UA76451C2 - N-(2-arylethyl)benzylamines as antagonists of 5-ht6 receptor, pharmaceutical composition - Google Patents

Abstract

The present invention provides compounds of formula (I), which are antagonists of the 5-HT6, receptor. , (I)

Description

Ai is selected from the group consisting of phenyl, unsubstituted phenyl group of said phenylsulfonyl is substituted or substituted by 1-3 groups, independently of unsubstituted or substituted by 1-3 groups, independently selected from the group consisting of from each other selected from the group consisting of day, hydroxy group, C1-Ca alkyl, C- hydrogen, C1-Ca alkyl, C1-Ca4 alkoxy group, halogen,

C 1 - alkoxy group, halogen, benzyloxy-, carboxy-cyano group, trifluoromethyl, nitro group and phenyl; rupu, Ci-C.alkoxycarbonyl, amido-, M-(C1- benzyl, and the phenyl group of the said benzyl

Ca alkyl)amido-, sulfonylamido-, cyano group, tril is unsubstituted or substituted by 1-3 groups, non-fluoromethyl, trifluoromethoxy-, nitro group and phenyl, depending on each other, selected from the group unsubstituted or substituted by C1-Ca alkyl , C1- includes hydrogen, C1-Ca alkyl, C1-Ca4 alkoxy group,

With an alkoxy group, halogen, cyano group or cyano-, nitro group, trifluoromethyl and halogen; and ra-trifluoromethyl; naphthyl, unsubstituted or substituted, selected from 1-2 groups independently selected from the group consisting of hydrogen, C1-C6 alkyl,

С1-Са4 alkoxy group, halogen, cyano group, trifluoro-K- and KE; methyl and nitro group; imidazolyl; and a radical, chose him from Z O, o

Kk E. de Oz is selected from the group including -O-,-5- and

SHE and Co | -MAe-, where Ku is selected from the group that includes vo-vgO; Its B: day and C-C alkyl; and Om and O5- -SVAt, where each of 2 , At is independently selected from the group consisting of water, where O1 is selected from the group consisting of -O-, -5- and -den, Ci-Ca alkyl, halogen and trifluoromethyl ; or

MA-, where Vo is selected from the group consisting of hydrogen, one or both of O4 and O5 is -M:; and where one or both are C-Ca alkyl; and 02 --Me; where each of Ra, Ve and V: va Ov is -Me, while the others are -SAy; wherein each Kp is independently selected from the group consisting of hydrogen, independently selected from the group consisting of hydrogen,

Ci-Ca alkyl, Ci-Ca alkoxy group, halogen, cyanogroup- Ci-Ca alkyl, Ci-Ca alkoxy group, halogen, cyano-, pu and trifluoromethyl, or Va and P» (or one of Re), nitro group and trifluoromethyl; together with the atoms with which they are combined, provided that Ka. is not phenylsulfonyl In the case, the benzene ring, unsubstituted or substituted- when X is -502-, -"CHe-, -CH(E)-, -CH(OH)- or -C(O)-; not 1-4 substituents, independently of each other and selected from the group including hydrogen, hydroxy- pharmaceutically acceptable salts of this compound; rupu, C1-Ca alkyl, Ci-Ca alkoxy-, trifluoromethoxy-, provided that this compound is not 3-ethoxybenzyl-|2-, 2,2.2-trifluoroethoxy group, trifluoromethyl, halo- (4-ethoxyphenyl)ethyl|iamin; Z-ethoxybenzyl-(2-(3- gen, carboxy group, C-Ca alkoxycarbonyl, amido-, ethoxyphenyl)ethyl|iamine; Z-ethoxybenzyl-|(2-(2-

M-(Ci-Cα alkyl)amido-, amino-, (Ci-Cα alkyl)amino-, ethoxyphenyl)ethyl|amine or M-(2-(3,4- acylamino group), where the mentioned acyl group is dimethoxyphenyl)ethyl |-3-phenoxybenzylamine, from the group consisting of C-C alkyl and phenyl, cyano-2. The compound according to item 1, where X is O-, nitro-, sulfonylamido group, phenyl, unsubstituted 3. The compound according to one of clauses 1 or 2, where Kz is hydrogen substituted or substituted by Si-Alkyl, /Si- 4. The compound according to any of clauses 1-3, where Ka is selected

a C 6 -alkyl group, a halogen, a cyano group or from the group consisting of fluorinated C 6 -C 6 -alkyl and trifluoromethyl; phenyloxy-, benzyloxy group, - phenyl, unsubstituted or substituted by one to three

МНО(О)2Ан, where Kn is selected from the group consisting of groups independently selected from

Ci-Ca alkyl and phenyl; and -5(O)pA, where p is 0, 1 or 2; groups including hydrogen, hydroxy group, Si- and B; selected from the group consisting of C1-C6 alkyl and C1-C6 alkyl, C1-C6 alkoxy, halogen, benzyloxy-, phenyl, unsubstituted or substituted with C1-C6 alkyl, carboxy, C1-C6 alkoxycarbonyl, amido-, M-

Ci-Ca alkoxy group, halogen, cyano group or (C1-Ca alkyl)amido-, sulfonylamido-, cyano group, trifluoromethyl; and Ki is selected from the group consisting of trifluoromethyl, trifluoromethoxy, nitro, and hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenyl, unsubstituted or substituted C1-C6 alkyl, trifluoromethyl, and halogen; С1-Са4 alkoxy group, halogen, cyano group or

Ag is selected from the group consisting of hydrogen and C-trifluoromethyl.

C3 alkyl; 5. A compound according to any of paragraphs 1-4, where Ki is phenyl,

Az is selected from the group consisting of hydrogen, fluorine and unsubstituted or substituted with one to three methyl groups; we, independently of each other selected from the group,

Ba is selected from the group consisting of hydrogen, allyl, Co- consisting of hydrogen, hydroxy, C1i-C6 alkyl, C1-

Са alkyl, fluorinated С2-Са alkyl, hexyl, phenyl, Са alkoxy group, halogen, benzyloxy-, carboxy- unsubstituted or substituted by 1-3 groups, independent, С1-Са alkoxycarbonyl, amido-, /М-(С1- from each other selected from the group consisting of alkyl)amido-, sulfonylamido-, cyano group, trihydrogen, hydroxy group, C1-C6alkyl, C-fluoromethyl, trifluoromethoxy-, nitro group and phenyl,

C 1 -C 1 -alkyl, halogen, benzyloxy-, carboxy - unsubstituted or substituted by C 1 -C 1 alkyl, C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 1 -C 3 -C

Ca alkyl)amido-, sulfonylamido-, cyano group, tri-trifluoromethyl. fluoromethyl, trifluoromethoxy-, nitro group and phenyl, 6. The compound according to any of items 1-4, where Ki is a radical, unsubstituted or substituted by C-Ca4 alkyl, C- selected from

With an alkoxy group, a halogen, a cyano group or a trifluoromethyl; naphthyl; phenylsulfonyl,

12. The compound of the formula HER

Kk, VE; Kk, Av

Wow! | And -

Кк: о, Кк о, ди with 7 where Ои is selected from the group including -О-, -5- and - У in

MAv-, where Ka is selected from the group consisting of hydrogen ! and Ci-Ca alkyl; and 02 ---Mx; where Va and Re (or one of the formulas (Iii)

Be), together with the atoms with which they are combined, where -. form a benzene ring, unsubstituted or substituted - selected from the group consisting of 0, MH and MK", where substituted with 1-4 substituents, independently of each other - not selected from the group consisting of Ci-Ca alkyl and selected from the group , which includes hydrogen, hydrophenyl, unsubstituted or substituted by 1-3 groups, si group, C-C alkyl, C-C alkyl, independently of each other selected from the group trifluoromethoxy-, 2,2,2-trifluoroethoxy group, tri- includes hydrogen, hydroxy group, C-Ca alkyl, Si- fluoromethyl halogen, carboxy group, C-Ca alkoxy group, halogen, benzyloxy-, carboxyg-

Ca alkoxycarbonyl, amido-, M-(C1-Ca alkyl)amido-, rupu, C1-Ca alkoxycarbonyl, amido-, /M-(C1- amino-, (C1-Ca alkyl)amino-, acylamino group, where Ca alkyl )amido-, sulfonylamido-, cyano group, tri-mentioned acyl group selected from the group including fluoromethyl, trifluoromethoxy-, nitro group and phenyl, C-Ce alkyl and phenyl; cyano-, nitro-, sulfoni- unsubstituted or substituted by C-Ca alkyl, Sil-amido group, Phenyl, unsubstituted or substituted by Ca-alkyl group, halogen, cyano group or

Ci-Alkyl, Ci-C« alkoxy group, halogen, trifluoromethyl; cyano group or trifluoromethyl; phenyloxy-, B and Kv - hydrogen or together with atoms with which the benzyloxy group, -MNYA(O)»Ay, where Re is selected from them are combined, form a benzene ring, for groups that include Ci-Alkyl and phenyl; and - the conditions that Kv and Ke are hydrogen, when U is MN"; (OB, where p is 0, 1 or 2; and P; selected from the group, B; selected from the group consisting of phenyl, unsubstituted including Ci-C6 alkyl and phenyl, unsubstituted or substituted or substituted with 1-3 groups, independently substituted by a C-Slalkyl, C1-Cα alkoxy group, on one selected from the group consisting of a halogen, a cyano group or a trifluoromethyl; and a day, a pdroxy group, a C-Cα alkyl, Si.

Ve is selected from the group consisting of hydrogen, Cs-Ca alkoxy group, halogen, benzyloxy-, carboxyg-

C1 alkyl, C1-C1 alkoxy group, trifluoromethyl and rupu, C1-C1 alkoxycarbonyl, amido-, /M-(C1- halogen. C1 alkyl)amido-, sulfonylamido-, cyano group, tri- 7. The compound according to item 6, where B: - indole-Z-yl, unsubstituted fluoromethyl, trifluoromethoxy-, nitro group and phenyl, or substituted with 1-4 substituents, independently one unsubstituted or substituted by C-C-Alalkyl, C- from one selected from the group including hydrogen, Ca by an apoxy group, a halogen, a cyano group or a hydroxy group, a C-C alkyl, a C-C alkoxy-, trifluoro-trifluoromethyl; naphthyl, unsubstituted or substituted methoxy-, 2,2,2-trifluoroethoxy group, trifluoro-substituted with one or two groups, independently of one tyl halogen carboxy group of the same selected from the group including hydrogen, С1-

C 1 -C 6 oxycarbonyl, amido-, M-(C 1 -C 1 alkyl)amido-, C 1 -C 6 alkyl, C 1 -C 6 alkoxy group, halogen, cyano group, amino-, (C 1 -C x alkyl)amino-, acylamino group, where trifluoromethyl and nitro group; and a radical selected from said acyl group is selected from the group consisting of C1-C6 alkyl and phenyl; cyano-, nitro-, sulfoni- Ki ! lamido group, phenyl, unsubstituted or substituted / K, and | p

Ci-C.alkyl, Ci-C4 alkoxy group, halogen, Kk o, ko, cyano group or trifluoromethyl; phenyloxy-, shk , benzyloxy group, -"МНО(О)2Ан, where Ky is selected from where O is selected from the group including -0-, -5- and - groups including Ci-C.alkyl and phenyl; and - MAv-, where Co is selected from the group including hydrogen 5(O)vBi, where p-- 0, 1 or 2 and P; selected from the group, and C1-Cx alkyl; and o - -Me; each of Ka, Be and E: a C 1 -C 6 alkyl and phenyl, unsubstituted or optionally selected from the group consisting of hydrogen substituted with C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, cyanogroup - halogen, cyano group or trifluoromethyl. pu and trifluoromethyl, or Ka and Ke (or one of Ke), 8. The compound according to item 1, which is M-(2-(6-fluoro-) together with the atoms with which they are combined, forming 1H-indole -3-yl)ethyl)-3-(2,2,3,3- benzene ring, unsubstituted or substituted tetrafluoropropoxy)benzylamine. not 1-4 substituents, independently of each other 9, The compound according to item 1, which is a hydrochloride M- selected from the group including hydrogen, hydroxy- (2-(6-fluoro-1H-indol-3-yl) ethyl)-3-(2,2,3,3-rupu, C-C alkyl, C1-C4 alkoxy-, trifluoromethoxy- tetrafluoropropoxy) benzylamine. 2,2,2-trifluoroethoxy group, trifluoromethyl, halo- 10. A pharmaceutical composition that contains a compound, a carboxy group, C-C-Alkoxycarbonyl, amido-, according to item 1 and a pharmaceutically acceptable diluent - MA (C1-C-Alkyl) amido-, amino-, (С1-Са4 alkyl)amino-, vach. an acylamino group, where said acyl group is selected from the group consisting of C1-Cα alkyl and phenyl; sia- which includes disorders of cognitive ability, various-, nitro-, sulfonylamido group, phenyl, memory disorders, psychoses, schizophrenia, disorders that are replaced or replaced by Si-Alkyl, /Si- are accompanied by anxiety, and Alzheimer's disease - with an alkoxy group, a halogen, a cyano group or a mer, which includes administration to a patient treated with trifluoromethyl; phenyloxy-, benzyloxy group, - there is such a treatment, an effective amount of the compound МНЗ(О)2Ай, where Ky is selected from the group including zap. 1. Ci-Cx alkyl and phenyl; and -5(O)6A, where p is 0, 1 or 2;

and EC; selected from the group consisting of Ci-Ca alkyl and Ci1-Ca alkyl; and 02 --M-; wherein each of Ka, Be and Hu is phenyl, unsubstituted or substituted with C 1 -C 4 alkyl, independently selected from the group consisting of hydrogen,

C1-C4 alkoxy group, halogen, cyano group or C1-C4 alkyl, C1-C4 alkoxy group, halogen, cyanogroup, trifluoromethyl; and Ki is selected from the group consisting of Pu and trifluoromethyl, or Ka and Ke (or one of Ke), including hydrogen, C1-C4 alkyl, C1-C4 alkoxy, together with the atoms to which they are bonded, trifluoromethyl and halogen; benzene ring, unsubstituted or substituted

Ag is selected from the group consisting of hydrogen and C1-C3 not 1-4 substituents, independently of each other alkyl; and selected from the group consisting of hydrogen, hydroxy, and pharmaceutically acceptable salts of this compound. group, C1-C4 alkyl, C1-C4 alkoxy-, trifluoromethoxy- 13. The compound according to item 12, where the component is 2,2,2-trifluoroethoxy group, trifluoromethyl, halo- gene, carboxy group, С1-Са4 alkoxycarbonyl, amido-,

Fa M-(C1-Cα alkyl)amido-, amino-, (C1-Cα alkyl)amino-, acylamino group, where the mentioned acyl group is selected

In B, on from the group, which includes C-C alkyl and phenyl; tia- is attached in the 4th or 6th position. no-, nitro-, sulfonylamido group, phenyl, unsubstituted 14. The compound according to item 13, where M is MW". replaced or replaced by Si-Salkil, /Si- 15. A compound according to any of paragraphs 12-14, where E7 is selected from an alkoxy group, a halogen, a cyano group, or an early group consisting of phenyl unsubstituted by trifluoromethyl; phenyloxy-, benzyloxy group, - or substituted by 1-3 groups, independently of MNZ(O)2Ay, where Ky is selected from the group that includes one selected from the group that includes hydrogen, hyd-C1-Ca alkyl and phenyl; and -5(O)oNi, where p is 0, 1 or 2; roxy group, C1-Ca alkyl, C1-Ca alkoxy group, halo- and Ri selected from the group including C1-Ca alkyl and gene, benzyloxy-, carboxy group, cSi-phenyl, unsubstituted or substituted by C1-Ca alkyl,

Ca alkoxycarbonyl, amido-, M-(C1-Ca alkyl)amido-, C1-Ca alkoxy group, halogen, cyano group or sulfonylamido-, cyano group, trifluoromethyl, tri-trifluoromethyl; and Ri is selected from the group consisting of fluoromethoxy, nitro, and phenyl, unsubstituted including hydrogen, C1-C4 alkyl, C1-C4 alkoxy, or substituted with C1-C6 alkyl, c-trifluoromethyl, and halogen.

With an alkoxy group, a halogen, a cyano group or 16. A pharmaceutical composition that contains splo-trifluoromethyl; and a radical selected from ku according to any of the paragraphs 12-15 and pharmaceutically acceptable diluent.

Kk VI B, 17. Method of treatment of disorders selected from the group,

Ak ta ro, which includes disorders of cognitive ability, wide-

A: 9) I 2 zophrenia, anxiety disorders, and Alzheimer's disease, which includes administered O: selected from the group consisting of -o-, -8- and - days to a patient in need such treatment,

MAe-, where Po is selected from the group consisting of hydrogen in an effective amount of the compound according to clause 12.

This invention is related to the field of pharma- Today, there are no known high-affinity, se- ceutical and organic chemistry and relates to compounds, lective agonists of the 5-HT2 receptor. Serotonin itself is an antagonist of the 5-HT2 receptor. nin has only moderate affinity for the receptor

The 5-NTe receptor is a member of the re-5-NTb (Ki-65nM) superfamily. The most selective agonist of serotonin receptors coupled to G-protein, and, known at this time, M,M-dimethyl-2-ethyl-5-dibo receptors of 5-HTa and 5-HT7, it is positively methoxytryptamine, has Ki -8inmM and combines with adenylate cyclase only 3.5 times (11). Receptor 5- greater selectivity relative to receptor 5-

RatTee was cloned for the first time in 1993 (2,3), and NTgga |9I. about the cloning of a human homologue with which the mentioned Recent interest in the 5-HT receptor has a common identity with 8995, to a greater extent due to the observation that the 5-HTe in the brain of rats we studied by antagonists of the human 5-HTe receptor |4 by quantitative determination of 190Й1. Amitriptyline belongs to these compounds

mRNA using nasern-blotting and polymer- (atigiriuiipe) (Ki-65nM) and atypical antipsychotics of the chain reaction with reverse transcription- means clozapine (siogaripe) (Kih59.5nM), olanzapine (KT-RSK), immunohistochemical and autoradio- (oiiaplaripe) (Ki-1OnNM) and quetiapine (dpieyaripe) by graphic means (2, 3, 5, 6, 7, 8). For (ZZNM). None of these compounds, however, is selecti- using these methods, high levels of the mentioned rhenium. The first selective antagonists of the receptor consistently found in the olfactory bulbs, ptor 5-NTv, which were reported to be Ko 04- hippocampus, striatum, adjacent nucleus 6790 and Ko 63-0563. Suitability of these antagonists (pisien5 assytrep5) and cortical areas. They are limited by their moderate affinity (Ki5OnmM in peripheral tissues, 5-HTe receptors are absent and 12nM, respectively) and poor pharmacokinetics, or the level of their presence is a very insignificant characteristic of them |11Y. It was reported (2. ZI.) about a number of antagonists of the 5-NTee receptor, the last of which is 5B-271,046 (12). This compound has a high affinity (Ki-1.2nM), selectivity (2200-fold) and is a model of cognitive function. relative to 255 receptors, enzymes, and ion channels) and 8095 bioavailability. For research, ЗВ-271046 enhanced the behavioral response (binding of the radiolabeled ligand) caused by the inhibitor cholinesterase pom, and autoradiographic studies was vycophysostigmine (rpuzoviidtipe) (18). The results of these selective ligands, radiolabeled studies allow us to make assumptions about it isotope, 1'2211-58-258,585 |13, 14). These compounds that the shielding of the 5-HT receptor facilitates are suitable tools for preclinical cholinergic transmission. During the study of micro-research of the 5-HT receptor. dialysis ip mimo. 58-271,046 (10mg/kg, subcutaneously) under

The main reason for the use of selective antagonists of the 5-HT receptor enhances the release of glutamate in the prefrontal cortex for the treatment of cerebral cortex disorders by lowering cognitive ability is based on three mechanisms (251. reasonable explanations: the ability of selective antagonists to 5-HT receptor agonists modulate the cholinergic effect of the antipsychotics clozapine and olanzapine on the glutamatergic function of nerve cells, rezapine on cognitive function. and non-selective antagonists on cognitive ability, the activity of selective 5-HTe receptor tama |4|. On the other hand, risperi- 5-HTe receptor antagonists in the case of modeling don (hysregidope) and a typical antipsychotic agent of cognitive ability in animals. haloperidol (PaiIoregidoi) do not have of considerable dispute

Selective antagonists of the 5-HT receptor are modulative to the 5-HT receptor. Clinical differences affecting cholinergic and glutamatergic function are observed in the case of these sets of medicinal nerve cells. Cholinergic and glutamatergic cells can be attributed to the screen- systems of nerve cells play an important role in the 5-HT2 receptor. Goldberg (Soidregd) and in the cognitive function. Cholinergic others have reported a lack of beneficial neural pathways are known to be important in the formation and effect of clozapine on cognitive ability during the process of memory consolidation. Anticholinergic tests with the use of clozazoa, which act on the central nervous system, foam for the treatment of a small group (M-15) do not impair cognitive function in animals and experimental patients with schizophrenia |19). On the contrary, during clinical studies, and the loss of cholinergic activity to this, Meltzer (Meijgeg) and others |20) under neurons is one of the main symptoms of the disease during studies on a somewhat larger

Alzheimer's And, on the contrary, it is known that in a group of schizophrenic patients (M-36), the observation of cholinergic function improves cognitive activity, improving some aspects of neurophysiological activity. Both of the two currently available appro- functions at six weeks and six months after lary agents for the treatment of disorder initiation of clozapine treatment. In non-curable cognitive ability in Alzheimer's disease, among schizophrenic patients who did not respond to tacrine (iasgipe) and donepezil (doper?ii), there is inhibitory treatment, clozapine was more effective than acetylcholinesterase. It is also known that Glu-placebo improves cognitive function by the tamatergic system of the prefrontal cortex by several indicators (21). This effect of posteri- the brain is involved in the cognitive fungus after six months and it was persistently maintained (26, 27). during the 12-month studies. The effect of olanza-

It was shown that blocking the function of receptin, risperidone, and haloperidol on the cognitive torus 5-HTe causes procholinergic effects of ip mimo. function was compared during multi-

