purified) are obtained. 5-. { 2 [1- (3-chloro-2-methoxyphenyl) -cyclohexylmethyl] -3,3,3-trifluoro-2-hydroxy-propylideneamino} -IH-quinolin-2 -one 375 mg (0.683 mmol) of the aldehyde described in the previous paragraph (together with the ester) are heated in 3.6 ml xylol with 109.4 mg (0.683 mmol) 5-amino-1H- quinolin-2-one and 388.3 mg (1.366 mmol) titanium-IV isopropylate for three hours at reflux. After cooling, the reaction mixture is mixed with a saturated solution of sodium chloride and ethyl acetate. After stirring vigorously for ten minutes, pour the mixture over Extrelut and elute with 100 ml of dichloromethane. After removing the solvent by centrifugation, the remaining residue is subjected to flash chromatography. Isolates, in addition to 145 mg of ester, 231.6 mg (66.9%, based on the aldehyde content) of the desired imine. XH-NMR (300 MHz, CDC13): d = 1.15-2.18 (9 H), 2.38-2.65 (2H), 2.96 (IN), 3.93 (3H), 4 , 61 (ÍH), 6,40-6,60 (2H), 6,62-6,81 (2H), 7,08 (ÍH), 7,29-7,59 (3H), 8,07 ( ÍH), 12.28 (ÍH). 5-. { (7-chloro-3-hydroxy-8-methoxy -3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclohexane-1, 1 '-naph' alen- -yl)] amino.}. -quinolin -2 (1H) -one 151.6 mg (0.299 mmol) of the imine described above are dissolved in 2.8 ml of dichloromethane, after adding 1.96 ml (1.796 mmol) of titanium tetrachloride to -15. After stirring for 4 hours at this temperature, saturated sodium bicarbonate solution is carefully added at 0 ° C. The reaction mixture is extracted three times with ethyl acetate, the combined organic extracts are washed with saline, dried and dried. The solvent is removed, after carrying out flash chromatography, 67.9 mg (44.8%) of the desired compound are obtained XH-NMR (300 MHz, CD3OD): d = 1.30-1.90 (8H), 2.18 (ÍH), 2.30 -2.50 (1H), 2.53-2.70 (HH), 2.90 (ÍH), 4.00 (3H), 5.19 (ÍH), 6.52 (1H), 6.62 (1H), 6.70 (ÍH), 7.09 (ÍH), 7.23 (1H), 7.38 (1H), 8.23 (HH). 5- . { (7-chloro-3,8-dihydroxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclohexane-1, 1'-naphthalen-4-yl)] amino.} - quinoline 2 (H H) -one 65.9 mg (0.13 mmol) of the cyclic ether described in the previous paragraph are mixed with 2.6 ml boron tribromide (1M in dichloromethane) and stirred for three hours at room temperature. The solution is carefully added dropwise to a saturated solution of sodium bicarbonate and the reaction mixture is then extracted three times with ethyl acetate.The combined organic extracts are dried with sodium sulfate and the residue left after removing the The solvent is subjected to flash chromatography, 51.3 mg (80.1%) of the desired phenol are isolated XH-NMR (300 MHz, DMSO-d6): d = 1.15-1.87 (8H), 2, 01 (ÍH), 2.40 -2.90 (3H, the DMSO signal also falls in this range), 5.29 (1H), 6.02 (1H), 6.20 (ÍH), 6.43 (ÍH), 6.48-6.65 (2H), 6.75 (1H), 7.15-7.30 (2H), 8.20 (ÍH), 9.10 (ÍH), 11.58 (ÍH) Example 264 5- { [7-Chloro-3,8-dihydroxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclohexane-1,1 '-naphthalen-4-yl) -lamino} -2H-isoquinolin-1-one 5-. { [7-chloro-3-hydroxy-8-methoxy -3- (trifluoromethyl) -3,4-dihydro-2 H-spiro (cyclohexane-1, 1'-naph'-talen-4-yl)] amino} -2H- isoquinolin-1-one 149.7 mg (0.295 mmol) of imine (prepared as described for example 263, using the corresponding starting materials) are cyclized with 1.93 ml (1.772 mmol) titanium tetrachloride. After usual work-up using conventional means and chromatography, 34.9 m (23.3%) of the desired compound are obtained. XH-NMR (300 MHz, DMS0-d6): d = 1.20-1.85 (8H), 2.05-2.50 (3H), 2.69 (1H), 3.93 (3H), 5.34 (HH), 5.98 (ÍH), 6.13 (ÍH), 6.80 (ÍH), 6.97 (ÍH), 7.05 (HH), 7.18 (ÍH), 7 , 20-7.38 (2H), 7.50 (1H), 11.25 (1H). 5-77 -chloro-3, 8-dihydroxy -3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclohexane-1,1'-naph: talen-4-yl)] amino} -2H-isoquinolin-1 -one 26.8 mg (0.053 mmol) of the ether described above is subjected to ether separation, as described in Example 263. After the usual development of the reaction and chromatography, 13.5 mg (51.8%) of the desired phenol are obtained. XH-NMR (300 MHz, DMS0-d6): d = 1.15-1.85 (8H), 2.00 (ÍH), 2.40-2.90 (3H), 5.30, (ÍH), 5.95 (ÍH), 6.09 (1H), 6.73 (HH), 6.81 (1H) , 7.04 (1H), 7.10-7.30 (3H), 7.50 (IH), 9.12 (IH), 11.23 (IH). Example 265 1'-Chloro-4 '- [(8-fluoro-2-methylquinazolin-5-yl) amino] -3', 4 '-dihydro-8' -methoxy-3 '- (trifluoromethyl) -spiro [cyclohexane -1, 1 '(2'H) -naphthalene] -3' -ol To 129.8 mg (0.248 mmol) of the corresponding imine, dissolved in 2.4 ml of dichloromethane, are added dropwise at 20 ° C. 61 ml (1.488 mmol) titanium chloride-IV. After stirring an hour and a half at a temperature between -20 ° C and + 5 ° C, the preparation is processed using conventional means. They are isolated after carrying out flash chromatography, 11.4 mg (8.8%) of the desired compound. MS (Cl): 524 (100%) Example 266 5-. { [7-chloro-3-hydroxy-8-methoxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclopropyl-1, 1'-naphthalen-4-yl)] amino} -quinolin-2 (1H) -one 3 - [1 - (3-chloro-2-methoxyphenyl) -cyclopropyl] -2-hydroxy-2 - (trifluoromethyl) propanal 15.12 g (56.27 mmol) were mixed. ) 3- [1- (3-chloro-2-methoxyphenyl) -cyclopropyl] -2-oxopropionic acid (this compound was prepared starting from the corresponding initial materials, analogously to that described in WO 98/54159 ) with 350 ml of ethanol and 6.3 ml of concentrated sulfuric acid. After boiling for five hours at reflux, the preparation is centrifuged until it is dried and the residue is mixed with 700 ml of saturated sodium bicarbonate solution. The aqueous phase is extracted three times with ethyl acetate and the combined organic extracts are washed with sodium bicarbonate solution and saline. After drying and removing the solvent, the residue is chromatographed on silica gel (elution medium ethyl acetate / hexane). 12 are obtained, 36 g (74%) of the desired ester. 6.18 g (20.83 mmol) ethyl-3- [1- (3-chloro-2-methoxyphenyl) -cyclopropyl] -2-oxopropionate are dissolved in 33 ml of tetrahydrofuran and mixed with 3.55 g (24 g). , 99 mmol) (trifluoromethyl) -trimethylsilane. After the addition of 51 mg of tetrabutylammonium fluoride, the preparation is stirred overnight. The reaction mixture is diluted with methyl tert-butyl ether, washed once with water and then with saline. After usual work-up using conventional means, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). The 5.65 g (66.4%) of the isolated product are mixed in 76 ml of tetrahydrofuran with 4.34 g. (13.75 mmol) of tetrabutylammonium fluoride and stirred one hour at room temperature. After mixing the reaction mixture with water, it is extracted with methyl-tert-butyl ether. After performing usual processing using conventional means, the residue is subjected to flash chromatography. 2.39 g (47.4%) of the desired compound are isolated: ethyl-2- [1- (3-chloro-2-methoxyphenyl) -cyclopropylmethyl] -3,3,3-trifluoro-2-hydroxypropionate. 0.850 mg (2.32 mmol) of the ester described above are dissolved in 8 ml of diethyl ether and mixed in portions, at 0 ° C, with 66 mg (1.74 mmol) aluminum lithium hydride. After stirring for two hours at a temperature between 0 and 5 ° C, 2.7 ml of saturated sodium bicarbonate solution are carefully added dropwise. Thoroughly stir ten minutes at room temperature. After extracting the aqueous phase several times with methyl tert-butyl ether, the combined organic extracts are treated as usual, using conventional means. After carrying out flash chromatography, 490 mg (65.5%) of a mixture consisting of scarcely two thirds of the desired aldehyde and one third of the ester are obtained. 5-. { 2- [1 - (3-chloro-2-methoxy-enyl) -cyclopropylmethyl] -3,3,3-trifluoro-2-hydroxy-propylideneamino} -lH-quinolin-2 -one 490 mg (0.972 mmol) of the aldehyde described in the previous paragraph (as a mixture with the ester) in 5.1 ml xylol are heated with 155.7 mg (0.972 mmol) 5-amino -lH-quinolin-2-one and 552.6 mg (1.944 mmol) titanium-IV isopropylate for three hours at reflux. After cooling, the reaction mixture is mixed with a saturated solution of sodium chloride and ethyl acetate. After exhaustively stirring for ten minutes, the mixture is poured onto Extrelut and eluted with 200 ml of dichloromethane. After removing the solvent, the remaining residue is subjected to flash chromatography. In addition to 93.9 mg of ester, 312.8 mg (69.2%, based on the aldehyde content) of the desired imine are isolated.

XH-NMR (300 MHz, CDC13): d = 0.63-0.75 (1H), 0.79-0.90 (1H), 1.04-1.19 (2H), 2.10 (1H) ), 3.10 (ÍH), 4.00 (3H), 4.73 (ÍH), 6.74 (ÍH), 6.64 (ÍH), 6.75 (ÍH), 6.88-7, 02 (2H), 7.29-7.43 (2H), 7.70 (HH), 8.10 (ÍH), 12.32 (HH). 5-. { [7-chloro-3-hydroxy-8-methoxy -3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclopropan-1, 1'-naphthalene] amino] -quinoline-2 (1 H) -one 232.8 mg (0.501 mmol) of the imine described above are dissolved in 4.7 ml of dichloromethane, after 3.3 ml (3.009 mmol) titanium tetrachloride is added dropwise at -20 ° C. After stirring for 4 hours at this temperature, saturated sodium bicarbonate solution is carefully added at 0 ° C. The reaction mixture is extracted three times with ethyl acetate, the combined organic extracts are washed with saline, dried and eliminated. The solvent: After carrying out flash chromatography, 111.8 mg (48%) of the desired compound are obtained XH-NMR (300 MHz, DMSO-d6): d = 0.78-1.15 (3H), 1, 78-2.09 (3H), 3.75 (3H), 5.06, (HH), 6.10-6.30 (3H), 6.45 (1H), 6.60 (HH), 6 , 98 (ÍH), 7,20 (ÍH), 7,30 (ÍH), 8,23 (ÍH), 11,60 (ÍH), Example 267 5- { [7-chloro-3,8- dihydroxy-3- (trifluoromethyl) -3,4-dihydro- 2H-spiro (cyclopropan-1, 1'-naph alen-4-yl)] amino} -2H-isoquinolin-1-one 5-. { [7-chloro-3-hydroxy-8-methoxy-3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclopropan-1,1-naphthalen-4-yl)] amino} -2H-i soquinolin-1-one 113.8 mg (0.245 mmol) of imine are cyclized (prepared as described in example 263, using the corresponding starting materials), dissolved in 2.3 ml of dichloromethane, with 1, 6 ml (1.472 mmol) titanium tetrachloride. After carrying out customary processing using conventional means and chromatography, 36.8 m (32.3%) of the desired compound are obtained. XH-NMR (400 MHz, DMSO-d6): d = 0.80-1.12 (3H), 1.82-2.09 (3H), 3.76 (3H), 5.09, (1H) , 5.95 (ÍH), 6.37 (1H), 6.68 (ÍH), 6.81 (1H), 6.96 (1H), 7.16-7.28 (2H), 7.30 (1H), 7.52 (1H), 11.30 (1H). 5-. { [7-chloro-3,8-dihydroxy -3- (trifluoromethyl) -3,4-dihydro-2H-spiro (cyclo-propane-1,1-naphthalen-4-yl)] amino} -2H-i soquinolin-1-one 22.7 mg (0.049 mmol) of the ether described above is subjected to ether separation as described in Example 263. After carrying out the usual reaction using conventional means in and chromatography afforded 10.9 mg (45.5%) of the desired phenor. XH-NMR (400 MHz, CD30D): d = 0.55-0.63 (IN), 0.73-0.84 (HH), 1.40-1.51 (1H), 1.80 (ÍH), 1.95-2.10 (2H), 5.02 (1H), 6.69 (ÍH), 6.75. (1H), 6.80 (ÍH), 6.98 (1H), 7.08 (1H), 7.25 (HH), 7.59 (HH). Exa 268 1'-chloro-4 '- [(8-fluoro-2-methylquinazolin-5-yl) amino] -3', 4 '-dihydro-3' - (trifluoromethyl) spiro [cyclopropan-1,1 '( 2'H-naphthalene] -3 ', 8'-diol 7'-chloro-4 - [(8-f-luoro-2-methyl-tyzolin-5-yl) amino] -3,4-dihydro-8' -methoxy- 3 '- (trifluoromethyl) -spiro [cyclopropan-1, 1' (2?) -naphthalene] -3'-ol A 121.3 mg (0.252 mmol) of the corresponding imine, dissolved in 2.4 ml of dichloromethane, Add drip at -20 ° C, 1.64 ml (1.512 mmol), titanium-IV chloride, after stirring an hour and a half at a temperature between -20 ° C and + 5 ° C the preparation is processed as is After a flash chromatography, 7.4 mg (6.1%) of the desired compound are isolated (with some impurities) XH-NMR (400 MHz, CDC13): d = 0.84-1.10 (3H) ), 1.92-2.13 (3H), 2.82 (3H), 3.79 (3H), 4.90 (1H), 5.65 (1H), 6.34 (IH), 7, 00 (ÍH), 7.16 (ÍH), 7.37 (ÍH), 9.35 (HH), 7'-chloro-4 '- [(8-fluoro-2-methyl-tzolin-5-yl] amino] -3. 4 ' -dihydro -3 '- (trifluoromethyl) spiro [cyclopropan-1, 1' (2 'H) -naphthalen] -3', 8'-diol 40 mg (0.083 mmol) of the corresponding imine are mixed at 0 ° C with 1.1 ml of an ÍM solution of boron tribromide in dichloromethane. After stirring three quarts of an hour at this temperature, a saturated solution of sodium bicarbonate is carefully added dropwise and then the reaction mixture is extracted three times with ethyl acetate. The combined organic extracts are washed with saline, dried and the solvent is removed. After carrying out flash chromatography 15 mg (38.6%) of the desired phenol are obtained. MS (Cl): 468 (100%). Exa 269 [6-Hydroxy-1-methoxy-8,8-dimethyl-5- (2-oxo-1,2-dihydroquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-2-yl] -acetonitrile Methyl -2-methoxy -3-methylbenzoate (RS 2690 F2) 199.9 g (1.45 mol) potassium carbonate are introduced into 1.5 1 dimethylformamide. At room temperature, 100 g (657.29 mmol) 2-hydroxy-3-methylbenzoic acid, dissolved in 250 ml of dimethylformamide, are added dropwise. After stirring for 30 minutes, 90 ml of methyl iodide are added dropwise and the preparation is stirred overnight. The reaction mixture is poured into ice-water and extracted three times with methyl-tert-butyl ether. The organic phases are washed with water and saline. After drying the solvent is removed and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). They are isolated 70.21 g (59.3%) of the desired compound. 'HN MR (300 MHz, CDC13): 6 = 2.32 (3H), 3.85 (3H), 3.93 (3H), 7.07 (ÍH), 7.35 (HH), 7.65 (ÍH). 2- (2-methoxy-3-methylphenyl) -propan-2-ol To 311.7 ml methylmagnesium bromide in diethyl ether are added dropwise 70.21 g (3M) (389.64 mmol) methyl-2 -methoxy-3-methylbenzoate, dissolved in 640 ml of tetrahydrofuran. With this, the reaction mixture is heated to prox. 48 ° C. The preparation is stirred three hours at room temperature. With cooling by an ice bath, approx. 1.5 1 saturated solution of ammonium chloride and stir for an hour thoroughly. After extracting three times with methyl tert-butyl ether, the combined organic extracts are washed with saline solution, seeca and the solvent is removed. 71.37 g (> 100%) of the desired compound are isolated, which is used raw in the next step. 'HN MR (300 MHz, CDC13): d = 1.65 (6 H), 2.33 (3 H), 3.89 (3 H), 4.55 (H), 6.99 (H), 7, 10 (1H), 7.18 (1H). Ethyl -4- (2-methoxy -3-methylphenyl) -4-methyl-2-oxopentanoate Prepare 71.37 g (395.96 mmol) 2- (2-methoxy-3-methylphenyl) -propan-2-ol and 149 g (791.92 mmol) ethereal ester of 2-trimethylsilanyloxyacrylic acid in 1.1 1 dichloromethane. At -78 ° C, 44.8 ml (379.91 mmol) of tin tetrachloride are added dropwise and the mixture is stirred for three hours at this low temperature. They are added by drip carefully 1, 4 1 of semiconcentrated potassium carbonate solution and the reaction mixture is brought to itself at room temperature. The preparation is filtered and the filtrate extracted three times with ethyl acetate. The combined organic extracts are washed with saline, dried with sodium sulfate and the solvent is removed. The residue is chromatographed several times on silica gel (elution medium: ethyl acetate / hexane). 45.81 g (41.6%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.30 (3H), 1.50 (6H), 2.30 (3H), 3,, 39 (2H), 3.78 (3H), 4.17 (2H), 6.97 (ÍH), 7.07 (HH), 7.15 (1H). Ethyl-2-hydroxy-4- (2-methoxy-3-methyl phenyl) -4-methyl-2- (trifluoromethyl) pentanoate. 20 g (71.90) ethyl-4- (2-methoxy-3-methyl) were combined. phenyl) -4-methyl-2-oxopentanoate and 12.3 g (86.28 mmol) (trifluoromethyl) trimethylsilane in 117 ml of tetrahydrofuran. At room temperature 180 mg tetrabutylammonium fluoride is added. (heat to 35 ° C). After stirring overnight 22.7 g (71.90 mmol) tetrabutylammonium fluoride is added and the preparation is stirred for three hours at room temperature. After diluting the methyl-tert-butyl ether, the organic phases are washed three times with water and once with saline. After drying and removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 16.33 g (65.2%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.19 (3H), 1.43 (3H), 1.49 (3H), 2.30-2.44 (4H), 2.82 (1H) , 3.50-3.68 (2H), 3.84 (3H), 4.00-4.13 (2H), 6.92 (1H), 7.00-7.10 (2H). 4- (2-methoxy -3-methylphenyl) -4-methyl- (trifluoromethyl) -pentane-1,2-diol 16.33 g (46.88 mmol) of the ester described above are dissolved in 160 ml of diethyl ether and it is mixed at 0 ° C and in portions with 3.56 g (93.76 mmol) lithium aluminum hydride. After stirring over the weekend at room temperature, a saturated solution of sodium bicarbonate is carefully added dropwise and then agitated thoroughly one hour. After extracting three times with methyl-tert-butyl ether, the combined organic extracts are washed with saline, dried and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane) after removal of the residue. solvent. 10.76 g (74.9%) of the desired diol are isolated. XH-NMR (300 MHz, CDC13): d = 1.49 (3H), 1.58 (3H), 1.84 (HH), 2.24 (ÍH), 2.36 (3H), 2.59. (HH), 2.88 (ÍH), 3.28-3.40 (2H), 3.88 (3H), 6.99 (1H), 7.10 (1H), 7.20 (2H). 4- (3-Bromomethyl-2-methoxy phenyl) -4-methyl-2- (trifluoromethyl) pentane -1,2-diol 3 g (9.79 mmol) 4- (2-methoxy-3-methylphenyl) are dissolved ) -4-Methyl- (trifluoromethyl) -pentane-1,2-diol in 22 ml of carbon tetrachloride and mixed with 1.91 g (10.60 mmol) NBS and 5 mg of benzoyl peroxide and fired 24 reflux hours. After filtering the succinimide in a glass fiber filter, it is again washed with dichloromethane and the solvent is removed. The residue (5.42 g> 100%) is used raw in the next step. [2-methoxy -3- (4,4,4-tri-fluoro-3-hydroxy-3-hydroxymethyl-1,1-dimethylbutyl) phenyl] acetonyl trichloride 5.42 g (14.07 mmol) of the bromine compound described above they are mixed with a mixture of dimethylformamide and water (14 and 10.5 ml) with 1.37 g (14.07 mmol) of potassium cyanide and stirred overnight at room temperature. The reaction mixture is mixed with water and extracted three times with methyl tert-butyl ether. The combined organic phases are washed with saline and after drying, the solvent is removed by centrifugation. After carrying out flash chromatography 2.6 g (55.8%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.49 (3H), 1.60 (3H), 1.72 (1H), 2.22 (1H), 2.50 (1H), 2.92. (1H), 3.20-3.45 (2H), 3.80 (2H), 3.88 (3H), 7.13 (1H), 7.30-7.42 (2H). (2-methoxy -3- (4, 4, 4-trifluoro-3-hydroxy-3-formyl-1,1-dimethylbutyl) phenyl] acetonyl trile 0.26 ml (2.99 mmol) oxalyl chloride is cooled 6.6 ml of dichloromethane at -78 ° C. After adding 0.42 ml (5.98 mmol) dimethyl sulfoxide, dissolved in 1.2 ml of dichloromethane, stirring is carried out for a further 10 minutes and then added dropwise. 900 mg (2.72 mmol) [2-methoxy-3- (4,4,4-trifluoro-3-hydroxy-3-hydroxymethyl-1,1-dimethylbutyl) phenyl] acetonitrile in 2.6 ml of dichloromethane. After stirring for two hours at -78 ° C., 1.88 ml (13.58 mmol) of triethylamine are added dropwise, the preparation is allowed to come to room temperature and then stirred for one hour and a half at room temperature. The water is extracted three times with dichloromethane, the combined organic extracts are washed with 1% sulfuric acid., with saturated solution of sodium bicarbonate and with saline solution. After drying and removing the solvent, the residue is subjected to flash chromatography. 599.4 mg (67.1%) of the desired aldehyde remain. XH-NMR (300 MHz, CDC13): d = 1.45 (3H), 1.51 (3H), 2.32 (1H), 3.20 (HH), 3.51 (ÍH), 3.78 (2H), 3.89 (3H), 7.09 (1H), 7.19 (HH), 7.35 (ÍH), 9.06 (HH). . { 2-methox: i-3- (4, 4, 4-trifluoro-3-hydroxy -1, 1 -dimethyl -3 - [(2-oxo-l, 2-dihydroquinolin-5 -limino) -methyl] - butyl) -phenyl} acetoni trilo 200 mg (0.607 mmol) of the aldehyde described above are heated in 3.4 ml xylol with 97.3 mg (0.607 mmol) 5-amino-1H-quinolin-2 -one and 345.1 mg (1.214 mmol) titanium-IV isopropylate for three hours at reflux. After the reaction is complete, saline and ethyl acetate are added. After stirring thoroughly for 30 minutes at room temperature, pour the preparation onto Extrelute and elute with 200 ml of dichloromethane. After removing the solvent the residue is subjected to flash chromatography. 228.7 mg (79.8%) of the desired imine are isolated. XH-NMR (300 MHz, CDC13): d = 1.45 (3H), 1.59 (3H), 2.38 (1H), 3.26 (1H), 3.34-3.55 (2H) , 3.85 (3H), 4.66 (ÍH), 6.29 (ÍH), 6.69-6.80 (2H), 6.90 (ÍH), 7.16 (1H), 7.30 -7.47 (2H), 7.51 (ÍH), 7.97 (ÍH), 12.18 (HH). [6-Hydroxy-1-methoxy-8,8-dimethyl-5- (2-oxo-1,2-dihydroquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene- 2-yl] -acetoni triole 141.2 mg (0.299 mmol) imine are mixed at 0 ° C with 4.5 ml of an ÍM solution of boron tribromide in dichloromethane and stirred for four hours. After dropping in a saturated solution of sodium bicarbonate, it is extracted three times with ethyl acetate. The combined organic extracts are washed with saline. After drying and removing the solvent the residue is subjected to flash chromatography. 8 mg (5.8%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.52 (3H), 1.70 (3H), 2.05 (ÍH), 2.19 (ÍH), 3.69 (2H), 3.79 (3H), 5.00-5.16 (2H), 5.64 (1H), 6.38 (ÍH), 6.50 (ÍH), 6.62 (ÍH), 7.05-7.19 (2H), 7.30 (ÍH), 8.15 (1H), 10.76 (1H). EXAMPLE 270 [5- (8-Fluoro-2-methylquinazolin-5-ylamino] -6-hydroxy-l-methoxy-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronafallen- 2-yl] -acetonitrile {2-methoxy -3- [4, 4, 4-tri-fluoro-3- (8-fluoro-2-methylquinazolin-5-yl-iminomethyl) -3-hydroxy-1, -dimethylbutyl] phenyl.} acetoni trilo 200 mg (0.61 mmol) of the aldehyde described in Example 269 are heated with 107.5 mg (0.61 mmol) 5-amino-8-fluoro-2-methylquinazolin and 345 , 1 mg (1.214 mmol) titanium tetrachloride in 3.4 ml xylol for 3 hours at reflux.After usual processing using conventional means and chromatography, 129.5 mg (43.7%) of the desired imine are isolated. XH-NMR (300 MHz, CDC13): d = 1.41 (3H), 1.67 (3H), 2.35 (1H), 2.99 (3H), 3.35 (1H), 3, 38-3.56 (2H), 3.85 (3H), 4.61 (ÍH), 6.50-6.60 (2H), 6.75 (ÍH), 7.17 (ÍH), 7, 45 (HH), 7.55 (ÍH), 9.47 (HH). [5- (8 ~ fluoro-2-methylquinazolin-5-ylamino) -6-hydroxy-1-methoxy-8, 8-dimethyl- 6- (trifluoromethyl) l) -5,6,7,8-tetrahydronaphthalen-2-yl] -acetonitrile 100.9 mg (0.21 mmol) of the above-described imine are cyclized and processed as usual with 3.1 ml of a 1M solution of boron tribromide in dichloromethane at 0 ° C. They are isolated after carrying out flash chromatography and following separation of plates, 7.5 mg (7.7%) of the desired compound. XH-NMR (300 MHz, CDC13): d = 1.58 (3H), 1.74 (3H), 2.09-2.28 (2H), 2.95 (3H), 3.78 (2H) , 3.83 (3H), 5.02 (ÍH), 5.30 (ÍH), 5.61 (ÍH), 6.69 (1H), 7.18-7.32 (2H), 7.50 (ÍH), 9.38 (ÍH). Example 271 1- (7-Fluoro-2-methylquinazolin-5-ylamino) -5-methoxy-4,4,6-trimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalene-2-ol 2 -hydroxy -4 - (2-methoxy -3-methyl phenyl) -4-methyl-2- (trifluoromethyl) pentanal 2 g (6.53 mmol) of 4- (2-methoxy-3-methylphenyl) -4- Methyl- (trifluoromethyl) -pentane-1,2-diol described in Example 269 are oxidized according to Swern analogously to that described in this example to give the aldehyde. After usual work up using conventional means and purification by flash chromatography, 1.20 g (60.3%) of the desired aldehyde are isolated. XH-NMR (300 MHz, CDC13): d = 1.46 (3H), 1.50 (3H), 2.23 (1H), 2.32 (3H), 3.38 (1H), 3.60 (HH), 3.85 (3H), 6.93 (ÍH), 7.00 (ÍH), 7.10 (1H), 8.95 (1H). 1, 1, 1- trifluoro-2- [(7-fluoro-2-methyl-tyzolin-5-ylimino) -methyl] -4 - (2-methoxy -3-methylphenyl) -4-methylpentan-2-ol 150 mg ( 0.493 mmol) of the described aldehyde are transformed as usual and as already described several times with 87.3 mg (0493 mmol) 5-amino-7-fluoro-2-methylquinazoline and 280.3 mg (0.986 mmol) tetraisopropylate. titanium in 2.5 ml xylol to give the imine. After chromatography, 174.9 mg (76.6%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.41 (3H), 1.65 (3H), 2.01 (3H), 2.29 (1H), 2.90 (3H), 3.49 (ÍH), 3.80 (3H), 4.55 (1H), 6.19 (ÍH), 6.50-6.60 (2H), 7.03 (HH), 7.40 (HH), 7.62, (1H), 9.30 (1H). 1- (7-f luoro-2-methylquinazolin-5-ylamino) -5-methoxy-4, 4,6-trimethyl-2- (trifluoromethyl) -1, 2, 3, 4 -tetrahydronaf talen 2 -ol They are cyclized 174.9 mg (0.377 mmol) of the imine described above with titanium tetrachloride in dichloromethane at 0 ° C. The execution, the processing and the chromatography is carried out as already described several times. 159.7 mg (91.3%) of the desired compound are isolated as a mixture of diastereomers in a ratio of 9: 1 (the NMR data refer to the major diastereomers). XH-NMR (300 MHz, CDC13): d = 1.59 (3H), 1.73 (3H), 2.10-2.28 (2H), 2.32 (3H), 2.86 (3H) , 3.81 (3H), 4.99 (ÍH), 6.05 (ÍH), 6.10 (breit, ÍH), 6.52 (ÍH), 6.89 (ÍH), 6.95-7 , 16 (2H), 9.20 (1H). Example 272 1- (7,8-difluoro-2-methylquinazolin-5-ylamino) -5-methoxy-4,4,6-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthale-2- ol 1, 1, 1-tri-fluoro-2 - [(7,8-difluoro-2-methyl-tyzoline-5-ylimino) -methyl] -4- (2-methoxy-3-methyl phenyl) -4-methylpentan-2 150 mg (0.493 mmol) of the described aldehyde are transformed as usual and as already described several times with 96.2 mg (0.493 mmol) 5-amino-7,8-difluoro-2-methylquinazoline and 280.3 mg (0.986 mmol) titanium tetraisopropylate in 2.5 ml xylol to obtain imine. After chromatography, 155.5 mg (65.5%) of the desired compound are isolated.

XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.63 (3H), 2.07 (3H), 2.28 (1H), 2.98 (3H), 3.50 (ÍH), 3.83 (3H), 4.49 (ÍH), 6.28 (ÍH), 6,52-6,62 (2H), 7,03 (ÍH), 7,62 (ÍH), 9.36 (ÍH). 1- (7,8-difluoro-2-methyl-tyzolin-5-ylamino) -5-methoxy-4,6-, -trimethyl-2 - (trifluoromethyl) -1, 2, 3, 4 -tetrahydronaf talen-2- ol 155.5 mg (0.323 mmol) of the imine described above are cyclized with titanium tetrachloride in dichloromethane a 0 ° C. The execution, processing and romatography is carried out as already described several times. 101.6 mg are isolated (65.3%) of the desired compound. XH-NMR (300 MHz, CDC13): d = 1.60 (3H), 1.73 (3H), 2.08-2.28 (2H), 2.32 (3H), 2.93 (3H) , 3.81 (3H), 4.93 (ÍH), 5.42 (1H), 5.81 (ÍH), 6.58 (ÍH), 6.95-7.09 (2H), 9.24 (ÍH). EXAMPLE 273 5- [2,6-Dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino] -2-methyl-2H-phthalazin-1-one 2 - (3-methoxyphenyl) -2-methylpropanonitrile 50 g (339.72 mmol) 3-methoxybenzyl cyanide in 530 ml of DMF are dissolved and 96.4 g (6792.4 mmol) methyl iodide are added. After cooling to 0 ° C, 21.5 g are added (492.2 mmol) NaH (55% suspension) portionwise to the reaction mixture over the course of four hours. After 18 hours at room temperature the preparation is poured over 700 ml of ice water and extracted three times with 500 ml of diethyl ether at a time. The combined organic phases are washed with water and saline. After drying with sodium sulfate, remove the drying medium and the solvent in a rotary evaporator by filtration. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 48.9 g (82.2%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.73 (6 H), 3.85 (3 H), 6.85 (1 H), 7.02 (H), 7.07 (1 H), 7, 31 (1H). 2- (3-methoxy phenyl) -2-methylpropanal 25 g (142.67 mmol) of the nitrile described above are dissolved in 570 ml of toluene. At -65 to -60 ° C, 178 ml of a 1.2 molar solution of DIBAH in toluene are added dropwise over the course of 75 minutes. After stirring for two hours at this temperature, 815 ml of a solution of 20% L- (+) - tartaric acid is added dropwise. After 150 milliliters the temperature has risen to -10 ° C. The rest of the tartaric acid solution is added continuously and the preparation is stirred for 16 hours thoroughly at room temperature. The reaction mixture is stirred twice with 600 ml of diethyl ether at a time. The combined organic extracts are stirred with water and saline, dried and the solvent is removed. The residue obtained (25.1 g = 98.8%) is used in the crude in the next step. XH-NMR (300 MHz, CDC13): d = 1.47 (6 H), 3.83 (3 H), 6.78-6.90 (3 H), 7.30 (H), 9.50 (1 H) ). Ethyl-E-4- (3-methoxy-enyl) -methylpent-2-enoate 33.6 g (114.3 mmol) triethylene ester of phosphonacetic acid are placed in 148 ml of tetrahydrofuran. At 0 ° C, 79.7 ml of a 2M solution of LDA in THF / heptane / ethylbenzene are added dropwise (one and a half hours). After stirring for 1 hour, 24.3 g (136.34 mmol) 2- (3-methoxyphenyl) -2-methylpropanal, dissolved in 130 ml of tetrahydrofuran, are added dropwise at 0 ° C. After stirring five duos at room temperature, the reaction mixture is poured onto 250 ml of dilute ammonium chloride and extracted twice with 400 ml of diethyl ether at a time. The combined organic extracts are treated as usual and the resulting residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 27.2 g (80.4%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.30 (3H), 1.49 (6H), 3.81 (3H), 4.20 (2H), 5.80 (1H), 6, 78 (1H), 6.85 (1H), 6.90 (1H), 7.12 (HH), 7.25 (HH). Ethyl -4 - (3-methoxyphenyl) -4-methylpentanoate 27.2 g (109.5 mmol) ethyl-E-4- (3-methoxyphenyl) -4-methylpent-2-eneat in 293 ml of ethyl acetate was mix with 2.72 g palladium on charcoal (10%) and stir 18 hours under a hydrogen atmosphere at room temperature. The catalyst is removed by filtering on a glass fiber filter and the residue remaining after copying (27, 2 g = 99.2%) is used raw, in the next reaction. XH-NMR (300 MHz, CDC13): d = 1.21 (3H), 1.32 (6H), 1.90-2.10 (4H), 3.82 (3H), 4.05 (2H) ), 6.74 (1H), 6.89 (ÍH), 6.93 (ÍH), 7.25 (1H). Ethyl-4- (3-methoxyphenyl) -2-hydroxy-4-methylpentanoate. 27.2 g (108.65 mmol) ethyl-4- (3-methoxyphenyl) -4-methylpentanoate are dissolved in 380 ml of tetrahydrofuran and the mixture of reaction is cooled to -70 ° C to -65 ° C. In the course of two hours, 304 ml of a 0.5 molar solution of potassium bis- (trimethylsilylamide) in toluene are added dropwise and then the reaction mixture is stirred for 75 minutes at -70 ° C. Then 39.7 g are added per drip (152.11 mmol) Davis's reagent, dissolved in 380 ml of tetrahydrofuran, over the course of 90 minutes. After stirring for two hours at -70 ° C, 195 ml of a saturated solution of ammonium chloride are slowly added dropwise, the cold bath is removed and the mixture is thoroughly stirred for 30 minutes. After extracting with diethyl ether (twice with 800 ml at a time), the combined organic extracts are treated as usual using conventional means with water and saline.

After removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 20.9 g (72.4%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.29 (3H), 1.40 (3H), 1.48 (3H), 1.85 (1H), 2.20 (1H), 2.50 (ÍH), 3.81 (3H), 3.99 (1H), 4.18 (2H), 6.76 (ÍH), 6.95 (ÍH), 7.00 (ÍH), 7.28 ( ÍH). Ethyl-4- (3-methoxy phenyl) -4-methyl-2-oxopentanoate 2019g (78.47 mmol) ethyl 4- (3-methoxyphenyl) -2-hydroxy-4-methyl-pentanoate are dissolved in 820 ml of dichloromethane and mixed with 273 ml of dimethyl sulfoxide. After the addition of 39.7 g (392.36 mmol) of triethylamine the preparation is mixed in portions with 31.2 g (196.18 mmol) S03 / pyridine complex and then stirred for 16 hours at room temperature. They are removed approx. 400 ml of dichloromethane in a rotary evaporator. The reaction mixture is then mixed with 312 ml of saturated ammonium chloride solution while cooling slightly and thoroughly stirring for 20 minutes. After extracting twice with diethyl ether (800 ml at a time), the combined organic phases are washed with water and saline. The residue remaining after removing the solvent is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 15.59 g (75.3%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.28 (3H), 1.48 (6H), 3.18 (2H), 3.80 (3H), 4.12 (2H), 6, 74 (ÍH), 6.90 (ÍH), 6.95 (1H), 7.25 (ÍH). Ethyl-4- (3-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2 - (trimethylsilyloxy) -pentanoate. 15.59 g (58.98 mmol) ethyl-4- (3-methoxyphenyl) - are dissolved. 4-Methyl-2-oxopentanoate in 96 ml of tetrahydrofuran and mix at 0 ° C with 10.1 g (70.78 mmol) (trifluoromethyl) -trimethylsilane. After the addition of 144.5 mg tetrabutylammonium fluoride is stirred two and three fourth hours at 0-5 ° C. The preparation is poured into 150 ml of ice water, extracted twice with diethyl ether (300 ml at a time) and the combined organic extracts are treated as usual using conventional means. After removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 17.10 g (71.3%) of the desired (contaminated) product is isolated, which is used as such in the next step. 4- (3-methoxyphenyl) -2- (trifluoromethyl) pentane -1,2-diol 6.77 g (16.65 mmol) (rae.) Ethyl-4- (3-methoxyphenyl) -4-methyl- are dissolved. 2- (trifluoromethyl) -2- (trimethylsilyloxy) -pentanoate in 61 ml of diethyl ether and mix at 0 ° C, in portions, with 1.26 g (33.31 mmol) aluminum hydride and lithium. The reaction mixture is stirred one hour at 5 ° C and one and a half hours at room temperature. For hydrolysis, the mixture is mixed by dripping with 30 ml of saturated NaHC03 solution while cooling in an ice bath. The mixture is stirred for one hour with an ice bath and exhaustively at room temperature overnight. The precipitate is filtered off and washed with diethyl ether. The filtrate is concentrated on a rotary evaporator and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 5.64 g (71.2%) of a mixture are isolated in which the trimethylsilyl group is partially in the primary and partly in the secondary hydroxyl group. Therefore, the mixture (5.64 g) is dissolved without further purification in 72 ml of tetrahydrofuran and mixed with 4 g (12.79 mmol) of tetrabutylammonium fluoride, trihydrate and stirred 90 minutes at room temperature. The reaction mixture is diluted with water and extracted twice with 150 ml of diethyl ether at a time. After washing the combined organic phase with water and saline, the solvent is dried and centrifuged. The crude product (5.8 g) is chromatographed on silica gel (elution medium: ethyl acetate / hexane) together with another preparation (used 7.97 g).; yield, 10.4 g of crude product). 10.07 g of the desired diol are isolated from the two preparations. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.53 (3H), 2.10-2.25 (1H), 2.80 (IN), 3.29-3, 48 (2H), 3.83 (3H), 6.78 (ÍH), 6.97 (1H), 7.00 (ÍH), 7.28 (HH). 4 - (3-methoxy phenyl) -2-hydroxy-2 - (trifluoromethyl) -pentanal .07 g (34.45 mmol) of the diol described above are oxidized according to Swern as described several times to obtain the corresponding aldehyde. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 7.16 g (71.6%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.38 (3H), 1.48 (3H), 2.32 (HH), 2.69 (ÍH), 3.69 (1H), 3.82. (3H), 6.78 (1H), 6.88 (ÍH), 6.93 (1H), 7.25 (HH), 8.88 (1H). 5- [4- (3-methoxyphenyl) -2-hydroxy-methyl-2- (trifluoromethyl) -pentylideneamino) -2-methyl-2H-phthalazin-1 -one 300 mg (1.033 mmol) of 4- (3-methoxyphenyl) ) -2-hydroxy-2- (trifluoromethyl) -pentanal described above are converted with 180.9 mg (1.033 mmol) 5-amino-2-methyl-2H-phthalazin-1-one to imine. After the reaction, customary processing and chromatography, 318.2 mg (68.8%) of the desired imine are obtained. XH-NMR (300 MHz, CDC13): d = 1.36 (3H), 1.55 (3H), 2.49 (HH), 2.78 (ÍH), 3.50 (3H), 3.90. (3H), 4.72 (ÍH), 6.40 (ÍH), 6.59 (ÍH), 6.78 (ÍH), 6.90 (1H), 7.05 (ÍH), 7.28 ( ÍH, in practice under chloroform), 7,53 (ÍH), 8,30 (1H), 8,43 (ÍH). 5- (2-Hydroxy -6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3-tetrahydro-d-naphthalen-1-ylamino-2-methyl-2H-phthalazin-1-one cyclized 100 mg (0.223 mmol) of imine as in example 146 with titanium tetrachloride in dichloromethane 43.4 mg (43.4%) of the desired compound were isolated as a mixture of diastereomers MS (ES +): 448 ( 100%) 5- [2,6-dihydroxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-trahydronaphthalen-1-ylamino] -2-methyl-2H-phthalazine-1- The 37 mg (0.082 mmol) of the ether described in the previous paragraph are converted to boron tribromide as in Example 146. After the reaction and the usual workup, conventional means are used to obtain 20.9 mg (58.4%) of the desired compound as a mixture of diastereomers.