Administration (into the vessels of the brain) to rats of a central, double-blind study on antisense oligonucleotides aimed at patients with schizophrenia |22). The group receiving the 5-HTb receptor sequence elicited behavioral olanzapine demonstrated a statistically significant response (yawning and pulling) that showed an improvement in cognitive function compared to the groups receiving haloperidol or rispe- (aigoripe). ) (15). Selective antagonist of the rhydone receptor. This effect was evident after 6-5-NTe NKo 04-6790 induced a behavioral response of one week of treatment and persisted for 54- (sucking) in a dose-dependent manner. This behavior is a weekly study. The results of studies on the fact that the reaction was blocked by anticholinergic saline animals allow us to suggest that these effects may be mediated by the central nervous system, but not by the treatment of acetylcholine in the prefrontal zone by thylopolamine (teiPPuiI5soroiatype ), in doses that, cerebral cortex |231|. as is known, are peripherally selective (16). Activity of selective antagonists of the receptor was also shown that Ko 04-6790 blocks behavioral 5-NTee in animal models of cognitive function. the reaction (rotation) caused by the introduction Thanks to the recent development of selective antagoscopolamine to rats with unilateral lesions of the 5-HT2 receptor, No-04,6790 and 5B-271,046, gray matter of the brain and striatum (6- several appeared activity notifications

ON-OA). This agent did not block the behavioral response of compounds in models of cognitive function. Selection (rotation) caused by the introduction of the 5-HT receptor antagonist 58-271046 by

DOPA (I-3,4-dioxyphenylalanine) or amphetamine improved cognitive performance when tested (17). In 04-6790, he reversed scopolamine-induced impairment of cognitive ability on the Morris water maze (Mogtiz mageg tae) when tested (241. These results are consistent with the data on object recognition testing, which constant administration of antisense oligonucleotides

of tides aimed at the sequence of the receptor 5- monocyclic aromatic heterocycle having

Thus, to the vessels of the brain caused a polyp- one heteroatom selected from the group, which includes the transformation of some indicators of cognitive activity into nitrogen, oxygen, and sulfur, where the mentioned 5-6-member test method on the Maurice water maze (16). noncyclic aromatic heterocycle is a faculty

As a result of the treatment, 58-271,046 was also positively condensed with the benzene ring; improvement of some indicators of cognitive active- Av is selected from the group that includes hydrogen and hundreds of old rats during behavioral C-C3 alkyl; and test with the production of instrumental their pharmaceutically acceptable salts. reflex when changing the spatial position (24). This invention also provides new pharmaceuticals

The compounds of this invention are selective, compositions that include: a compound of formula I or high-affinity antagonists of the 5-HT receptor and, II and a pharmaceutically acceptable diluent. thus providing the possibility of a valuable As the compounds of formula I and formula I are the treatment of disorders mediated by receptor antagonists of the 5-HTe receptor, said 5-HTe compounds. formulas ! and formulas II are suitable for treatment

This invention provides compounds of formula I: treatment of various disorders. Thus, in another embodiment, the present invention provides methods of treating disorders associated with 5-HT, comprising: administering to a patient in need thereof an effective amount of a compound of the formula | or

Formula I of formula II. That is, this invention provides a method of using a compound of formula I or formula I and its pharmaceutical compositions for the treatment of

X is selected from the group consisting of -O-, -MIN-, -5-, 5-NTv-linked divins. More specifically, this invention -502-, -СНе-, -СН(Е)-, -СН(ОН)- and -С(0)-; provides a treatment method for disorders selected from the group

Bi is selected from the group consisting of facultatives comprising cognitive impairment, vno-substituted phenyl, facultatively substituted age-related cognitive impairment, naphthyl, optionally substituted 5-6-membered minor cognitive impairment, demonocyclic aromatic heterocycle having depressive disorders (including depression, mania, one heteroatom selected from the group consisting of manic-depressive psychoses), psychoses (zocre- nitrogen, oxygen and sulfur, where said 5-6--mol ma, schizophrenia), disorders accompanied by nocyclic aromatic heterocycle is facultative- anxiety (including, in particular, generalized tive condensed with a benzene ring. disorder accompanied by anxiety, disorder that

Ag is selected from the group that includes hydrogen and is accompanied by panic fear and obsessive-

C-C3 alkyl; compulsive disorder), idiopathic Par-

Az is selected from the group consisting of hydrogen, quinone, and Parkinson's disease caused by the drug fluorine and methyl; chemical means, epilepsy, convulsions, migraine (in

Va selected from the group consisting of hydrogen, allyl, including throbbing headache), syndrome

C2-Ca alkyl, fluorinated C2-Ca4 alkyl, facultatives - deterrence from taking narcotic substances vno substituted phenyl, optionally substituted (including such substances as opiates, nicotine, phenyl sulfonyl, optionally substituted ben- tobacco products, alcohol, benzodiazepines, cocaine, zyl and optionally substituted 5-6-ene sedatives, hypnotics, etc.), nocyclic aromatic heterocycle disorders that have sleep (including narcolepsy), deficiency of one or two heteroatoms selected from the group that hy/syndrome "hyperactivity, behavioral disorders, includes nitrogen, oxygen and sulfur, provided that KA is not disorders of learning ability, dementia (y is an optionally substituted phenylsulfonyl including Alzheimer's disease and dementia, if X - -502- , -"СНе-, -СН(БЕ)-, -СН(ОН)- or - caused by AIDS), Huntington's chorea, disturbed-

С(О0)-; and cognitive ability as a result of reconstruction - their pharmaceutically acceptable salts. arterial surgery and transplantation, etc.

This invention also provides compounds of formula II: stroke, cerebral ischemia, spinal cord injury, brain injury, ate perinatal hypoxemia, cardiac arrest, and hypoglycemia.

Chemical damage to nerve cells, dementia due to vascular diseases, polyinfarct dementia, amyotrophic lateral sclerosis and

Formula P multiple sclerosis, comprising: administration to a patient in need thereof of an effective amount of a compound of formula I or an effective amount of a compound

In selected from the group including 0, MH and ME", formula II. wherein Co is selected from the group consisting of C1-C6 alkyl and In addition, this invention also provides optionally substituted phenyl; methods of obtaining compounds of formula I and formula

B5 and Kv - hydrogen or together with atoms, from which - II and their intermediate chemical compounds. they are combined and form a benzene ring. Below are the terms used in provided that K5 and Kb are hydrogen, when U is Mo; this description, have the following meanings:

AND? selected from the group consisting of facultati- The term "C1-C3 alkyl" means an unbranched intrasubstituted phenyl, optionally substituted or branched alkyl chain having from naphthyl, optionally substituted 5-6 membered one to three carbon atoms and includes methyl, trifluoromethyl ; and KE; selected from the group consisting of ethyl, propyl and isopropyl. includes hydrogen, C1-Cα alkyl, C1i-C4 alkoxy group,

The term "optionally substituted phenyl" means trifluoromethyl and halogen. The mentioned term, zocre- means a radical of the formula ma, means furyl, thienyl, pyrrolyl, pyridyl, benzofuryl, benzothienyl, indolyl and quinolinyl; each of them is optionally substituted according to the description given above.

The term "fluorinated C2-Ca4 alkyl" means a straight or branched alkyl ring containing from 1 group to 3 groups, regardless of whether it has from two to four carbon atoms selected from the group consisting of hydrogen, hydroxy substituted by one or more fluorine atoms. group, C1-C4 alkyl, C1-C4 alkoxy group, halogen, be , amido-, M-(С1-Са alkyl)amido-, sulfonylamido-, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 2,2,3,3,3-cyano group, trifluoromethyl, trifluoromethoxy-, nit - pentafluoropropyl, 2,2,3,3-tetrafluoropropyl, 4,4,4- group and phenyl, optionally substituted C1-Ca4 trifluorobutyl, 3,3,4,4,4-pentafluorobutyl, etc. alkyl, C1-C4 alkoxy group, halogen, cyano- The term "optionally substituted by phenylsulphur and trifluoromethyl. | Y lfonyl" means a radical of the formula

The term "optionally substituted naphthyl" means a radical of the formula o - (x where K;) includes from 1 group to 3 groups, regardless of where Be includes from 1 group to 2 groups, independently selected from the group consisting of hydrogen, C1-Ca alkyl, selected from the group including hydrogen, C1-Cα alkyl, C1-Cα alkoxy group, halogen, cyano group, trifluoro-

Ci-Ca alkoxy group, halogen, cyano group, trifluoromethyl, nitro group and phenyl. | And methyl and nitro group. The term "optionally substituted phenyl"

The term "optionally substituted //5-6- means a radical of the formula one-membered monocyclic aromatic heterocycle having one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, wherein said 5-6-membered monocyclic aromatic heterocycle is optionally fused with benzene, where Kk includes from 1 group to 3 groups, regardless of the ring" means radicals of the formula selected from the group including hydrogen, C1i-Ca alkyl,

Ci-Ca alkoxy group, cyano-, nitro group, trifluorome-

V. K til and halogen.

CI The term "optionally substituted //-5-6-

A, and | 2-membered monocyclic aromatic heterocycle,

In o ko; having one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur" means that O1 is selected from the group consisting of -O-, -5- dikals of the formula and -MAv-, where Ku is selected from groups including hydrogen and Ci-Ca alkyl, and 02 - -M-, Va, where each Ke, and Ok.

Ag is independently selected from the group consisting of C-Cl and C-C4 alkyl, C-C. an alkoxy group, a halogen, a hydrogen cyano group and a trifluoromethyl or Ka and Ke (or one of Ke), together with the atoms with which they are combined, form a benzene ring, which facultade Oz is selected from the group that includes -O -,-5- is optionally substituted with 1-4 substituents, regardless of -MVe-, where Ku is selected from the group consisting of hydrogen, hydroxy-denium and C-Ca alkyl; and Ox and O5 - -"СВt, where each Kt is rupu, C1i-Ca alkyl, C1-Ca4 alkoxy-, trifluoromethoxy- independently selected from the group consisting of hydrogen, x 2.2.2-trifluoroethoxy group, trifluoromethyl, halo- Si-Ca alkyl, halogen and trifluoromethyl or one or more, a carboxy group, C-C-Alkoxycarbonyl, amido-, both Ox and Oz - -M-; and where one or both Ov - -

M-(C1-Cα alkyl)amido-, amino-, (C1-Cα alkyl)amino-, M-, while the others are -"SVy; where each Bal is an independent acylamino group, where said acyl group is selected from the group consisting of hydrogen, C1-C4 and from the group consisting of C1-C6 alkyl and phenyl; cyano-alkyl, Ci-Ca alkoxy group, halogen, cyano-, nitrogen-, nitro-, sulfonylamido group, phenyl, faculty group and trifluoromethyl. The mentioned term is specifically replaced by Si-S. oalkyl, /Ci-C4 means furyl, thienyl, thiazolyl, pyrazolyl, imidazo- alkoxy group, halogen, cyano group and trilyl, triazolyl, oxazolyl, thiazolyl, isoxazolyl, thiofluoromethyl; phenyloxy-, benzyloxy group, - zoxazolyl, pyridyl, pyrimidyl, pyridizanyl and pi-

MNB(O)2H, where Ky is selected from the group consisting of radizinyl; each of them // optional

Ci-Ca alkyl and phenyl; and -(O)rAi, der - 0, 1 or 2 is substituted as described above. Yes; selected from the group consisting of C1-C6 alkyl and

C1-C4 alkoxy group, halogen, cyano group and one to four carbon atoms and includes methyl. Preference is given to compounds where X is selected from the group consisting of -O-, -MH- and -5-, and bi-butyl and tert-butyl. greater preference is given to compounds where X - -O-.

The term "C2-Ca4 alkyl" means unbranched. Preference is given to compounds where Ki is a facu- or branched alkyl chain having optionally substituted phenyl or optionally two to four carbon atoms and includes ethyl, substituted 5-6 monocyclic aromatic propyl, iso-propyl, butyl, t-butyl, isobutyl and a heterocycle having one heteroatom, selec-tert-butyl. ny from the group including nitrogen, oxygen and sulfur, where

The term "C1-C4 alkoxy group" means an unbranched 5-6-membered monocyclic aromatic tinned or branched alkyl chain, which heterocycle is optionally condensed with a benzene ring having from one to four carbon atoms. with an oxygen atom, and includes methoxy-, ethoxy-, When Ki is optionally substituted with propoxy-, iso-propoxy-, butoxy-, iso-butoxy-, phenyl, preferred substituents, sec-butoxy- and tert-butoxy group. are from 1 group to 3 groups, independently selected from groups

The term "halogen" means an atom of chlorine, fluorine, py, including hydrogen, C1-C6 alkyl, halogen, benbromine or iodine. xyloxy-, carboxy-, C1-C4 alkoxycarbonyl group

The term "a pharmaceutically acceptable salt of an acid, amido-, M-(C1-Ca alkyl)amido-, sulfonylamido-, thi" means a salt of an acid. cyano group, trifluoromethyl, trifluoromethoxy-, nit-

Compounds of formula I or formula I! and intermediate rogroup and phenyl, optionally substituted C1-C4 chemical compounds, the description of which is given, form alkyl, C1-C. an alkoxy group, halogen, cyano- pharmaceutically acceptable salts of various acids and trifluoromethyl. more popular organic and inorganic acids - In the case when Ki is optionally substituted and include physiologically acceptable salts, which are phenyl, substituents that are given more are often used in pharmaceutical chemistry. Such advantages, there are from 1 group to 3 groups, regardless of selection, also form part of the present invention. early ones from the group including hydrogen, C1-Ca4 alkyl,

Pharmaceutically acceptable salts are obtained for halogen, cyano group and trifluoromethyl. with the help of pharmaceutically acceptable acids, which are well known in the art. Such salts include Nale- or fluorine. harvest pharmaceutically acceptable salts, the list of which In the case of a compound where Ki is optionally substituted- is given in Yuoshgppai! oh Rpaptaseciisa! bsiepse, 66, ny 5-6--ene monocyclic aromatic gel- 2-19 (1977)), which are known to the skilled person- a heterocycle having one heteroatom selected from this. Typical inorganic acids that use groups including nitrogen, oxygen, and sulfur, which are mentioned for the preparation of such salts, include the 5-6-ene monocyclic aromatic he-hydrogen chloride, hydrogen bromide, hydrogen iodide- the terocycle is optionally condensed Benzene, nitric, sulfuric, phosphoric, hypophosphoric, ash ring, preference is given to compounds, metaphosphoric, pyrophosphoric acids, etc. Because they are condensed with a benzene ring, where salts obtained from organo- indolyl is preferred and night acids are even more preferred, for example, aliphatic mono- and indol-3-yl are preferred. dicarboxylic acids, phenyl-substituted alkanoic In the case that Ki is indol-Z-yl, the groups that give preference to hydroxyalkanoic and hydroxyalkanedionic acids are depicted as a radical, given- acids, aromatic acids, aliphatic and aronic acids below: parent sulfonic acids . Such pharmaceutically acceptable salts thus include chloride, Kc, bromide, iodide, nitrate, acetate, phenylacetate, trifluoroacetate, acrylate, ascorbate, benzoate, chlorbene and their zoate, dinitrobenzoate, hydroxybenzoate, methoxy- | --in, benzoate, methylbenzoate, o-acetoxybenzoate, -dele isobutyrate, phenylbutyrate, o-hydroxybutyrate, tin-1,4-dicarboxylate, hexine-1,4-dicarboxylate, caprate, caprylate, cinnamate, citrate, formate, fumarate, glycolate, heptanoate, hippurate, lactate, malate, a) Vo selected from the group including hydrogen and maleate, hydroxymaleate, malonate, mandelate, me-Ci-Ca alkyl, where hydrogen is more preferred; zylate, nicotinate, isonicotinate, oxalate, "phthalate, p) Bp selected from the group consisting of hydrogen and tetraphthaplat, propiolate, propionate, phenylpropio-Ci-Ca alkyl, where hydrogen is more preferred; nat, salicylate, sebacate, succinate, suberate , benzo-c) On selected from the group including hydrogen, lsulfonate, p-bromobenzenesulfonate, chlorobenzo-Ci-Ca alkyl, Ci-C4 alkoxy group and halogen, where bisulfonate, ethylsulfonate, 2- hydrogen is more preferred; hydroxyethylsulfonate, methylsulfonate, naphtha- 4) Re selected from the group consisting of hydrogen, lin-1-sulfonate, naphthalene-2-sulfonate, naphtha-Ci-C alkyl, Ci-C. alkoxy-, trifluoromethoxy-, lin-y,5- sulfonate, p-toluenesulfonate, xylenesu-2,2,2-trifluoroethoxy group, trifluoromethyl, halophonate, tartrate I, etc. and -5(O)p0Bi, where p - 2 and K) - phenyl, optional

As with any pharmaceutically active group, substituted C-C4 alkyl, C1i-C. alkoxy group, of these compounds, some groups are preferred trifluoromethyl, where more preference is given to their end use. Variants of embodied halogen; of the present invention, which are preferred, are) Ag selected from the group that includes hydrogen, given for compounds of the formula I below: C-C4 alkyl, C-C4 alkoxy group, halogen, nitro-,

cyano group, trifluoromethyl and -5(O)p6A, where p is 2 and according to the above definition, all starting

AND; - phenyl, optionally substituted С1-Са alkyl - materials and reagents are well known and proper, where greater preference is given to halogen; and thus appreciated in this field and easily accessible

In A" selected from the group consisting of hydrogen, by them or by methods obtained by

C1-Cα alkyl, C1-C4 alkoxy group, halogen, trifluoro are given in this description. It is clear that hydrogen and halogen can be attached to the methyl, cyano, and nitro groups, where preference is given below, if necessary. use protection groups to receive

Preference is given to compounds where Ka is a part of compounds of formula I or formula II. Selection from the group consisting of С2-Са4 alkyl, fluorinated application and removal of appropriate protecting groups

C2-Ca alkyl and optionally substituted phenyl. stu is well known and properly appreciated

In the case when Ka is a C2o-C4 alkyl, the groups that are particularly preferred in this field are propyl, isopropyl, Tneodoga Stgeepe (UMieu-Ipiegwsiepse)|. and butyl.

In the case when Ka is a fluorinated C2-Ca alkyl, the preferred groups are 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, k u. / gg in 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 2,2,3,3,3- pentafluoropropyl and 2,2,3,3-tetrafluoropropyl. (1) (2) how

In the case when Ka. is optionally substituted step a e (that is phenyl, preferred groups include x-B, are from 1 group to 3 groups independently selected from step 8 formula I group, which includes hydrogen, C1-C6 alkyl, C1i -Cα alko- in roxy group, halogen, cyano group and trifluoromethyl.

Variants of the embodiment of the present invention, which are preferred, are given for the compounds of the formula HER (3) (4) below:

Preference is given to compounds where K7 is facu- Scheme A depicts alternative methods ltatively substituted phenyl or optionally to obtain compounds of the formula | by hydroamino-substituted 5-6-ene monocyclic aromatization. A heterocycle having one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur according to one of the alternative variants of Scheme A, where step a, a suitable compound of formula (1) contacts said 5-6-ene monocyclic aromatic with a suitable compound of formula (2) in the reaction, the hydro-heterocycle is optionally condensed from roamination to give a compound of formula |. benzene ring. A suitable compound of formula (1) is the compound, Ki and

In the case where K7 is optionally substituted with phenyl which is desired in the final product of the formula, the preferred substituents, or such a compound, providing groups are from 1 to 3 groups, independently selected from those desired in the final product of formula I. Additives including hydrogen, C1-Cα alkyl, C1i-C4 alkoxy compound of formula (2) is a compound, X, Kz and Kα group, halogen, cyano-, trifluoromethoxy group and which are desired in the final product formula trifluoromethyl. or such a compound that provides groups,

In the case of compounds where K7 is optionally substituted in the final product of formula I, a 5-6-hellenic monocyclic aromatic gel. According to another alternative version of Scheme A, a heterocycle having one heteroatom selected from step a, a suitable compound of (3) contacts groups containing nitrogen, oxygen, and sulfur, where mentioned, with a suitable compound of formula (4) in a reaction worthy of 5-6-ene monocyclic aromatic heroamination to obtain a compound of formula |. therocycle is optionally fused with a ben- A suitable compound of formula (3) is a compound, Ki and an ash ring, preference is given to compounds of which Bg are desired in the final product of the formula that are condensed with a benzene ring, where or such a compound that provides groups, indolyl is preferred and those desired in the final product of formula I are even more preferred. Indol-3-yl is preferred, where the compound of formula (4) is more preferred, X, K3 and K4 are indol-3-yl given above for the formula that is desired in the final product is formula I. or such a compound that ensures the production of groups,

Compounds of formula II, which are preferred in the final product of formula I. and having attachment points, are depicted below: Hydroamination, presented in Scheme A, stage a, can be carried out under various conditions, for example, by hydrogenation from by using a suitable catalyst or a suitable reducing agent. For example, a suitable amine of formula (1) reacts with a suitable aldehyde of formula (2) (or, alternatively, a suitable amine

Although only formulas (4) and a suitable aldehyde of formula (3)) are presented, compounds of formula I, compounds of formula I and a suitable reducing agent to give compound II are prepared as described in Scheme A of formula I. The aforementioned reaction carried out in the attachment and Scheme B below. In the schemes below, no solvent, e.g., methanol, ethanol, all substituents, unless otherwise indicated, correspond to tetrahydrofuran or mixtures of methanol or eth-

nol and tetrahydrofuran, dichloromethane and 1,2- A suitable compound of formula (7) is a compound where A dichloroethane. The mentioned reaction can be carried out - an activating group, the description of which is given above, and Ki in the presence of a drying agent, for example, su- which is desired in the final product of the formula |. of sodium sulfate, copper sulfate, or molecular A suitable compound of formula (4) is a compound, description sat. The mentioned reaction is carried out in the presence of which is given in Scheme A. Suitable compounds of the formula - about 1 to 20 molar equivalents of suitable formulas (4) and (7) are, in general, available from a commercial reducing agent, for example, sodium borohydride, cyan- from these sources and can also be obtained from sodium phosphonoborohydride and sodium triacetoxyborohydride, the description of which is given here or by methods, sodium. Before adding a suitable reducing agent known in the art. it may be useful to obtain schiffs The reaction for obtaining an amide is shown in the Scheme of bases In the case of the use of cyanoborohydride in B, stage a is easily carried out in numerous ways, three, which may be useful to control and are easily accessible to an experienced specialist, in that the regulation of pH during the course of the reaction, which is among the methods that are traditionally used for known in this field. The mentioned reaction, in general, synthesis of peptides. Such methods can be carried out at temperatures from 0"C to tempering with acid, halogen anhydride, activation of solvent distillation. In general, reactions with ethers, activated amides take from 1 hour to 72 hours. The product can also be isolated with anhydrides. and purified by methods well known in the art. To facilitate the preparation of the amide, e.g., by filtration, extraction, evaporation, trituration, cross-coupling, e.g., carbodiimides with or without matography and recrystallization, well-known reagents may be used. the use of well-known impurities, for example

Scheme A, optional stage p (not shown- M-hydroxysuccinimide, 1-hydroxybenzotriazole na), acid salt and compounds of the formula | receive from etc. In such reactions, couplings are used using a pharmaceutically acceptable acid, usually in a molar ratio of approximately 1:1.5. The preparation of acid salts is well known and well appreciated in the art. they are generally carried out in an inert aprotic solvent, for example, pyridine,

Scheme B in dimethylformamide, dichloromethane, chloroform, in, C i. Togdichloroethane, acetonitrile, tetrahydrofuran, etc. In such coupling reactions, the use of a suitable base, for example, n) (5) (1 (1)) triethylamine or M,M-diisopropylethylamine, can be useful to induce the formation of NO precipitate. preferably, carried out at a temperature from approximately 100 °C to approximately 60 °C until the reaction is complete, which,

AL, ra v Y yd, as a rule, occurs in the range from 1 to 48 hours. After the completion of the reaction, the product o c) 9 (8) can be isolated and purified by methods well known in the art, for example, filtration, , stewing, evaporation, trituration in . powder, chromatography and recrystallization in D» tion. According to an alternative version, for example, halogen anhydride can be used in the formula of this reaction. t It may be useful to use a suitable os- . new to remove the acid formed under

Scheme B depicts alternative methods of reaction time; suitable bases include, for obtaining compounds of the formula | by obtaining clades, triethylamine, M,M-diisopropylethylamine, M- and one a amide. ians C B methylmorpholine, pyridine, etc. As a rule, the stasis is one of the alternative chemicals in which approximately 1:1.5 molar ratios of stage a, a suitable compound of the form 0) are brought into contact with anhydride and an amine. The mentioned reaction can also be carried out with a suitable compound of formula (5) in the reaction in various inert aproton-

The wine amide with the formula (6) is obtained. in these solvents, for example, in pyridine, dichlormeridate No. We have a compound of the formula (I), the description of which dissolves in chloroform, 1,2-dichloroethane, tetrahydrofu- as! WE ve on ohem And with a sobbing urge to wound, etc. The reaction according to the variant given by the formula (5) is a compound where is an activating group, which is preferably carried out at a temperature from about - as a rule, it takes place between hours and days, and Х, Кз and Як о are desirable in avezpe. about 12 hours After the completion of the reaction, the product of the formula va. such a compound can be isolated and purified by methods well known in the art, such as filtration, of the form I. by extraction, evaporation, trituration in another alternative variant of Scheme B, powder, chromatography and recrystallization - stage a, a suitable compound of formula (7) contacts this

With a suitable compound of formula (4) in a reaction with an alternative option, for example, amide oxidation to give a compound of formula (8). halogen anhydride can be used in the reaction

Schotten-Bauman. Under the conditions of carrying out such a reaction, according to scheme B (optional stage, non-coctions, as a rule, 1-10 molar equivalents are used), acid salts and compounds of the formula | amine valences are obtained. In such coupling reactions, usually with the use of a pharmaceutically acceptable acid, a suitable base for the lot is used. The preparation of acid salts is well known and the removal of the acid formed during the reaction in an appropriate way appreciated in the field. tions, e.g., sodium hydroxide, potassium hydroxide, According to Schemes A and B (optional stage, not sodium carbonate, potassium carbonate, bicarbonate shown), which will be properly evaluated by the stage, potassium bicarbonate, etc. The above-mentioned reaction can be carried out by a person skilled in the art, the compound of the formula I, where Co - can be carried out in various mixtures of soluble hydrogen, can be alkylated to obtain a compound of, for example, dichloromethane, chloroform, eth- where Co is not hydrogen. Methods of alkylation of such acetate, tetrahydrofuran, etc.; and water The reaction of secondary amines is well known in the art and a preferred embodiment is discussed in Scheme C, step c, below. according to Schemes A and B, which will be properly close to 80"C until its completion, which, as a rule, is estimated by an experienced specialist, according to the methods, takes place within 1 hour to about 2 hours. the description of which is given in Schemes A and B are obtained

After the completion of the reaction, the product can be isolated and purified by methods well known in formulas (9) and (10) below: the art, for example, by filtration, extraction, evaporation, trituration, e, c, chromatography and recrystallization. C and S

Alternatively, for example, an anhydride (symmetric (9) (10) or mixed) can be used in this reaction. Such anhydrides are prepared in a number of ways known in the art. As A suitable compound of formula (9) is a compound, as a rule, approximately 1:1.5 molar U, H5 and Ke are used which are desired in the final product in the ratio of anhydride to amine. A suitable compound of formula (10) can be a co- compound of formula (10) in which A is an activating group, as described in the acid formed during the reaction. above, and U, K5 and Ke which are desirable in the final

Suitable bases include, for example, triethylamine, M,M-diisopropylethylamine, M-methylmorpholine. On the Schemes, nave-bonate of sodium, etc. The mentioned reaction can be carried out below, all substituents, unless specified, can be carried out in various solvents. The reaction for the opposite corresponds to the previously given variant, which is preferred, is carried out at a value and the starting material and all reactants are at a temperature from about 02С to about well-known and properly evaluated at 602С before its completion, which, as a rule, takes place this field. Scheme C shows the methods of drying in the range from 1 hour to approximately 12 hours. After obtaining the compounds of formula (1). After completion of the reaction, the product can be isolated and purified by methods well known in the art, including, for example, filtration, extraction, H 1 evaporation, trituration, chromatography, distillation, and recrystallization. and you are stage I 1

Scheme B, stage b, shows the reduction (2au stage a (25) (1)) of a compound of formula (6) or formula (8) with hydrogenation of a compound of formula |... stage c

For example, a compound of formula (6) or formula B, or B, (8) is contacted with a suitable reducing agent with the resulting compound of formula I. Suitable reducing agents of stage 4 (c) are reducing agents , capable of reducing amide to amino 17) (26) (27) 1) well, and their number includes borane reagents, for example, the borane-dimethyl sulfide complex, the reaction in Scheme C, stage a, shows the reaction of hydride transfer methods, for example, the hydride of the aldehyde of the formula (24) and nitromethane from aluminum and lithium aluminum hydride, etc. Mentioned by re-obtaining the compound of formula (25). A suitable reaction is carried out in a solvent, for example, the tetraaldehyde of the formula (24) is an aldehyde, Ki of which is hydrofuran or diethyl ether, with the desired application in the final product of the formula I. The reaction is, as a rule, from 71 equivalents to 10 anion of nitromethane with aldehydes to obtain reducing agent equivalents. The mentioned reaction, as pranitroolefins is well known and properly explained, is carried out at a temperature from about estimated in this field. |Modegp Zupipeiiys Neasiyopv, 0"С to the distillation temperature of the selected solution- N.O. Noyse (294 eu. Tne Vepiatip/Sittipdvnik, and its duration is, as a rule, from 1h Rybiizpipd Sotrapu 19721. to about 48h. The product can be isolated and For example, a suitable aldehyde of formula (24) can be purified by methods well known in this halo- condense with nitromethane to obtain a compound, for example, rapid cooling, filter of formula (25). evaporation, grinding in the presence of an excess of nitromethane, pulverization, chromatography and The reaction is carried out in a suitable solvent, recrystallization. for example, tetrahydrofuran, nitromethane and dimer-

tylsulfoxide. The reaction is carried out using a compound of formula (25) can be reduced from about 1.1 to about C moles using reagents such as sodium borohydride. equivalents of a suitable base, for example. ,M-diisopropylethylamine, ammonium salts, Na-, etc. An intermediate chemical compound, 2-nitroethyl, can be an example of ammonium acetate. The reaction is carried out at temperatures from approximately -20"C to the temperature of the wash in this field, for example, by rapid cooling of the selected solvent, and its duration is, as a rule, from 2h to 48h. The product of digestion, trituration, coupling reaction can be isolated and purified by chromatography and recrystallization. Purification by methods well known in the field, including the intermediate chemical compound, 2-nitroethyl, clad, extraction, evaporation, chromatog- can be recovered using a variety of methods, for example, by hydrogenation or with

Scheme C, stage p, depicts the reduction using hydride transfer reagents, such as compounds of formula (25) to give compound fo- discussed above. In addition, the intermediate chemical formula (1), where K2g is hydrogen. compound, 2-nitroethyl, can be reduced by do-

For example, a suitable compound of the formula (25) with a hypogam of metals, for example, zinc, is hydrogenated over a suitable catalyst to give the required amine of the formula (1), where E2 is hydrogen. for example, with ReneiF nickel or palladium cata- In Scheme C, stage c is represented by the faculty. In the case of using Raney nickel, negative alkylation of the compound of formula (1), where Co is this reaction is carried out in a suitable solvent, hydrogen, to obtain the compound of formula (1), where Co is, for example, ethanol, methanol, water and their is hydrogen. mixtures It may be useful to carry out hydrogenation. For example, a compound of formula (1) where Co - ionization under acidic conditions, for example, with application, is contacted with a suitable alkylating agent of hydrochloric or sulfuric acid. In the case of Vol. A suitable alkylating agent is an agent, the use of a palladium catalyst, the advantage of which transfers the EC group to the final product is palladium on charcoal and the reaction of rmula I. Suitable alkylating agents are carried out in a suitable solvent, for example, C-C3 alkyl halides. The mentioned reaction of ethanol, methanol, tetrahydrofuran, water and theirs is carried out in a suitable solvent, for example, mixtures. It can be advantageous to perform hydrogen-dioxane, tetrahydrofuran, tetrahydrofuran mixtures under acidic conditions, for example, using wound/water or acetonitrile. The reaction is carried out in the presence of 1.0-6.0 molar equivalents of hydrogen chloride, trifluoroacetic acid or sulfuric acid. The reaction, as a rule, is carried out with a dark base, for example, sodium carbonate, bicarbonate temperatures from the ambient temperature of sodium serenate, potassium carbonate, potassium bicarbonate, up to 70 "C. The reaction is carried out with hydrogen under triethylamine or M,M -diisopropylethylamine. The reac- at a pressure of 15 lb/in? (1o33kPa) to tion is usually carried out at temperatures of 120 lb/in2 (827kPa) in an apparatus designed -18"C to the solvent distillation temperature. For reactions under pressure, for example, in a galley, the duration of the reactions is from 1 hour to the ParraF hydrogenation plant. The product can Tt2h. The product can be isolated and purified by carefully removing the catalyst by methods well known in the art, such as filtration or evaporation. The product can be purified by extraction, evaporation, pulverization, chromatography, and recrystallization. recrystallization. Alternatively, for example,

Alternatively, for example, a compound of formula (1), where Kg is hydrogen, is subjected to a suitable compound of formula (25) in contact with a hydroamination with an aldehyde or ketone, with an appropriate reducing agent. Suitable reducing agents are compounds of formula (1), where Kg is not hydrogen. include hydride transfer reagents, e.g. Suitable aldehydes include formaldehyde, clad, aluminum hydride and lithium aluminum hydride, etc. acetaldehyde, propionaldehyde and acetone. The reaction

The mentioned reaction is carried out in a solvent, carried out according to the description given in Scheme A, for example, tetrahydrofuran or diethyl ether, stage a. using, as a rule, from 1 equivalent to According to another alternative option, for example, equivalents of reducing agent. The above-mentioned reaction, such as a compound of formula (1), where EK" is hydrogen, is usually carried out at a temperature from approx. 0"C to obtain an amide or carbamate from 0"C to the temperature of distillation selected by further reduction with by obtaining a compound of the factor, and its duration is, as a rule, from the formula (1) where Kg is not hydrogen. To suitable 1Th to about 48h. The product can be released- aldehydes belong to formaldehyde, acetaldehyde, and be purified by methods well known in propionaldehyde and acetone.The reaction is carried out according to this field, for example, by rapid cooling, the description given in Scheme A, stage a. filtration, extraction, evaporation, Scheme C, stages a and is shown alterna- trituration, chromatography and tive option approach to obtaining compounds by pre-recrystallization.

In addition, a suitable compound of the form of a suitable compound of formula (7) and a suitable mule (25) can be reduced in two steps to an amine of formula (26) to give an amide of the compound of formula (1). For example, the vinyl group (27) undergoes further reduction to obtain the compound of formula (1). A suitable compound for fortyl ether, with the use, as a rule, of mule (7) is the compound described in Scheme B. 1 to 12 molar equivalents of reducing agent. I will remember

A suitable amine of the formula (26) is an amine that, as a rule, is carried out at the temperature of baking the final compound of the formula | necessary KE". from approximately 0"C to the temperature of distillation selected

It will be clear to the skilled person that there is a lot of early solvent, and its duration is, as amides of formula (27) are commercially available and usually from 12h to about 48h. Product available in this field. can be isolated and cleared in ways, good

The preparation and reduction of the amide in Scheme C are known in the art, for example, by rapid cooling, as described in Scheme B, by filtration, extraction, precipitation

Scheme O shows methods of obtaining compounds of formula (1) by grinding, grinding into powder, chromatography, where Ki is facultation and recrystallization. tively substituted indol-3-yl. In Scheme 0, stage c, a suitable indole of formula (28) is formed to give the compound

Scheme 0 mule (30). Suitable indole of formula (28) corresponds to the description given in step a, above. o For example, a suitable indole of the formula (28) reacts with a suitable reagent for the transfer of the form

MD olive / 5th stage 5 lu, for example, with Vilsmeier's reagent, which is ordered (29) In stings from dimethylformamide. In general, use (28) And approximately 1 molar equivalent of the reactant transfer stage 4 in; MN today's formyl. The mentioned reaction is carried out. in stage c and j in a suitable solvent, for example, benzene, di- 2 7 stage (red Bi - methylformamide, tetrahydrofuran or diethyl oo indol-3-yl ether. The reaction is carried out at a temperature of 100 degrees Celsius, approximately -70" C to approximately 202C, and its duration

M / stage is M / is from h to bh. The reaction product can (30) (31) be isolated and purified by methods well known in the art. These methods include ext.

Scheme 0, step a, depicts the two-step fermentation, evaporation, chromatography and reaction of the suitable indole of formula (28) first recrystallization. that with oxalyl chloride, then with a suitable amine fo- In scheme 0, stage y, a suitable indole of the formula (26), B2MH»g, to obtain a compound of the formula (28) contacts with (CH3)»M-СНАСН-МО » from the shell (29). A suitable indole of formula (28) is an indole derivative of a compound of formula (30). A suitable indole where 7" represents optional substituents in the positions of formula (28) corresponds to the description given in positions 2- and 4-7 of the indole, which is desirable for the final stage a, above. of the product of formula I. A suitable amine of the form For example, a suitable indole of formula (28) of relay (26) corresponds to the description in Scheme C above. reacts with 1-dimethylamino-2-nitroethylene. In general,

For example, a suitable indole of formula (28) interacts with approximately 1-2 molar equivalents of reactants in approximately 1 equimolar amounts. The mentioned reaction is carried out in the presence of oxalyl chloride with the preparation of an intermediate chemical solvent, for example, trifluoroacetic acid compound, keto acid chloride. The mentioned reaction or dichloromethane, which includes approximately 2- cation, is carried out in a suitable solvent, for example, 15 equivalents of trifluoroacetic acid. Reaction of clades, diethyl ether or tetrahydrofuran. carried out at a temperature of approximately -06

The reaction, as a rule, is carried out at a temperature of up to about 20"C, and its duration, as a rule, is from 02C to 402C, and its duration is from 1 hour to 24 hours. The reaction product can last from 2 hours to 48 hours . The intermediate chemical compound can be isolated and purified by methods well known in the art. These methods include extraction by methods well known in the art. , evaporation, recrystallization, chromatography, and recrystallization. According to Scheme 0, stage e and i, the reaction of Hali, an intermediate chemical compound, ketoaldehyde chloride of formula (30) with the production of nitroolefinic acid, is used directly after the formula (31) and recovery of the nitroolefin from the separation. The intermediate chemical compound, the chloride anhydride- by obtaining the compound of formula (1), where Ki is the faculride of a keto acid, is contacted with a suitable amine, tatively substituted indol-3-yl ohm. These stages can

VoMN", as determined above by methods, the description shall be carried out by the methods described above. on Scheme C.

Scheme 0, step b, depicts the reduction of a compound of formula (29) to a compound of formula (29) as will be properly appreciated by one skilled in the art. by a person skilled in the art, at stages not shown, the indole nitrogen (1) where Bi is optionally substituted in the compound of formula (1) can be substituted by badol-3-yl. harvesting, with the use of suitable protection groups

For example, the compound of formula (29) reduces an amine to give compounds where Ki is, with the use of a suitable reducing agent, monosubstituted indole-3-yl. As will also be appropriate, for example, lithium aluminum hydride obtained in this way was evaluated by an experienced specialist, based on formula (1), where Ri is an optional substituent, the description of which is given in Scheme C, group K", which is indole -3-clay. The mentioned reaction is carried out in non-hydrogen, different co-solvents can be introduced, for example, tetrahydrofuran or dieb.

Scheme E depicts methods of obtaining methylacetamide, tetrahydrofuran, pyridine and di-formula (2) compounds, where X is -O-or -5-. methyl sulfoxide. The reaction is carried out in the presence of approximately 1-3 molar equivalents of suitable

Scheme E of a base, for example, potassium hydride, sodium hydroxide, sodium hydride, sodium carbonate, carbonate

Siv stage b. This is potassium, cesium carbonate, M, M-vee "lived in diisopropylethylamine, triethylamine, etc. Reaction lk 15) is carried out at a temperature of approximately -307C

It is stable up to about 100°C, and its duration, as a rule, is from 2h to 48h. The product of the reaction can be isolated and purified by well-known methods.

This is the stage we are in this field. These methods include extraction, evaporation, chromatography and (1) 0) recrystallization. y and A, where Of course, in the case of using M-oxide halostedmya and ХІ X is -0- pyridine, M-oxide is removed by reduction or -5- to obtain Ka, which is desired in the final

En stage 5. products of formula I. Such reductions are easily accomplished. they are carried out by an experienced specialist and include cata- ov. Both lytic reduction over a palladium catalyst (12) (63) using hydrogen or ammonium formate in a suitable solvent, for example, methanol,

Scheme E, stage a, depicts the production of ethanol, water, and their mixtures. of the acetal of a suitable compound of the formula (11) with the obtaining of the compound of the formula (12). A suitable combination, when a suitable reactant for the group transfer of formula (11) is a compound, X and Kz of which are B and Ba is an alkanol, the combination can be carried out by them in the final compound of formula 1. Such reactions using the Mitsunobu reaction, which is good recovery of acetal is easily carried out using techniques available in this field. We will carry out the mentioned reaction, well known in this field. (Rhoiesiipd Stgoire in a suitable solvent, for example, tetrahyp Ogdapis Zupiyevia.

Ip(exsiepse)|. phosphine, for example, triphenylphosphine or liga-

For example, the compound of formula (11) is contacted with a phosphine resin and dialkylazodicarboxylate under conditions of acid catalysis with a suitable alcohol, a plate, for example, diethylazodicarboxylate,

NORK. A suitable alcohol is an alcohol that deprotects propyl azodicarboxylate or di-treats the acetal, which preserves the stability of butyl azodicarboxylate. The reaction, as a rule, reactions at stage B and can be removed at stage c with is carried out at a temperature from the temperature of obtaining the compound of formula (2). The suitable environment is up to 60"C. The duration of alcohols includes methanol, ethanol, propanol, 1,3-reactions, as a rule, is from 1 hour to 12 hours. propanediol, ethylene glycol, etc. The product can be isolated by well-known methods

In Scheme E, step p, a suitable compound is formed in this field, for example by extraction, and mules (11), formula (12) or formula (14) are reacted with evaporation. After that, the product can be purified with a Ka group transfer reagent, as needed, by methods well known in the field, to obtain a compound of formula (2), formula (13) for example, distillation, chromatography, or formula (15), respectively . Suitable co-recrystallization. compounds of formula (11), formula (12) and formula (14) Scheme E, stage c, shows the cleavage of compounds, X and Kz of which are desired in the terminal protecting group of the acetal of formula (13) with the resulting product of formula I. Available and suitable for them compounds of formula (2). Such cleavage of the protective reaction presented in Scheme E, there are a number of rhenium groups are easily carried out by methods well-known in the field. (Rgoiesiipud Sptosrv ip Ogdapis product. These reagents include halo- Zupipeviv, Tpeodoga Stgeyepe (UMieu-Ipiegzsiepse)). pyridines, M-oxides of halopyridine, allyl halides, For example, the compound of formula (13) contacts in

C2-C4 alkanols, C2-C4 alkyl halides and sulfonic acids in the aqueous medium from odenate, fluorinated C2-C4 alkanols, fluorinated C2-C4 by oxidizing compounds of formula (2). alkyl halides and sulfonates, optionally In Scheme E, stage a, a bromine compound of the formula substituted phenyl having at least one atom (153 is formed to give a compound of form- fluorine or chlorine, optionally substituted phenyls (2). sulfonyl halides or anhydrides and optional For example, the compound of formula (15) is metallatively substituted benzyl halides by treatment with a metallating reagent,

For example, in the case when a suitable reagent, for example, butyllithium. The above-mentioned reaction is carried out by the transfer of the Ka group in a suitable solvent, for example, hexane, anhydride, a suitable compound of formula (11), formo-benzene, toluene, tetrahydrofuran or diethylvol (12) or formula (14) combines on the main air. The reaction, as a rule, is carried out under the following conditions to obtain the compound of formula (2), the amount of which is approximately 1-1.5 molar equivalents of formula (13) or formula (15), respectively. I mentioned the metallizing reagent. The metalation reaction is carried out in a suitable solvent, it is carried out at a temperature from about -707С, for example, acetonitrile, dimethylformamide, di- to about 202С, and its duration, as a rule,

is from 1 hour to two hours. After that, the metallized radiation is carried out using a suitable variety treated with a catalyst transfer reagent, for example, copper salts. The duration of formyl, for example, dimethylformamide, or the reaction is, as a rule, from 2h to 48h. with alkyl chloroformate, with the formation of the compound fo- The product of the coupling reaction can be isolated and rmula (2) or an alkoxycarbonyl compound, which can be purified by methods well known in this halo- can be converted into an aldehyde according to the above. These methods include extraction, extraction, and description. The reaction product can be isolated and purified, chromatographed, and recrystallized by methods well known in the art. To tion. These methods include extraction, vaporization, chromatographic and recrystallization. of the given compound of formula (17), after metallization

Scheme E depicts methods of obtaining compounds as described in Scheme E, stage a, with the preparation of formula (2) from the universal chemical intermediate of formulas (18)-(21), respectively. At these stages, the compound (17), which is easily obtained by the acetal as described above. Az which is desirable in the final product of the formula | and which is not adversely affected by the conditions

The scheme is the metalation of the mentioned reaction. In general, these reactions

This is carried out in a solvent and at a temperature that is used for the production of metallized metals

OV 13) varieties. The products of these reactions can be isolated and purified by methods well known in stage a | with shk in this field, including rapid cooling, vo. I, iron and extraction, evaporation, grinding into a powder, chromatography and recrystallization of stalin Y Sh-k Y by this. y y p - stage C For example, on Scheme RE, stage Y, metallized t waist B 7 . p. 2, where the compound of formula (17) contacts with a suitable di- tyu КЬ с--я КО Хн я moh che Kt, sulfide (К45-)2 to obtain a compound of formula biz stage is Chvsyayu o stage | g (18). A suitable disulfide is one that

In waist y and s Va, which is desirable in the final product of the formula х, stage пз І and which ensures the preparation of compounds where Х - -5-. Suitable disulfides include С1и-Са alkyd 38 Я Я Я: Ах г Дия steel disulfides, optionally substituted phenyl disulfides, optionally substituted benzyl disulfides, and optionally substituted benzyl disulfides. The mentioned reaction is carried out with

In KO. chat t, using approximately 1-2 molar equivalents of them. . . p ra ov (98) of suitable disulfide. As a rule, the reaction is carried out in the same solvent used in

OV 35 is used for metallization and at temperatures from about -78°C to about 50°C. The duration of the reaction is, as a rule, from 12 hours to 48 hours.