MS (ES +): 434 (100%). Example 274 1- (8-Fluoro-2-methylquinazolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene- 2,6-diol 4- (3-methoxyphenyl) -1,1-tri-fluoro-2-. { [8-Fluoro-2-methylquinazolin-5-ylimino] -methyl} -4-methyl-pentan-2-ol 400 mg (1.722 mmol) 4- (3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pentanal are converted to imine as in example 146 with 305.1 mg ( 1,722 mmol) 5-amino-8-fluoro-2-methylquinazoline. After chromatography, 494.4 mg (79.8%) of the desired imine are isolated. XH-NMR (CDC13): d = 1.34 (3H), '1.58 (3H), 2.40 (HH), 2.79 (ÍH), 3.00 (3H), 3.48 (3H) ), 4.78 (ÍH), 6.29-6.42 (2H), 6.74 (ÍH), 6.90 (1H), 7.00 (HH), 7.28-7.40 (2H) ), 9.64 (ÍH). 1- (8-Fluoro-2-methyl-tyzolin-5-ylamino) -6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-te trahidronaf talen-2-ol (AM 2016 150 mg (0.347 mmol) of imine are cyclized in 2.5 ml of dichloromethane at 0 ° C, with 1 ml of titanium tetrachloride as in example 146. After chromatography on silica gel (elution medium: methanol / dichloromethane) 87.1 mg (58.1%) of the desired compound are obtained. XH-NMR (300 MHz, CD30D): d = 1.42 (3H), 1.58 (3H), 2.08-2.23 (2H), 2.87 (3H), 3.79 (3H) , 5.28 (1H), 6.73 (1H), 6.82 (ÍH), 6.99 (ÍH), 7.23 (HH), 7.68 (ÍH), 9.68 (HH). 1- (8 ~ fluoro-2-methyl-tyzolin-5-ylamino) -4, -dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalene-2,6-diol 60 mg (0.133 mmol ) 4- (3-methoxyphenyl) -1,11-trifluoro-2- ([8-fluoro-2-methylquinazolin-5 -limino] -methyl) -4-methylpentan-2-ol while cooling with ice, with 1.3 ml of a 1M solution of boron tribromide in dichloromethane. After 45 minutes of stirring at room temperature the reaction mixture is mixed with ice and a saturated solution of sodium bicarbonate is added dropwise until a pH of 8 is reached. The bath is removed and the mixture is thoroughly stirred for 15 minutes. After extracting with ethyl acetate, the combined organic extracts are washed with water and then with saline solution. After drying, the solvent is removed and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). . You get finally 19, 5 mg (33.5%) of the desired compound. XH-NMR (300 MHz, CD3OD): d = 1.41 (3H), 1.56 (3H), 2.07-2.21 (2H), 2.89 (3H), 5.24 (1H) , 6.60 (1H), 6.78-6.91 (2H), 7.13 (1H), 7.59 (1H), 9.68 (1H). Example 275 5- (2,6-Dihydroxy-4, -dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H-isoquinolin-1-one 5- [2-hydroxy] -4- (3-methoxyphenyl) -4-methyl -2- (trifluoromethyl) pentylideneamino] -2H- i soquinolin-1 -ona 271 mg (0.936 mmol) 4- (3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pentanal are transformed, as already described several times, with 150 mg (0.936 mmol) 5-amino-2H-isoquinolin-1-one to obtain imine. After chromatography, 341.1 mg (84.5%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.33 (3H), 1.55 (3H), 2.39. (1H), 2.79 (ÍH), 3.56 (3H), 4.95 (ÍH), 6.38-6.55 (2H), 6.78 (ÍH), 6.79-6.95 (2H), 7.09 (ÍH), 7.12-7.35 (3H), 8.31 (HH), 11.09 (HH). 5- (2-Hydroxy -6-methoxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-1-ylamino) -2H-isoquinoline-l -one 150 mg (0.347) mmol) of the imine described above are cyclized as in example 274 with titanium tetrachloride in dichloromethane to obtain the desired compound. After chromatography, 18.8 mg (12.5%) are isolated. XH-NMR (300 MHz, CD3OD): d = 1.42 (3H), 1.58 (3H), 2.05-2.24 (2H), 3.79 (3H), 5.15 (1H) , 6.73 (1H), 6.89 (1H), 6.96 (ÍH), 7.05 (HH), 7.10-7.25 (2H), 7.49 (HH), 7.70 (1 HOUR) . 5- (2,6-dihydroxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H -i-soquinolin-1-one 90 mg are cyclized ( 0.208 mmol) of the imine described above as in Example 274 directly with boron tribromide to obtain free phenol. After carrying out customary processing using conventional means and chromatography, 53.8 mg (61.7%) of the desired compound are obtained in the form of a mixture of diastereomers in a ratio of 3: 2.

MS (ES +): 419 (100%). Example 276. 5- (2,6-Dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-etrahydronaf-alen-1-ylamino) -1H. -quinolin-2 -one 5- [2-hydroxy-4- (3-methoxy-phenyl) -4-methyl-2- (trifluoromethyl) -pentylideneamino] -IH-quinolin-2 -one 300 mg (1.033 mmol) 4- ( 3-methoxyphenyl) -2-hydroxy-2- (trifluoromethyl) -pentanal are transformed as already described several times, with 165.4 mg (1.033 mmol) 5-amino-lH-quinolin-2 -one to give imine. After chromatography, 414.3 mg (92.7%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.33 (3H), 1.53 (3H), 2.40 (1H), 2.78 (1H), 3.58 (3H), 4.85. (1H), 6.08 (ÍH), 6.49 (ÍH), 6.72-6.83 (2H), 6.90 (HH), 7.08 (HH), 7.28-7.38 (3H), 8,18 (ÍH), 12,53 (ÍH). 5- (2-Hydroxy-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-1-ylamino) -IH-quinolin-2 -one 150 mg (0.347 mmol) of the imine described above is cyclized as in example 274 with titanium tetrachloride in dichloromethane to obtain the desired compound. After chromatography, 35.8 mg (23.8%) of diastereomers A and another 14.3 mg (9.5%) of diastereomer mixture are isolated. The spectroscopic data refers to the purified diastereomer. XH-NMR (300 MHz, CD30D): d = 1.42 (3H), 1.59 (3H), 2.05-2.24 (2H), 3.80 (3H), 5.18 (1H) , 6.52 (ÍH), 6.61 (ÍH), 6.65-6.79 (2H), 6.95 (HH), 7.20 (ÍH), 7.39 (HH), 8.23 (ÍH). 5- (2,6-dihydroxy -4,4-dimethyl-2- (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-1-ylamino) -lH-quinolin-2-one 90 mg (0.208) are cyclized mmol) of the imine described above as in example 274 directly with boron tribromide to obtain free phenol. After carrying out customary processing using conventional means and chromatography, 37.6 mg (43.1%) of the desired compound are obtained in the form of a mixture of diastereomers in a ratio of 4: 1. MS (ES +): 419 (100%). Example 277 7-Fluoro-l- (8-fluoro-2-methylquinazolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1,2,3, 4-tetrahydronaphthalen-2,6-diol 4-bromomethyl-1-fluoro-2-methoxybenzene 41.7 g (297.54 mmol) 2-fluoro-5-methylanisole are heated at reflux overnight with 59.9 g ( 327.48 mmol) N-bromsuccinimide and 145 mg of benzoyl peroxide in 945 ml of carbon tetrachloride. The reaction mixture is filtered on a glass fiber filter and the residue (72.85 g> 100%) is used crude in the next step after removing the solvent. (4-Fluoro-3-methoxyphenyl) -acetoni tril 72.85 g of the bromine compound described above are introduced into a mixture of 330 ml of dimethylformamide and 209 ml of water. After the addition of 32.5 g (498.86 mmol) of calcium cyanide at room temperature (slight heating), the preparation is stirred overnight at room temperature. The reaction mixture is poured into ice-water and extracted three times with methyl-tert-butyl ether. The combined organic extracts are washed with saline and after drying the solvent is removed by centrifugation. The residue is chromatographed on silica gel (elution material ethyl acetate / hexane). They are isolated 33, 34 g (61.4%) of the desired nitrile. XH-NMR (CDC13): 3.72 (2H), 3.93 (3H), 6.83 (HH), 6.93 (1H), 7.09 (HH). 2- (4-Fluoro-3-methoxyphenyl) -2-methylpropionitrile 16.67 g (100.93 mmol) (4-fluoro-3-methoxyphenyl) -acetonitrile are placed with 30.1 g (211.96 mmol) of Methyl iodide in 158 ml of dimethylformamide. At 0 ° C, 8.50 g (211.96 mmol) of a 55-60% suspension of sodium hydride are added in portions. After stirring overnight at room temperature, the reaction mixture is poured into ice-water and then exted three times with methyl-tert-butyl ether. The combined organic exts are washed with water and saline. After drying and removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 5.11 g (26.2%) of the desired compound and 6.18 g of the monometyl compound are isolated, which is re-alkylated. XH-NMR (CDCl 3): 1.72 (6 H), 3.92 (3H), 6.95 (IH), 7.00-7.12 (2H). 2- (4-fluoro or -3-methoxyphenyl) -2-methylpropionaldehyde 9.37 g (48.50 mmol) 2- (4-fluoro-3-methoxyphenyl) -2-methylpropionitrile are reduced with 39.98 ml (72 , 48 mmol) of a 1.2M solution of DIBAL in toluene at -78 ° C, as described in some previous examples. Isopropanol and tartaric acid are used for the hydrolysis. 9.31 g of a mixture consisting of one third of initial material and two thirds of the desired aldehyde are isolated. This mixture is again subjected to a reaction with DIBAL at -78 ° C and after processing gives a mixture (9.18 g) consisting of the nitrile, the aldehyde and the respective alcohol. This mixture is reduced once more with DIBAL, but this time at a temperature of -10 to 0 ° C. After hydrolyzing with isopropanol they are isolated 1.45 g of the desired aldehyde and 5.68 g of the respective alcohol.

This alcohol is oxidized as already described several times under Swern conditions to obtain aldehyde. After carrying out customary processing and purification using conventional means, 5.09 g of the desired aldehyde are isolated.

XH-NMR (CDCl 3): 1/48 (6 H), 3.90 (3 H), 6.75-6.87 (2 H), 7.09 (H), 9.49 (H). Ethyl- (E) - (4-fluoro-3-methoxyphenyl) -4-methylpent-2-enoate 6.10 g 27.23 mmol) triethylphosphonium acetate are dissolved in 16.5 ml of tetrahydrofuran. At 0 ° C, 14.9 ml (29.12 mmol) LDA are added dropwise and the preparation is stirred 30 minutes at 0 ° C. After adding 5.34 g (27.22 mmol) of the aldehyde described above, dissolved in 16.5 ml of tetrahydrofuran, dropwise, the reaction mixture is stirred overnight at room temperature. At 0 ° C, water is carefully added dropwise, stirred vigorously for ten minutes and then stirred three times with methyl tert-butyl ether. The combined organic extracts are washed with saline and dried. After removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 5.75 g (79.3%) of the desired compound are isolated. . XH-NMR (CDC13): 1.29 (3H), 1.48 (6H), 3.90 (3H), 4.20 (2H), 5.80 (IN), 6.79-6.90 (2H), 7.02 (HH), 7.10 (ÍH). Ethyl - (4-f luoro -3-methoxyphenyl) -4-methyl-pentanoate 5.75 g (21.59 mmol) ethyl- (E) - (4-fluoro-3-methoxyphenyl) -4-methylpent-2-enoate hydrogenate in 80 ml of ethanol with the aid of 307.3 mg Pd / C (10%) overnight in a hydrophobic atmosphere. The reaction mixture is aspirated through a glass filter and the solvent is removed. 5.69 g (98.3%) of the desired compound that is used in the crude form is isolated in the next step. XH-NMR (CDCl 3): 1.22 (3H), 1.31 (6H), 1.90-2.10 (4H), 3.90 (3H), 4.08 (2H), 6.83. (1H), 6.91 (ÍH), 7.00 (ÍH). Ethyl -4- (4-fluoro-3-methoxyphenyl) -2-hydroxy-4-methylpentanoate 5.69 g (21.21 mmol) ethyl- (4-fluoro-3-methoxyphenyl) -4-ethylpentanoate are transformed as in Example 273 with 7.76 g (26.70 mmol) Davis reagent. After processing therein described and chromatography on silica gel (elution medium: ethyl acetate / hexane), 2.98 g (49.5%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.29 (3H), 1.40 (3H), 1.48. (3H), 1.83 (ÍH), 2.20 (ÍH), 2.56 (ÍH), 3.85-3.99 (4H), 4.13 (2H), 6.90 (1H), 6.95-7.08 (2H). Ethyl -4 - (-fluor or -3-methoxyphenyl) -4-methyl-2-oxopentanoate 2.78 g (9.78 mmol) ethyl-4- (4-fluoro-3-methoxyphenyl) -2-hydroxy-4-methylpentanoate are oxidized as in example 273 with S03 / Py in dichloromethane to give the respective ketoester.

After flash chromatography 2.48 g (89.9%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.28 (3H), 1.48 (6H), 3.15 (2H), 3.90 (3H), 4.12 (2H), 6, 88 (1H), 6.90-7.03 (2H). 4- (4-f-ruoro-3-methoxyphenyl) -2-hydroxy-4-methylphenyl-2- (trifluoromethyl) pentanal 2.48 g (8.79 mmol) ethyl-4- (4-fluoro-3-methoxyphenyl) 4-methyl-2-oxopentanoate are converted by means of the sequence described in Example 273, trifluorometation with Ruppert's reagent, reduction of the ester with lithium aluminum hydride to obtain alcohol and then oxidation of the alcohol according to Swern to obtain the aldehyde. Finally, 382.3 mg of the desired aldehyde are isolated in the three steps.

XH-NMR (300 MHz, CDC13): d = 1.38 (3H), 1.48 (3H), 2.32 (1H), 2.66 (1H), 3.68 (1H), 3.90 (3H), 6.80-6.92 (2H), 7.02 (1H), 8.88 (1H). 1,1, 1 -tri l or o- 4- (4-fluoro-3-methoxyphenyl) -2- 1 (8-fluo-ro-2-methyl-tyzolin-5-ylimino) -methyl] -4-methylpentan-2 -ol 127.4 mg (0.413 mmol) 4- (4-fluoro-3-methoxyphenyl) -2-hydroxy-4-methylphenyl-2- (trifluoromethyl) -pentanal are transformed with 73.2 mg (0.413 mmol) 8- fluoro-2-methyquinazolin and 235.1 mg (0.827 mmol) titanium-IV isopropylate in 2.2 ml xylol as already described several times in the respective imine. After carrying out an instantaneous chromatography, they are isolated, 5 mg (71.7%) of the desired compound. XH-NMR (CDC13): d = 1.35 (3H), 1.56 (3H), 2.44 (1H), 2.72 (1H), 2.99 (3H), 3.68 (3H) , 4.77 (ÍH), 6.38 (ÍH), 6.70-6.90 (3H), 7.38-7.48 (2H), 9.65 (HH). 7-Fluoro-1- (8-fluoro-2-methylquinazolin-5-ylamino) -4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4- te trahidronaf talen- 2,6-diol mg (0.043 mmol) of the imine described above are transformed with 0.6 ml boron tribromide (IM solution in dichloromethane) at 0 ° C and thus converted to the cyclized phenol. After carrying out flash chromatography, 7.1 mg (36.6%) are isolated. XH-NMR (CD3OD): d = 1.41 (3H), 1.56 (3H), 2.06-2.22 (2H), 2.89 (3H), 5.24 (1H), 6, 84 (HH), 6.89-7.04 (2H), 7.59 (HH), 9.69 (ÍH). Example 278 5- [7-Fluoro-2-hydroxy-6-methoxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino] -1H-quinoline-2 - ona 5 [4- (4-f luoro-3-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidenamino] -IH-quinolin-2-one 127 mg (0.413 mmol) of the aldehyde described in the example 277 are transformed as described therein with 66.32 mg (0.413 mmol) 5-amino-1H-quinolin-2-one to obtain imine. After carrying out flash chromatography, 89.2 mg (47.9%) of the desired compound are isolated. XH-NMR (CDC13): d = 1.37 (3H), 1.53 (3H), 2.43 (1H), 2.71 (1H), 3.71 (3H), 4.85 (1H) , 6.10 (ÍH), 6.70-6.92 (4H), 7.30-7.42 (3H), 8.15 (1H), 12.42 (HH). 5- [7-Fluoro-2-hydroxy-6-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-1-ylamino] -1H-quinolin-2-one 89.2 mg (0.198 mmol) of the imine described above in 1.9 ml of dichloromethane are transformed with 1.3 ml (1.188 mmol) of titanium tetrachloride in cyclic ether. After carrying out flash chromatography, 5.7 mg of the desired compound are obtained. XH-NMR (CDCl 3): d = 1.40 (3H), 1.60 (3H), 2.00-2.29 (2H), 3.88 (3H), 5.00 (1H), 5, 07 (1H), 5.68 (ÍH), 6.45-6.60 (3H), 6.85-7.02 (2H), 7.32 (HH), 8.20 (HH), 10, 05 (1H).

Example 279 6-Fluoro-1- [(2-methylquinolin-5-yl) amino] -4-ethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2,5-diol XH-NMR ( 300 MHz, CD30D); d = 0.97 (s, 3H), 1.79 (qdd, 1H), 1.96 (qdd, 1H), 2.19 (dd, 1H), 2.36 (dd, 1H), 2.73. (s, 3H), 3.40 (m, 1H), 4.98 (d, ÍH), 5.12 (d, ÍH), 6.60 (d, 1H), 6.89 (d, 2H), 7.23 (d, ÍH), 7.43 (d, ÍH), 7.51 (t, ÍH), 8.11 (d, ÍH). Examples 280 and 281 5-. { [7-bromo-2,5-dihydroxy-4,4-dimethyl-2 - (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -quinolin-2 (ÍH) -one, Diastereomer A and 5 -. { [7-bromo-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (HH) -one, Diastereomer B Using a procedure analogous to that described in Example 10, starting with 800 mg of 4- (4-bromo-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and 348 mg of 5-amino-quinolin-2 (1H) -one, the corresponding imine is obtained. It is obtained by reaction of 800 mg of imine with 7.9 ml solution of boron tribromide (1 H in dichloromethane) 16 mg of diastereomer A of 5. { [7-Bromo-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one (Fraction A) and 79 mg of diastereomers B of 5-. { [7-bromo-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (HH) -one Fraction A: XH-NMR (CD3OD): d = 1.40 (s, 3H), 1.55 (s, 3H), 1.90 (d, ÍH), 2, 25 (d, ÍH), 5,22 (s, ÍH), 6,11 (d, ÍH), 6,58 (d, ÍH), 6,67 (d, ÍH), 7,12-7,30 (m, 3H), 8.20 (d, ÍH). Fraction B: XH-NMR (CD3OD): d = 1.54 (s, 3H), 1.65 (s, 3H), 2.05 (d, 1H), 2.14 (d, ÍH), 5, 13 (s, 1H), 6.53 (d, ÍH), 6.62 (d, ÍH), 6.72 (d, 1H), 6.87 (s, 1H), 6.94 (s, ÍH) ), 7.40 (t, ÍH), 8.22 (d, ÍH). Example 282 l, 6-Dihydroxy-8,8-dimethyl-5- (l-oxo-1,2-dihydroisoquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2 carbonitrile 75 mg (0.166 mmol) 5- (6-chloro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino) -2H are dissolved Isoquinolin-1-one in 1.3 ml l-methyl-2-pyrrolidinone and are transformed with 16.27 mg (0.332 mmol) of sodium cyanide and 36.27 mg (0.166 mmol) of nickel-II bromide, as described in Example 160 in the microwave. The black reaction mixture is placed on a glass fiber filter. After washing with ethyl acetate, the filtrate is mixed with another 60 ml of ethyl acetate. Stir with water and saline. After drying, the solvent is removed and the residue is chromatographed on silica gel (amino plate; methanol / dichloromethane elution medium). 16.2 mg (22.1%) of the desired nitrile are isolated. MS (ES +): 444 (100%); IR (Mikroskop, Matrix: Diamond): 2230. Example 283 (rae.) 5-. { [6-fluoro-2,5-dihydroxy-4,4-7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one 5 Amino-isoquinolin-1 (2H) -one 2-Methyl-3-nitrobenzoic acid methylenic ester 30 g (165.6 mmol) 2-methyl-3-nitrobenzoic acid are placed benzoic acid in 150 ml of methanol and after the addition of 2.9 ml of concentrated sulfuric acid is cooked at reflux for two days. After cooling the crystallizate is aspirated (25.55 g = 79%) and used as such in the next step. XH-NMR (300 MHz, DMSO-d6): d = 2.50 (3H), 3.85 (3H), 7.56 (IH), 8.00 (1H), 8.05 (1H). Methylene ester of 2- (bromomethyl) -3-nitrobenzoic acid .55 g (130.9 mmol) acid methyl ester are placed 2-Methyl-3-nitrobenzoic acid in 300 ml of carbon tetrachloride with 25.6 g (141.7 mmol) N-bromosuccinimide and mixed with 62.8 mg of benzoyl peroxide. After boiling for seven days at reflux, the succinimide is aspirated after cooling and then the filtrate is centrifuged to dryness. The residue is the desired compound that is used in the rough in the next step. aH-NMR (300 MHz, CDC13): d = 4.00 (3H), 5.66 (2H), 7.55 (HH), 7.95 (HH), 8.10 (HH). 5-nitroisocoumarin 16.4 g (84.03 mmol) methyl ester of 2-methyl-3-nitrobenzoic acid are stirred with 26.8 g (225.1 mmol) dimethylacetal of N, N-dimethylformamide in 85 ml of dimethylformamide during 12 hours at 130 ° C. The solvent is removed on a rotary evaporator, the residue is taken up with methyl-, tert-butyl ether and washed three times with water. After washing with a saturated NaCl solution, the organic phase is dried. After removing the drying medium by filtration and removing the solvent, the residue is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). They are isolated 8.73 g (54.4%) of the desired compound. XH-NMR (300 MHz, CDC13): d = 7.39 (1H), 7.45 (HH), 7.68. (1H), 8, 49 (ÍH), 8, 65 (ÍH). 5-Nitroisoquinolin-1 (2H) -one 2.51 g (13.13 mmol) 5-nitroisocoumarin are added in 100 ml of ethanol. Ammonia is injected under pressure in the autoclave. The product precipitates and is extracted. 1.98 g (79.7%) of the desired compound are isolated. XH-NMR (300 MHz, DMSO-d6): d = 6.97 (ÍH), 7.45 (HH), 7.65 (ÍH), 8.43 (HH), 8.57 (ÍH), 11 , 5 (ÍH). 5-aminoisoquinolin-1 (2H) -one 268.3 mg (1.51 mmol) 5-nitroisoquinolinyl (2H) -one are incorporated with 376.5 mg of ammonium chloride and 2.6 ml of water in 14 ml. ml of ethanol and 5.4 ml of tetrahydrofuran. After addition of 1.23 g of zinc powder (heating to 30 to 35 ° C) per portion, stir two zwei hours. The reaction mixture is aspirated onto a glass fiber filter and washed again with ethyl acetate. After washing the filtrate with water and saturated sodium chloride solution, the organic phase is dried as usual with conventional means. The drying medium is removed and the solvent is removed, which gives 196.5 mg (88.1%) of the desired amine. XH-NMR (300 MHz, DMSO-d6): d = 5.6 (2H), 6.68 (HH), 6.87.45 (1H), 7.00 (HH), 7.17 (HH) 7.39 (1H), 11.7 (1H). 2- (3-fluoro or -2-methoxy-4-methyl phenyl) -2-methylpropanone tri lo 14.48 g (91.56 mmol) 2,6-difluoro-3-methylanisole are dissolved in 800 ml of toluene. After the addition of 272.2 ml (137.35 mmol) of a 0.5 molar solution of potassium hexamethyldisilazide in toluene, 25.31 g (366.26 mmol) isobutyronitrile are added dropwise. The preparation is stirred for 10 days at room temperature and then poured into HCl IM solution. After extracting three times with methyl-tert-butyl ether, the combined organic extracts are washed with a saturated NaCl solution and dried. After centrifugation and chromatography on silica gel (elution medium: ethyl acetate / hexane), 10.32 g (49.5%) of the desired compound are obtained.

H-NMR (300 MHz, CDC13): d = 1.77 (6 H), 2.29 (3 H), 4.09 (3 H), 6.86 (H), 6.95 (H). 2- (3-Fluoro-2-methoxy-4-methylphenyl) -2-methylpropanal 10.32 g (45.33 mmol) of nitrile described above are dissolved in 138 ml of toluene. Under protective gas, 37.4 ml of a 1.2 molar solution of DIBAH in toluene are added dropwise at -70 ° C. After stirring for three hours, 7.92 ml of isopropanol are added dropwise and, after brief exhaustion, 516 ml of a 10% solution of L- (+) - tartaric acid. The temperature increases and the preparation is thoroughly stirred at room temperature overnight. The reaction mixture is stirred twice with methyl tert-butyl ether. The combined organic extracts are stirred with saline, dried and the solvent is removed. Since the obtained residue (11.61 g> 100%) still contains approx. 30% initial material, it is again subject to reduction conditions, with the difference that when processing, isopropanol is omitted. 9.94 g of a product are isolated, which in addition to the desired aldehyde also contains the initial product and the respective alcohol. This mixture is mixed again with a 1.2M DIBAH solution in toluene versetzt, although this time at -20 ° C and stirred again at -10 to 0 ° C, to obtain a unitary compound. After carrying out customary processing using conventional means and chromatography on silica gel (elution medium: ethyl acetate / hexane), 5.82 g of the respective alcohol and 1.50 g of the aldehyde are finally obtained. The alcohol (5.82 g = 27.42 mmol) is converted to aldehyde by oxidation under Swern conditions at -78 ° C. After carrying out customary processing using conventional means and chromatography on silica gel (elution medium: ethyl acetate / hexane), they are isolated., 22 g (90.6%) of the desired aldehyde. X H-NMR (300 MHz, CDCl 3): d = 1.38 (6 H), 2.29 (3 H), 3.85 (3 H), 6.83-6.98 (2 H), 9.59 (H) ). Ethyl ester of (E / Z) -4 - (3-fluoro-2-methoxy-4-methylphenyl) -4-methylpent-2-ene To a solution of 8.62 g (32.96 mmol) triethic ester of 2-ethoxy-phosphonacetic acid in 20 ml of absolute THF are added dropwise at 0 ° C, 17.1 ml of a 2 molar solution of LDA in THF. After stirring 40 minutes at 0 ° C, 6.72 g (31.96 mmol) 2- (3-fluoro-2-methoxy-4-methylphenyl) -2-methylpropanal, dissolved in 20 ml of THF, are added dropwise. , at 0 ° C. After stirring overnight at room temperature, the reaction mixture is carefully mixed with 80 ml of water and extracted three times with methyl-tert-butyl ether. The combined organic extracts are washed with saline, dried and after filtering the drying medium the solvent is removed by centrifugation. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 8.74 g (84.3%) of a mixture is isolated from which, in addition to the desired compound, it also still contains starting material (aldehyde), which is separated in the next step.

(E / Z) -4- (3-Fluoro-2-methoxy-methyl) nyl) -4-methylpent-2-ene acid 8.74 g (26.95 mmol) of ethyl ester (E) are mixed / Z) -4- (3-fluoro-2-methoxy-4-methylphenyl) -4-methylpent-2-ene with 245 ml an IN NaOH solution in ethanol / water (2: 1) and stir overnight room temperature . The ethanol is removed on a rotary evaporator and the residue is diluted with water and extracted twice with methyl tert-butyl ether. The combined organic extracts contain the unconverted aldehyde of the reaction described above. The aqueous phases are carefully acidified with cooling by an ice bath, with concentrated hydrochloric acid until pH 3. and extracted three times with 300 ml of methyl-tert-butyl ether at a time. These ether extracts are washed with saline, dried, the solvent is removed and the residue (6.41 g = 80.3%) is used in the crude in the next step. The recovered aldehyde is again subjected to the sequence of a Homer-Wittig reaction and subsequent saponification. In this manner, another 2.29 g of the desired compound is obtained from (E / Z) -4- (3-fluoro-2-methoxy-4-methylphenyl) -4-methylpent-2-ene. Since the compound is an E / Z mixture (it does not have a 1: 1 ratio), only the position of the signals is indicated in the NMR spectrum. XH-NMR (300 MHz, CDCl 3): d = 0.98, 1.40, 1.53, 2.21, 3.38, 3.75-3.88, 6.72-6.85.7, 00 4- (3-Fluoro-2-methoxy-4-methylphenyl) -4-methyl-2-oxo-pentanoic acid 8.70 g (29.36 mmol) of (E / Z) -4- (3-fluoro) acid -2-methoxy-4-methylphenyl) -4-methylpent-2-ene obtained in the previous preparation is mixed with 139 ml of 1 molar sulfuric acid and 13.9 ml of ethyl acetate and stirred at 90 ° C for two days. of bath temperature. After cooling, the preparation is basified with solid potassium carbonate (care, foam). It is extracted three times with methyl-tert-butyl ether and the combined organic extracts are discarded after DC control. The aqueous phase is acidified with conc. Hydrochloric acid. and stirred three times with methyl-tert-butyl ether. The ether extracts are washed with saline, dried and the solvent is removed. The remaining residue (6.04 g = 76.6%) is used raw in the next step. XH-NMR (300 MHz, CDC13): d = 1.48 (6 H), 2.25 (3H), 3.50 (2H), 3.93 (3H), 6.82 (1H), 6.95 (1H). Ethyl 4- (3-fluoro-2-methoxy-4-methylphenyl) -4-methyl-2-oxo-pentanoic acid ester. 6.04 g (22.52 mmol) 4- (3-fluoro-2) acid are dissolved. -methoxy-4-methylphenyl) -4-methyl-2-oxo-pentanoic acid in 140 ml of ethanol, mixed with 2.5 ml of sulfuric acid and refried for six hours. The ethanol is removed on a rotary evaporator and the residue is carefully mixed with 300 ml of saturated sodium bicarbonate solution. Extract three times with ethyl acetate. The combined organic extracts are washed once with a saturated solution of sodium bicarbonate and once with saline. After drying, separating the drying medium by filtration and removal of the solvent by centrifugation, the residue is chromatographed on silica gel (elution medium: ethylacetate / hexane). 5.58 g (83.7%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.29 (3H), 1.47 (6H), 2.23 (3H), 3.40 (2H), 3.95 (3H), 4, 17 (2H), 6.79 (OH), 6.90 (1H). Ethyl 4- (3-fluoro-2-methoxy-4-methylphenyl) -4-methyl-2-trifluoromethyl-2-trimethylsilyloxypentanoic acid ester 5.58 g (18.83 mmol) ethyl ester of acid are dissolved 4- (3-fluoro-2-methoxy-4-methylphenyl) -4-methyl-2-oxo-pentanoic acid in 30 ml of THF and mix at 0 ° C with 3.21 g (22.6 mmol) ( trifluoromethyl) -trimethylsilane and 46.1 mg tetrabutylammonium fluoride. After stirring 6 hours at 0-5 ° C, the preparation is poured into ice water. It is extracted three times with methyl-tert-butyl ether and the combined organic extracts are washed with saline. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 7.5 g (90.8%) of the desired compound are obtained. 4- (3-fluoro-2-metho) and-4-methylphenyl) -4-methyl -2- (tri-fluoromethyl) -pent an-1. , 2-diol 7.5 g (17.1 mmol) 4- (3-fluoro-2-methoxy-4-methylphenyl) -4-methyl-2- (trifluoromethyl) -2-trimethylsilyloxy- ethyl ester are dissolved. pentanoic acid in 60 ml of diethyl ether and mixed in portions, at 0-5 ° C with 1.3 g (34.2 mmol) LiAIH4. After stirring for 5 hours at room temperature, 60 ml of saturated NaHC03 solution are carefully added dropwise to the reaction mixture while cooling in an ice bath. One hour is agitated exhaustively at room temperature. After extraction with methyl tert-butyl ether, the organic phase is stirred with saline, dried and the solvent is removed. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 3.65 g (65.8%) of the desired diol are obtained. MS (Cl): 342 (100%), 181 (18%). 4 - (3-f'-luoro-2-methoxy-4-methyl-ethyl) -2-hydroxy-4-methyl-2 - (tri-fluorodil) pentanal 1.57 g (12.31 mmol) chloride are incorporated. of oxalyl in 27 ml of dichloromethane and cooled to -78 ° C. After adding 1.93 g DMSO, dissolved in 5.2 ml of dichloromethane, dropwise, the preparation is repeated for five minutes. Then 3.65 (11.26 mmol) 4- (3-fluoro-2-methoxy-4-methylphenyl) -4-methyl-2- (trifluoromethyl) -pentane-1,2-diol, dissolved in water, is added dropwise. 11.5 ml dichloromethane. After stirring for two hours, the preparation is carefully mixed with 6.61 ml (56.28 mmol) of triethylamine. After exhaustively stirring an hour and a half at room temperature, water is added and the preparation is stirred twice with dichloromethane. The combined organic extracts are washed with 1% sulfuric acid, saturated sodium bicarbonate solution and saline solution. After drying the organic phase, the solvent is removed. There remain 2.79 g (76.9%) of the aldehyde that is used in the rough in the next step. XH-NMR (300 MHz, CDC13): d = 1.41 (3H), 1.45 (3H), 2.15-2.30 (5H), 3.29 (1H), 3.60 (1H) ), 4.02 (3H), 6.70-6.82 (2H), 9.10 (1H). (rae.) -5-. { [4- (3-Fluoro-2-methoxy-4-methyl phenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} isoquinolin-1 (2H) -one 150 mg (0.465 mmol) 4- (3-fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal, 74.5 mg (0.465 mmol) 5-amino-isoquinolin-1 (2H) -one and 264.4 mg (0.930 mmol) titanium tetraisopropylate are stirred in 2.5 ml xylol for five hours at 120 ° C. The mixture is diluted with ethyl acetate and washed once with saline. The solvent is removed by centrifugation and the residue is subjected to flash chromatography. 98.6 mg (45.6%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.58 (3H), 1.89 (3H), 2.29 (1H), 3.30 (1H), 4.00 (3H), 4.79 (ÍH), 6.38 (ÍH), 6.67-6.78 (2H), 6.80 (ÍH), 7.20 (1H), 7.38 (ÍH), 7.55 (1H), 8.32 (1H), 11.0 (1H). (rae.) 5-. { [6-fluoro-2-hydroxy-5-methoxy-4, 4,7'-trimethyl-2- (trifluoromethyl) -l, 2,3,4-tetrahydronaphthalen-1-yl] amino} -i soquinolin -1 (2H) -one) A 98.6 mg (0.212 mmol) of the mixture described in the previous step rac-5. { [4- (3-fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} isoquinolin-1 (2H) -one, carefully add by drip at 0.degree. C. 1.39 ml (1.27 mmol) titanium tetrachloride and then stir for three hours at room temperature. The reaction mixture is carefully mixed at 0 ° C, with a saturated solution of sodium bicarbonate. After extracting three times with ethyl acetate, the combined organic extracts are washed with saturated NaCl solution. After drying over sodium sulfate, the solvent is removed and the remaining residue is subjected to flash chromatography. 63.3 mg (64.2%) of the desired compound are isolated. XH-NMR (300 MHz, CD3OD): d = 1.52 (3H), 1.67 (3H), 2.05-2.20 (5H), 3.98 (3H), 5.10 (1H) ), 6.80-6.95 (2H), 7.08 (1H), 7.19 (1H), 7.40 (1H), 7.70 (1H). (rae.) 5-. { ['6-fluoro-2, 5-dihydroxy -4,4,7-trimethyl-2- (tri-f'oromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} isoquinolin-1 (2H) -one 59.7 mg (0.128 mmol) (rae.) 5-. { [6-fluoro-2-hydroxy-5-methoxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} Isoquinolin-1 (2H) -one are mixed at 0 ° C with 1.3 ml of a 1 molar solution of boron tribromide in dichloromethane and stirred for one hour at 0-5 ° C. Then a saturated solution of sodium bicarbonate is carefully added at -10 ° C. After stirring for 10 minutes thoroughly at room temperature, the preparation is extracted three times with methyl-tert-butyl ether. The organic phases are dried and the residue is subjected to flash chromatography after removing the solvent centrifugation by centrifugation. 46.5 mg (80.3%) of the desired compound are isolated. XH-NMR (300 MHz, CD3OD). d = 1.56 (3H), 1.70 (3H), 2.00-2.20 (5H), 5.09 (HH), 6.65 (ÍH), 6.85 (ÍH), 7 , 05 (ÍH), 7,18 (ÍH), 7,39 (ÍH), 7,68 (ÍH). Example 284 (rae) 5-. { [6-fluoro-2, 5-dihydroxy-4,4, 7-trimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (1H) -one 5 Aminoquinoline-2 (IR) -one 4,5 g 5-nitroquinolin-2 (1H) -one (Chem. Pharm. Bull. 29, 651 (1981)) are hydrogenated at 200 ml of ethyl acetate and 500 ml of methanol, in the presence of 450 mg of palladium on activated carbon as a catalyst, at normal pressure, with hydrogen, until complete transformation. The catalyst is removed by filtration through diatomaceous earth and the reaction solution is concentrated in vacuo. 3.8 g of the title compound are obtained as a yellow solid. XH-NMR (DMSO): d = 5.85 (bs, 2H), 6.27 (d, ÍH), 6.33 (d, ÍH), 6.43 (d, ÍH), 7.10 (t , HH), 8.07 (d, 1H), 11.39 (bs, HH) rac-5. { [4- (3-Fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2-trif'-loromethyl) -pentylidene] amino} isoquinolin-2 (IR) -one 150 mg (0.465 mmol) 4- (3-fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal (described in example 1), 74.5 mg are stirred. (0.465 mmol) 5-amino-isoquinolin-2 (1H) -one and 264.4 mg (0.930 mmol) titanium tetraisopropylate werden in 2.5 ml xylol for 5 hours at 120 ° C. The mixture is diluted with ethyl acetate and washed once with saline. The solvent is removed by centrifugation and the residue is subjected to flash chromatography. 132.2 mg (61.2%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.56 (3H), 1.82 (3H), 2.29 (1H), 3.28 (1H), 3.98. (3H), 4.70 (ÍH), 6.30-6.45 (2H), 6.70-6.80 (2H), 7.30 (ÍH), 7.40 (ÍH), 7.63. (1H), 8.07 (1H), 12.27 (1H). (rae.) 5 -. { [6-Fluoro-2-hydroxy-5-methoxy -4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} Isoquinolin-2 (IR) -one A 132.2 mg (0.285 mmol) of the mixture described in the previous step, rac-5. { [4- (3-fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2 - (trifluoromethyl) pentylidene] amino} isoquinolin-2 (1H) -one are carefully added dropwise at 0 ° C 1.86 ml (1.708 mmol) titanium tetrachloride and then stirred for three hours at room temperature. The reaction mixture is carefully mixed at 0 ° C with a saturated solution of sodium bicarbonate. After extracting three times with ethyl acetate, the combined organic extracts are washed with saturated NaCl solution. After drying with sodium sulfate, the solvent is removed and the remaining residue is subjected to flash chromatography. 106.7 mg (80.7%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.52 (3H), 1.68 (3H), 1.98-2.25 (5H), 3.95 (3H), 4.60 (1H) ), 4.99 (1H), 5.49 (1H), 6.49-6.62 (3H), 6.80 (ÍH), 7.35 (ÍH), 8.16 (HH), 10, 40 (ÍH). (rae.) 5-. { [6-fluoro-2, 5-dihydroxy -4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} isoquinolin 2 (IR) -one) 101.4 mg (0.218 mmol) (rae.) 5-. { [6-fluoro-2-hydroxy-5-methoxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-2 (1H) -one are mixed at 0 ° C, with 2.2 ml of a 1 molar solution of boron tribromide in dichloromethane and stirred for one hour at 0-5 ° C. A saturated solution of sodium bicarbonate is added dropwise at -10 ° C. After stirring extensively for 10 minutes at room temperature, the preparation is extracted three times with methyl-tert-butyl ether. The organic phases are dried and the residue is subjected to flash chromatography after removing the solvent. 93.7 mg (95.3%) of the desired compound are isolated.