Scheme P, stage a, shows the substitution reaction. For example, Scheme PE, stage c, the metalation of an aromatic amine of a suitable shell, the compound of formula (17) comes into contact with a suitable antimony. and mercuric chloride (ca lfonyl fluoride (Ka5O»P) to give a suitable thiol compound (KA5H) to give a compound of formula (19). A suitable sulfonyl fluoride is formula 18). The 7th compound of the form (17) is a sulfonyl fluoride that tolerates Ka. ve which is the desired method of need, to the final product of formula 1, and which is also used to obtain compounds where X is -502-. To the duct of the formula I. Kya suitable alcohol (RON) or suitable sulfonyl fluorides belongs to the facul- suitable TOLU (Be) is desirable in Kntsevoi tatively substituted phenylsulfonyl fluoride. The given reaction is carried out with the use of slaked copper-doped SS ap- nite alcohols and thiols, fluorinated C2-Ce alkyl alcohols of 1-3 molar equivalents of suitable alcohols and thiols, optionally substituted phenols of sulfonyl fluoride. The reaction, as a rule, is carried out by thiophenols, optionally substituted benzyls, in the same solvent that was used for metallization and at temperatures from about -78"С to approximately 0"C. The duration of the reaction with a suitable alcohol (BKAOH) or a suitable thiol is, as a rule, from 2 hours to 12 hours. (Be5H) are combined to obtain the compound for- For example, in Scheme E, stage y, metallated mud (13). The above-mentioned reaction is carried out when the compound of the formula (17) comes into contact with a suitable neutral solvent, for example, dimethylformamide, dihydride (CaC(O)CI) to obtain the compound dimethylacetamide and dimethylsulfoxide. Reaction - formulas (20). A suitable anhydride chloride is such that this is carried out using approximately 1.1-3 xporanhydrides, which transfers Ra, as needed, to molar equivalents of a suitable alcohol or thiol. of the final product of the formula I, and which provides complete sKisalsnno Suitable bases, when obtaining compounds where Х - С(О). To suitable clades of potassium hydoid. those of sodium chloride belong to C2-C4 alkylchlorohydric potassium carbonate, I or hydride, such as Xia, fluorinated C2-Cya alkylchloroanhydrides, facul. and tatively substituted phenylchloroanhydrides, faculty

tively substituted benzylchloroanhydrides and facultatively substituted 5-6-membered monocyclic aromatic heterocyclochloroanhydrides. The mentioned reaction is carried out in stage 5 using approximately 0.8-1.2 mol equivalents of suitable hydrogen chloride. The reaction, as a rule, is carried out in exactly the same a) (32) solvent that was used for metallization stage a stage c and at temperatures from approximately -78"С to about - stage a lysno 50"С. The duration of the reaction is, as a rule, from 1Th to 12h. /g in Sn

For example, in Scheme E, step E, the metalated compound of formula (17) is contacted with a suitable al- (53, where (33) dehyde (KAS(O)H) to give the compound of formula A is -OH Shu (21). A suitable aldehyde is one which transfers Ka, as required, to the final product of formula I, and which ensures the preparation of compounds, Slk, where X is -CH(OH)-. Suitable aldehydes include mok x

Co-Ca alkylaldehyde, fluorinated Co-Ca alkylal- (5) dehyde, optionally substituted phenylaldehyde, optionally substituted benzylaldehyde and pha carboxylation with the formation of an aromatic heterocycloaldehyde. The mentioned compounds of formula (5), where A is -OH. the reaction is carried out using approximately 1- For example, the compound of formula (15) metalates

From molar equivalents of suitable aldehyde. According to the description of Scheme E, stage i, after which the metaaction is usually carried out in that the dissolved variety is treated with carbon dioxide, which was used for metallation, and with the preparation of the compound of the formula (5), where A - - ON. at temperatures from about -502C to about 50C. The reaction product can be isolated and purified from 50C. The duration of the reaction is, according to methods well known in the field. These methods include extraction, evaporation,

Chromatography and recrystallization will be properly evaluated by the skilled person. to a specialist, compounds of formula (18)-(21) can undergo a number of other transformations, which are shown in Scheme c, stage Y, the bromine compound of formula ends, by vaing a suitable chloroformate or carbonate of the compounds of formula I, which have different groups on X. These with obtaining the compound of formula (32). Suitable transformations are well known and are found in chloroformate or carbonate is such a chloro- within the capabilities of an experienced specialist. These performate or carbonate carrying a transformation group include the oxidation of sulfides (sta- BO(O)C-, where K is methyl, ethyl or benzyl. action 7), which can be carried out with the help of per- For example, the compound of the formula (15 ) metal oxide, superacids and other reagents known in this sia according to the description of Scheme E, stage y, after which meta- branches; reduction of benzyl alcohol (stage 9), the caught variety is treated for approximately 1-3 mo- which can be carried out with the help of a number of ly equivalents of suitable chloroformate reagents, for example, triethylsil- or carbonate. The reaction, as a rule, is carried out in n/trifluoroacetic acid; halogenation of benzytomine to the very solvent that was used for mineral alcohol with the production of fluorine (stage n) during metalation and at temperatures from about - with the help of such reagents as diethyl trifluoride - 78"C to about 50"C. The duration of the reaction, as laminosulphur and fluorinating agents; recovery, as a rule, is from 1 hour to 24 hours. The ketone product (step y) with the help of various reactions can be isolated and purified by methods such as hydride transfer or benzyl oxidation, which are well known in the art. These sposol alcohol (stage y), which can be carried out by biv, include extraction, evaporation, chroma- with the help of manganese dioxide or the reaction of light photography and recrystallization. rna In Scheme b, stage c, a suitable compound for

In Scheme E, stage ), compounds of the formula (13) and mule (33) react with the group transfer reagent of the formula (18)-(23) to remove the protecting group from Ba, as needed, to obtain the compound of the formula by obtaining the aldehyde of the formula (2), as described in (32). A suitable compound of formula (33) is a compound

Scheme E, stage c. ka, X and Kz of which are desired in the final product

Scheme C depicts methods of obtaining compounds of formula I. Reagents that transfer Ka correspond to formula (5). give a description of Scheme E.

For example, in the case when a suitable reactant for the transfer of the Ka group is a halide or an anhydride, a suitable compound of formula (34) combines under basic conditions to obtain a compound of formula (33). The mentioned reaction is carried out in a suitable solvent, for example, dimethylformamide, tetrahydrofuran or pyridine. The reaction is usually carried out in the presence of about 1-3 molar equivalents of a suitable base, for example, carbo-

sodium nitrate, potassium carbonate, cesium carbonate, Scheme H

M,M-diisopropylethylamine, triethylamine, etc. The reaction is carried out at a temperature from approximately 30°C to approximately 1007°C, and its duration, as a rule, is from 2h to 48h. The product of reaction B is 153 x y MA (35) x can be isolated and purified by methods, well, step c, step y, known in the art. These methods include extraction, evaporation, chromatography, step e kov, and recrystallization.

Alternatively, for example, in case 5 (35), when a suitable reagent for the transfer of the SB pear, where and Pi Ra is an alkanol, the coupling can be carried out with water using the Mitsunobu reaction, which is well known in the art and the description of which is given in ex stage 4, etc

Schemes E. and NM. and so on,

In Scheme b, stage y, a protective group is cleaved from the complex ether of fogi 0 and 37 rmula (32) to obtain a compound of formula (5), where A is -OH. Such remote grafting of protective groups is easily carried out at one stage by methods well known in the art. |Rgoiesiipa To in not t

Stor ip Ogdapis bZupiyeziv. Tpeodoga Stgeepe nori same TK (UMieu-Ipiegvsivpse))|. (2 (4

Scheme b, stage is, the compound of formula (5), where A is -OH, turns into a compound of formula (5), where Scheme H, stage a, bromine compound of the formula

A - an activating group, for example, halogen anhydride, (15) is converted to a nitrile of the formula (35). activated ester, activated amide or For example, a compound of formula (15) is treated with an anhydride. Obtaining such activated intermediates with copper cyanide () to obtain a compound of the formula

CHEMICAL compounds is a well-known and proper chi- (35). This reaction is carried out in a suitable variety evaluated in this field. factor, for example, dimethylformamide. reaction,

For example, halogen anhydride can be obtained, as a rule, is carried out in the presence of approximately 1- with the help of a number of reagents, for example, from molar equivalents of copper (I) cyanide. The reaction of oxalyl chloride, oxalyl bromide, and thionyl chloride is carried out at a temperature from approximately tempethionyl bromide, phosphorus oxychloride, trichloride of the environment to approximately phosphorus and phosphorus pentachloride; mixed 1002C, and its duration, as a rule, is from anhydrides of substituted phosphoric acid, about 48 hours. The product of the reaction can be isolated and purified by methods well known in this field. These methods include extraction, precipitated carboxylic acid, for example, formic acid, chromatography and recrystallization of acid, acetic acid, propionic acid, etc. butyric acid, isobutyric acid, pivalic Scheme H, stage B, a nitrile compound of the formula ether, for example, phenol complex (4), where P2 is hydrogen. ether, p-nitrophenol ester, M- For example, the nitrile compound of the formula (35) hydroxysuccinimide ester, //M- is brought into contact with sodium borohydride in the presence of hydroxyphthalimide ester, 1- cobalt chloride. The mentioned reaction is carried out by a hydroxybenzotriazole ester or by acting in a suitable solvent, for example, a methanated amide, for example, imidazole, dimethylpyl or ethanol. The reaction, as a rule, is carried out by razole, triazole, obtained by methods that are at a temperature from about 0"C to 502C. Tri- are well known and properly evaluated in this reaction time, as a rule, is from 1 hour to alkali. Such activated intermediate chemical compounds can be isolated and purified or obtained and isolated before use by extracting with aqueous acid according to the above schemes.

Scheme H depicts methods of obtaining recrystallization compounds. formula (4). Alternatively, for example, the nitrile compound of formula (35) is hydrogenated over a suitable catalyst, for example, nickel (RenaiF). In the case of using RaneyFd nickel as a catalyst, said reaction is carried out in a suitable solvent, and suitable solvents will, as a rule, include ammonia, for example, ethanol/ammonium hydroxide. The reaction is generally carried out at temperatures from ambient to 50°C. The reaction is carried out under pressures from 15 psi (103 kPa) to 120 psi (827 kPa) in an apparatus designed to

in order to carry out reactions under pressure, add copper oxide (5.5 g, 69.5 mmol). Heat with slag, in Parr's hydrogenation unit. The product is a mouth-refrigerator. After 24 hours, cool to can be isolated by carefully removing the room temperature, dilute the catalyst with dichloromethane by filtration or evaporation. and filter. Concentrate the filtrate under

The product can be purified by extraction, vacuum evaporation to obtain a yellow oil. by grinding, crushing into powder, chromatography. Chromatograph the oil on silica gel with elution and recrystallization. by a mixture (95:5) of hexane:EUAc with the obtained

Scheme H, stage c, nitrile compound of the formula of the target compound. (35) is converted to the amide of formula (36). According to the method of Example 1, the following solutions were obtained

For example, the compound of the formula (35) is treated with: acid or base under the conditions of hydrolysis with a) 2-(3-(2-fluorophenoxy)phenyl)-(1,3)dioxolane; by harvesting the compound of formula (36). The mentioned reaction p) 2-(3-(3-fluorophenoxy)phenyl)-(1,3)dioxolane; carried out in a suitable solvent, for example, c) 2-(3-(naphth-2-yloxy)phenyl)-(1,3)dioxolane; ethanol, isopropanol, dimethyl sulfoxide, each a) 2-(3-(naphth-1-yloxy)phenyl)-(1,3)dioxolane; of which includes water. Hydrolysis of aromatic nitri-e) 2-(3-(pyrid-3-yloxy)phenyl)-(1,3)dioxolane; lu to the amide is well known and properly B) 3-(pyridin-3-yloxy)benzaldehyde; valued in this field. The reaction product can be isolated 9) C-(pyrimidin-5-yloxy)benzaldehyde; and cast and purified by methods well known in n) 3-(pyridin-4-yloxy)benzaldehyde. this field. These methods include extraction, Example 2 evaporation, chromatography and overlap-3-11,3)|dioxolan-2-ylphenyl)phenylamine stabilization. Mix 2-(3-bromophenyl)-1,3-dioxolane (0.7 ml,

Scheme H, step 4, depicts the preparation of amide 4, Zmmol), aniline (0.4ml, 4.7mmol), tert-butoxide of formula (37) by reacting the compound sodium formate (0.bg, b,Ommol), VIMAR ( 2,2-ly (5) and a suitable amine of the formula Nama" in the reaction bisidiphenylphosphine)-1,1-binaphthyl) (10,Omg, the formation of amide. With a suitable amine of the formula O,Omol), Rag(aba)z (30 ,Omg, 0.01 mmol) and toluene

We" have an amine that gives KE", as needed, to the end- (20 ml). Heat at a temperature of 80°C. Due to the product of formula I. Suitable methods are to cool the extract to room temperature for 18 hours, the dilution of amides is well known in this field and their description is washed with ether (40 ml), filtered and concentrated in the above Scheme B. cotton wool to obtain a residue Chromatograph

Scheme H, step is, the amide compound of formula (36) residue on silica gel eluting with mixture or (37) is reduced to the compound of formula (4). (9:1) of hexane:EOAc with obtaining the target

Such reductions of amides are easily carried out for bows. description in the above Scheme B and are known in According to the method of Example 2, the following compounds were obtained. Who:

Scheme H, stage I, the compound of the formula (2) and a) benzyl-(3-(/1,3|dioxolan-2-ylphenyl)-amine; a suitable amine of the formula Nam" undergo hydro-p) (3-P1,3 |dioxolan-2-ylphenyl)-pyridine-3-amination to obtain the compound of formula (4). ilamine;

Such hydroamination is easily carried out as described in (3-β1,3|dioxolan-2-ylphenyl)-pyridin-4-some in the above Scheme B and with the help of ylamine; and other methods known in the field. a) (3-P1,3|dioxolan-2-ylphenyl)-pyridine-2-

As will be properly assessed by an experienced ilamine. by a specialist, the compounds of formula II are easily obtained by Example Using methods similar to the methods described above. Mix 2-(3-bromophenyl)-1,3-dioxolane (3.Oml,

This invention is further illustrated by the following- 20.0mmol) and tetrahydrofuran (100ml). Cooled down further with examples and preparations. These applications are up to a temperature of approximately -787C. Add drops and preparations are purely illustrative and do not drop by drop a solution of p-butyllithium, a 1.6 M solution in hexane (13.4 ml, 21.0 mmol) intended for any limitation of this. After 10 minutes, add the invention. phenyl disulfide (4.3 g, 20.0 mmol) in the form of

The terms used in the examples and rank in tetrahydrofuran (5Oml). After 1Th of heating, preparations have their usual value, if warmed to room temperature for an hour, unless otherwise specified. For example, "C" means degrees after which the reaction is quickly stopped by adding Celsius; "M" means normal or normo- of cold water (150ml) and extract with ether. ality; "M" means molar or molarity; Extract the combined organic layers successively "mmol" means millimole or millimoles; "g" means distilled water and brine, followed by gram or grams; "ml" means milliliter or milliliter - dry (Ma»50O»4), filter and concentrate; "vol. pl." means melting point; "roseol" to give a residue. Chromatograph means a saturated aqueous solution of sodium chloride; the residue is eluted with a mixture (9:1) of hexa-, etc. In the "H NMR spectra, all chemical shifts are given in nu:ETAc with obtaining the target compound. unless otherwise specified. According to the method of Example C, the following solutions were obtained

Example 1 onions: 2-(3-(4-butorphenoxy)phenyl)-(1,3)dioxolane a) 2-(3-p-tolylsulfanylphenyl)-(1,9|-dioxolane.

Mix 4-fluorophenol (3.0 g, 227 mmol), 2-(3- Example 4 bromophenyl)-1,3-dioxolane (5.0 ml, 33.mmol), car- 2-(3-benzenesulfonylphenyl)-|1 . Heat to 907 and do-dioxolane (1.0g, 3.bmol) and dichloromethane (15ml).

Cool to a temperature of approximately -787C. Do-2-(3-(-fluorobenzyl)phenyl)-|1,3|-dioxolane to give a suspension of t-chloroperbenzoic acid (2.3 g, Mix (3-P1,3|dioxolan-2-ylphenyl)-phenyl-7 .2 mmol) in dichloromethane (1 Oml). After 30 minutes, methanol (2.3 g, 8.9 mmol) and dichloromethane (50 ml) were added. warm to room temperature, then add Cool to a temperature of approximately -782C. Cra- 1M solution of sodium thiosulfate (20ml). After 15 minutes, add a solution of trifluoride (diethyl- add a saturated solution of sodium bicarbonate. Wil-amino)sulfur (1.7 ml, 12.9 mmol) drop by drop. After 10 min, the reaction was quickly stopped by adding cold water and the layer with dichloromethane. Combine the organic layers and extract with dichloromethane. Combine the organics, successively wash with distilled water and the layers and successively wash with distilled water with salt, then dry (Mag50O4), filter and brine, then dry (Mag50O4), filter and concentrate to obtain a residue. filter and concentrate to obtain a residue

Chromatograph the residue eluting with EtOAc. Chromatograph the residue eluting to give the target compound. with a mixture (7:3) of hexane:E(Ac) with obtaining the whole

According to the method of Example 4, the following compounds were obtained. bows: Example 9 a) 2-(3-"toluene-4-sulfonyl)-phenyl)-|1,3|-Z-nitrodibenzofuran dioxolane. Mix dibenzofuran (20.0 g, 0.11 mol) and

Example 5 acetic acid (8Oml). Heat (3-11,3|dioxolan-2-ylphenyl)phenylmethanol to a temperature of 65"C. Add 9895 nitric acid solution (20.0g,

Mix 2-(3-bromophenyl)-1,3-dioxolane 11, vmol). (10.Oml, 66.Omol) and tetrahydrofuran (100ml) and temperature to obtain a solid. Cool to a temperature of approximately -787C. Filter the solid, wash with water, and drop by drop add p-butyllithium solution, 1.6M, dry to obtain the target compound. solution in hexane (44.0ml, 6b, mol). After 10 minutes, Example 10, using a cannula, add a solution of benzaldehyde M-dibenzofuran-Z-ylamine (7 bml, 66, mol) in tetrahydrofuran (5Oml). Che- Mix Z-nitrodibenzofuran (22.0g, res 1h heat to room temperature. After 0 Tmol), Raney nickel (2.75g) and ethanol (365ml) and 18h quickly stop the reaction by adding hal- hydrogenate at room temperature and under water and extract with dichloromethane. Combined pressure of 40 psi:? (276 kPa). After 18 hours, remove the organic layers and successively wash, distill, filter and concentrate the filtrate with deionized water and brine, then dry the residue by harvesting. Chromatograph the residue with (Mag2504), filter and concentrate eluting with a mixture (9:1) of hexane: EtOAc to give a residue. Chromatograph the residue to yield the target compound. elution with a mixture (7:3) of hexane:ETOAc to obtain the target compound. Z-bromodibenzofuran

Example 6 Mix M-dibenzofuran-3-ylamine (2.Og, (3-11.3|dioxolan-2-ylphenyl)phenylmethanone 10.vmmol), water (20ml) and concentrated bromo-

Mix (3-P1,3|dioxolan-2-ylphenyl)-phenyl-hydrochloric acid (bml). Cool to room temperature - methanol (5.0g, 18.5mmol) and a solution of 18-crown-b ture 0"C. Add a solution of sodium nitrite (0.7g, (16Omg, 0.bmmol) in dichloromethane. Add perman- 10, vmmol) in water (1bml). After 15 minutes, add potassium precipitate (8.8g, 55.5mmol). Heat the above-mentioned mixture to the mixture of copper bromide (1.7g, turns about 40"C. After 4 hours, cool to 12.3 mmol) in water (9.2 mL) and hydrogen bromide at room temperature, add water and sulfuric acid (4 mL). Heat to ambient temperature - day - sodium (6b, 0g). Increase the basicity of 1M different medium. After 18 hours, add water and sodium hydroxide (approximately boOml) and extract with dichloromethane. Combine the organic compounds with dichloromethane. Combine the organic layers and successively wash the layers with distilled water and successively wash with distilled water and brine, then dry (Mg5O4), filter with brine, then dry (Mg50O»4), filter and concentrate to give the residue and concentrate to obtain a residue. Chromatograph the residue eluting with Chromatograph the residue eluting with a mixture (8:2) of hexane: EtOAc to obtain total

ES with obtaining the target compound. your compounds.