X H-NMR (300 MHz, CD 3 OD): d = 1.58 (3 H), 1.69 (3 H), 2.00-2.20 (5 H), 5.10 (H), 6.51 (H) ), 6.55-6.74 (3H), 7.39 (1H), 8.22 (1H). Example 285 (rae.) 6-Fluoro-1- [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4 -tetrahydronaphthalen-2,5-diol 5-Amino-8-fluoro-2-methylquinazoline To a solution of 3.35 g (20.25 mmol) chloral hydrate and 21.27 g (149.7 mmol) of sodium sulfate in 72 ml of water is added a solution of 2.4 g (18.6 mmol) 2,5-difluoro-niline in 11 ml of water at 50 ° C and 1.6 ml conc. hydrochloric acid. (37%), which had previously been stirred at this temperature for 1 h. "Another 30 min is stirred at room temperature and heated for 45 min at 125 ° C after adding 4.09 g (58.9 mmol). ) hydroxylammonium chloride in 19 ml water and this temperature is maintained during min After cooling and after one more hour, the light brown precipitate is separated by filtration, washed with water and dried. 3.0 g (15.0 mmol) of the hydroxylimine are obtained as an intermediate product, which is dissolved in portions in 15 ml concentrated sulfuric acid at 60 ° C. After the addition is finished, it is heated for 2 hours at 80 ° C and 4 hours at 90 ° C. Allow to cool and pour the solution onto 100 g of ice. Extract with ethyl acetate, wash the organic phases with water, it is dried with sodium sulfate and concentrated. After chromatography on silica gel with hexane-ethyl acetate (0-45%), 1.2 g (7.1 mmol) of the 4,7-difluorisatino are obtained. In the course of 10 min. 1.8 ml of a 30% solution of hydrogen peroxide to isatine in 30 ml of 1 molar sodium hydroxide are added dropwise. After stirring 2 hours at room temperature, it is cooled to 0 ° C and 5 ml of 4 molar hydrochloric acid are added and diluted with 50 ml of water. It is extracted with ethyl acetate, dried over sodium sulphate, concentrated and thus 1.47 g of the 3,6-difluorrantranilic acid is obtained quantitatively, which is transferred without further purification. The 3,6-difluorrantranilic acid is heated in 8 ml acetic anhydride for 45 min at 100 ° C. After cooling, the formed acetic acid and the excess of ac anhydride are removed. Acetic acid in azeotropic form with toluene under vacuum. The residue is mixed while cooling with ice, with 40 ml of a 25% ammonia solution and stirred for 72 hours. It is diluted with water and acidified with acetic acid. It is extracted with ethyl acetate, the organic phases are washed with water, dried over sodium sulfate and concentrated. The 1.03 g (5.25 mmol) 5, 8-difluoro-2-methyl-3H-quinazolin-4-one and 6 g phosphorus pentachloride thus obtained are heated in 20 ml phosphoryl chloride for 12 h at 125 ° C. . After cooling, it is poured into saturated NaHCO 3 solution and extracted with ethyl acetate. The organic phase is dried and the solvent is separated. 1.7 g 4-chloro-5,8-difluoro-2-methylquinazoline, which are dissolved in 60 ml of ethyl acetate and 5 ml of triethylamine, are obtained quantitatively. 600 mg of palladium on carbon are added and the mixture is stirred for 2 h (absorption of 480 ml of hydrogen) under a hydrogen atmosphere at normal pressure. The solution is separated from the catalyst by filtration with Celite and washed again with 100 ml of ethanol and evaporated. After chromatography on silica gel with hexane-ethyl acetate-ethanol (0-40%), 550 mg of 5,8-difluoro-2-methylquinazoline are obtained. To 240 mg (1.3 mmol) 5, 8-difluoro-2-methylquinazoline, 300 mg (1.13 mmol) 18-crown-6 in 10 ml of DMF is added 890 mg (13.7 mmol) sodium azide. and heat the mixture for 8 h at 125 ° C. The solvent is removed under vacuum and chromatographed on silica gel with ethyl acetate and 52 mg of product is obtained. XH-NMR (300 MHz, CDC13); d = 2.92 (s, 3H), 4.31 (br., 2H), 6.67 (dd, ÍH), 7.38 (dd, ÍH), 9.37 (s, ÍH). 1, 1, 1-tri-fluoro-4- (3-fluoro-2-methoxy -3-methyl phenyl) -2- [(8-fluoro-2-methyl -quinazoliyl-5-yl) iminomethyl] -4-methylpentan -2-ol 150 mg (0.465 mmol) 4- (3-fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal (described in Example 1), 83, 7 mg (0.465 mmol) 5-amino-8-fluoro-2-methylquinazoline and 264.4 mg (0.930 mmol) titanium tetraisopropylate are stirred in 2.5 ml xylol for five hours at 120 ° C. The mixture is diluted with ethyl acetate and washed once with saline. The solvent is removed by centrifugation and the residue is subjected to flash chromatography. 152.8 mg (68.2%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.55-1.66 (6H), 2.29 (1H), 3.00 (3H), 3.30 (1H) ), 3.98 (3H), 4.60 (ÍH), 6.29 (ÍH), 6.67 (ÍH), 6.78 (ÍH), 7.43 (ÍH), 7.71 (ÍH) , 9.49 (ÍH). (rae.) 6-Fluoro-l - [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -5-methoxy -4,4,7-trimethyl-2- (trifluoromethyl) -1, 2, 3 4- tetrahydronaph thalen-2-ol A 152.8 mg (0.317 mmol) of the mixture described in the previous step, 1,1-l-trifluoro-4- (3-fluoro-2-methoxy-3-methylphenyl) -2- [(8-Fluoro-2-methyl-quinazolyl-5-yl) iminomethyl] -4-methylpentan-2-ol are added dropwise carefully at 0 ° C, 2.1 ml (1.902 mmol) titanium tetrachloride and then it is stirred for three hours at room temperature. The reaction mixture is carefully mixed at 0 ° C, with a saturated solution of sodium bicarbonate. After extracting three times with ethyl acetate, the combined organic extracts are washed with saturated NaCl solution. After drying with sodium sulfate, the solvent is removed and the remaining residue is subjected to flash chromatography. 121.8 mg are isolated (79.7%) of the desired compound. XH-NMR (300 MHz, CDC13): d = 1.57 (3H), 1.72 (3H), 2.05-2.29 (5H), 2.95 (3H), 3.97 (3H) ), 4.93 (ÍH), 5.63 (ÍH), 5.90 (ÍH), 6.68 (ÍH), 6.90 (ÍH), 7.50 (ÍH), 9.35 (ÍH) . (rae.) 6-fluoro-l - [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -4,4,7-trimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalene -2, 5-diol 111.2 mg (0.231 mmol) (rae,) 6-fluoro-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -5-methoxy-4, 4, 7 -trimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-2-ol are mixed at 0 ° C with 3.2 ml of a 1 molar solution of boron tribromide in dichloromethane and stirred for one hour and medium at 0 - 5 ° C. At 0 ° C, saturated sodium bicarbonate solution is now carefully added dropwise. After shaking exhaustively 10 min. at room temperature, the preparation is extracted three times with ethyl acetate. The organic phases are dried and the residue is subjected to flash chromatography after removing the solvent. Isolate 66.4 mg (61.5%) of the desired compound. XH-NMR (300 MHz, CD3OD): d = 1.59 (3H), 1.70 (3H), 2.00-2.20 (5H), 2.88 (3H), 5.20 (1H) ), 6.68 (ÍH), 6.85 (ÍH), 7.58 (ÍH), 9.65 (1H). Example 286 (rae.) 5-. { [6-fluoro-2, 5-dihydroxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one 5-amino-2-methyl phthalazin-1-one: 3-bromo-4-nitrophalide 5.37 g 4-nitroftalide (Tetrahedron Lett. (2001), 42, p. 1647-50), 8.04 g N-bromosuccinimide and 196 mg of benzoyl peroxide are heated in 80 ml benzotrifluoride at reflux and exposure to light until complete transformation. It is poured into water, extracted with dichloromethane, washed several times with water, dried and the solvent is removed in vacuo. 7.24 g 3-bromo-4-nitro-phthalide is obtained as a solid. XH-NMR (300 MHz, CDC13), d = 7.26 (s, ÍH), 7.88 (t, ÍH), 8.30 (d, ÍH), 8.56 (d, ÍH) 5-ni phthalazin-1-one: 18.25 g hydrazine sulfate and 14.88 g sodium carbonate are stirred in 300 ml of DMF at 100 ° C for one hour. 7.24 g of 3-bromo-4-nitro-phthalide in 100 ml of DMF are then added and the mixture is stirred at 100 ° C. for a further 4 hours. It is poured into water, extracted several times with ethyl acetate and the organic phases are washed with water and saline. It is dried and the solvent is removed in vacuo. After recrystallization from ethyl acetate, 2.35 g 5-nitro-phthalazin-1-one is obtained as a solid.

XH-NMR (300 MHz, DMSO-d6), d = 8.05 (t, 1H), 8.57-8.66 (m, 2H), 8.73 (s, ÍH), 13.13 (bs) , H) 2-methyl-5-nitro phthalazin-1-one 1.6 g of 5-nitro-phthalazin-1-one and 2.31 g of calcium carbonate are stirred for 10 min. at room temperature in 60 ml of DMF. 1.1 ml of methyl iodide are added and the mixture is stirred overnight. It is poured into water, extracted several times with ethyl acetate and the organic phase is washed with water and saline. It is dried and the solvent is removed in vacuo. 1.57 g 2-methy-5-nitro-phthalazin-1-one is obtained as a yellow solid. XH-NMR (300 MHz, DMSO-d6), d = 3.73 (s, 3H), 8.05 (t, ÍH), 8.62 (d, 2H), 8.75 (s, ÍH) 5 -Amino-2-methyl-phthalazin-l -one 1.57 g 2-methyl-5-nitro-phthalazin-1-one and 130 mg of palladium on active carbon are suspended in 45 ml of ethyl acetate and hydrogenated with hydrogen at normal pressure. It is filtered through diatomaceous earth and the solvent is removed under vacuum. 1.26 g 5-amino-2-methyl-phthalazin-1-one is obtained in the form of a yellow solid. XH-NMR (300 MHz, CDC13), d = 3.81 (s, 3H), 7.00 (d, 1H), 7.50 (t, ÍH), 7.80 (d, 1H), 8, 16 (s, ÍH) (rae.) -5-. { [4- (3-fluoro-2-methoxy-4-methylf-enyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} 2-methyl-phthalazinon-1-one 400 mg (1.241 mmol) (rae.) 4- (3-fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) are stirred. pentanal, 271.4 mg (1,241 mmol) 5-amino-2-methyl-phthalazin-1-one and 705.5 mg (2.482 mmol) titanium tetraisopropylate in 7 ml xylol for 5 hours at 120 ° C. After cooling, the mixture is diluted with ethyl acetate and washed once with saline. The aqueous phase is extracted twice with ethyl acetate. The combined organic extracts are dried and the solvent is removed. The residue is subjected to flash chromatography. They are isolated 40, 9 mg (68.5%) of the desired compound. XH-NMR (300 MHz, CDC13), d = 1.39 (3H), 1.60 (3H), 1.78 (3H), 2.28 (1H), 3.31 (1H), 3.90 (3H), 3.99 (3H), 4.58 (ÍH), 6.38 (1H), 6.78 (ÍH), 6.89 (ÍH), 7.58-7.68 (2H), 8.27-8.35 (2H). (rae.) 5-. { [6-fluoro-2,5-dihydroxy-4,7,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one and (rae.) 5-. { [6-fluoro ^ -hydroxy-d-methoxy ^^^ - trimethyl ^ - (trifluoromethyl) -1,2,4,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one 100 mg (0.208 mmol) (rae.) -5-. { [4- (3-fluoro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} 2-methyl-phthalazinon-1-one is mixed at 0 ° C with 2.1 ml of an ÍM solution of boron tribromide in dichloromethane and stirred for two hours at 0-5 ° C. After carefully mixing with a saturated solution of sodium bicarbonate, the preparation is extracted three times with ethyl acetate. The combined organic extracts are washed with saline, dried and the residue that remains after the solvent is removed by centrifugation is subjected to flash chromatography. 38.1 mg of a mixture consisting of the desired compound and the corresponding ether are isolated. First the ether is separated from the phenol, by means of HPLC (Chiralcel OD 20μ, elution medium: hexane / ethanol). The respective racemates are then separated by means of chiral HPLC (Chiralpak AD 20μ, elution medium: hexane / 2-propanol or hexane / ethanol) to give their respective enantiomers, so that the following four compounds result: (+) - 5- . { [6-fluoro-2, 5-dihydroxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] mino} -2-methylphthalazin-1-one, (-) -5-. { [6-fluoro-2, 5-dihydroxy-4,7,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one, XH-NMR (300 MHz, CD30D), d = 1.59 (3H), 1.70 (3H), 2.03-2.20 (5H), 3.86 (3H), 5.20 (ÍH), 6.63 (ÍH), 7.23 (ÍH), 7.60-7.72 (2H), 8.58 (1H). (+) -5- { [6-fluoro-2-hydroxy-5-methoxy-4, 4,7-trimethyl-2- (rifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one XH-NMR (300 MHz, CD30D), d = 1.40 (3H), 1.59 (3H), 2.09 (1H), 2.20-2.35 (4H) ), 3.52 (3H), 3.80 (3H), 5.34 (IH), 7.08 (1H), 7.52 (1H), 7.62-7.78 (2H), 8, 60 (1H). (-) -5- . { [6-fluoro-2-hydroxy-5-methoxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -2-methylphthalazin-1-one Example 287 (rae.) 5-. { [6-chloro-2,5-dihydroxy-4,4,7-trimethyl-2 - (trifluoromethyl) -1,2,3,4-tetrahydronaph alen-1-yl] amino} -isoquinolin-1 (2H) -one 2- (3-chloro-2-methoxy-4-methylphenyl) -2-ethylpropanenitrile 17.6 g (100.8 mmol) 2-chloro-6-fluoro-3-methylanisole are dissolved in 880 ml of toluene. After the addition of 27.8 g (403.2 mmol) nitroisobutyric acid are added dropwise 302.4 ml (151.2 mmol) of a 0.5 molar solution of potassium hexamethyldisilazide in toluene over the course of 40 minutes (increase in temperature 27 ° C). After stirring for 19 days at room temperature, the preparation is mixed with 300 ml of water and 400 ml of ethyl acetate and then acidified with 10% sulfuric acid until a pH of 4 is reached.

The aqueous phase is stirred with 200 ml of ethyl acetate. The combined organic extracts are washed with water and twice with saturated NaCl solution and then dried. After centrifugation and chromatography on silica gel (elution medium: ethyl acetate / hexane), 12.01 g (53.4%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.75 (6 H), 2.40 (3H), 4.09 (3H), 6.99 (ÍH), 7.09 (1H). 2- (3-Chloro-2-methoxy-4-methyl phenyl) -2-methylpropanal 11 g (49.17 mmol) of the nitrile described above are dissolved in 196 ml of toluene gelost. At -65 ° C to -60 ° C, 61.5 ml of a 1.2 molar solution of DIBAH in toluene are added dropwise under nitrogen. After stirring for two hours at -65 ° C, 280 ml of a 20% solution of L- (+) - tartaric acid are added dropwise. The temperature rises to 0 ° C. The ice bath is removed and the preparation is thoroughly stirred for two hours at room temperature. The reaction mixture is stirred twice with diethyl ether. The combined organic extracts are stirred with water and saline, dried and the solvent is removed. Chromatography on silica gel (elution medium: ethyl acetate / hexane) gives 6.12 g of the desired compound. XH-NMR (300 MHz, CDC13): d = 1.38 (6 H), 2.39 (3 H), 3.79 (3 H), 7.03 (H), 7.13 (1 H), 9, 59 (ÍH). (E / Z) -4- (3-chloro-2-methoxy-4-methylphenyl) -2-ethoxy-4-methylpent-2-ene acid ethyl ester To a solution of 7.45 g (27.79 mmol) 2-ethoxy phosphonacetic acid triethylene ester, dissolved in 30 ml of absolute THF, 14.9 ml of a 2 molar solution of LDAm in THF are added dropwise at 0 ° C over the course of 20 minutes. After stirring 45 minutes at 0 ° C, 6.3 g (27.79 mmol) 2- (3-chloro-2-methoxy-4-methylphenyl) -2-methylpropanal dissolved in 18 ml of THF are added dropwise. , at 0 ° C. After stirring overnight at room temperature the reaction mixture is poured into 100 ml of water and extracted twice with 250 ml of diethyl ether at a time. The combined organic extracts are washed with water and saline, dried and after filtering the drying medium, the solvent is centrifuged. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). They are isolated 8, 4 g, which in addition to the desired compound also still contain starting material (aldehyde), which is separated in the next step. (E / Z) -4 - (3-chloro-2-methoxy-methylphenyl) -2- e -toxy-4 -methyl Ipen t-2-ene acid 8.4 g (24.65 mmol) ethyl ester of (E / Z) -4- (3-chloro-2-methoxy-4-methylphenyl) -2-ethoxy-4-methylpent-2-ene are mixed with 246 ml of a 1N solution of NaOH in ethanol / water (2: 1) and stirred 19 hours at room temperature. The ethanol is removed on a rotary evaporator and the residue is extracted twice with diethyl ether. The combined organic extracts are washed once with 50 ml of water. After drying the solvent is removed. The residue (unreacted aldehyde from the reaction described above) is 2 g and is reused in the Homer Wittig reaction with subsequent saponification. The combined aqueous phases are acidified carefully, with ice bath, with concentrated hydrochloric acid to a pH of 3 and extracted twice with 300 ml of diethyl ether at a time. These extracts are washed with water and saline, dried, the solvent is removed and the residue (5.62 = 72.9%) is used crude in the next step. Given the compound is an E / Z mixture in a different ratio of 1: 1, only the position of the signals is indicated in the NMR spectrum. XH-NMR (300 MHz, CDC13): d = 0.98, 1.40, 1.57, 2.31, 2.38, 3.39, 3.78, 3.80-3.90, 5, 79, 6.79, 6.88-6.98, 7.18. 4- (3-chloro-2-methoxy-4-methyl-phenyl) -4-methyl-2-oxo-pentans-aure. 7.30 g (23.34 mmol) of the acid of (E / Z) -4- (3 - chloro-2-methoxy-4-methylphenyl) -2-ethoxy-4-methylpent-2-ene obtained in the previous preparation, at ambient temperature, with 143 ml of 1 molar sulfuric acid and 20 ml of ethyl acetate and stir 30 hours at 90 ° C bath temperature. After stirring for 3 days at room temperature, stirring for a further 2 days thoroughly at 90 ° C. The preparation is basified with solid calcium carbonate in an ice bath (pH 9) (care, foam). It is extracted twice with diethyl ether and the combined organic extracts are discarded after DC control. The aqueous phase is acidified with concentrated hydrochloric acid, in an ice bath, to pH 4 and stirred twice with diethyl ether. The ether extracts are washed with water and saline, dried and the solvent is removed. The remaining residue (5.37 g = 80.8%) is used crude in the next step. XH-NMR (300 MHz, CDC13): d = 1.50 (6 H), 2.34 (3 H), 3.50 (2 H), 3.89 (3 H), 6.97 (H,), 7, 15 (1H). Ethyl 4 - (3-chloro-2-methoxy-4-methylphenyl) -4-methyl-2-oxo-pentanoic acid ester 5.37 g (18.86 mmol) 4- (3-chloro-2) acid are dissolved. -methoxy-4-methylphenyl) -4-methyl-2-oxo-pentanoic acid in 112 ml of ethanol, concentrated sulfuric acid (2 ml) was added and the mixture was refluxed for 5 hours. The wird ethanol is removed in a rotary evaporator and after careful addition of 50 ml of water the residue is mixed with a saturated solution of sodium bicarbonate. It is extracted twice with ethyl acetate. The combined organic extracts are washed with water and saline. After drying, filtering the drying medium and centrifuging the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 4.81 g (81.6%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.30 (3H), 1.48 (6H), 2.36 (3H), 3.40 (2H), 3.90 (3H), 4, 18 (2H), 6.92 (1H), 7.10 (1H). ethyl ester of acid (rae.) 4 - (3-chloro-2-methoxy-4-methylphenyl) -methyl-2- (trifluoromethyl) -2- trimethylsilyloxy-pentanoic 4.8 g (15.35 mmol) ethyl ester of 4- (3-chloro-2-methoxy-4-methylphenyl) -4-methyl-2-oxo-pentanoic acid are dissolved in 25 ml of THF, mixed at 0 ° C with 2.62 g (18.41 g. mmol) (trifluoromethyl) -trimethylsilane and 37.6 mg tetrabutylammonium fluoride and stir an hour and a half at 0-5 ° C. The preparation is poured into 50 ml ice water and extracted twice with diethyl ether. The combined organic extracts are washed with water and saline. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 4.4 g (63%) of the desired compound are obtained.

XH-NMR (300 MHz, CDC13): d = 0.03 (9 H), 1.22 (3H), 1.38 (3H), 1.42 (3H), 2.35 (3H), 2, 52 (ÍH), 2.69 (ÍH), 3.78 (ÍH), 3.99 (3H), 4.03 (ÍH), 6.90 (ÍH), 7.00 (1H). Ethyl ester (rae.) 4 - (3-Chloro-2-methoxy-4-methylphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxypentanoic acid 4.4 g (9.67 mmol) ethyl ester of acid (rae.) 4- (3-chloro-2-methoxy-4-methylphenyl) -4-methyl-2- (trifluoromethyl) -2-trimethylsilyloxypentanoic are dissolved in 56 ml of tetrahydrofuran and mixed with 3.05. g (9.67 mmol) tetrabutylammonium fluoride trihydrate and stirred for one hour and a half at room temperature. The reaction mixture is diluted with water and extracted twice with diethyl ether. The organic phases are washed with water and saline. After drying the solvent is removed and the remaining residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 1.26 g of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.20 (3H), 1.40 (3H), 1.49 (3H), 2.29-2.40 (4H), 2.82 (1H) , 3.55 (ÍH), 3.65 (1H), 3.98 (3H), 4.08 (1H), 6.90 (ÍH), 7.02 (1H). (rae.) 4 - (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and (rae.) 4- (3-chloro-2-methoxy- 4-methylphenyl) -4-methyl -2- (tri fl uoromethyl) pentane -1,2-diol 1.05 g (2.74 mmol) ethyl ester of acid (rae.) 4- (3-chloro-2) -methoxy-4-methylphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxy-pentanoic are dissolved in 10 ml of diethyl ether and at 0 ° C, mixed in portions with 78 mg (2.06 mmol) LiAIH4.

After stirring one hour at 0 ° C and one hour more at 0-10 ° C, the reaction mixture is mixed by dropwise, in an ice bath, with 2.4 ml of saturated NaHCO 3 solution. Agitate 30 minutes in an ice bath and an hour and a half thoroughly at room temperature. The precipitate is filtered off, washed with ethyl acetate and the filtrate is concentrated in a rotary evaporator. After chromatographing the residue on silica gel (elution medium: ethyl acetate / hexane), 425 mg (45.8%) of the aldehyde and 420.4 mg (44.9%) of the diol are obtained. Aldehyde: XH-NMR (300 MHz, CDC13): d = 1.46 (3H), 1.49 (3H), 2.28 (1H), 2.39 (3H), 3.30 (1H), 3 , 59 (ÍH), 4,00 (3H), 6,89-7,00 (2H), 9, 06 (ÍH). Alcohol: XH-NMR (300 MHz, CDCl 3): d = 1.48 (3H), 1.57 (3H), 1.82 (1H), 2.20 (1H), 2.38 (3H), 2 , 55 (ÍH), 2.91 (1H), 3.29-3.46 (2H), 4.00 (3H), 6.96 (HH), 7.16 (HH). (rae.) -5- ([4- (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-methyl-2- (trifluoromethyl) pentylidene] amino) isoquinoline-1 (2H) -one stir 225 mg (0.664 mmol) (rae.) 4- (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal, 106.3 mg (0.664 mg) mmol) 5-amino-isoquinolin-1 (2H) -one and 0.39 ml (1.338 mmol) titanium tetraisopropylate in 3.6 ml or xylol for two and a half hours at 120 ° C. After cooling, the preparation is poured into 15 ml of saturated saline and diluted with ethyl acetate. After exhaustively stirring 20 minutes at room temperature, it is filtered on a column filled with Extrelute. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 224.7 mg (70.3%) of the desired compound are isolated. XH-NMR (300 MHz, DMS0-d6): d = 1.49 (3H), 1.52 (3H), 1.89 (3H), 2.25 (1H), 3.04 (1H), 3 , 89 (3H), 6,15 (ÍH), 6,65 (1H), 6,72 (1H), 6,79 (ÍH), 6,99 (1H), 7,20 (ÍH), 7, 37 (1H), 7.57 (1H), 8.06 (HH), 11.35 (1H). (rae.) 5- ([6-chloro-2-hydroxy-5-methoxy -4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4 -tetrahydronaphthalen-1-yl] amino) -i soquinolin- 1 (2H) -one 130 mg (0.27 mmol) of the mixture described in the previous step (rae.) -5- are dissolved. { [4- (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} Isoquinoline-1 (2H) -one in 1.6 ml of dichloromethane and mixed at 0 ° C by dripping with 0.8 ml (0.81 mmol) titanium tetrachloride and then stirring for two and a half hours at room temperature. The reaction mixture is carefully mixed at 0 ° C with a saturated solution of sodium bicarbonate (pH 8). Dilute with ethyl acetate, remove the ice bath and stir 15 minutes thoroughly at room temperature. After extracting twice with ethyl acetate, the combined organic extracts are washed with saline. After drying with sodium sulfate, the solvent is removed and the remaining residue is chromatographed on silica gel. 71.3 mg (54.8%) of the desired compound are isolated. XH-NMR (300 MHz, CD OD): d = 1; 55 (3H), 1.65 (3H), 2.05-2.28 5H), 3.95 (3H), 5.14 (ÍH) , 6.85 (ÍH), 7.00-7.12 (2H), 7.19 (ÍH), 7.40 (1H), 7.70 (HH). (rae.) 5-. { [6-chloro-2,5-dihydroxy-4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-l- (2H-one 40 mg (0.083 mmol) (rae.) 5- { [6-chloro-2-hydroxy-5-methoxy-4, 4, 7-trimethyl-2- (trifluoromethyl) -1,2,3, 4-tetrahydronaphthalen-1-yl] amino.}. -isoquinolin-1 (2H) -one are mixed at room temperature with 0.8 ml of a 1 molar solution of boron tribromide in dichloromethane and stirred for four hours at room temperature, since there is still initial material left, another 0.8 ml of boron tribromide solution is added and the mixture is stirred for 16 hours at room temperature. ° C with a saturated solution of sodium bicarbonate (pH 8) The preparation is mixed with ethyl acetate and the ice bath is removed.After an exhaustive stirring of 10 minutes at room temperature, the preparation is extracted twice with ethyl acetate. The organic phases are washed with water and saline, dried and after removing the solvent the residue is chromatographed on silica gel (elution medium: methanol / dichloromethane). 19.9 mg (51.2%) of the desired compound are isolated.

^ - MR (300 MHz, DMSO-OR6): d = 1.50 (3H), 1.65 (3H), 1.92-2.20 (5H), 5.28 (1H), 5.90 (ÍH), 6,09 (ÍH), 6,69 (ÍH), 6,80 (ÍH), 7,03 (ÍH), 7,18 (ÍH), 7,25 (ÍH), 7,50 ( ÍH), 8.90 (ÍH), 11.24 (1H). Example 288 (rae) 5-. { [6-chloro-2,5-dihydroxy-4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -quinolin-2 (ÍH) -one (rae.) -5-. { [4- (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} i soquinolin-2 (IR) -one 225 mg (0.664 mmol) of (rae.) 4- (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2- (trifluorome) are mixed. -ethyl) pentanal (described in example 287) and 106.3 mg (0.664 mmol) of 5-amino-isoquinolin-2 (HH) -one (described in example 2) with 3.6 ml of xylol. After the addition of 0.39 ml (1.288 mmol) of titanium tetraisopropylate, the preparation is stirred for two and a half hours at 120 ° C. The mixture is poured into 15 ml of saturated saline and diluted with 20 ml of ethyl acetate. The reaction mixture is filtered through Extrelute and washed with 300 ml of a mixture of ethyl acetate / dichloromethane. The resulting solution is centrifuged and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 248.5 mg (77.8%) of the desired compound are isolated. XH-NMR (300 MHz, DMS0-d6): d = 1.38 (3H), 1.53 (3H), 1.85 (3H), 2.20 (1H), 3.05 (1H), 3 , 85 (3H), 6,18 (ÍH), 6,32 (ÍH), 6,52 (ÍH), 6,65 (ÍH), 7,00 (ÍH), 7,18 (ÍH), 7, 39 (ÍH), 7.58 (1H), 8.09 (1H), 11.78 (ÍH). (rae.) 5-. { [6-chloro-2-hydroxy-5-methoxy-4,7,7-trime-il-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} isoquinolin-2 (1H) -one A 130 mg (0.270 mmol) of the mixture described in the previous step of (rae.) -5-. { [4- (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl-2-trifluoromethyl) pentylidene] amino} iso-quinolin-2 (1H) -one, dissolved in 1.6 ml of dichloromethane, 0.8 ml (0.81 mmol) of titanium tetrachloride is added dropwise at 0 ° C, and then the preparation is stirred by two hours at 0 ° C and two hours at room temperature. The reaction mixture is introduced at 0 ° C by dropwise into a saturated solution of sodium bicarbonate and mixed with ethyl acetate. After removing the cold bath, it is agitated exhaustively another 15 minutes at room temperature. After extracting twice with ethyl acetate, the combined organic extracts are washed with a saturated solution of NaCl. After drying with sodium sulfate, the solvent is removed and the residue is chromatographed on silica gel (elution medium ethyl acetate / hexane). 82 mg (63.1%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.53 (3H), 1.66 (3H), 2.00-2.25 (5H), 3.96 (3H), 4.80 (1H) ), 5.01 (1H), 5.58 (1H), 6.49-6.62 (3H), 6.92 (ÍH), 7.35 (HH), 8.19 (HH), 10, 25 (ÍH). (rae.) 5-. { [6-chloro-2,5-dihydroxy-4,4,7-trimethyl-2 - (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} isoquinolin-2 (1H) -one 43 mg (0.089 mmol) of (rae.) 5- are mixed. { [6-chloro-2-hydroxy-5-methoxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} Isoquinolin-2 (1H) -one at room temperature with 0.9 ml of a 1 molar solution of boron tribromide in dichloromethane, and stirring for two and a quarter hours at room temperature. A saturated solution of sodium bicarbonate is added at -30 ° C by drip. After diluting with ethyl acetate, the cold bath is removed and, after the preparation is thoroughly stirred for 10 minutes at room temperature, it is extracted twice with ethyl acetate. The combined organic phases are washed with water and saline, dried, and, after removal of the solvent, the residue is chromatographed on silica gel (elution medium: methanol / dichloromethane). 37.8 mg (90.6%) of the desired compound are isolated. XH-NMR (300 MHz, CD30D): d = 1.58 (3H), 1.70 (3H), 2.00-2.24 (5H), 5.12 (HI), 6.51 (1H) ), 6.62 (ÍH), 6.70 (1H), 6.80 (ÍH), 7.39 (ÍH), 8.22 (ÍH). Example 289 (rae.) 6-Chloro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4 -tetrahydronaphthalen-2,5-diol (rae.) 1, 1, 1-tri-fluoro-4- (3-chloro-2-methoxy-4-methylphenyl) -2 [(8-fluoro-2-methyl -quinazolyl- 5-yl) iminomethyl] -4-methylpentan-2-ol 225 mg (0.664 mmol) of (rae.) 4- (3-chloro-2-methoxy-4-methylphenyl) -2-hydroxy-4-methyl are mixed. -2- (trifluoromethyl) pentanal (described in example 287) and 117.6 mg (0.664 mmol) of 5-amino-8-fluoro-2-methylquinazoline with 3.6 ml of O-xylol. After the addition of 0.39 ml (1.288 mmol) of titanium tetraisopropylate, the preparation is stirred for two hours at 120 ° C. The mixture is poured into 15 ml of saturated saline and diluted with 20 ml of ethyl acetate. The reaction mixture is filtered through Extrelute and washed with 300 ml of a mixture of ethyl acetate / dichloromethane. The resulting solution is centrifuged and the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 217.5 mg (65.7%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.52 (3H), 1.65 (3H), 2.29 (1H), 3.00 (3H), 3.35 (ÍH), 3.92 (3H), 4.59 (ÍH), 6.48 (ÍH), 6.77 (ÍH), 7.00 (ÍH), 7.44 (1H), 7.78 ( ÍH), 9.39 (ÍH). (rae.) 6-chloro-l - [(8-fluoro-2-methyl-tyzolin-5-yl) amino] -5-methoxy -4,4,7'-trimethyl- (trifluoromethyl) -1, 2, 3 , 4-te trahidronaf talen 2-ol 110 mg (0.221 mmol) of the mixture described in the previous step of (rae.) 1,1,1-trifluoro-4- (3-chloro-2-methoxy-3) are dissolved. -methylphenyl) -2- [(8-fluoro-2-methyl-quinazolyl-5-yl) iminomethyl] -4-methylpentan-2-ol in 1.3 ml of dichloromethane, and carefully mix at 0 ° C with 0 , 66 ml (0.663 mmol) of titanium tetrachloride. After stirring for two hours at 0 ° C and another two hours at room temperature. The reaction mixture is combined at 0 ° C by dripping with a saturated solution of sodium bicarbonate. After diluting with ethyl acetate, the cold bath is removed and the preparation is thoroughly stirred at room temperature. After extracting twice with ethyl acetate, the combined organic extracts are washed with a saturated solution of NaCl. After drying with sodium sulfate, the solvent is removed and the residue is subjected to chromatography on silica gel (elution medium: methanol / dichloromethane). 76.5 mg (69.5%) of the desired compound are isolated as a mixture of diastereomers 9.-1. Below are the most important signals of the diastereomers. XH-NMR (300 MHz, CD3OD): d = 1.57 (3H), 1.69 (3H), 2.08-2.29 (5H), 2.89 (3H), 3.95 (3H) ), 5.28 (HH), 6.87 (ÍH), 7.05 (ÍH), 7.59 (1H), 9.65 (1H). (rae) 6-chloro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene- 2, 5-diol 40 mg (0.08 mmol) of (rae.) 6-chloro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -5-methoxy-4, 4 are mixed, 7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol at room temperature with 0.8 ml of a 1 molar solution of boron tribromide in dichloromethane, and stirred for four hours at room temperature. As no conversion occurs, another 0.8 ml of boron tribromide solution is added. The reaction is complete after stirring for 16 hours at ambient temperature. A saturated solution of sodium bicarbonate is carefully added dropwise at -30 ° C, and the preparation is diluted with ethyl acetate. After removing the cold bath, it is stirred thoroughly for 10 minutes at room temperature. The preparation is extracted twice with ethyl acetate. The combined organic phases are washed with water and saline, dried and the residue is chromatographed on silica gel (elution medium: methanol / dichloromethane) after removal of the solvent. 38.2 mg (98.4%) of the desired compound are isolated. XH-NMR (300 MHz, CD3OD): d = 1.60 (3H), 1.72 (3H), 2.05-2.25 (5 H), 2.88 (3H), 5.22 (ÍH), 6.80-6.90 (2H), 7.59 (HH), 9.68 (1H) . Example 290 (rae) 5-. { [7-chloro-6-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino} -isoquinolin-1 (2H) -one 2- (4-chloro-3-fluoro-2-methoxyphenyl) -2-me ti Ipropanoni tri 1 o 16.78 g (93.97 mmol) of 3-chloro are dissolved. 2,6-difluoro-anisole in 800 ml of toluene. After the addition of 25.97 g (375.88 mmol) of isobutyronitrile, 283.97 ml (140.95 mmol) of a 0.5 molar solution of potassium hexamethyldisilazide in toulol are added dropwise. Then the temperature is increased to 28 ° C. The preparation is stirred for seven days at 60 ° C. After mixing with water and ethyl acetate, the reaction mixture is brought to pH 4 with sulfuric acid. After extracting twice with ethyl acetate, the combined organic extracts are washed with water and with a saturated solution of NaCl, and dried. After centrifugation and chromatography on silica gel (elution medium: ethyl acetate / hexane), 7.46 g (21.4%) of the desired compound are obtained. XH-NMR (300 MHz, CDC13): d = 1.75 (6 H), 4.10 (3H), 6.95-7.14 (2H). 2- (4-chloro-3-fluoro-2-methoxyphenyl) -2-methylpropanal _ 7.46 g (32.78 mmol) of the previously described nitrile are dissolved in 131 ml of toluene. Drip 41.1 ml of a 1.2 molar solution of DIBAH in toulol, between -65 ° C and -60 ° C under nitrogen. After stirring for two hours at -65 ° C, 374 ml of a 10% solution of L- (+) - tartaric acid are added dropwise. The preparation is stirred overnight at room temperature. The reaction mixture is extracted three times with diethyl ether. The combined organic extracts are washed with water and saline, dried and the solvent is removed. 7.35 g (97.2%) of the desired compound are obtained, which is used crude in the next step. Ethyl ester (E / Z) -4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-ethoxy-4-methylpent-2-enoic To a solution of 10.3 g (38.83 mmol ) of 2-ethoxy-phosphonoacetic acid triethyl ester, dissolved in 34 ml of absolute THF, 19.9 ml of a 2 molar solution of LDA in THF (1.25 equivalents) are added dropwise at 0 ° C. After stirring for 45 minutes at 0 ° C, 7.35 g (31.86 mmol) of 2- (4-chloro-3-fluoro-2-methoxyphenyl) -2-methylpropanal, dissolved in 21 ml of THF, are added. , by dripping at 0 ° C. After stirring over the weekend at room temperature, the reaction mixture is poured into water and extracted three times with diethyl ether. The combined organic extracts are washed with water and saline, dried and the solvent is centrifuged after filtering the drying media. The residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 8.41 g of the desired compound combined with starting material (aldehyde) are isolated, which is separated in the next step. (E / Z) -4- (4-Chloro-3-fluoro-2-methoxyphenyl) -2-ethoxy-4-methylpent-2-ene acid. 8.41 g (24.39 mmol) of ethyl ester are mixed. (E / Z) -4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-ethoxy-4-methylpent-2-enoic acid with 222 ml of IN NaOH in ethanol / water (2: 1), and stir overnight at room temperature. The ethanol is removed in a rotary evaporator and the residue is extracted three times with methyl-tert-butyl ether, after mixing with water. As the organic extract still contains untransformed aldehyde combined with the desired acid, it is extracted with NaOH ÍM. The solvent is removed after drying the organic extract. A total of 1.59 g of residue (untransformed aldehyde from the reaction described previously) is obtained, which is again subjected to a Homer Wittig reaction to continue the process. The combined aqueous phases are acidified carefully in a cold bath, with concentrated hydrochloric acid, and extracted three times with methyl-tert-butyl ether. This ethereal extract is washed with saline, dried, the solvent is removed and the crude residue (5.99 = 77.5%) is used in the next step. This is constituted by the compound with an E / Z mixture that does not have a 1: 1 ratio, so that in the NMR spectrum only the location of the signals can be established. XH-NMR (300 MHz, CDC13): d = 0.98.1,40,1,49-1,59,3,40,3,78-3,90,5,72, 6,70,6, 92-7.09. 4- (4-chloro-3-fluoro or -2-methoxyphenyl) -4-methyl-2-oxo-pentanoic acid 6.06 g (19.13 mmol) of the above obtained preparation of acid (E / Z) are mixed. ) -4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-ethoxy-4-methylpent-2-enoic with 126 ml of a 1 molar solution of sulfuric acid and 12.6 ml of ethyl acetate a room temperature, and stirred for nine days with a bath temperature of 90 ° C. The preparation is basified in an ice bath with solid potassium carbonate (pH 9) (carefully, presents foam) and extracted three times with methyl-tert-butyl ether. The aqueous phase is acidified in a cold bath with concentrated hydrochloric acid until pH 4, and is stirred three times with methyl-tert-butyl ether. The ether extracts are washed with water and saline, dried, and the solvent is removed. A total of 2.23 g of remaining residue is obtained. As there is still a product present in the first ethereal phase, it is concentrated and the solid residue is taken up in water and methyl tert-butyl ether. After acidifying, the aqueous phase is extracted twice more with methyl-tert-butyl ether. After carrying out the usual processing using conventional means, the combined organic extracts make it possible to obtain 3.21 g of the desired product. In toral, 5.44 g (98.5%) of acid is obtained, which is used in the crude in the next step. XH-NMR (300 MHz, CDC13): d = 1.45 (6 H), 3.55 (2H), 3.97 (3H), 6.95-7.10 (2H). Ethyl 4- (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2-oxopen tanic acid ester 5.44 g (18.84 mmol) of 4- (4-chloro) acid are dissolved. 3-fluoro-2-methoxyphenyl) -4-methyl-2-oxo-pentanoic acid in 117 ml of ethanol, mixed with 2.1 ml of concentrated sulfuric acid and heated to reflux for six hours. The reaction mixture is poured into 250 ml of saturated sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic extracts are washed with a saturated solution of sodium bicarbonate and with saline. After drying, filtering the drying media and centrifuging the solvents, 5.19 g (87%) of the desired compound are obtained.