Example 7 Example 12

Z-benzylbenzaldehyde Dibenzofuran-Z-carbaldehyde

Mix (3-P1,3|dioxolan-2-ylphenyl)-phenyl- Mix 3-bromodibenzofuran (0.5g, 2.0mmol) methanol (2.3g, 8.7mmol) and sodium iodide (5.3g, and tetrahydrofuran (ZOml). Cool to temp- 35.0mmol) in acetonitrile (25ml). With the help of a thermometer, approximately -78°C. Add the solution of the third syringe, add dichloromethylsilane (2.1 ml, butyllithium, 1.6 M solution in hexane (2.2 ml, 17.4 mmol). After 10 minutes, dilute EtOAc and pro- , after which heat to a temperature, wash with water, a saturated bicarbonate solution of approximately 02C for 10 minutes. Cool to temperature of sodium, 1095 sodium thiosulfate solution, then temperature of approximately -78C, and add dimethylformamide. Dry the organic layers (Ma250O5), amide (0.5 ml, 5.9 mmol). Warm to room temperature, filter and concentrate to obtain a precipitate, quickly stop the reaction by adding the excess. Chromatograph the residue eluting with cold water and extract with dichloromethane. with a mixture (9:1) of hexane: EtOAc to obtain whole- Combine the organic layers and successively wash the compounds. distilled water and brine, after which

Example 8 dry (Ma»50O»4), filter and concentrate

cotton wool to obtain the remainder. Chromatograph phenatroline (1.3g, b6.2mmol), transdibenzylidene - the residue eluting with a mixture (8:2) of hexa-ketone (0.1g, 0.3mmol), cesium carbonate (2.6g, nu:EUAs to obtain the target compound 7.9 mmol) and iodobenzene (1.6 ml, 14.3 mmol) in

Example 13 xylene (40 ml). Heat at a temperature of approx.

C3-(thiazol-2-yloxy)benzaldehyde melts at 1107°C. After 24 hours, cool to room temperature

In a sealed test tube, mix at -2- temperatures, dilute with dichloromethane and nasibromothiazole (2.Oml, 22.2 MMmol), with a 3-part ammonium chloride solution. Separate the hydroxybenzaldehyde (1.8g, 15.0mmol) and carbolayers, and extract the aqueous layer with dichloromethane. potassium nitrate (2.1g, 15.0mmol) in dimethylformamide. Combine the organic layers and wash successively (20ml). Heat to a temperature of 1007C. Through distilled water and brine, then cool for 48 hours, pour into water (150 ml) and extra-dry (Ma»50O»4), filter and concentrate with ether. Combine organic layers, cotton wool to obtain a residue. Chromatograph and successively wash with distilled water and the residue eluting with a mixture (8:2) hexa-brine, then dry (Ma5O), filter: EtOAc to obtain the target compound. digest and concentrate to give a residue. According to the method of Example 16, the following solutions were obtained

Chromatograph the residue with the elution mixture: 1-phenyl-1H-indole-4-carbaldehyde. (9:1) hexane"E(OAc) to obtain the target compound Example 17. 3-phenylulfanylbenzaldehyde

Example 14 Mix 2-(3-phenylsulfanylphenyl)-I|1,31-b-bromo-1H-indole dioxolane (0.3g, 1.1mmol) and acetonitrile (8.0ml),

Mix 4-bromo-2-nitrotoluene (5.0g, add a solution of hydrochloric acid (1M, 23.1mmol), dimethylformamide (50ml), dimethylformamide (2.00ml). After 18 h, concentrate under vacuum from tylformamide-dimethylacetal (9.0 mL, 69.4 mmol) by removing most of the acetonitrile, and pyrrolidine (2.0 mL, 23.1 mmol). Heat to room temperature with water and extract with ether. Obratura 11070. Cool to room temperature, combine the organic layers and wash once at saturation temperature, dilute with ether and a clear solution of sodium bicarbonate, then with brine. wash with water Combine the organic layers, and concen- Dry (Ma»5Oy) the organic layers, filter and treat to obtain a residue. Combine the mixture and concentrate to give the target compound. shock and 8095 aqueous solution of acetic acid According to the method of Example 17, the following solutions were obtained (120 ml), and heated at a temperature of 757C. Portion of onions: we add zinc dust (13.1g, 200.5mmol). Na- a) Z-benzenesulfonylbenzaldehyde; heat to a temperature of 85"7C. After 2 hours, cool p) 3-p-tolylsulfanylbenzaldehyde; and filter. Dilute the filtrate with simple c) 3-(p-tosyl)benzaldehyde; ether, wash with water, dry (Mag5Oa) and con- -benzylaminobenzaldehyde; concentrate to obtain a residue. Chromatograph- e) 3-phenylaminobenzaldehyde; elute the residue with elution with a mixture (9:1) of hec-I) 3-benzoylbenzaldehyde; sane: ETOAc to obtain the target compound. 9) 3-(x-fluorobenzyl) ) benzaldehyde;

According to the method of Example 14, the following compounds were obtained: 3-(4-fluorophenoxy)benzaldehyde; bows: 4-bromo-1H-indole. i) 3-(2-fluorophenoxy)benzaldehyde;

Example 15 |) 3-(3-fluorophenoxy) benzaldehyde; 1nH-indole-b6-carbaldehyde K) C-(naphth-2-yloxy)benzaldehyde;

Mix hexane-washed potassium hydride (1.3 g, I) C3-(naphth-1-yloxy)benzaldehyde; 10.7 mmol) and simple ether (20 ml). Cool to t) C-(pyruvidine-3-ylamino)benzaldehyde; at a temperature of approximately 0"C, and add a solution of 6-n) 3-(pyridin-4-ylamino)benzaldehyde; bromo-1H-indole (2.1 g, 10.7 mmol) in simple ether o) 3-(pyridin-2- ylamino)benzaldehyde; and (5ml). After 15 minutes, cool to a temperature of about -78°C, and add a solution of tert-butyllithium, Example 18 1.4M solution in hexane (14.Oml, 10.7 mmol). After 2 g of naphth-2-ylethylamine, add a solution of dimethylformamide (1.7 ml, Mix naphth-2-yl acetonitrile (1.0 g, 20.0 mmol) in ether (ml). Slowly add nickel chloride hexahydrate after 10 min. (I) (0.7g, warm to room temperature, then pour out C, mmol) and tetrahydrofuran (30ml). Drop by drop to a cold 1M solution (melting temperature, add the borane-ice complex drop by drop) of phosphoric acid and extract with EACs. of tetrahydrofuran, 1M solution in tetrahydrofuran

Combine the organic layers and wash sequentially (24 Oml, 24.0 mmol). After 1 hour, evaporate with distilled water and brine, then harvest the residue. Chromatograph on silica gel, dry (Mg50O54), filter and concentrate with elution with a mixture (8:2) EUAs:MeOOnH « 295 watts to obtain a residue. Chromatograph MNAOH to obtain the target compound. residue with elution with a mixture (9:1) of hexa- According to the method of Example 18, the following spon-:EOAc was obtained with the target compound. bows: 2-naphth-1-ylethylamine.

According to the method of Example 15, the following compounds were obtained: Example 19: 1H-indole-4-carbaldehyde. B5-methanesulfonyltryptamine

Example 16 Mix 2-(3-chloropropyl)-(1,3)-dioxolane 1-phenyl-1H-indole-b-carbaldehyde (6.69 g, 44.5 mmol), hydrochloride (4-

Mix 1H-indole-b-methanesulfonylphenyl)hydrazine (9.92g, 44.5mmol), carbaldehyde (0.9g, 6.2mmol), the complex compound and MagHPO»X (1.58g, 11.1mmol) in ZObOml in a sealed test tube a mixture of copper (I) metrifluoromethane sulfate (0.2 g, 0.0 mmol), ethanol/water (1:1). Heat with reverse cooling

lynch After 4.5 hours, cool to the temperature of obtaining the target compound: m.p. 84-8970. M5 of the environment, after which evaporate from (ASRI): t/e 212.0 (Ma1). Analysis for Sti4NioRM: obtaining a residue. Dissolve the residue in 1M numerically: C, 79.60; H, 4.77; M, 6.63; established: C, Mahon solution and extract with dichloromethane. 79.33; N, 4.92; M, 6.64.

Combine the organic layers, wash with brine, dry (Mag25054) according to the method of Example 21, filter, then concentrate to obtain a residue. Chromatography - a) 5-phenyl-1H-indole: m.p. 71-747"C. M5 (ASRI): elute the residue on silica gel with an elution temperature of 194.0 (Ma-1). Analysis for Si4NiiiM: calculated: with a mixture of dichloromethane/2M solution of MH3 (methanol) C, 87.01; H, 5.74; M, 7.25; determined: C, 86.67; H, (84/16) with obtaining the target compound in the form of 5.82; M, 7.31. light brown solid: m.p. r) 4-phenylphenethylamine hydrochloride: (Exclude- 134-138"C, M5 (ASRI) (mass spectrometry from chemistry - Chromatograph the residue on silica gel by ionization under atmospheric pressure): t/e using a mixture of dichloromethane/2M solution 239.1 (Mat). Analysis for С11Н14М2025: calculated: МН3 (methanol) (90/10) with obtaining the final

C, 55.44; H, 5.92; M, 11.76; established: C, 55.33; product The hydrogen chloride salt was obtained in ethyl

H, 5.97; M, 11.48. lactate: M5 (ASRI): t/e 198.1 (Ma1). Analysis for

Example 20 Si4NivSIM: calculated: C, 71.94; H, 6.90; M, 5.99;

M-tert-butoxycarbonyl-2-(b-chloro-1H-indole-3- was determined: C, 71.66; H, 6.90; M, 5.94. yl)ethylamine Example 22

Mix di-tert-butyldicarbonate (1.2g, 7-cyano-1H-indole 5.34mmol), b-chlorotryptamine (866.4mg, 4.45mmol) Mix 7-bromoindole (4.72g, 24.0mmol) and cy- and Mmanso»z (598.2 mg) in dioxane (5 Oml). Copper anide (4.30 g, 48.1 mmol) in 1-methyl-2-pyrrolidine was stirred at ambient temperature. (4O0ml). Heat to a temperature of 200"C. Through

Evaporate after 15 hours to obtain a residue, cool to room temperature for 2.5 hours, and partition the residue between water and dichloromethane. a mixture of water-ethyl acetate (200 ml, 1/1) with

Separate the layers and extract the aqueous layer by solid respiration. Filter through lormethane. Combine the organic layers, wash the Celite, extract the filtrate with ethyl acetate, add brine, dry (Mg25O4), filter, filter the organic layers, wash with brine, dry, then evaporate to obtain the target compound Ma»5O», filter and evaporate ip masio from ki in the form of a light yellow oil. receiving the balance. Chromatograph the residue

Example 21A on silica gel with elution with a mixture of hec-

M-methyl-2-(b-chloro-1H-indol-3-yl)ethylamine sane:ethyl acetate (10:1) to obtain (1.87 g) the whole

Mix M-tert-butoxycarbonyl-2-(b-chloro-1H) compound as a yellow solid indol-3-yl)ethylamine (1.3g, 4.41mmol) and dry tet-colored: . (t, 1H), 7.60- to a suspension of GPIAIN cooled in an ice bath, 7.62 (t, 1H), 7.94 (a, 1nH, 2-8.0H), 12.03 (ri, 1H). (1.0g, 26.5mmol) in dry tetrahydrofuran Example 23 (30ml) Reflux 3-formyl-5-cyano-1H-indole

After 2 hours, cool to ambient temperature. Drop by drop, add phos oxychloride of the medium and mix. After 15 hours, add (11.76 g, 76.67 mmol) to dimethylformamide and quickly stop the reaction by adding cold (24 mL) while simultaneously maintaining the temperature of a saturated solution of MabzOx (100 mL/mol), alternating at a level not lower than 107C. Heat to boiling temperature for 1 hour at ambient temperature and mix the medium, then filter under vacuum for 15 minutes at ambient temperature. Wash the precipitate with tetrahydrofuran, remove the medium. Add the solution drop by drop 5- evaporate the filtrate and wash to obtain a residue. cyanoindole (10.00 g, 70.34 mmol) in dimethylform

Chromatograph the residue on silica gel with eluting amide (30 ml) while simultaneously maintaining the temperature with a mixture of dichloromethane/2M solution of MH solution below 35". After 1 hour, pour the reaction mixture (methanol) (84/16) to obtain the target compound: with ice (30 Oml), after which with

M5 (ASRI): t/e 209.0 (Ma1). add 5M Mmaon solution (54ml) with stirring.

Example 218 Slowly add an additional amount of 5M solution of 5-(4-fluorophenyl)-1H-indole maone (19.7 ml), then heat to the temperature of

Mix 5-bromoindole (5.00 g, 25.50 mmol) and heat at 90°C for 1 min, then cool to room temperature.

RYA(RAZR)4 (1.47g, 1.28mmol) in toluene (510ml). rature of the environment with the receipt

After 30 minutes, add a solution of 4-fluorobenzeneboron precipitate. Filter the precipitate, wash with water and extract the acid (5.35 g, 38.2 mmol) in ethanol (153 ml), dry to obtain the target compound: m.p. 248- then add a saturated solution of Mansoz 25070. M5 (ASRI): t/e 171.0 (Ma1). Analysis for (255 ml). Heat under reflux. SchioNeM2O: calculated: C, 70.58; N, 3.55; M, 16.46;

After 4 hours, cool to ambient temperature - set: C, 70.41; H, 3.53; M, 16.33. of the medium, pour into a saturated solution According to the method of Example 23, the following mixture (250 ml) was obtained and the organic layer was separated. Extracts: extract the organic layer with ethyl acetate. Combine a) C-formyl-5-(4-fluorophenyl)-1H-indole; t.pl. organic extracts, washed with brine, dried, 215-2177"6. M5 (ASRI): m/e 2391 (M--1). Analysis for then evaporated to give a residue. Si5NiOE MO: calculated: C, 75.30; H, 4.21; M, 5.85;

Chromatograph the residue on silica gel with eluent: C, 74.94; H, 4.17; M, 5.84; washing with a mixture of ethyl acetate/hexane (10/90) with

B) C-formyl-5-phenyl-1H-indole; t.pl. 225070. spectrometry with electrospraying, t/e:

M5 (ASRI): t/e 222.1 (Ma1). Analysis for SiBNia MO: 2121 (M-1). calculated: C, 81.43; N, 5.01; M, 6.33; established: i) 3-(2-nitrovinyl)-6-bromo-1H-indole; t.pl. 2107C,

C, 81.04; H, 5.05; M, 6.36; with schedule Analysis for SuNuvVg"Og: calculated: c) 3-formyl-6-methyl-1H-indole; mp. 178-180. C, 44.97; H, 2.64; M, 10.49; found: C, 44.62;

M5 (ASRI): t/e 159.9 (Ma-1). Analysis for StioNeMO: H, 2.70; M, 10.49. calculated: C, 75.45; H, 5.70; M, 8.80; established: I) 3-(2-nitrovinyl)-7-fluoro-1H-indole; t.pl. 176-

C, 75.60; H, 5.78; M, 8.97; 180"C0. M5 (ASRI): m/e 207.1 (Ma1). Analysis for a) 3-formyl-b-cyano-1H-indole; mp. 24670. M5 SiOH7eM2O": calculated: C, 58 ,26; H, 3.42; M, 13.59; (ASRI): t/e 171.0 (Mat). Analysis for SiONeM2gO: found: C, 58.01; H, 3.31; M , 13.26. numerically: C, 70.58; H, 3.55; M, 16.46; established: Example 26

C, 70.51; H, 3.59; M, 16.40; iii 3-(2-nitroethyl)-5-cyano-1H-indole e) 3-formyl-b-trifluoromethoxy-1H-indole; t.pl. Add sodium borohydride (25.65g, 67dmol) 189-19270. M5 (ASRI): t/e 230.0 (Ma1). Analysis for a solution of 3-(2-) pre-cooled in an ice bath

SioNeEzMO»: calculated: C, 52.41; H, 2.64; M, 6, 11; nitrovinyl)-5-cyano-1H-indole (12.68 g, 59.5 mmol) was found to be: C, 52.31; H, 2.61; M, 6.09. a mixture (1:11) of MeOH/dimethylformamide (bOOml).

In 3-formyl-7-cyano-1H-indole; IN NMR (Z0OMHC, After 1.5 hours add roseol (b0Oml), after which

OM50-yv) 5 7.41 (B 1H, 9U-7.6Htsu), 7.80-7.82 (t, 1H), bring the pH to approximately 7 with the help of 5M solution- 8.42-8.50 ( t, 2H), 10.02 (5 1H), 13.06 (Big, 1H). rank of NSI. Evaporate under reduced pressure to obtain 9) C-formyl-6-bromo-1H-indole; t.pl. 197-20026. addition of methanol, after which extract dichlo-

Analysis for SeNeHg MO: calculated: C, 48.25; H, 2.70; rmethane Combine organic extracts, rinse

M, 6.25; established: C, 47.87; H, 2.68; M, 6.17. brine, dry (Mg5O), then evaporate n) 3-formyl-7-fluoro-1H-indole; t.pl. 211-21476. with the receipt of the balance. Chromatograph the residue

M5 (ASRI): t/e 163.9 (Ma1). Analysis for SeNeEMO: shock on silica gel eluting with dichloromethane with calculated: C, 66.26; H, 3.71; M, 8.59; established: obtaining, after evaporation, the target compound

C, 66.12; H, 3.67; M, 8.56. in the form of colorless prisms: t.pl. 132-1367S. M5

Example 25 (ASRI): t/e 215.0 (Ma1). Analysis for Si1NeMzO»:

C-(2-nitrovinyl)-5-cyano-1H-indole calculated: C, 61.39; H, 4.22; M, 19.52; installed

Mix 3-formyl-5-cyano-1H-indole (10.6 boOg, but: C, 61.09; H, 4.10; M, 19.16. 63.32 mmol) and ammonium acetate solution (10.60 g) According to the method of Example 26, the following sponitromethanes (6 bOml) were obtained. Heat to a temperature of 907C. onions: a) 3-(2-nitroethyl)-7-cyano-1H-indole; 1N. NMR

After 2 hours, cool to ambient temperature - (ZO0MHz, OM5O-ae) 3.39 (i, 2Н, 9У-6.9Гцу), 4.87 (Йи, it medium with the formation of a precipitate. Filter - 2Н, 9де7.0ГШ), 7.17 (B 1H, 9U-7.4Hz), 7.38 (t, 1), dig the sediment, wash with a mixture (1:11) MeonN/water 7.63 (9, 1H, 0-7.4Hz) . Mass spectrometry from electrosprayed onions: t.pl. 247-2517S. M5 (ASRI): t/e 214.0 (Mat). yum, t/e: 214.1 (M-1).

By the method of Example 25, the following compounds were obtained. Example 27: 5-cyanotryptamine a) 3-(2-nitrovinyl)-5-(4-fluorophenyl)-1H-indole; Add zinc dust (16.22g, 248 1mmol) t.p.l. 217-220"6. M5 (ASRI): m/e 282.2 (Ma1). Anatirma in portions up to 2M solution of NCI (300, Oml). Crystallization for С15Н10ЕМ2О»2: calculated: С, 68.08; Н , 3.93; add 3-(2-nitroethyl)-5-cyano-1 H-

M, 9.92; established: C, 67.73; N, 3.92; M, 9.73; indole (2.25 g, 10.5 mmol) as a solution in meta-o); C3-(2-nitrovinyl)-5-phenyl-1H-indole; M5 zeros (300, Oml). Heat to boiling. After 2.5 hours (ASRI): t/e 2651 (M--1); cool to ambient temperature, sulfur c) 3-(2-nitrovinyl)-b-methyl-1H-indole; М5 of the mixture, bring the pH to 11 with the use of 5M (АСРИ): t/e 203.1 (М--1); Mahon's solution, filter through a layer of celite, a) 3-(2-nitrovinyl)-6-cyano-1H-indole; t.pl. wash with water, then extract the filtrate at "250" C. M5 (ASRI): t/e 212.0 (M-1). Analysis for dichloromethane. Combine organic extracts,

Si1nH7MzO»: calculated: C, 61.97; H, 3.31; M, 19.71; washed with brine, dried (Magn50O4), after which the following was determined: C, 62.09; H, 3.34; M, 20.06; and evaporate to give the target compound: m.p. is). 3-(2-nitrovinyl)-b-trifluoromethoxy-1H-indole; 102-105"7C, M5 (ASRI): t/e 186.1 (M1). Analysis for mp. 139-1437C. M5 (ASRI): t/e 273.0 (M--1). Sy NiyMa: calculated: C, 71.33, H, 5.99, M, 22.69;

In 3-(2-nitrovinyl)-6-phenoxy-1H-indole: "H NMR determined: C, 71.03; H, 5.91; M, 22.64. (0M50O av) 12.1 (5 , 1H), 8.38-8.34 (y, 1H), 8.20-8.19 According to the method of Example 27, the following compounds were obtained: . , 7.02-7.00 (t, 2H), 6.95-6.92 (t, 1H). (ZO00MHz, OM50O-av) 2.76-2.82 (t, 4H), 7.15 (I, 1H, 9) 3-(2-nitrovinyl)-5-(pyridin-3-yloxy)-1H - ue7.6Hz), 7.31 (5, 1H), 7.58 (a, 1H, uU-7.4Hz), 7.91- indole: IZM5 (mass spectrometry with scattering 7.94 (t, 1H ), 11.80 (rg, 1H); ion mass spectrometry) 282 (Ma); "H NMR (OM50-ав) 9.5 (р5, 1Н), electrospraying, t/e: 186.1 (Mya1), 1841 8.36-8.32 (t, 2Н), 8.26-8, 24 (t, 2H), 7.98-7.95 (t, (t-1). 1H), 7.79-7.78 (t, 1H), 7.55-7.53 (t, 1H ), 7.34-7.31 According to the method of Example 27, the following compounds were obtained (t, 1), 7.27-7.24 (t, 1H), 7.02-7.00 (t, 1H). : a) 6-bromotryptamine, m.p. 114-1167 C. Analysis n) 3-(2-nitrovinyl)-7-cyano-1H-indole 1H NMR for CioNiiB/IM2: calculated: C, 50.23; H . 4.49; M, 11.47. uU-7.2Gu), 8.09-8.14 (t, 1H), 8.36-8.46 (t, ЗН); mass- Example 28

M-tert-butoxycarbonyl-2-(5-cyano-1H-indole-3-) Mix HyAlNae (2.66g, 70.17mmol) and anhydrous ethylamine tetrahydrofuran (70.0ml) and cool the suspension

Mix di-tert-butyl dicarbonate and 5-zium solution in an ice bath. Add cyanotryptamine (1.33g, 7.15mmol) and a 2M solution of 5-(4-fluorophenyl)-3-(2-nitrovinyl)-1H-indole drop by drop.

Mmaon (4.2 ml) in tetrahydrofuran (bOml). Through (3.30g, 11.69mmol) in dry tetrahydrofuran

Agree at ambient temperature (30,Oml). Heat under reflux. evaporate to obtain a residue. Dissolve the residue in water and extract with dichloromethane. Mix the medium and mix. After 15 hours, combine the organic extracts, wash with brine, quickly stop the reaction by adding cold dry (Mag25O4) and evaporate to obtain a saturated solution of Mag25O4 (100 ml/mol), and the excess. Chromatograph the residue on silica gel with stirring at ambient temperature, eluting with a mixture of dichloromethane/2K solution above. After Tghd, filter. Wash the sediment

МНЗ3 (methanol) (97/3) with obtaining the target spolu- with tetrahydrofuran, and evaporate the filtrate from the peel: m.p. 129-1327"0. M5 (ASRI): t/e 286.2 (M-1). harvesting the residue. Chromatograph the residue on

Analysis for Si6NioMzO2: calculated: C, 67.35; H, silica gels eluting with a mixture of dichloromethane-6.71; M, 14.73; established: C, 67.16; H, 6.68; M, well/2M solution of МН3 (methanol) (80/20)) from the obtained 14.46. yum of the target compound. Get hydrogen chloride

According to the method of Example 28, the following compounds were obtained in diethyl ether: m.p. 225070. M5 (ASRI): bows: a) // M-tert-butoxycarbonyl-2-(6-cyano-1 H- t/e 255.0 (M--1). Analysis for Sib6NieSIEM»2: calculated indole- C3-yl)ethylamine. but: C, 66.09; H, 5.55; M, 9.63; installed: C,

Example 29 65.78; H, 5.48; M, 9.58.

M-tert-butoxycarbonyl-2-(5-amido-1H-indole-3- According to the method of Example 32, the following polyethylamine bows were obtained:

Mix water (64.0 ml) and Mmaon (8.53 g) and a) 5-phenyltryptamine; t.pl. 244-2467"C. M5 is heated to a temperature of approximately 5"C on ice (ASRI): t/e 237.1 (Ma1). Analysis for SivNi?SiIMe: baths. Add a solution of M-tert-butoxycarbonyl-2-(5-calculated: C, 70.45; H, 6.28; M, 10.27; established cyano-1H-indol-3-yl)ethylamine (1, 85g, 6.50mmol) in no: C, 70.75; H, 6.33; M, 10.27, (separated as hydroethanol (128.0 ml), after which add to the cooled chloride); of the solution. Drop by drop add 3095 solution B) b-methyltryptamine; t.pl. 139-141760. M5 grade of peroxide (6.4 ml) with simultaneous maintenance (ASRI): t/e 175.0 (Ma1). Analysis for Si1Ni4Me2: holding the temperature at a level below 5"С. Calculated through ЗОхв: С, 75.82; Н, 8.10; М, 16.08; established: heat to ambient temperature - С, 76.05 ; H, 8.26; M, 16.12. sh. After 22 hours, decompose the excess peroxide c) b--trifluoromethoxystriptamine; M5 (ASRI): t/e by adding 2095 sodium bisulfite solution 245.0 (Mat). Analysis for C11NiEzM2gO: calcd: (45.00ml) with stirring After 30 min, evaporate C, 54.10; H, 4.54; M, 11.47; found: C, 53.92; under reduced pressure to remove ethanol and H, 4.50; M, 11.06. extract the resulting aqueous solution with ethylace-9) 7-fluorotryptamine; M5 (ASRI): m/e 179.0 tatom. Combine the organic extracts, wash (Mat). Analysis for SionNiiEMeg: calculated: C, 67.40; brine, dry (Mg5Oy), then evaporate H, 6.22; M, 15.72; found: C, 67.06; H, 6.11; M, with a residue. Chromatograph the residue on silica gel eluting with a mixture of dichloromethane/2M solution of MNH (methanol) (96/4)) from the obtained sicarbonyl-1H-indole, after evaporation, of the target compound: Mix b-carboxy-1H-indole and ethanol, m.p. 65-687"C. M5 (ASRI): t/e 304.2 (Mt). Analyze (110ml) and cool to a temperature of 5"7C. Drop for SivNgiMzOz: calculated: C, 63.35; N, 6.98; M, drop by drop add concentrated H25O»4 (96965, 13.85; determined: C, 63.26; H, 6.99; M, 13.71. 11.0vml) while simultaneously maintaining the temperature

According to the method of Example 28, the following compounds were obtained at levels below 10"C. Heat with reflux: a separator. After 4 hours, cool and pour into a) M-tert-butoxycarbonyl-2-(b-amido-1H-indole) mixture of ice/water, bring the pH to about 9 and

Z-yl)ethylamine: M5 (ASRI): m/e 302.3 (M-1). extract with ethyl acetate. Combine organic

Example 30 extracts, washed with brine, dried (Mag5Ox),

B5-amidotryptamine then concentrate to obtain a residue.

Dissolve M-tert-butoxycarbonyl-2-(5-amido-Chromatograph the residue on silica gel eluting with 1H-indol-3-yl)ethylamine (1.83 g, 6.04 mmol) in dioxaning with chloroform to obtain, after precipitation no (25, Oml). Drop by drop, add a 4M solution of the target compound: m.p. 72-7570. M5

NOI in dioxane (7.5 ml). After 18 hours, filter (ASRI): t/e 189.9 (M--1). solid and washed with diethyl ether with Example 34 obtaining, after drying, the target compound 3-(2-nitrovinyl)-b-ethoxycarbonyl-1H-indole in the form of hydrochloride: m.p. 192-19570. M5 Mix 1-dimethylamino-2-nitroethylene (1.93 g, (ASRI): t/e 202.0 (M--1). 16.58 mmol) and trifluoroacetic acid (10.00 ml) and

According to the method of Example 30, these were obtained by mixing until dissolution. Add (6- bows: a) b-amidotryptamine: t.pl. 169-17370. M5 ethoxycarbonyl-1H-indole (3.14 g, 16.58 mmol), and (ASRI): m/e 204.1 (M--1). stir at room temperature

Example 32 environment. After 1 hour, pour the 5-(4-fluorophenyl)tryptamine reaction mixture into an ice/water mixture, extract with ethyl acetate, then evaporate to obtain a residue. Re-

stir the residue in warm ethanol, cool to room temperature, then (5.44g, 30.87mmol) and Hg5Ox (9695, 30.9ml). Cool, filter and dry to obtain the whole product to a temperature of approximately 0"C. Drop by drop of your compound in the form of a dark yellow powder, add smoking NMO"z (2.06g, liquid: m.p. 241760. M5 ( ASRI): t/e 261.1 (MA). 32.72 mmol) with simultaneous maintenance of the

Analysis for CizNi2M2Og: calculated: C, 60.00; H, temperatures below 107C. After completing 4.65; M, 10.76; established: C, 59.99; N, 4.63; M, adding heat to a temperature of around 10.59. environment After 2.5 hours, pour the resulting mixture

Example 35 into an ice/water mixture, extract with dichloromethane. 3-(2-nitroethyl)-6-ethoxycarbonyl-1H-indole Combine the organic extracts, wash with brine,

Mix 3-(2-nitrovinyl)-b-ethoxycarbonyl-1H-, dry (Ma»5O»4), then concentrate from indole (4.0g, 15.37mmol) and MovNaia (726.7mg, obtaining a residue. Chromatograph residue 19.21 mmol) in 10000 ml of tetrahydrofuran mixture on silica gel eluted with a hexane/methanol mixture (9:1) and stirred at room temperature. After 1.5 hours of concentration, 1-methyl-2-nitro-4-tritrate to obtain a residue. Divide trifluoromethoxybenzene: M5 (АСРИ): t/e 2201 excess between brine and ethyl acetate, wash (M-1). brine, combine the organic layers, dry. Mix 1-methyl-2-nitro-4- (Mag2504), then evaporate to obtain the target trifluoromethoxybenzene (3.73 g, 16.8 mmol), a pyro compound in the form of a yellow powder: t .pl. lidin (1.32g, 18.55mmol), M,M- 124-1277"6. M5 (ASRI): m/e 263.0 (Ma1). Analysis for dimethylformamide dimethyl acetal (6.03g,

CizNiaM2Ol: calculated: C, 59.54; H, 5.38; M, 10.68; 50.58 mmol) and dry dimethylformamide (35 ml). established: C, 59.40; H, 5.36; M, 10.53. Heat to about 105". Through

According to the method of Example 35, the following compounds were obtained: remove dimethylformamide under reduced pressure to obtain an oily residue. Zmi- a) 3-(2-nitroethyl)-6-cyano-1H-indole: vol. 2141, mix the residue and ethyl acetate, wash with brine, (M-1). Analysis for Si1NeMzO»: calculated: C, 61.39; dry (Ma»5O»4), then concentrate with

H, 4.22; M, 19.52; established: C, 61.05; N, 4.09; M, by obtaining M,M-dimethyl-2-(2-nitro-4-19,19.trifluoromethoxyphenyl)vinylamine. p) 3-(2-nitroethyl)-6-bromo-1H-indole; Mix M,M-dimethyl-2-(2-nitro-4-c) 3-(2-nitroethyl)-6-methanesulfonyl-1H-indole; trifluoromethoxyphenyl)vinylamine m.p. 162-16470. M5 (ASRI): t/e 2691 (Mt). (4.64 g, 16.6 mmol) and Raney nickel? (900mg) in a) 3-(2-nitroethyl)-6-benzenesulfonyl-1H-Indole ethanol (10Oml). Hydrogenate under pressure (exception: 75 ml of TNRE was used). bp/in:? (410kPa) and at ambient temperature

Example 36 of excess environment. After 18 hours, pass propyltribu-b-ethoxycarbonyltryptamine through a layer of celite, concentrate the filtrate with

Mix PO (440 mg) and a solution of 3-(2- by obtaining a residue and chromatograph on silin-nitroethyl)-6b-ethoxycarbonyl-1 H-indole (3.55 g, kageli Ki eluting with a mixture of hexa- 13.54 mmol) in ethyl acetate (100 ml) . Hydrogenated/Ethyl Acetate (30/70) obtained after precipitation under a pressure of bpm? (410kPa) and when the target compound is darkened in the form of a powder, the temperature of the environment is not. After 4 hours, completely white: temp. 59"C. M5 (ASRI): t/e filter through a layer of celite, and concentrate to 200.0 (M-1). filtrate with a residue. Chromatograph - Example 39 cotton residue on silica gel eluting with a mixture of 2-phenylphenethylamine and dichloromethane /2M solution of MHz (methanol) Mix 2-phenylphenylacetonitrile (4.69 g, (85/15) with 24.26 mmol of the target obtained after evaporation) and diethyl ether (1 Oml) and add drop by drop the compound in the form of a not quite white powder to a cooled (-107C) solution of ru: m.p. 127-1317"6. M5 (ASRI): t/e 233.0 (M-1). PANA (2.76g, 72.8immol) in diethyl ether

Analysis for SizNieM2O»: calculated: C, 67.22; H, (100 ml). Heat to an ambient temperature of 6.94; M, 12.06; established: C, 66.87; H, 6.96; M, environment. After 2 hours, quickly stop the reaction - 11.86. addition of a cold saturated solution of

According to the method of Example 36, the following sodium sulfate (100 ml/mol) was obtained. Filter precipitate: you, dry the obtained filtrate (Ma»5O54), a) b-cyanotryptamine: m.pl. 144-14776b. Filter M5 and concentrate to obtain (ASRI): t/e 186.0 (Ma1). Analysis for SNiiMz: the balance. Chromatograph the residue on silica gel: C, 71.33; H, 5.99; M, 22.69; established: with elution with a mixture of dichloromethane/2M solution

C, 71.10; H, 5.89; M, 22.38. MHz (methanol) (95/5) with obtaining the target compound

B) 6-methanesulfonyltryptamine: m.p. 149 in the form of yellow oil. Receive 15376. M5 (ASRI): t/e 239.1 (Ma1). Analysis for hydrogen chloride salt in diethyl ether: m.p.

SiNiaM2O»5: calculated: C, 55.44; H, 5.92; M, 197-19970. M5 (ASRI): t/e 198.1 (M'-1). Analysis for 11.76; established: C, 55.12; H, 5.82; M, 11.97. SiaNiveSIM: calculated: C, 71.94; H, 6.90; M, 5.99; c) 6-benzenesulfonyltryptamine: m.p. 169- established: C, 72.15; H, 6.84; M, 6.09. 17276. M5 (ASRI): t/e 301.0 (Mt). Example 40

Example 38 7-chloro-1H-indole b-trifluoromethoxy-1H-indole According to the method of U. May. Spent (1990, 33, 2777), add 2-chloroaniline solution drop by drop

(5.8g, 45.45mmol) in anhydrous toluene (8Oml) to the acid, which can be used without adding a cold 1M solution of BSiZ (50Oml) in dichloromethane. which cleaning

After the addition is complete, stir the reaction according to the procedure described in 9. Oh. this mixture at a temperature of 0"C for 10 min. Spet. 1997, 62, 6507, mix ethyl ether M-(2-

After 10 minutes at a temperature of 0"C, add chloroacetonitrile (34.33g, 110mmol), triethylamine (300ml), dichloro- (13.72g, 11.53ml, 181 .8 mmol, 4 equiv.) and trichloride of bis(triphenylphosphine)palladium (II) (5.4 g, 7.7 mmol) and aluminum (6.67 g, 500 mmol, 1.Eq.), followed by copper iodide (I) ( 1.47g, 7.7mmol). Remove the solution, heat under reflux (7657). Due to the dark color, fill M2 twice, then cool to room temperature over time. With vigorous stirring, quickly add (cool the reaction mixture on ice for three to 16 hours baths, methylsilyl)acetylene (16.21g, 165mmol, 23.32ml). add a 2M solution of HCIII (61.4ml), then heat. Heat to a temperature of 80"C. When, according to the data, the reaction mixture is brought to a boil. After 45 minutes, cool the basket chromatography will be confirmed in an ice bath, neutralize the 2M acid in the absence of starting material, add water and Maon method with maintaining the reaction temperature, filter through a layer of celite and evaporate the mixture at a level below 157C until the pH level filtrate and mass to obtain a residue. The decomposition will reach approximately 5. Transfer the reaction mixture to the residue with water, extract the ESO, mix in a separatory funnel and remove the organic layer. organic layers and evaporate to obtain an oil

Extract the aqueous layer with dichloromethane of a dark brown color. Absorb oil (2x200ml). Combine the organic layers, dry with silica gel, and add to a short silica gel co-ode Ma5O", filter and remove the solvent of the flask, balanced with 10095 hexane. Wash the oil to give 1-(2-amino-33-chlorophenyl)-2-10095 with hexane (2L) and elute the product 195 with chloroethane, which can be used without nom EOAc in hexane. Combine fractions containing additional cleaning. product and remove the solvent ip massio from the obtained

Dissolve 1-(2-amino-3-chlorophenyl)-2-one 5-trifluoromethyl-2-xporethanone (7.0g, 34.30mmol) in 1095% aqueous trimethylsilanylethynylphenylamine in the form of oil and 1,4-dioxane (75ml) . Carefully add the red/Orunate colored Mavnay; M5 (15): t/2 330 (2.6 g, 68.6 mmol, 2 equiv.) as a solid (Mann). we Heat to boiling. After 4 hours, cool to Carefully add Man (10.83g, 6095 solution at room temperature, dilute with water (300ml) oil, 270.8mmol, eq.) to EYN (200ml). After and extract with dichloromethane (2x200ml). Combine, cool, add a solution of 5-trifluoromethyl-2-, dry the organic layers over Md5O", pro- trimethylsilanylethynylphenylamine (22.3g, filter and remove the solvent from the mass of 67.7mmol) in EYN (400ml) with energetic alternately in the flask of light brown oil. shuffling After 2 hours, heat with reverse

Clean the oil with high-efficiency oil degreaser. After 4 hours, evaporate the mass for liquid chromatography (silica gel mobile phase: remove EN, dilute the obtained precipitate with a 100965 hexane:5095 solution of EOAS in hexane and extract the EOAS. Combine the organic layers, 5Och) to obtain the target compound in the form of a wash brine, dry over MozO»4, brownish-colored oil profile: "H NMR (Z0OMHCts, av-lter and evaporate to obtain a dark oil

OM5O-yv): 5.16 (t, 1H), 5.39 (y, 1H), 5.70 (p5, 1H), color. Absorb the oil with silica gel and add 6.59 (1), 7.09 (t, 2H); M5 (EBu (mass) to a short silica gel column. Wash 2095 spectrometry with elastic scattering: t/lg 154, with a solution of EIOAc in hexane. Combine the fractions containing the product and remove the solvent from the obtained

According to the method of Example 40, the following dark brown oil was obtained. Subject the onions: the oil to additional purification with high-a) 5-bromo-7-ethyl-1H-indole: IN NMR (300 MHC, effective liquid chromatography (a column with dioc- a6-OM5O-yv): 1.25 (i, ЗН ), 2.85 (t, 2H), 6.41 (t, 1H), silicon dioxide) using a gradient from 190 7.02 (M, 1H), 7.36 (t, 1H), 7.55 ( t, 1H), 11.28 (65, of a solution of ESO in hexane to 1595 of a solution of EBO in 1H); M5(E5 yuyu): t/2 224, 226 (MAN); analysis for sleigh. Combine the fractions containing the product and

SzzoNioVgM: calculated; C, 53.60; H, 4.50; M, 6.25; add solvent to obtain the target compound is established; C, 53.50; H, 4.34; M, 6.22. in the form of an orange solid:

Example 42 IN NMR (300 MHz, d6-OM5O-yv): 6.58 (t, 1H), 7.28 v-trifluoromethyl-1H-indole (t, 1H), 7.61 (6 1H), 7.74 (t, 2H), 11.51 (rv, 1H);

Mix //2-bromo-5-trifluoromethylphenylamine M(EI!k): t/2 185 (Mk). (27.06 g, 112.74 mmol) and 200 ml of pyridine. Cool according to the method of Example 42 and obtain the following precipitates in an ice bath and add ethyl chloroform: a) 5-isopropyl-1H-indole: M5(EBzh): t/2 160 at (18.35g, 169.11ml, 1 ,5 eq.). After completion of (MH) (Е5)-: t/x 158 (М-НУ. addition, stand the reaction mixture with slow Example 44 heating to room temperature. After 6-fluoro-5-methoxy-1H-indole, evaporate ip massio with obtaining Dissolve fuming nitric acid (24 ml) in

Dissolve the residue in a mixture of ESO/water and transfer to concentrated H25O4 in a round-bottomed flask. For the dividing watering can. Separate the layers, extract with a pipette drop by drop the aqueous layer of ESO (2x300ml), combine the organic layers with stirring, add 3,4-layers, dry over Mda5O»4, filter and difluorobromobenzene (20g, 104mmol). After verifying, evaporating the mixture to obtain ethyl ether, adding and stirring the reaction mixture at

M-(2-bromo-5-trifluoromethylphenyl)carbamine at room temperature for 2 hours, pour out the

cation mixture into a mixture of water and ice and extracted according to the method of Example 42 and using 2 EBOs (2 x 250 ml). Collect and combine organic bromo-4-(trifluoromethoxy)aniline to obtain ether layers, dry over M9z5BoO»m, filter, and mol ether M-(2-bromo-4- remove the solvent to obtain 1-bromo-4,5 - trifluoromethoxyphenyl)carbamic acid: "NN of difluoro-2-nitrobenzene in the form of oil light-NMR (ZOOMHts, СОСИzv): 1.34 (I, ЗН), 4.25 (t, 2Н), yellow color. 7.19 ( t, 1H), 7.41 (t, 1H), 8.20 (a, 1n); M5(E5-):

Add 1-bromo-4,5-difluoro-2-nitrobenzene (24 g, t/2 326, 328 (M-H); analysis for SiONeVI/EzMOz: vol. 100 mmol) to a solution of sodium methoxide (1.2 equiv.) in numerous; C, 36.6096; H, 2.7650; M, 4.2692; install

Meon. After the addition is complete, stir the leno; C, 36.50; H, 2.67; M, 3.97; from which the reaction mixture is obtained at room temperature in pro-ethyl ether M-(4-trifluoromethoxy-2- for 2.5 hours. Remove the solvent and mass. Dissolve the residue of trimethylsilanylethynylphenyl)carbamic acid with water and extract EBO; from which the target compound is obtained in the form (g2x250ml). Combine the organic layers, dry the yellow oils: M(E5-): t/2 200 (M-H). over Md5O", filter and remove the solvent Example 47 ip maszo to obtain 1-bromo-4-fluoro-5-methoxy-2-4-phenyl-1H-indole nitrobenzene in the form of a yellow solid according to the method of Carrer (Sagteg) and Sheppard : "H NMR (ZO0MHCz, SOCIz): 3.99 (5, ЗН), (zperraga) in zupia. 1994, 93-94, target compound 7.26 (t, 7), 7.83 (y, yin) ; M5(BEOyu (mass- obtained from 4-bromoindole: "H NMR (300MHZ, av-spectrometry with field desorption): t/2 249, PM5O-yv): 6.56 (t, 1H), 7.08 ( t, 1H), 7.17 (t, 1H), 251 (Mk); analysis for C7H5VgEMOz: calculated: C, 7,AZ (t, 5H), 7.67 (t, 2H), 11.27 (p5 , 1H); M(EZ"): 33.63; H, 2.02; M, 5.60; determined: C, 33.79; H, t/2 194 (MAN); (E5-): t /2 192 (M-H). 1.98; M, 5.62. Example 48

Mix 1-bromo-4-fluoro-5-methoxy-2-(2-nitro-5-trifluoromethylphenyl)-acetonitrile nitrobenzene (20.5g, 82mmol) and Ri on wood According to method Step 5 App. Spent 1988, 203-208, coal (sulfidated) in tetrahydrofuran (b0Oml) the target compound is obtained using 4- and hydrogenated under a pressure of boOlb/in? of nitrobenzotrifluoride (15 g, 78.49 mmol): MB(E5-): (414 kPa) for 4 hours. Filter the reaction mixture through a layer of celite to remove the catalyst and remove the solvent to obtain 2-5-trifluoromethyl-1H-indole bromo-5-fluoro-4-methoxyaniline as a solid According to the method of Gieridz App. Spec. 1988, 203-208, a brown-colored substance, which can be obtained using (2-nitro-5-

According to the method of Example 42, with the use of 2-trifluoromethylphenyl)acetonitrile: In NMR of bromo-5-fluoro-4-methoxyaniline, ethyl (33OO0MHz, a6-0M50-a66) is obtained: 6.60 (t, 1H), 7.36 (t, 1H), y ether M-(2-bromo-5-fluoro-4- 7.53 (t, 1H), 7.57 (t, 1H), 7.94 (t, 1H), 11, 51 (rv, methoxyphenyl)carbamic acid in the form of 1H); MB(E5-): t/2 184 (M-N). brownish solid substance; "H NMR Example 50 (300 MHz, SOCI3): 1.33 (I, 3H), 3.85 (5, 3H), 4.23 (4, 3-formyl-4-methoxy-1H-indole 2H), 7 .09 (a, 1), 7.97 (ra, 18); MB(BO kyu): t/: 291, With vigorous stirring to dimethylpho- 293 (M; ethyl ether M-(5-fluoro-4-methoxy -2-ramide (which was cooled in an ice bath) of trimethylsilanylethynylphenyl)carbamic acid - add phosphorus oxychloride (1.1 eq.). After solidification in the form of a yellow solid: after addition, stir in an ice bath

M5(E5Yu: t/2 310 (MH); (EB-): t/2 308 (M-H); and for 7-10 minutes, after which, with vigorous stirring, add the target compound in the form of a solid substance: "H 4-methoxy-1H-indole solution (5g)

NMR (300 MHz, SOCI3): 3.93 (5, 3H), 6.48 (t, 1H), in anhydrous dimethylformamide. Continue 7.15 (t, ZN), 8.11 (p5, 1); М5(ЕБюЮ): t/; 166 stirring at a temperature of 0"C. After Th (MAN); (E5-): t/x 164 (M-NU; analysis for SeNzEMO: heat to room temperature. After 16h from calculated: С, 65.45; Н, 4.88; M, 8.48; established: carefully add with vigorous stirring

C, 65.17; H, 4.97; M, 8.70. d4eq. 2M Mahon solution. Heat to temperature

Example 45 to approximately 80"C, then cool. Pour the 5,6-difluoro-1H-indole reaction mixture into cold water with vigorous stirring.