XH-NMR (300 MHz, CDC13): d = 1.30 (3H), 1.45 (6H), 3.40 (2H), 3.98 (3H), 4.20 (2H), 6, 92-7.50 (2H). Ethyl ester of (rae.) 4 - (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-trimethylsilyloxypentanoic acid 5.19 g (16.38 mmol) are dissolved. ) of 4- (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2-oxo-pentanoic acid ethyl ester in 26 ml of THF, mixed at room temperature with 2.79 g (19, 66 mmol) of (trifluoromethyl) -trimethylsilane and 40.1 mg of tetrabutylammonium fluoride, and stir for two days. The reaction mixture is mixed with methyl tert-butyl ether and washed with water and saline. The organic phase is dried and, after removing the solvent, the residue is chromatographed on silica gel (elution medium: ethyl acetate / hexane). 4.71 g (62.6%) of the desired compound are obtained. Ethyl acid ester (rae.) 4- (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxy-pentanoic 4.71 g (10.26 mmol) are dissolved. ) of (rae.) 4- (4-Chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-trimethylsilyloxy-pentanoic acid ethyl ester in 57 ml of tetrahydrofuran, and mixed with 3.24 g (10.26 mmol) of tetrabutylammonium fluoride trihydrate. After stirring for a weekend at room temperature, the reaction mixture is combined with water and extracted three times with methyl-tert-butyl ether. The combined organic extracts are washed with saline. After drying, the solvent is removed and the residue is subjected to chromatography on silica gel (elution medium: ethyl acetate / hexane). 3.07 g (77.4%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.25 (3H), 1.38 (3H), 1.47. (3H), 2.45 (1H), 2.75 (ÍH), 3.50 (ÍH), 3.75 (ÍH), 4.03 (3H), 4.13 (HH), 6.89 ( 1H), 7.00 (1H). (rae.) 4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (tri-fluorodil) pentanal 1.00 g (2.59 mmol) are dissolved ( rae.) of 4- (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxy-pentanoic acid ethyl ester in 9.5 ml of diethyl ether, and mixed with 73.7 mg (1.94 mmol) of LiAlH4, at 0 ° C in portions. Subsequently, it is stirred at 0 ° C and a DC is made every quarter hour. After stirring for 20 minutes at 0 ° C, the reaction mixture is dripped into a cold bath with 2.4 ml of saturated NaHCO 3 solution. It is thoroughly stirred for 30 minutes in an ice bath and overnight at room temperature. The precipitate is extracted, washed with ethyl acetate and the filtrate is concentrated on a rotary evaporator. After an instantaneous chromatography of the residue, 560.2 mg of product are obtained. This comprises a 3: 2 mixture of aldehyde with the initial ester. (rae.) -5-. { [4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (tri-fluoromethyl) pentylidene] amino} isoquinolin-1 (2H) -one 560 mg of the mixture of (rae.) 4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal are heated. and (rae.) 4- (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxy-pentanoic acid ethyl ester (as the aldehyde accounts for two-thirds of the mixture, the 560.2 mg of mixture contains 336.1 mg (0.981 mmol) of aldehyde), with 157.1 mg (0.981 mmol) of 5-amino-isoquinolin-1 (2H) -one and 0.557 mg (1.962 mg). mmol) of titanium tetraisopro-pilate in 6 ml of 0-xylol, for two hours at 120 ° C. After cooling, the preparation is diluted with ethyl acetate and mixed with saline. The organic phase is separated and processed using conventional means. After carrying out flash chromatography, 144.7 mg (30.4%) of the desired compound is obtained (measured according to the ratio of aldehyde in the mixture). XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.58 (3H), 2.38 (1H), 3.19 (1H), 4.03 (3H), 4.78. (ÍH), 6.65 (ÍH), 6.70-6.83 (3H), 7.20 (1H), 7.44 (1H), 7.62 (1H), 8.35 (HH), 10.95 (1H). (rae.) 5-. { [7-chloro-6-fluoro-2, 5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaphthalen-1-yl] amino.} - isoquinolin-1 (2H) -one 80 are mixed, 3 mg (0.166 mmol) of (rae.) 5- { [4- (4-Chloro-3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentylidene] amino. Isoquinolin-1 (2H) -one at room temperature with 1.7 ml a 1 molar solution of boron tribromide in dichloromethane, and stirred for two and a half hours at room temperature. ice and then a saturated solution of sodium bicarbonate (pH 8) is added dropwise.After adding ethyl acetate and stirring thoroughly for ten minutes at room temperature, the aqueous phase is extracted twice with ethyl acetate. The combined extracts are washed with water and saline, dried and, after removal of the solvent, the residue is subjected to flash chromatography, 24.6 mg (31.6%) of the desired compound are isolated H-NMR (300 MHz , DMS0-ds): d = 1.50 (3H), 1.60 (3H), 1.90-2.14 (2H), 5.31 (HH), 5.92 (ÍH), 6.18 (ÍH), 6.70 ( ÍH), 6,80 (ÍH), 7,05 (ÍH), 7,19 (1H), 7,27 (1H), 7,52 (ÍH), 10,05 (ÍH), 11,25 (ÍH) ). Example 291 (Rae) 7-chloro-6-fluoro-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3 , 4-tetrahydronaphthalene-2,5-diol (rae.) 1,1,1-trifluoro-4- (4-chloro-3-fluoro-2-methoxyphenyl) 2- [(8-fluoro-2-methyl- quinazolyl-5-yl) iminomethyl] -4-methylpentan-2-ol 457 mg of the mixture of (rae.) 4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-hydroxy-methyl are mixed. -2- (trifluoromethyl) pentanal and 4- (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxy-pentanoic acid ester (described) example 290) (as the aldehyde represents two thirds of the mixture, the 457 mg of mixture contains 305.3 (0.891 mmol) of aldehyde) and 158 mg (0.891 mmol) of 5-amino-8-fluoro-2 -methylquinazoline with 5.5 ml of O-xylol. After the addition of 506.6 mg (1.782 mmol) of titanium tetraisoprophylate, the preparation is stirred for two hours at 120 ° C. The mixture is diluted with ethyl acetate and combined with saline. After thorough stirring for ten minutes, the reaction mixture is filtered through Extrelute and eluted with dichloromethane. The resulting solution is centrifuged and the residue is subjected to flash chromatography. 295.8 mg (66.1%) of the desired compound are isolated. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.52 (3H), 2.34 (IH), 3.00 (3H), 3.21 (1H), 4.00 (3H), 4.59 (ÍH), 6.58 (1H), 6.70 (1H), 6.85 (ÍH), 7.49 (ÍH), 7.78 (1H), 9.49 ( ÍH). (rae.) 7-Chloro-6-fluoro-1- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3 , 4-tetrahydronaphthalene-2, 5-diol 295.8 mg (0.589 mmol) of (rae.) 1,1,1-trifluoro-4- (4-chloro-3-fluoro-2-methoxyphenyl) -2 are mixed. - [(8-fluoro-2-methyl-quinazolin-5-yl) iminomethyl] -4-methylpentan-2-ol at 0 ° C with 6.1 ml of a 1 molar solution of boron tribromide in dichloromethane, and Stir for two hours between 0 and 5 ° C. The reaction mixture is combined with ice. After carefully adding a saturated solution of sodium bicarbonate, it is diluted with ethyl acetate and stirred thoroughly for ten minutes. The aqueous phase is extracted twice with ethyl acetate. The organic phases are washed with water and saline, dried and, after removing the solvent, the residue is subjected several times to flash chromatography. 38 mg (13.2%) of the desired compound are isolated. aH-NMR (300 MHz, CD30D): d = 1.60 (3H), 1.70 (3H), 2.05-2.21 (2H), 2.83 (3H), 5.23 (1H) 6.80-6.92 (2H), 7.59 (1H), 9.68 (1H). Example 292 (rae.) 7-Chloro-6-fluoro-1- [(7-fluoro-2-methylquinazolin-5-yl) amino] -4,4-dimethyl-2- (trifluoromethyl) -1,2,3 , 4-tetrahydronaphthalene-2,5-diol 5-amino -7-fluoro-2-methyl-tilquinazoline 17 g (70.5 mmol) of 3,6-difluoro-2-N-pivaloylaminobenzaldehyde (L. Florvall, I) are added. Fagervall, L.-G-Larsson, SB Ross, Eur.J. Med. Chem. 34 (1999) 137-151), 9.2 g of acetamidine hydrochloride, 13.4 g of potassium carbonate and 10.4 g of molecular sieves (4A) in 70 ml of butyronitrile. Heat with vigorous stirring for 17 hours at 145 ° C, and remove the solvent in vacuo. After chromatographing the residue on silica gel with hexane / ethyl acetate (0-70%), 4.5 g of 7-fluoro-5-N-pivaloylamino-2-methyquinazoline are obtained. Dissolve 1 g (3.82 mmol) of 7-fluoro-5-N-pivaloylamino-2-methyquinazoline in 74 ml of toluene, and cool to -70 ° C. 9.5 ml (11.4 mmol) of a 1.2 M solution of diisobutylaluminum hydride in toulol are added dropwise over 30 minutes. Allow the reaction mixture to warm to -40 ° C and stir for four hours at -40 ° C. Water is added slowly, stirred for 30 minutes at room temperature until a precipitate is obtained and the filtration media is removed through Celite. The phases are separated, washed with a saturated solution of sodium chloride and dried with sodium sulfate. After chromatography on silica gel (elution medium: ethyl acetate / hexane), 64 mg of product are obtained. XH-NMR (CDC13); d = 2.83 (s, 3H), 4.67 (br, 2H), 6.50 (dd, ÍH), 6.93 (dd, 1H), 9.23 (s, 1H). (rae.) 1, 1, 1-trifluoro-4- (4-chloro-3-fluoro-2-methoxy phenyl) -2 [(7-fluoro-2-methyl-q-quinolyl-5-yl) iminomethyl] -4 -methylpentan 2-ol 400 mg of the mixture of (rae.) 4- (4-chloro-3-fluoro-2-methoxyphenyl) -2-hydroxy-4-methyl-2- (trifluoromethyl) pentanal and (rae) are mixed. .) 4- (4-chloro-3-fluoro-2-methoxyphenyl) -4-methyl-2- (trifluoromethyl) -2-hydroxy-pentanoic acid ethyl ester (described in Example 8) (as the aldehyde represents two thirds of the mixture, the 400 mg of the mixture contains 266.6 (0.778 mmol) of aldehyde) and 137.8 mg (0.778 mmol) of 5-amino-7-fluoro-2-methylquinazoline with five ml of O-xylol . After the addition of 442.3 mg (1.56 mmol) of titanium tetraisopropylate, the preparation is stirred for two hours at 120 ° C. The mixture is diluted with ethyl acetate and mixed with saline. After thorough stirring for ten minutes, the reaction mixture is filtered through Extrelute and eluted with dichloromethane. The resulting solution is centrifuged and the residue is subjected to an instantaneous chromatography. 312.4 mg (80%) of the desired compound are isolated. The yield is based on the aldehyde contained in the mixture. XH-NMR (300 MHz, CDC13): d = 1.40 (3H), 1.60 (3H), 2.36 (HH), 2.92 (3H), 3.23 (HH), 4.01 (3H), 4.49 (ÍH), 6.49 (ÍH), 6.65 (ÍH), 6.89 (1H), 7.45 (1H), 7.79 (1H), 9.32 (ÍH). 1 HOUR) . (rae.) 7-chloro-6-fluoro-l- [(7-fluoro-2-methylquinazolin-5-yl) amino] -4,4,7-trimethyl-2- (trifluoromethyl) -1, 2, 3 , 4-tetrahydronaphthalen-2, 5-diol 312.4 mg (0.622 mmol) of (rae.) 1,1,1-trifluoro-4- (4-chloro-3-fluoro-2-methoxyphenyl) -2 are mixed. - [(7-fluoro-2-methyl-quinazolyl-5-yl) iminomethyl] -4-methylpentan-2-ol at 0 ° C with 6.4 ml of a 1 molar solution of boron tribromide in dichloromethane, and Stir for two hours between 0 and 5 ° C. The reaction mixture is combined with ice. After carefully adding a saturated solution of sodium bicarbonate, it is diluted with ethyl acetate and stirred thoroughly for ten minutes. The aqueous phase is extracted twice with ethyl acetate. The organic phases are washed with water and saline, dried and, after removing the solvent, the resin is subjected several times to flash chromatography. 51 mg (16.7%) of the desired compound are isolated.^? - NMR (300 MHz, CD3OD): d = 1.60 (3H), 1.70 (3H), 2.15 (2H), 2.79 (3H), 5.31 (1H), 6, 70-6.88 (3H), 9.58 (1H). In a manner analogous to the preparation of the compounds described in examples 283-292, the structures described below are synthesized, using the corresponding initial materials. Example 293 1- (7,8-difluoro-2-methyl-tyzolin-5-ylamino) -6-fluoro-5-methoxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4- tetrahydrsnaphthalen-2-ol Example 294 5-7, 8-difluoro-2-methylquinazolin-5-ylamino) -2-fluoro-3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8- tetrahydronaf alen-1,6-diol Examples 295 and 296 1- (2-ethylquinazolin-5-ylamino) -6-fluoro-5-methoxy-4,4,7-trimethyl-2- (trifluoromethyl) -1, 2, 3,4- tetrahydronaphthalen-2-ol, Diastereomer A, and 1- (2-ethylquinazolin-5-ylamino) -6-fluoro-5-methoxy-4,4,7-trimethyl-2- (trifluoromethyl) -1, 2,3,4-tetrahydronaph alen-2-ol, Diastereomer B Example 297 5- (2-ethylquinazolin-5-ylamino) -2-fluoro-3,8,8-trimethyl-6- (trifluoromethyl) -5,6 , 7,8-tetrahydronaphthalene-1,6-diol, Diastereomer A Example 298 5- (2-ethylquinazolin-5-ylamino) -2-fluoro-3,8,8-trimethyl-6- (trifluoromethyl) -5,6 , 7,8-tetrahydronaphthalen-1,6-diol, Diastereomer B Examples 299 and 300 5- (2-methylquinzol-5-ylamino) -2-fluoro-3,8,8-trimethyl-6- (trifluoromethyl) useful) -5, 6,7, 8-tetrahydronaphthalene-1,6-diol, Diastereomer A, and 5- (2-methylquinazolin-5-ylamino) -2-fluoro-3, 8, 8-trimethyl-6- ( trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol, Diastereomer B Examples 301 and 302 (+) - 5 -. { [6-fluoro-2, 5-dihydroxy-4,4,7-trimethyl-2- (t (fluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-yl] amino.}. -quinolin-2 ( ÍH) -one and (-) -5- { [6-fluoro-2, 5-dihydroxy-4,4,7-trimethyl-2- (trifluoromethyl) -1, 2,3,4-tetrahydronaphthalen-1 -yl] amino.}. -quinolin-2 (1H) -one 83 mg of 5- { [6-fluoro-2,5-dihydroxy-4,7,7-trimethyl-2- (trifluoromethyl) are separated. -1,2,3, 4-tetrahydronaphthalen-1-yl] amino.}. -quinolin-2 (1H) -one racemic on a chiral column (Chiralpak AD-H 514, eluents: hexane / ethanol), - with In order to obtain the corresponding enantiomers, 34 mg of the (+) enantiomer and 33 mg of the (-) enantiomer are obtained [a] D = +41.1 + 0.5 (c = 0.51, methanol) [a] D = -41.8 ± 0.4 (c = 0.505, methanol) Examples 303 and 304 (+) - 6-fluoro-l- [(8-fluoro-2-methylquinazolin-5-yl) amino] -4 , 4, 7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2,5-diol and (-) - 6-fluoro-1- [(8-fluoro-2-methylquinazolin-5 -yl) amino] -4,4,7-trimethoxy-2- (rifluoromethyl) -1, 2, 3, 4- tetrahydronaphthalen-2, 5-diol 50.8 mg of 6-fluoro-1- [(8-fluoro-2-methyl-quinazolin-5-yl) amino] -4,4,7-trimethyl-2- ( trifluoromethyl) -1,2,4,4,4-tetrahydronaphthalene-2,5-diol on a chiral column (Chiralpak AD-H 5p. , eluents: hexane / ethanol), in order to obtain the corresponding enantiomers. 25.3 mg of the (+) enantiomer and 23.8 mg of the (-) enantiomer are isolated. [α] D = +57.8 ± 1.1 (c = 0.50, methanol) [a] D = -53.3 ± 0.3 (c = 0.50, methanol). EXAMPLE 305 5- [7-Chloro-6-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino] -1H-quinoline- 2-one Example 306 5- [7-Chloro-6-fluoro-2-hydroxy-5-me oxy-4,4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino ] -1,3 dihydroindol-2 -one Example 307 5- [7-Chloro-6-fluoro-2,5-dihydroxy-4,4-dimethyl-2- (rifluoromethyl) -1,2,4,4-tetrahydronaphthalene -1-ylamino] -1,3-dihydroindol-2 -one Example 308 7-Chloro-1- (7,8-difluoro-2-methylquinazolin-5-ylamino) -6-fluoro-5-methoxy-4, 4- dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol Example 309 3-Chloro-5- (7,8-difluoro-2-methylquinazolin-5-ylamino) -2-fluoro- 8 , 8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol Examples 310 and 311 7-chloro-1- (2-ethylquinazolin-5-ylamino) -6-fluoro- 5-methoxy-4, 4-dimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol, Diastereomer A, and 7-chloro-l- (2-ethylquinazolin-5-ylamino) - 6-fluoro-5-methoxy-4, 4-dimeti l-2- (trifluoromethyl) -1, 2,3,4-tetrahydronaph alen-2-ol, Diastereomer B Example 312 3-Chloro-5- (2-ethylquinazolin-5-ylamino) -2-fluoro-8, 8-dimethyl-6- (trifluoromethyl) - 5,6,7,8-tetrahydronaphthalene-1,6-diol Examples 313 and 314 3-chloro-5- (7-fluoro-2-methylquinazolin-5-ylamino) -2-fluoro-8,8-dimethyl-6 - (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol, enantiomer A, and 3-chloro-5- (7-fluoro-2-methyl-tyzolin-5-ylamino) -2-fluoro- , 8-dimethyl-6-difluoromethyl) -5,6,7,8-tetrahydronaf-alen-1,6-diol, enantiomer B 22.5 mg of the racemic compound 3-chloro-5- (7-fluoro-2 -methylquinazolin-5-ylamino) -2-fluoro-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol on a chiral column (Chiralpak AD-H 511, eluents: hexane / ethanol), in order to obtain the corresponding enantiomers. 10.5 mg of the enantiomer A (retention time: 5.28 minutes) and 9.9 mg of the B-enantiomer are isolated (retention time 10.79 minutes). Examples 315 and 316 (+) - 3-chloro-5- (8-fluoro-2-methyl-tyzolin-5-ylamino) -2-fluoro-8,8-dimethyl-6- (trifluoromethyl) -5,6,7, 8-tetrahydronaphthalene-1,6-diol, enantiomer A, and (-) - 3-chloro-5- (8-fluoro-2-methylquinazolin-5-ylamino) -2-fluoro-8, 8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol, enantiomer B 40 mg of the racemic compound (+) -3-chloro-5- (8-fluoro-2-methylquinazolin-5-) are separated ilamino) -2-fluoro-8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol on a chiral column (Chiralpak AD 100, eluents: hexane / ethanol), in order to obtain the corresponding enantiomers. 16 mg of each respective enantiomer are obtained. [α] D = +53.11 ± 0.6 (c = 0.555, methanol) [a] D = -46.0 ± 0.6 (c = 0.58, methanol). Example 317 3-Fluoro-4,7-dihydroxy-5,5-dimethyl-8- (2 -oxo-1,2-dihydroquinolin-5-ylamino) -7- (trifluoromethyl) -5,6,7,8- tetrahydronaphthalene-2-carbonitrile IR (Mikroskop, Matrix: Diamond): 2232 Example 318 3-Fluoro-4,7-dihydroxy-5,5-dimethyl-8- (2 -oxo-1,3-dihydroindol-4-ylamino) -7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile IR (Mikroskop, Matrix: Diamond): 2238 Example 319 6-chloro-l- (7-fluoro-2-methylquinazolin-5-ylamino ) -5-methoxy-4,4,7-trimethyl-2"(t -fluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol Example 320 2-chloro-5- (7-fluoro-2-methyl-quinazolin) -5-ylamino) -3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol Example 321 6-chloro-1- (7,8-difluoro- 2-methylquinazolin-5-ylamino) -5-methoxy-4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol Example 322 2-chloro-5- (7 , 8-difluoro-2-methylquinazolin-5-ylamino) -3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol Example 323 4- [6 - chlorine-2-hid Roxy-5-methoxy-4,4,7-trimethyl-2 - (trifluoromethyl) -1,2,3,4-i tetrahydronaphthalen-1-ylamino] -1,3-dihydroindol-2 -one Example 324 4 - ( 6-Chloro-2,5-dihydroxy-4,4,7-trimethyl-2 - (trifluoromethyl) -1,2,3,4-tetrahydrona-alen-1-ylamino] -1,3-dihydroindol-2 -one Example 325 6-Chloro-5-methoxy-4, 4,7-trimethyl-1- (2-methylquinazolin-5-ylamino) -2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalene-2-ol Example 326 2-Chloro-3,8,8-trimethyl-5- (2-methyl-tyzolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol Examples 327 and 328 ( +) -6-chloro-l- (7-8-difluoro-2-methylquinazolin-5-ylamino) -5-methoxy-4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4- tetrahydronaphthalen-2-ol and (-) - 6-chloro-l- (7,8-difluoro-2-methylquinazolin-5-ylamino) -5-methoxy-4,7,7-trimethyl-2- (trifluoromethyl) - 1,2,3, 4-tetrahydronaphthalen-2-ol 88 mg of 6-chloro-1- (7,8-difluoro-2-methylquinazolin-5-ylamino) -5-methoxy-4, 7-7 are separated. trimethyl-2- (trifluoromethyl) -1, 2, 3, 4-tetrahydronaf alen-2-ol race mica in a chiral column (Chiralpak AD-H 50, eluents: hexane / ethanol). 42.6 mg of the (+) enantiomer and 41.3 mg of the enantiomer (-) are obtained. [α] D = +36.9 ± 0.6 (c = 0.50, methanol) [a] D = -32.8 + 0.3 (c = 0.51, methanol). Example 329 (+) -2-chloro-5- (7-8-difluoro-2-methylquinazolin-5-ylamino) -3, 8, 8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol. 33.9 ml of the ether described in example 45 ((+) enantiomer) are processed with tribromide boron, using conventional means. 30.1 mg (91.4%) of free phenol of enantiomers are isolated. [α] D = + 49.1 + 0.3 (C = 0.55, methanol). Example 330 (-) -2-chloro-5- (7,8-difluoro-2-methyl-tyzolin-5-ylamino) -3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8- tetrahydronaphthalene-1,6-diol 37.2 ml of the ether described in example 45 (enantiomer (+)) are processed with boron tribromide, using conventional means. 30.9 mg (85.6%) of free phenol of enantiomers are isolated. [α] D = -44.7 + -0.4 (c = 0.55, methanol). Examples 331 and 332 (+) - 6-chloro-l- (7-flusro-2-methylquinazolin-5-ylamino) -5-methoxy-4,4,7-trimethyl-2 - (trifluoromethyl) -1,2, 3,4-tetrahydronaphthalen-2-ol and (-) -6-chloro-l- (7-fluoro-2-methylquinazolin-5-ylamino) -5-methoxy-4,4,7-trimethyl-2- (trifluoromethyl) ) -1,2,3,4-tetrahydronaphthalen-2-ol 143 mg of 6-chloro-1- (7-fluoro-2-methyl-zolin-5-ylamino) -5-methoxy-4, 4 are separated. Racemic 7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-2-ol on a chiral column (Chiralcel OD-H 5E1, eluents: hexane / ethanol). 58.4 mg of the (+) enantiomer and 51.2 mg of the (-) enantiomer are obtained. [α] D = +30.51 ± 0.7 (c = 0.50, methanol) [a] D = -27.3 ± 0.8 (c = 0.51, methanol). Example 333 (+) -2-chloro-5- (7-fluoro-2-methylquinazolin-5-ylamino) -3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene- 1,6-diol 51 ml of the ether described in example 49 ((+) enantiomer) are processed with boron tribromide, using conventional means. 47.3 mg (95.5%) of free phenol of enantiomers are isolated. [α] D = +41.6 + 0.8 (c = 0.55, methanol). Example 334 (-) -2-chloro-5- (7-fluoro-2-methylquinazolin-5-ylamino) -3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-te rahydronaftalen -1,6-diol 44.5 mg of the ether described in Example 49 ((-) enantiomer) are processed with boron tribromide, using conventional means. 41.4 mg (95.8%) of free phenol of enantiomers are isolated. [α] D = -40.2 ±, 6 (c = 0.57, methanol). Examples 335 and 336 (+) - 5 - [6-chloro-2-hydroxy-5-methoxy-4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino ] -1H-quinolin-2-one and (-) -5- [6-chloro-2-hydroxy-5-methoxy-4,4,7-trimethyl-2- (trifluoromethyl) -1, 2, 3, 4 -tetrahydronaphthalen-1-ylamino] -1H-quinolin-2-one 124 mg of 5- [6-chloro-2-hydroxy-5-methoxy-4, Racemic 4, 7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino] -lH-quinolin-2-one on a chiral column (Chiralcel OJ-H 513, eluents: hexane / ethanol). They are obtained 54.7 mg of the (+) enantiomer and 47.8 mg of the (-) enantiomer. [] D = +37.0 + 0.6 (c = 0.57, methanol) [a] D = -46.6 + 0.4 (c = 0.54, methanol). Example 336 (+) - 5 - [6-chloro-2,5-dihydroxy-4,4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino] -1H- quinolin-2-sna 47.3 mg of the ether described in Example 334 (enantiomer (+)) are processed with boron tribromide, using conventional means. 42.6 mg (92.8%) of free phenol of enantiomers are isolated. [α] D = +53.3 + 0.4 (c = 0.52, methanol). Example 337 (-) -5- [6-chloro-2,5-dihydroxy-4, 4,7-trimethyl-2- (trifluoromethyl) -1,2,3,4-tetrahydronaphthalen-1-ylamino] -1H- quinolin-2-one 42.4 mg of the ether described in Example 334 ((-) enantiomer) are processed with boron tribromide, using conventional means. 39.4 mg (95.8%) of free phenol of enantiomers are isolated. [α] D = -56.3 +, 4 (c = 0.54, methanol). Example 338 1,6-dihydroxy-3,8,8-trimethyl-5- (2-oxo-2,3-dihydroindol-4-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene- 2- IR carbonitrile (Mikroskop, Matrix: Diamond): 2235. Example 338 5- (7-Fluoro-2-methylquinazolin-5-ylamino) -1,6-dihydroxy-3,8,8-trimethyl-6- (trifluoromethyl) ) -5, 6,7, 8 -tetrahydronaphthalene-2-carbonitrile IR (Mikroskop, Matrix: Diamond): 2228. Analogously to the preparation of the compounds described in examples 283-292, the structures described below are synthesized, using the corresponding ini-cial materials: 3-fluoro-4, 7-dihydroxy-5, 5-dimethyl-8- (1-oxo-l, 2-dihydroisoquinolin-5-ylamino) -7- (trifluoromethyl) -5,6 , 7,8-tetrahydronaphthalen-2-carbonitrile 3-fluoro-4,7-dihydroxy-5,5-dimethyl-8- (2-methyl-1-oxo-1,2-dihydroisoquinolin-5-ylamino) -7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-4,7-dihydroxy-5,5-dimethyl-8- (2-methyl-1-oxo-1,2-dihydrophthalazine- 5-ylamine) -7- (trifluoro methyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-4,7-dihydroxy-5,5-dimethyl-8- (1-oxo-l, 2-dihydroftalazin-5-ylamino) - 7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-8- (7-fluoro-2-methylquinazolin-5-ylamino) -4; 7-Dihydroxy-5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-8- (8-fluoro-2-methylquinazolin-5-ylamino) -4 , 7-dihydroxy-5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-2-carbonitrile 3-fluoro-8- (7,8-difluoro-2-methylquinazolin-5-ylamino ) -4,4-dihydroxy-5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-2-carbonitrile 3-fluoro-8- (2-methylquinazolin-5-ylamino) -4 , 7-dihydroxy-5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonylaryl 3-fluoro-8- (2-ethylquinazolin-5-ylamino) -4, 7-dihydroxy-5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-8- (2-methylquinolin-5-ylamino) -4, 7- dihydroxy-5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-8- (2,6-dimethyquinolin-5-ylamino) -4,7-dihydroxy -5,5-dimethyl -7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-2-carbonitrile 3-fluoro-8- (6-chloro-2-methylquinolin-5-ylamino) -4, 7- dihydroxy-5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-8- (6-fluoro-2-methylquinolin-5-ylamino) -4, 7 -dihydroxy-5, 5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-4,7-dihydroxy-8- (lH-indazol-4-ylamino) - 5,5-dimethyl-7- (trifluoromethyl) -5,6,7,8-tetrahydronaf-alen-2-carbonitrile 3-fluoro-4,7-dihydroxy-5,5-dimethyl-8- (naphthalene-1-ylamino ) -7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-4,7-dihydroxy-5,5-dimethyl-8- (naphthalene-2-ylamin) 7- (trifluoromethyl) -5,6,7 , 8-tetrahydronaphthalene-2-carbonitrile 3-fluoro-4,7-dihydroxy-5,5-dimethyl-8- (6-hydroxynaphthalen-1-ylamino) -7- (trifluoromethyl) -5,6,7,8- tetrahydronaphthalene-2-carbsnitrile 3-fluoro-4,7-dihydroxy-5,5-dimethyl-8- (5-hydroxynaph-talen-1-ylamino) -7- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene -2-carbonitrile 3-chloro-2-fluoro-5- (6-hydroxynaphthalen-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-1, 6- diol 3-chloro-2-fluoro-5- (5-hydroxynaphthalen-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol chloro-2-fluoro-5- (naphthalen-1-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 3-chloro-2-fluoro -5- (naphthalen-2-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-1,6-diol 3-chloro-2-fluoro-5- (lH -indazol-4-ylamino) -8,8-dimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-1,6-diol 3-chloro-2-fluoro-5- (5-chloro- 1H-indazol-4-ylamine) -8,8-dimethyl-6- (trifluoromethyl) -5,6, 7,8-tetrahydronaphthalen-1,6-diol 5- (7,8-difluoro-2-methylquinazolin-5-ylamino) -1,6-dihydroxy-3,8,8-trimethyl-6- (trifluoromethyl) -5 , 6,7,8-tetrahydronaphthalene-2-carbonitrile 5- (8-fluoro-2-methylquinazolin-5-ylamino) -1,6-dihydroxy-3,8,8-trimethyl-6- (trifluoromethyl) -5, 6,7,8-tetrahydronaphthalene-2-carbonitrile 5- (2-methylquinazolin-5-ylamino) -1,6-dihydroxy-3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8 -tetrahydronaphthalene-2-carbonitrile 5- (2-ethylquinazolin-5-ylamino) -1,6-dihydroxy-3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2- carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (2-oxo-l, 2-dihydroquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2 -carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (1-oxo-l, 2-dihydroisoquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene- 2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (2-methyl-1-oxo-1,2-dihydroisoquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7 , 8- tetrahydronaphta len-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (1-oxo-l, 2-dihydroftalazin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8 -tetrahydronaphthalen-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (2-methyl-l-oxo-l, 2-dihydroftalazin-5-ylamino) -6- (trifluoromethyl) -5, 6,7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (2-methylquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8 -tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (2,6-dimethylquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene- 2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (6-chloro-2-methylquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2 -carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (6-fluoro-2-methylquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2- carbonitrile 1,6-dihydroxy-5- (lH-indazolyl-4-ylamino) -3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 1, 6 dihydroxy-5- (5-chloro-l) H-indazolyl-4-ylamino) -3, 8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (naphthalene-1-ylamino) - 6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (naphthalen-2-ylamino) -6- (trifluoromethyl) -5 , 6,7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (6-hydroxy-naphthalen-1-ylamino) -6- (trifluoromethyl) -5,6, 7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-3,8,8-trimethyl-5- (5-hydroxy-naphthalen-1-ylamino) -6- (trifluoromethyl) -5,6,7,8 -tetrahydronaphthalene-2-carbonitrile 2-chloro-5- (1H-indazol-4-ylamino) -3,8,8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-1, 6 diol 2-fluoro-5- (lH-indazol-4-ylamino) -3,8, 8-trimethyl-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 2-chloro- 3, 8, 8-trimethyl-5- (naphthalene-1-ylamino-6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 2-fluoro-3, 8, 8-trimethyl- 5- (naphthalen-1-ylamino-6- (trifluoromethyl) -5,6,7,8-tet rahydronaphthalen-1, 6-diol 2-chloro-3, 8, 8-trimethyl-5- (6-hydroxynaphthalen-1-ylamino) - (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 2-fluoro-3, 8, 8-trimethyl-5- (6-hydroxynaphthalen-1-ylamido) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-1,6-diol 2-chloro-3 , 8, 8-trimethyl-5- (5-hydroxynaphthalen-1-ylamino) - (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-l, 6-diol 2-fluoro-3, 8, 8-trimethyl- 5- (5-hydroxynaphthalen-1-ylamido) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalen-1,6-diol 1,6-dihydroxy-8,8-dimethyl-5- ( 2-methylquinazolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-8,8-dimethyl-5- (2-ethylquinazolin-5-ylamino ) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-8,8-dimethyl-5- (7-fluoro-2-methylquinazolin-5-ylamino) -6 - (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-8,8-dimethyl-5- (7,8-difluoro-2-methylquinazolin-5-ylamins) -6- (trifluoromethyl) -5,6,7,8- tetrahydronaphthalene-2-carbonitrile 1,6-dihydroxy-8,8-dimethyl-5- (8-fluoro-2-methylquinazolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaphthalene-2 -carbonitrile 1, 6-dihydroxy-8,8-dimethyl-5- (2-oxo-l, 2-dihydroquinolin-5-ylamino) -6- (trifluoromethyl) -5,6,7,8-tetrahydronaf-alen-2 -carbonitrile.