According to the method of Example 42, 2-bromo is obtained by stirring to obtain a solid substance. 4,5-difluoroaniline; from which is obtained ethyl Filter the solid substance and dry it in water M-(2-bromo-4,5-difluorophenyl)carbamine in a fume oven at room temperature from the obtained acid; from which the ethyl ether M-(4,5-amine of the target compound is obtained. Acidify the filtrate and ext. difluoro-2-trimethylsilanylethynyl- react with EOAc. Combine the organic layers and phenyl)carbamic acid; from which it is obtained to wash 5095 with brine. Collect the organic layer, the target compound as an orange solid, dry (M9505), filter and remove the yellow color; "H NMR (300 MHz, av-OM5O-av): the solvent with the preparation of the target compound in the form of 6.43 (t, 1H), 7.38 (t, 2H), 7.50 (t, 1H), 11, 25 (p5, di of a light purple solid substance. 1H); M5(E5-): t/2 152 (M-NU. Analysis for SvH5ggM: The total yield of the target compound is 5.44 g: calculated: C, 62.75 ; H, 3.29; M, 9.15; established: M5 (EB'yuk): t/2 175 (MN), 160 (M-CHz)"; (EB-): t/2

C, 62.41; H, 3.12; M, 8.98. 174 (M-N).

Example 46 Using the method of Example 50, the following solutions were obtained

B-trifluoromethoxy-1H-indole onions:

a) 3-formyl-b-methoxy-1H-indole, "NN NMR a) 3-formyl-4-phenyl-1P-indole, 1H NMR (ZOO0MGCs, ae-YUM50): 3.79 (5, ЗН) ; 6.85 (ai, 1Hn); 6.98 (Z0OMHCts, dv-0OM50O): 7.07 (t, 1H), 7.30 (t, 1H), 7.46 (t, 1H); 7, 92 (0, 1H); 8.15 (5, 1H); 9.86 (5, 1H); 11.92 (t, 6H), 7.53 (t, 1H), 8.20 (p5, 1H ), 9.37 (5, 1H), (rb5, 1H); M5 (E5-): t/2 176 (MAN) ХЕ5-): t/2 174 12.40 (p5, 1H), M5(E5 -yu): t/2 222 (MAN); (E5-): t/2 (M-H); 220 (M-H); p) 3-formyl-7-methoxy-1H-indole; C) 00 / 3-formyl-6-phenyl-1H-indole, HER 00 nNMR c) 3-formyl-4-chloro-1H-indole; (30OMHCc, d-SOOM50): 7.35 (t, 1H), 7.49 (t, 3H), 7.71 a) 3-formyl-b-chloro-1H-indole, "H NMR (300MHC, (t, 3H), 8.15 (t, 1H), 8.33 (a, 1H), 9.96 (c, 1H), d6-OM5O-yv): 7.24 (aa, 1), 7.56 (a, 1), 8.06 (a, 12.20 (B5, 1H ), M5(EI k): t/2 221 (M)X; 1H), 8.33 (5, 1H), 9.93 (v, 1H), 12.21 (rve, 1H); M5 5) 3-formyl-5-isopropyl-!H-indole, "NN NMR (Eb-): t/2 182, 180 (MAN); (E5-): t/2 180, 178 (M- (zZzO0MGЦc , avb-Y0M50): 1.24 (a, 6H), 2.99 (t, 1H), 7.15

Well; (t, 1), 7.41 (t, 1H), 7.94 (t, 1H), 8.22 (t, 1H), e) 3-formyl-7-chloro-1H-indole, "H NMR (Z00MHC, 9.90 (in, 1H), 12.02 (rb5, 1H); M5(E5-): 188 (M.H); do-OM5O): 7.23 (Her, 1H), 7, 35 (4, 1), 8.05 (a, tn), (E5-): t/2 186 (M-H), 8.38 (re, 1H), 9.95 (5, 1H), 12 ,54 (re, 1H); M5 (E5-k): In 3-formyl-4,6-difluoro-5-methoxy-1-methyl-1 H- t/2 182, 180 (MAN); (E5- ): t/2 180, 178 (M-H); indole: "H NMR (300 MHz, SOSIzv): 3.81 (in, ЗН), 4.02

In 3-formyl-4-fluoro-1H-indole, "H NMR (30OMHC, (5, 3H), 6.92 (t, 1H), 7.77 (v, 1H), 10.14 (9, 1H ); dv-0OM50): 7.01 (t, 1H), 7.24 (t, 1H), 7.36 (a, tn), M5(E5-): t/2 226 (MAN); and 8 .30 (c, 1H), 10.03 (y, 1H), 12.48 (p5, 1H); M5 (E5-): i). 3-formyl-4,6-difluoro-1-methyl-1H -indole: "N t/2 164 (MAN); (E5-): t/2 162 (М-Н); NMR (300 MHz, de-OM5O): 3.87 (5, 3H), 7.10 (t, 1H), 9) 3-formyl-5-methoxy-b6-trifluoromethyl-1H- 7.A1 (t, 1H), 8.32 (5, 1H), 9.93 (0, 1); M5(E5-): indole, "H NMR (300 MHz, a6-OM50): 3.91 (z, ZN), 196 (MAN)". 7.77 (a9, 1), 7.95 (re, 1H), 8.42 (5, 1H), 9.96 (5, Example 51 1H), 12.29 (rv5, 1H); M5 (Eb-): t/2 244 (MAN); (E5- 3-(2-nitrovinyl)-4-methoxy-1H-indole y: m/2 242 (M-H); Mix ammonium acetate (dried after ob- n) 3-formyl-b-chloro-5- methoxy-1H-indole, "H treatment with toluene and removal of toluene and fat) in

NMR (300 MHz, d6-0OM50): Z3M88 (5, ЗН), 7.58 (in, as a solid (0.75 eq.), nitromethane 1Н), 7.71 (5, 1Н), 8.26 (in , 1H), 9.91 (5, 1H), 12.08 (2b0eq.) and 4-methoxy-1H-indole-3-carbaldehyde (рb5, 1H); M5 (EBb-): t/2 210, 212 (MAN); (E5-): t/2 (5.4 g; 30.62 mmol). Heat to a temperature of about 208, 210 (М-Н); lyzno 65"С. After, according to the data of thin-layer

NMR (Z300MHz, as-0M50): 3.89 (v, ZN), 7.1Zt (aa, reaction approaching completion, add 1H), 7.47 (ai, tn), 8.23 (5, 1H) , 10.5 (5, 1H), 12.39 silica gel and evaporate ip massio to remove (p5, 1H); M5 (Eb-k): t/2 210, 212 (MAN) (E5-): t/2 nitromethane. Transfer silica gel from reaction 208, 210 (M-H)U; mixture to the upper part of a short silica gel ) 3-formyl-b-trifluoromethyl-1H-indole, "H NMR column and elute with 2595 acetone solution in hec- (ZOOMHCc, av-YOM50): 7.52 (j, 1), 8, 27 (9, 1), 8.51 sled with receipt, after evaporation, target (t, 1H), 9.99 (in, 1H), 12.47 (rev, 1H), M5(E5-k): t /2 of the compound, which can be used in the next 214 (MAN); (E5-): t/2 212 (М-Н); stage without additional purification.

K) 3-formyl-5-methoxy-2-methyl-1H-indole, "H According to the method of Example 51, the following compounds were obtained: , ZH), 6.78 bows: (aa, 1), 7.27 (0, 1H), 7.56 (t, 1H), 10.00 (5, 1H), a) 3-(2-nitrovinyl )-b6-methoxy-1H-indole; 11.85 (65, 1H); M5(E5-): t/2 190 (MAN) (E5-): t/2 B) 3-(2-nitrovinyl)- 7-methoxy-1H-indole, "H NMR 188 (M-H); (ZO0MHz; avb-0М50): 3.95 (5, ЗН), 5.02 (t, 1Н), 6.86

I) 3-formyl-6-fluoro-5-methoxy-1H-indole, "H (a, 1), 7.17 (B 1), 7.50 (a, 1), 8.38 (9, 1H), 12.40

NMR (300 MHz, de-0OM50): 3.87 (5, ЗН), 7.35 (α, 1Н), (05, 1Н); M5 (EbBu: t/2 219 (MN) w; (E5-): t/2 217 7.71 (a, 1H), 8.21 (5, 1H), 9.89 (c, 1H), 12.03 (B5, 1H); (m-n);

MO (EB5th): t/2 194 (MAN); (E5-): t/2 192 (M-H); c) 3-(2-nitrovinyl)-4-chloro-1H-indole, "H NMR t) 3-formyl-5,6-difluoro-1H-indole, "H NMR (30OMHCc, dv-YOM50): 5, 08 (t, 1H), 7.24 (t, 2H), 7.51 (ZOOMHCts, de-YOM50): 7.56 (t, 1H), 7.92 (t, 1H), 8.36 (da , tn), 8.12 (a, tn), 8.92 (a, 1), 12.6 (rev, 1H); (5, 1H), 9.92 (in, 1H), 12.25 (re, 1H); M5(E5-): t/2 M5(E5-): t/2 221, 223 (M-H); 182 (MAN): (E5-): t/2 180 (М-Н); a) 3-(2-nitrovinyl)-b-chloro-1H-indole, "H NMR p". : 5.03 (t, 1), 7.22 (da, tn), (ZOOMHCts, av-0OM50): 7.72 (y, 1), 7.91 (a, 1n), 8.40 7, 58 (a, 1H), 8.03 (t, 2H), 8.38 (j, 1), 12.23 (B5, (5, 1H), 9.93 (c, 1H), 12.29 ( re, 1H); M5(E5-): t/2 1H); M5 (E5-): t/2 223, 221 (M-H); 198 (MAN); (E5-): t/2 196 (М-Н); f) 3-(2-nitrovinyl)-7-chloro-1H-indole, "H NMR o) 3-formyl-5-trifluoromethoxy-1H-indole, "H (zZO0MHCz, ae-0M50): 7.23 (i) 1), 7.36 (a, 1), 7.97

NMR (300 MHz, ae-OM50): 7.24 (t, 1H), 7.61 (t, (a, tn), 8.06 (9, yin), 8.33 (p, 1H), 8, 40 (a, tn), 1H), 7.97 (re, 1H), 8.42 (y, 1H), 9.95 (c, 1H), 12.35 12.58 (rev, 1H); M5 (Eb-): t/2 225, 223 (MAN); (E5- (rb5, 1); M5(E5-): t/2 230 (MAN); (E5-): t/2 228 ): t/2 223, 221 (M-H); (M-H)U; analysis for SioNeEzMO": calculated; C, Y) 3-(2-nitrovinyl)-4-fluoro-1H-indole, 52.4138; H, 26391; M, 6.1122; established; C, 9) 3-(2-nitrovinyl)-5-methoxy-b--riftomethyl-52.70; H, 2.73; M, 6.13; 1H-indole, M5 (EbBzh): t/2 286 (Mk); (E5B-): t/2 285 g) 0/0 3-formyl-4,6-difluoro-5-methoxy-1H-indole, (m-n);

M5 (EB F): 212 (MAN); (E5-): 210 (M-H); M) 3-(2-nitrovinyl)-b-chloro-5-methoxy-1H-indole,

І) 3-(2-nitrovinyl)-4-chloro-5-methoxy-1H-indole, (t, 1), 7.30 (9, 1H), 11.19 (p5, 1H); M5(E5-k): t/2

IN NMR (Z00MHZ, do-OM50): 3.88 (5, ZN), 5.03 (t, 178, 180 (MAN); (E5-): t/2 193 (M-H); 2), 7.13 (9, 1), 7.46 (a, tn), 8.08 (a, 1H), 12.42 I) b-chlorotryptamine, "H NMR (300MHC, dv- (rb5, 1H); M5(E5-): t/2 151, 153 (M-H); OM50): 2.89 ( 2H), 3.42 ( 2H), 6.96 (aa, 1), 7.17 ) C- (2-nitrovinyl)-b-trifluoromethyl-1H-indole, (05, 1H), 7.935 (t, 1H), 7.52 (0, 1H), 10.91 (rv, 1H);

M5(E5 kyu): t/2 257 (MAN); (E5-): t/2 255 (M-H); M5 (E5-): t/2 197, 195 (M-А-Н)", 180, 178 (М-МНг)";

K) 3-(2-nitrovinyl)-5-methoxy-2-methyl-1H-indole, (E5-): m/2 195, 193 (M-H);

IN YAME (zZ000MHC, av-OM50): 2.58 (z, ЗН), 3.84 (c, e) 7-chlorotryptamine, "H NMR (Z00OMHC, dv-

ZN), 6.82 (t, 1H), 7.28 (t, 2H), 7.89 (a, 1H), 8.29 (a, OM50): 2.91 (i, 2H), 3, 43 (2H), 6.98 (i, 1H), 7.13 1H), 12.14 (p5, 1H); MB(E5-): t/2 233 (MAN); (E5-): (a, 1), 7.20 (p5, 1), 7.51 (y, 1), 11.15 (p5, 1H); t/2 231 (M-N); M5 (E5-): t/2 197, 195 (MAN), 180, 178 (М-А-МН2)»U;

I) 3-(2-nitrovinyl)-6-fluoro-5-methoxy-1H-indole; (E5-): t/2 195, 193 (M-H); t) 3-(2-nitrovinyl)-5,6-difluoro-1H-indole; In 4-fluorotryptamine, p) 3-(2-nitrovinyl)-6-chloro-5-fluoro-1H-indole; 9) 5-methoxy-b-trifluoromethyltryptamine, o) 3-(2-nitrovinyl)-5-trifluoromethoxy-1H-indole; M) b-chloro-5-methoxytryptamine, Н/NMR p) 0/0 3-(2-nitrovinyl)-4,6-difluoro-5-methoxy-1H-(300MGCs, d6-0M50): 2, 89 (i, 2H), 3.42 (ii, 2H), 3.84 indole; (5, 3H), 7.12 (p5, 1H), 7.19 (5, 1H), 7.36 (5, 1H), 8.01 a) 3-(2-nitrovinyl)-4-phenyl- 1 H-indole; (65, 1H); M5 (EB-): m/2 225, 227 (MaH)", 208, 210 g) 3-(2-nitrovinyl)-6-phenyl-1H-indole; (M-MH»g); (E5- ): m/2 223, 225 (M-H); 8) 3-(2-nitrovinyl)-5-isopropyl-1H-indole; i) 4-chloro-5-methoxytryptamine, X NMR

10) C3-(2-nitrovinyl)-4,6-difluoro-5-methoxy-1- (30OMHCc, 4d6-0M50): 3.10 (i 2H), 3.43 (i, 2H), 3.81 methyl-1H-indole: 1H NMR (300MGHc, a6-OM50): 3.82 (5, 3H), 6.95 (y, 1), 7.18 (t, 1H), 7.25 (aa, tn), (I, ЗН), 3.92 (5, ЗН), 7.53 (t, 1Н), 7.84 (t, 1Н), 8.30 10.93 (Бб5, 1); MO( E5-): t/2 208, 210 (M-MH»2)" (E5- (t, 2H); M5(E5-): t/2 269 (MAN); and y: t/2 223, 225 (M-H); i) 3-(2-nitrovinyl)-4,6-difluoro-1-methyl-1H-|) b--rifluoromethyltryptamine, indole. K) B-methoxy-2-methyltryptamine, 1H NMR

Example 52 (zZO0MHz, ae-OM50): 2.28 (z, ZN), 2.80 (y, 2H), 3.31 4-methoxytryptamine (ri, 2), 6.59 (aa, tn), 6 .88 (a, 1), 7.09 (a, tn);

Mix HIAINa (6.78g; 178.74mmol; beq.) and MO(EB5-): t/2 188 (MAMHn)(E5-): t/2 203 (M-NU; anhydrous tetrahydrofuran. Dissolve 3-(2 - 1) 6-fluoro-5-methoxytryptamine; nitrovinyl)-4-methoxy-1H-indole (6.5 g; 29.79 mmol) in t) 5,6-difluorotryptamine; anhydrous tetrahydrofuran and with energetic per- n) b-chloro-5-fluorotryptamine; add drop by drop to the solution o) 5-trifluoromethoxytryptamine;

Tsaiina. After completion of the addition, heat with p) 4,6-difluoro-5-methoxytryptamine; Refrigerant. Cool a) 4-phenyltryptamine after 1 hour; to ambient temperature and pe- u) 6-phenyltryptamine; stir After 16 hours, sharply cool the excess 8) 5-isopropyltryptamine;

SPAIN according to the description in U. May. Spent 1995, 38, 2050. O 4,6-difluoro-5-methoxy-1-methyltryptamine: "H

Filter the gray suspension through NMR (300 MHz, SOCIv): 3.0 (t, 4H), 3.67 (5, 3H), a pad of celite and wash the celite with ethyl acetate. Yield - 3.98 (5, ЗН), 6.85 (t, 2Н);; and digest the filtrate to obtain a residue. i) 4,6-difluoro-5-methoxy-1-methyltryptamine: "H

Chromatograph the residue on silica gel with eluting NMR (300 MHz, d6-0OM50): 2.92 (i, 2H), 3.39 (I, 2H), eluting with a mixture of SNCl3/uMmEon/lChNAOn (95:10:1), 3.69 (5, ЗН), 6.75 (t, 1Н), 7.13 (t, 2Н); M5(E5U): then Tl mixture of SNSIZD IMeOH/MNAOH (90:10:1), as t/2 211; (MAN) 194 (M-AMN»g) U. mobile phase. Combine the fractions containing the product, Example 53, and evaporate to obtain the target compound into Hydrochloride 4-methoxytryptamine in the form of a yellow-brown solid. Dissolve 4-methoxytryptamine (1g, 5.2bmmol). , a6-OmM50): 2.96 (i, 2H); in Meon and add MNaASi (0.97 eq, 0.27g, 3.42 (I, 2H); 3.83 (5, 3H); 6.42 (ad, 1H); 6.93 (t, ZN); 5.100mmol). After 30 minutes, evaporate the mass for 10.7 (v, 1H); M5 (Eb-): t/2 191 (MAN); 174 (M- removal of MeOH to obtain a thick oil

МНг)"; 159 (М-ОСН»з)"; (E5-): t/2 189 (М-Н). orange color Dissolve butter in Meon, i

According to the method of Example 52, the following drops were obtained drop by drop with vigorous mixing of onions: add to EBO (200 ml) with the formation of a sticky a) b-methoxytryptamine, "H NMR (300 MHz; av- white precipitate. Stir with heating with

OM5090): 2.86 (I, 2H); 3.42 (I, 2H); 3.75 (5, ZN); 6.62 by obtaining the target compound in the form of a solid (aa, 1n); 6.83 (t, 1H); 6.97 (p5, 1H); 7.37 (t, 1H); substances: "H NMR (de-OOM5O, Z0OMHC): 3.06 (p5, 4 10.55 (5, 1H); M5 (Eb-): t/2 191 (MAN); 174 (M- H); 3.86 (5, ZN); 6.46 (ai, 1H); 7.06-6.9 (t, ZN); 7.93

Mnh); (EB-): t/2 189 (MN); (p5, 1H); 10.9 (c, 1H); M5 (Eb-yu): t/2 191 (MAN)"; p) 7-methoxytryptamine, "H NMR (30OMHC, av- 175 (M-CH3)"; 174 (M-MHg)"; (E5-): 189 (M-NU; ana-

OM5O): 2.88 (i, 2H), 3.42 (i, 2H), 3.89 (in, ЗН), 6.61 Lyses for C11Ni5SIM2O: calculated: C, 58.2788; H, (ad, 1H), 6.89 (, 1H), 7.02 (t, 1H), 7.10 (a, 1H), 10.85 6.6692; M, 12.3566; established C, 58.18; H, 6.73; (rb5, 18); M5 (Eb-): t/2 191 (MAN), 174 (M-MH»2)"; M, 12,15. (E5-): t/2 189 (M-H); Example 54 c) 4 -chlortryptamine, "H NMR (300 MHz, av- Hydrochloride of 5,6-difluorotryptamine

OM50): 3.11 (i, 2H), 3.44 (ii, 2H), 6.99 (t, 2H), 7.22 The target compound was obtained by the method of Example 53: -0Ω50): 2.97 (t,