Claims

CLAIMS Compounds of the general formula (I), where R x and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group or which can be substituted, a C 1 -C 6 alkoxy group or can be substituted, an alkylthio-C? -C? group, a perfluoroalkyl-C? -C5 group, a cyano group, a nitro group, or R1 and R2 together are a group selected from the groups -0- ( CH2) n-0-, -0- (CH2) n-CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + ?, -N (C1-C3 alkyl) ) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with carbon atoms of the directly adjacent ring, or they are NR8R9, where R8 and R9 can be independently of each other, hydrogen, -alkyl-C? -C5 or (CO) -alkyl-Ci-Cs, RX1 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a (C1-C10) alkyl group that can be substituted, an alkoxy- (C? -C? 0) group, an alkylthio- (Ci-Cio) group, a perfluoroalkyl group - (C1-C5), R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0) group which can be substituted, an alkoxy- group (C1) -C10), R3 is an alkyl-C? -C? 0 group which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a cycloalkyl- (C3-) group C7) which can be substituted, a heterocyclyl group which can be substituted, an aryl group which can be substituted, a mono- or bicyclic heteroaryl group which can be independently substituted by one or more groups selected from alkyl- (C1) groups -C5) which in turn can be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups, where R13 means hydrogen-alkyl or Ci-Cs, alkoxy- (C1-C5) groups, halogen atoms, groups hydroxy, NR8R9 groups, exomethylene groups, oxygen, which may contain 1-4 nitrogen atoms, and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this groupcan be bound at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or several places, R4 is a hydroxy group, an OR10 group or an O (C0) R10 group where R10 means any hydroxy protecting group or an alkyl group -C? -C? O, R5 is an alkyl- (Ci-Cio) group, or an alkyl- (Ci-Cio) group which may be partially or fully fluorinated, a (C3-C7) cycloalkyl group, a group alkyl- (Ci- C8) cycloalkyl (C3-C7), an alkenyl- (C2- C8) cycloalkyl group (C3-C), a heterocyclyl group, an alkylheterocyclyl- (C? -8) group, an alkenylheterocyclyl group - (C2-C8), an aryl group, an alkylaryl group- (Ci- Cs), an alkenylaryl- (C2-C8), alkynylaryl- (C2-C8) groups, a mono- or bicyclic heteroaryl group, an alkylheteroaryl- (C? -C8) or an alkenylheteroaryl- (C2-C8), an alkynylheteroaryl- (C2-C8) group which can be substituted by 1-2 keto groups, 1-2- (C1-) alkyl groups C5), 1-2 alkoxy- (C1-C) groups 5), 1-3 halogen atoms, 1-2 exomethylene groups, containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms, where these groups can be linked in any position with the tetrahydronaphthalene system and which may be hydrogenated at one or several places, R5 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a ring cycloalkyl- (C3-Ce) • 2. Stereoisomers of the general formula (I), where R x and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group or which can be substituted, a C 1 -C 6 alkoxy group or which may be substituted, an alkylthio-C? -C? group, a perfluoroalkyl-Ci-Cs group, a cyano group, a nitro group, or Rx and R2 together are a group selected from the groups -0- ( CH2) n-0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + ?, -N (alkyl? -C? -C3) - (CH2) n +?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms, or are NR8R9 , where R8 and R9 can be independently of one another, hydrogen, -alkyl-Ci-Cs or (CO) -alkyl-Ci-Cs, Rxx is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0) group which can be substituted, an alkoxy- (C? -C? 0) group, an alkylthio- (Ci-Cio) group, a perfluoroalkyl- (C1-C5) group,
R 12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (Ci-Cio) group that can be substituted, a (C 1 -C 10) alkoxy group, R 3 is an alkyl- C? ~ C? 0 which can be substituted by a group selected from 1-3 hydroxy groups, halogen atoms, 1-3 C1-Cs alkoxy groups, a (C3-C) cycloalkyl group which can be substituted, a heterocyclyl group which can be substituted, an aryl group which can be substituted, a mono- or bicyclic heteroaryl group which can be independently substituted by one or more groups selected from among (C1-C5) alkyl groups which in turn can be substituted to be substituted by 1-3 hydroxy groups or 1-3 CO-OR 13 groups, where R 13 signifies hydrogen or C 1 -C 5 alkyl, alkoxy- (C 1 -C 5) groups, halogen atoms, exomethylene groups that can be substituted, mono- or bicyclic heteroaryl group which may contain 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be linked at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, an OR10 group or an O (C0) R10 group where R10 means any hydroxy-protecting group or a C-C6-alkyl group, R5 is a (C1-C5) alkyl group, or a (C1-C5) -alkyl group which may be partially or fully fluorinated, a cycloalkyl- (C3-C7), an alkyl- (C? -8) cycloalkyl group (C3-C), an alkenyl- (C2-C8) cycloalkyl (C3-C7) group, a heterocyclyl group, an alkylheterocyclyl- (C? -C8), an alkenylheterocyclyl- (C2-C8), an aryl group, an alkylaryl- (C? -C8), an alkenylaryl- (C2-C8), alkylaryl- (C2-C8), a group mono- or bicyclic heteroaryl, an alkylheteroaryl- (C? -C8) or an alkenylheteroaryl- (C2-C8), an alkynylheteroaryl- (C2-C8) group which can be substituted by 1-2 keto groups, 1- 2 alkyl- (C1) groups -C5), 1-2 (C1-C5) alkoxy groups, 1-3 halogen atoms, 1-2 exomethylene groups, containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms, where these groups can be linked at any position with the tetrahydronaphthalene system and which can be hydrogenated at one or several places, R6 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl- (C3-Ce) ring. with the proviso that at least three of the radicals R1, R2, R11 and R12 is not hydrogen. 3. Compounds of the general formula (I), where R1 and R2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C-C? alkyl group or which can be substituted, a C alco-C? alkoxy group or can be substituted, an alkylthio-C? -C? group, a perfluoroalkyl-Ci- C5 group, a cyano group, a nitro group, or Rx and R2 together are a group selected from the groups -0- (CH2) n -0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + 1, -N (C-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with ring carbon atoms directly adjacent, or are NR8R9, where R8 and R9 can be independently from each other, hydrogen, -alkyl-Ci-Cs or (CO) -alkyl-Ci-Cs, R1X is a hydrogen atom, a hydroxy group, an halogen, a cyano group, an alkyl- (C? -C? 0) group which can be substituted, an alkoxy- group (C? -C? 0), an alkylthio- (Ci-Cio) group, a perfluoroalkyl group lo- (C1-C5),
R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0) group that can be substituted, a (C1-C10) alkoxy group, R3 is a alkyl-C? -C? 0 group which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 groups to the COXI-C1-C5, a cycloalkyl- (C3-C) group which can be substituted, a heterocyclyl group that can be substituted, an aryl group which can be substituted, a mono- or bicyclic heteroaryl group which can be independently substituted by one or more groups selected from among (C1-C5) alkyl groups which in turn can be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups, wherein R13 means hydrogen or Ci-Cs alkyl, (C1-C5) alkoxy groups, halogen atoms, hydroxy groups, NR8R9 groups, exomethylene groups, oxygen, which may contain 1-4 nitrogen atoms, and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group may be attached in any position to the amine of the tetrahydronaphthalene system and may be hydrogenated in one or several places, R4 is a hydroxy group, an OR10 group or an O (C0) RX0 group where Rx0 means any hydroxy protecting group or an Ci-Cio alkyl group, R5 is an (C1-C10) alkyl group , or an alkyl- (C? ~ Cio) group which may be partially or fully fluorinated, R6 and R7 are, independently Among them, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl- (C3-Ce) ring.
4. Compounds of the general formula (I), where R x and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 0 alkyl group which can be substituted, a C 1 -C 6 alkoxy group or can be substituted, an alkylthio-CC? group, a perfluoroalkyl-C-C5 group, a cyano group, a nitro group, or together they are a group selected from the groups -0- (CH2) n-0-, -0 - (CH2) n-CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + ?, N (C-C3-alkyl) - (CH2) n + ?, - NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms, or are NR8R9, where R8 and R9 can independently be hydrogen, -alkyl-Ci-Cs or (CO) -alkyl-Ci-Cs, Rxx is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a group alkyl- (C? -C? 0) which can be substituted, an alkoxy- (C? -C? 0), an alkylthio- (Ci-Cio), a perfluoroalkyl- ( C1-C5), R12 is a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, an alkyl- (C? -C? 0) group that can be substituted, an alkoxy- (C1-C10) group ), R3 is an alkyl-C? -C? 0 group which can be substituted by 1-3 hydroxy groups, halogen atoms, 1-3 alkoxy-Ci-Cs groups, a cycloalkyl- (C3-C) group which may be substituted, a heterocyclyl group which may be substituted, an aryl group which may be substituted, a mono- or bicyclic heteroaryl group which may be independently substituted by one or more groups selected from alkyl- (C1) groups -C5) which in turn can be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups, where R13 means hydrogen or C alquilo-C5 alkyl, alkoxy- (C1-C5) groups, halogen atoms, exomethylene groups , oxygen, which may contain 1-3 nitrogen atoms, and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be bound in any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or several places, R4 is a hydroxy group, an OR10 group where R10 is a C-C? alkyl group, R5 is an alkyl group- (C1-C5) ), or a (C 1 -C 5) alkyl group which may be partially or fully fluorinated, R 6 and R 7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl- (C3-CT) ring.
5. General stereoisomers (II), where R1 and R2 are, independently hydrogen, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group, a C 1 -C 0 alkoxy group, an alkylthio-C a -C group; or, a perfluoroalkyl-Ci- C5 group, a cyano group, a nitro group, or together are a group selected from the groups -0- (CH2) n-0-, -0- (CH2) "- CH2, -0 -CH = CH-, - (CH2) n + 2, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with ring carbon atoms directly adjacent, or they are NR8R9, where R8 and R9 can be independently of each other, hydrogen, C-C5-alkyl or (CO) -alkyl-C? -C5, R3 is a -C? -C? alkyl group or can be to be substituted by 1-3 hydroxy groups, halogen atoms, a phenyl group which may be substituted, a mono- or bicyclic heteroaryl group which may be substituted by 1-3 keto groups, 1-2 C1-Cs alkyl groups, -2 alkoxy- (C1-C5) groups, 1-3 halogen atoms, 1-2 exomethylene groups, containing 1-3 atoms of nitrogen, and / or '1-2 oxygen atoms and / or 1-2 sulfur atoms, where this group can be attached at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, R5 is a (C1-C5) alkyl group, or an alkyl- (C? -C5) group which may be partially or fully fluorinated, an aryl group, a C-C8 alkylaryl group, a group C2-C8 alkenylaryl, a C3-C cycloalkyl group, a (C?-C8) cycloalkyl (C3-C), a C2-C8 alkenyl group) C3-C7 cycloalkyl, R6 and R7 alkylaryl group they are, independently of one another, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl- (C3-C6) ring.
6. Compounds of the general formula (II) where R 1 and R 2 are, independently of each other, a hydrogen atom, a hydroxy group, a halogen atom, a C 1 -C 6 alkyl group, a C 1 -C 6 alkoxy group, an alkylthio group C? -C? O, a perfluoroalkyl-Ci- Cs group, a cyano group, a nitro group, or together are a group selected from the groups 0- (CH2) n_0-, -0- (CH2) n -CH2, -0-CH = CH-, - (CH2) n + 2, -NH- (CH2) n + 1, N (C-C3-alkyl) - (CH2) n + ?, -NH-N = CH-, where n is = 1 or 2 and the oxygen atoms in the final position and / or carbon atoms and / or nitrogen atoms are bonded with directly adjacent ring carbon atoms, or are NR8R9, where R8 and R9 can be independently yes, hydrogen, alkyl-Ci-Cs or (CO) -alkyl-C? -C5, R3 is an alkyl-C? -C? group or can be substituted by 1-3 hydroxy groups, halogen atoms, 1- 3 alkoxy-C? -C group or a C3-C7 cycloalkyl group which can be substituted, a heterocyclyl group which can be substituted, an aryl group which can be substituted, a hete group mono- or bicyclic roaryl substituted by one or more groups selected from Ci-Cs-alkyl groups (which may be substituted by 1-3 hydroxy groups or 1-3 COOR13 groups), alkoxy- (C1-C5) groups, halogen, exomethylene groups, containing 1-3 nitrogen atoms and / or 1-2 oxygen atoms and / or 1-2 sulfur atoms and / or 1-2 keto groups, where this group can be attached at any position with the amine of the tetrahydronaphthalene system and can be hydrogenated at one or more places, R4 is a hydroxy group, an OR10 group, where R10 represents a C1-C10 alkyl group, R5 is an alkyl group (C1-C5), or a alkyl- (C? -C5) group which may be partially or fully fluorinated, R6 and R7 are, independently of each other, a hydrogen atom, a methyl or ethyl group or together with the carbon atom of the tetrahydronaphthalene system, a cycloalkyl ring - (C3-Ce) •
7. Stereoisomers of the general formula I, according to claims 1-6, wherein the radi Lime R5 is a trifluoromethyl or pentafluoromethyl group.
8. Stereoisomers of the general formula I, according to claims 1-6, in the form of the salts with physiologically tolerable anions.
9. Use of the stereoisomers of one of the preceding claims, for preparing a medicament.
10. Use of the stereoisomers of claims 1-5, in the treatment of inflammatory diseases.
11. Pharmaceutical preparations containing at least one stereoisomer of claims 1-5 or their pharmaceutically compatible mixtures and vehicles.
12. Process for preparing the stereoisomers of the general formula I, characterized in that stereoisomers of the general formula III are cyclized where the radicals R1, R11, R12, R3, R4, R5, R6, and R7 have the indicated meanings, if necessary adding inorganic acids u. organic or Lewis acids to obtain compounds of the formula I