AN), 7.27 (t, 1H), 7.36 (t, 1H), 7.53 (t, 1H), 11.20 acetone. Heat and add EBSO to the cloud point, (p5, 18); M5(Eb5-): t/2 197 (MAN), 180 (M-МН»2)»; after which place overnight in the freezer (E5-): t/2 195 (M-H). with obtaining the target compound in the form of crystals

Example 55 is a white solid; "N NMR

Hydrochloride of 4-phenyltryptamine (zzOO0MHz, ab-0M50): 3.02 (t, 4H), 7.06 (t, 1H), 7.39

NCI solution (4.6 bml of 4M solution of NCI in 1.4- (t, 1H), 7.45 (y, 1), 7.55 (t, 1H), 11.30 (p5, 1), dioxane) drop add dropwise to the solution 4- M5(EB-): t/2 245 (MAN), 228 (M-MH»g)"; (E5-): t/2 phenyltryptamine (3.33g, 14.09mmol) in mixture 243 (M-H)-; analysis for C11H11EzM2O: calculated; C,

ESUAS/ESO with the production of a solid substance. From- 46.7144; H, 3.9203; M, 8.3809; established; C, filter the solid and dry for 46.55; H, 3.62; M, 8.27. overnight in a vacuum oven at room temperature with Using the method of Example 58, the following compound was obtained by obtaining the target compound in the form of a solid: a) Oxalate of 4,6-difluoro-5-substance not quite white in color; "H NMR of methoxytryptamine: "H NMR (300 MHz, av-OM50): (ZOOMHC, de-0OM50): 2.54 (t, 4H), 6.82 (t, 1H), 7.14 3.04 (t , 4H), 3.85 (5, ЗН), 7.10 (t, 1H), 7.22 (t, 1H), (61), 7.27 (t, 1H), 7.41 (t, 5H), 7.68 (re, 2H), 11.29 (p5, 1H); M5(E5 kyu): t/2 227 (MAN); (E5-): t/2 11.28 (р5, 1Н); M5(E5-): t/2 237 (MAN), 220 (M- 225 (M-H); analysis for CizNi«P2M2O5: calculated; C,

Mnh); (E5-): t/2 235 (M-H); analysis for SivNi?SIM"; 49.3718; H, 4.4620; M, 8.8576; established; WITH,

Calculated; C, 70.4517; H, 62818; M, 10.2696; 49.68; H, 4.57; M, 8.60. established; C, 70.26; H, 6.16; M, 10,20. Example 60

Example 56 Oxalate of 4-fluorotryptamine

5-chloro-6-fluorotryptamine hydrochloride A solution of oxalic acid (1.44 g, 1.2 equiv.) in

The target compound is obtained by the method When acetonitrile is added drop by drop from energy class 55: "H NMR (Z300MHz, avb-OM50): 3.00 (t, with stirring to a solution of 4-

AN), 7.37 (t, 1H), 7.53 (a, 1), 7.59 (a, 1H), 11.28 of fluorotryptamine in acetonitrile. Heat and add (b5, 1); M5(E5-): t/2 213 (MAN), 196, 198 (M- Meon with obtaining a solution. Add ESO to the point

Mnh)y; (E5-): t/2 211, 213 (М-Н). ki turbidity, and cool the solution in the freezer

Example 57 chamber with the production of a solid substance. filter-

4-Chlorotryptamine oxalate digest the solid and dry overnight

A solution of oxalic acid (1.32 g, 1.3 equiv.) in a vacuum oven at a temperature of 45702 from the obtained

Meon add drop by drop with vigorous stirring the target compound in the form of a solid with stirring to a solution of 4-chlorotryptamine in a yellow-brown color: "H NMR (300MHC, ao-

EOAc (2.2 g, 11.3 mmol). After the addition is complete, OM50): 3.07 (t, 4H), 6.73 (t, 1H), 7.04 (t, 1H), add EBSO to the cloud point and place to 7.22 (t, 2H ), 11.30 (p5, 18); M5 (Eb-): t/2 179 freezers with the production of solid matter (MAN); (EB-): t/2 177 (M-N). guilt Filter off the solid and wash Example 61 with ether. Dry in a vacuum oven at room temperature to obtain the target solution. Oxalic acid solution (3.91 g, 1.2 eq.) is added drop by drop with an energetic color to onions in the form of a not quite white solid. : "H NMR (ZO00MHCts, av-OM50): 3.11 (t, 2H), stirring to a solution of b-fluoro-5- 3.2 (t, 2H), 7.04 (t, 2H), 7, 34 (t, 2H), 11.44 (rv, methoxytryptamine in EtOAc/MeonH. Add ESO with 1H); M5 (EB5-): t/2 195 (MAN), 178 (M-MHg)"; (EB-): obtaining a solid substance, filter t/2 193 (М-Н); analysis for Si2NizSIM2Oal: calculate the solid substance and dry it overnight in a vacuum: C, 50.6263; H, 4.6026; M, 9.8396; installed: a smart oven at a temperature of 60"C with the receipt

C, 50.56; H, 4.57; M, 9.66. of the target compound: "H NMR (300 MHz, d6-0OM50): 3.0

Using the method of Example 57, we obtained (t, 4H), 3.85 (5, ЗН), 7.21 (t, ЗН), 10.89 (р5, 1Н); the following compounds: M5(EB-): t/2 209 (MAN)"; analysis for CizNivEM2Obv: a) Oxalate of 6b-phenyltryptamine: 3.05 (t, 4H), calculated: C, 52.3496; H, 5, 0690; M, 9.3919; established 7.31 (t, ЗН), 7.45 (i, 2Н), 7.65 (t, 4Н), 11.10 (65, adjusted: С, 52.06 ; H, 4.91; M, 9.20. 1H), MB(EZ Yu: t/2 237 (MaH)U, 220 (M-MH»2)"; (E5-): Example 62 t/2 235 (M-H); 2-(2-(7-fluoro-1H-indol-3-yl)ethyl)isoindole-1,3-

B) Oxalate of 4,6b-difluoro-5-methoxytryptamine: dione

IN NMR (Z00MHC, de-0M5O): 3.04 (t, 4H), 3.85 (5, Mix 2-fluorohydrazine hydrochloride (3.25Hg,

ZN), 7.10 (t, 1H), 7.22 (t, 1H), 11.29 (rv, 1); 20 mmol) and 2-(4,4-diethoxybutyl)-isoindole-1,3-dione

MO(EB A): t/2 227 (MAN); (EB-): t/2 225 (M-N); (6.99g, 24mmol) and dissolve in 495 aqueous solution analysis for SiZNi4P2M2gOv: calculated; C, 49.3718; H, H2g5O»x. Heat the reaction mixture with the reverse 4.4620; M, 8.8576; established; C, 49.68; H, 4.57; refrigerator After 2 hours, cool to room temperature

M, 8.60; and environmental factors. Increase c) Oxalate b5-isopropyltryptamine; "H NMR basicity of the reaction mixture with the help of 3090 (Z0O0MHCts, 49-0M50): 1.25 (0, 6H), 3.01 (t, 4H), 6.99 of an aqueous solution of MNAOH to a pH of approximately 11. Ex- (t , 1), 7.17 (t, 1H), 7.27 (t, 1H), 7.36 (05, 1H), triturate with dichloromethane (2x100ml). Combine 10.85 (p5, 1H); M5 (E5-): t/2 203 (MAN), 186 (M- organic phases, dry over Mao", filter-

МНг)"; (EB5-): t/2 201 (М-Н). cotton wool and remove the solvent to obtain oil

Example 58 is orange. Absorb silica oil

5-trifluoromethoxytryptamine oxalate and add to the upper part of the short silica-

A solution of oxalic acid (1.3 eq.) in acetone of a gel column equilibrated with 1595 solution was added to a solution of 5-trifluoromethoxytryptamine in EOAc in hexane. Wash 1595 with a solution of EOAc in hexane (1500ml), then 3095 with a solution of E(OAc in hexane. Mix 1,3-difluoro-2-methoxy-5-nitrobenzene sani (2000ml) with the result, after evaporation, (10.12g, 53, 51 mmol) and 4-chlorophenoxyacetonitrile of the target compound in the form of a yellow solid (11.21 g, 66.89 mmol, 1.25 equiv.) in dimethyl sulfocto- color: "H NMR (300 MHz, ae-0 M50): 3.03 (It , sit (150 ml). For 5 hours, drop by drop 2H), 3.85 (I, 2H), 6.91 (t, 2H), 7.25 (t, 1H), 7.36 (a, add to the suspension solid Mahon (powder-like 1H), 7.83 (t, 4H), 11.32 (p5, 1H); M5 (BE): t/2 308 ny, 10.70g, 267.55mmol, 5eq.) Through 18 hours (M) pour the reaction mixture into a cold aqueous solution

Example 63 well NSI and extract ESO (2x150ml). Combine

Oxalate 7-fluorotryptamine organic layers, washed with brine and evaporated with

Dissolve 2-(2-(7-fluoro-1H-indole-3-) to obtain a residue. Chromatograph the residue of yl)ethyl)isoindole-1,3-dione in 25 ml of tetrahydrofuran. on silica gel with elution with 2095 EAsC solution

Add ethanolamine in hexane with vigorous stirring to give, after evaporation, (2,4-(63.4g, 62.65ml, 1038mmol, 100eq)) and heat to difluoro-33-methoxy-6b-nitrophenyl)acetonitrile at 7070. After 1.5 hours, cool to a room temperature of yellow oil: M5(E5-): t/2 227 nat. After 18 hours, pour the reaction mixture (M-NU.) into water (250 ml) containing a 5 M solution of Mahon. ) of acetonitrile in cyclization according to the description in the organic layers and washed with 0.1 M solution of Mmaon. Ivzgaei U. Spet. 1966, 4, 155-159 gives oil. Chroma-

Collect the organic layer, dry it over Mdzoh, tograph the oil on silica gel with elution, filter and remove the solvent in massio with a 20906 solution of EIHUAcS in hexane to obtain, after obtaining the target compound in the form of an oil, evaporation, the target compound in the form of a solid color. substances of dark red color; "N NMR

Drop by drop with vigorous stirring (ZOOMHts, а6-О0М50): 3.85 (р5, ЗН), 6.46 (t, 1Н), then add a solution of oxalic acid (0.62g, 7.12 (а, 1Н) ), 7.36 (t, 1H), 11.35 (p5, 1H); M5(E5-): 1.2 eq;) in Meon to the base solution (1.02g, t/72 182 (M-H) 5.72 mmol) in EAs. Heat the cloudy suspension. Using the method of Example 65, the following compounds were obtained under reflux during ZOhv: a) 4,b-difluoro-1H-indole. "H NMR, then cool to obtain a solid substance - (ZOOMHz, SOSIz"): 4.68 (a, 2H), 6.14 (t, 2H), 6.57 wine. Filter the solid and dry (65, 2 ); M5(E5Bu): t/2 205, 207 (МН) from which the target compound was obtained in a vacuum oven overnight at a temperature of 60"С with the formation of the target compound in the form of Example 66 a not quite white solid substance: "Н 4 , 6b-difluoro-5-methoxy-1-methyl-1H-indole

NMR (300 MHz, a6-OM50): 3.04 (t, 4H), 6.96 (t, Mix 4,6-difluoro-5-methoxy-1H-indole (7.5g, 2H), 7.30 ( t, 1), 7.38 (a, 1H), 11.51 (65, 1H); M5 40.95 mmol) and cold dimethylformamide (Eb-yu): t/2 179 (MAN)U, 162 (M- МН»г)»; (E5-): t/2 177 (100ml) and treat the Mann mixture (18g, 45.05mmol, (M-H)U; analysis for Sti2NizEM2Ol: calculated: C 1/Eq.) with vigorous stirring. Through pri- 53.7318; H 4.8849; M 10.4431; established: C, add iodomethane 53.50 drop by drop for about 10 minutes; N, 4.86; M, 10.32. (11.62 g, 81.90 mmol, 2 eq.). After completing the pre-

Example 64 giving, stir the reaction mixture at room

Oxalate b-trifluoromethyltryptamine at that temperature for several hours until

Add b-trifluoromethyltryptamine to the mixture (171) acetone/ESO. Drop by drop, add chewing gum to the absence of the starting material. Dilute oxalic acid (1.2 equiv.) in acetone, dilute the reaction mixture with water, and extract ESO by crushing the solid. Filter the solid (2 x 150 ml). Combine the organic layers, dry the substance and dry in a vacuum oven over Mda5O", filter and remove the solvent overnight to obtain the target compound: ME(EZ'Zh): t/2 with the oil obtained. Chromatograph the oil on 212 (М-МН2)"; (Е5-): t/2 227 (М-Н). silica gel eluting with 1095 EIHUAs solution in

Example 65 hexanes to obtain, after evaporation, the target 4,6b-difluoro-5-methoxy-1H-indole compound in the form of a light yellow oil:

Dissolve 2,6-difluoro-4-nitrophenol (in. IN NMR (300 MHz, SOCI3): 3.72 (5, ZN), 3.97 (5, ZN),

It is not egocentric. Spent 1976, 13, 1253; 10g, 6.50 (a, 1H), 6.84 (a, 1H), 6.98 (j, 13); M5 (E5 k): t/2 57.11 mmol) in ZO00 ml of benzene. Drop by drop 198 (MAN); analysis for SiONeB»MO: calculated: add a solution of 1-methyl-3-p-tolyltriazene (9.37 mg, C, 60.91; H, 4.60; M, 7.10; determined: C, 60.93; H, 62.82 mmol, 1 eq.) in benzene (150 ml). After that 4.63; M, 7.25. as according to the data of thin-layer chromatography Using the method of Example 66, the absence of starting material was obtained, the following compounds were obtained: a) 4,6-difluoro-1-methyl-1 H-indole. transfer the reaction mixture to a separatory funnel, wash Example 67 with a 1M HCl solution, then with a saturated M-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3-Manso solution and then with water. Dry the organophenoxybenzylamine layer over Mda5oO", filter and remove the solvent to obtain a residue. Crystallize - the residue from a mixture of MeOH/water to obtain 1,3- "S.g of difluoro-2-methoxy-5-nitrobenzene in the form of needle-like crystals of white color; "H NMR (300 MHz, I

SOS"): 4.25 (I, ZN), 7.80 (y, 2H). N

Mix 3-phenoxybenzaldehyde (5.bml, Preparation of oxalate: Add a solution of free 26.7mmol), 5-methoxytryptamine (5.0g, 26.7mmol) base (8.7g, 23.5mmol) in EOAcC (50ml) to dissolve and ZA molecular sieves (1.0g) in methanol (50ml) in oxalic acid (2.1g, 23.5mmol) in ЕХОАСС atmosphere of argon and heat under reflux (5ml) to obtain a precipitate. Collect the sediment with a shutter for 4 hours. Filter molecularly from a methanol/diethyl ether mixture through a fine sieve, then add slowly in portions to obtain a solid. Filter sodium borohydride (3.0 g, 60.0 mmol). Mix the solid substance, wash it with diethyl ether, at room temperature for an hour and concentrate, dry overnight in a vacuum oven under reduced pressure, dissolve the concentrate at 50"C to obtain the target compound in a concentrated reaction mixture in a 1M hydroxide solution as oxalate, m.p. 188-190"C, corresponding to sodium (10O0ml) and extract with dichloromethane NMR, mass spectroscopy: t/2 373.2 (Mk), analysis: (3x5Oml). Combine the organic layers and consistently calculate for C2bNovbM2gOv: C, 67.52; H, 5.67; M, washed with distilled water (50 ml) and dissolved in 6.06, determined: C, 67.38; H, 5.46; M, 6.04. scrap (50ml), dry the organic layer (Ma»5Oy) and, according to the method of Example 67, were obtained such concentrate to obtain a residue. Chromatogluts separated in the form of oxalate, except for raffining the residue on silica gel with elution of the indicated: mixture (9:1) EOAc:Meon with 295 MNAOH solution to obtain the target compound. se n (i

About Wa che n me! 7 THEIR HER 8 Her 777777 dan 77777777 t.pl. 203-2057C, mass spectroscopy: t/72 343.1 (MU), analytical

H lyse: calculated for Co5HgaM2gO»v: C, 69.43; H, 5.59; M, 6.48, established: C, 69.25; H, 5.42; M, 6.37 square meters 106-1087C, mass spectroscopy: t/72 359.2 (MU), analysis: calculated for C22NhaM2O«5: C, 66.95; H, 5.39; M, 6.25, established: C, 66.19; H, 5.49; M, 6.13 square meters 203-2057С, mass spectroscopy: t/72 391.2 (MU), 70Н -505- analysis: calculated for С25НгаМ2Ов5: С, 62.49; H, 5.03; M, 5.83, established: C, 62.05; H, 5.21; M, 5.82 square meters 198-2007C, mass spectroscopy: t/2 389.3 (MU), analysis 71 |B-methoxy -5- analysis: calculated for SobNoeM2O55: C, 65.25; H, 5.48; M, 5.85, established: C, 64.50; H, 5.63; M, 5.73 square meters 142-1447C, mass spectroscopy: t/72 421.1 (MU), analytical 72 |B-methoxy| -502- lyse: calculated for SobNovM2gO?75: C, 61.16; H, 5.13; M, 5.49, established: C, 61.14; H, 5.38; M, 5.25 square meters 190-1927C, mass spectroscopy: t/72 373.2 (MU), 73n-5-4-methylphenyl lysis analysis: calculated for SobNovM2O«5: C, 67.51; H, 5.67; M, 6.06, established: C, 67.44; H, 5.69; M, 6.13 square meters 212-2147C, mass spectroscopy: t/72 405.4 (MU), analysis of 74 n -505- 4-methylphenyl lysis: calculated for C26NoeM2Ov5: C,63.14; H, 5.30; M, 5.66, established: C, 62.59; H, 5.70; M, 5.29 square meters 214-2167C, mass spectroscopy: t/72 389.3 (MU), ana- 75 |B5-methoxy | -CH(BR)- lyse: calculated for С27Но7ЕМ2гО5: С, 67.77; H, 5.69; M, 5.85, established: C, 67.52; N, 5.77; M, 5.64 square meters 216-2187C, mass spectroscopy: t/2 359.2 (MU), 76 n -CH(P)- analysis: calculated for C2bNo5EM2gOg: C, 69.63; H, 5.62; M, 6.25, established: C, 69.55; H, 5.36; M, 5.95 square meters 199-2027С, mass spectroscopy: t/72 371.1 (MU), ana- 77 |B-methoxy| -SNeolysis: calculated for C27NgviMgOv: C, 70.42; H, 6.13; M, 6.08, established: C, 69.73; H, 6.25; M, 6.05 square meters 222-2247C, mass spectroscopy: t/72 341.2 (MU), 78 n-Snelyse analysis: calculated for SobNovM2Oal: C, 72.54; H, 6.09; M, 6.51, established: C, 72.23; H, 6.08; M, 6.37 square meters 146-148, mass spectroscopy: t/2 387.2, analysis: ob- 79 |B5-methoxy sn(On)- calculated for С27Но8вМ2Ов: С, 68.05; H, 5.92; M, 5.88, established: C, 67.29; H, 6.03; M, 5.51

And t.pl. 167-1697C, mass spectroscopy: t/72 357.3 (MU), analysis

Н сНн(Он)- lyse: calculated for СобНовМ2О5: C, 69.94; N, 5.87; M, 6.27, established: C, 68.11; H, 6.07; M, 6.06 81 |B-methoxy| -MNA | phenyl,. /|hlpl. 170-172"C, mass spectroscopy: t/g2 372.3 (MU), anach

NO NNYA PNYA PON Bi aiva established: С, 67.24; H, 6.08; M, 8.54 square meters 196-1987C, mass spectroscopy: t/72 342.2 (MU), 82 n -MH analysis: calculated for Cg25Hg5MZO»x: C, 69.59; H, 5.84; M, 9.74, established: C, 67.57; H, 6.06; M, 8.84 square meters 203-2057C, mass spectroscopy: t/72 386.2 (MU), ana- 83 |B-methoxy!| -MH- benzyl lyse: calculated for C27HhoMzO5: C, 68.20; H, 6.15; M, 8.84, established: C, 67.46; H, 6.14; M, 8.79 square meters 204-2067C, mass spectroscopy: t/72 356.3 (MU), analysis of 84 n -MH- benzyl lysis: calculated for SobH2?7MzOl: C, 70.10; H, 6.11; M, 9.43, established: C, 68.48; H, 5.95; M, 9.26 square meters 126-1287C, mass spectroscopy: t/72 297.5 (MU), analysis: calculated for SiNgM2gO: C, 72.94; H, 6.80; M, 9.45, 85 | 5-methoxy H was determined: C, 71.78; H, 6.71; M, 9.20 (allocated as the base) t.pl. 143-1457C, mass spectroscopy: t/72 267.3 (MU), analytical

Н Н lyse: calculated for Si17NivM2gO: C, 76.66; H, 6.81; M, 10.51, established: C, 75.11; H, 6.61; M, 10.22 (highlighted as the base) t.pl. 204-2067C, mass spectroscopy: t/72 361.1 (MU), analysis of 87 5-fluorine: calculated for C25NozEM2gOv: C, 66.66; H, 5.15; M, 6.22, established: C, 66.83; H, 5.17; M, 6.30 t.pl. 196-1987C, mass spectroscopy: t/72 423.1 (MU), analysis of 88 |5-methoxy naphth-1-yl lyse: calculated for SzoNovM2gOv: C, 70.30; H, 5.51; M, 5.47, established: C, 68.11; H, 5.56; M, 5.52 square meters 210-2127С, mass spectroscopy: t/72 393.2 (MU), analytical

H naphth-1-yl lyse: calculated for SgoNgaM2gOv: C, 72.19; H, 5.43; M, 5.81, established: C, 72.10; H, 5.40; M, 6.66 square meters 186-1887C, mass spectroscopy: t/72 391.2 (MU), analysis

B-methoxy Z-fluorophenyl lyse: calculated for С26Но5ЕМ2гОв: C, 64.99; H, 5.24; M, 5.83, established: C, 63.10; H, 5.11; M, 5.67 square meters 217-2197C, at a yield of 7595, which corresponds to the data of 94 N 3-fluorophenyl NMR, mass spectroscopy: t/72 361.1 (MU), analysis: calculated for Co5NaozEM2gO»v: C, 66.66; H, 5.15; M, 6.22, established: C, 66.12; H, 5.22; M, 6.34 square meters 184-1867С, mass spectroscopy: t/72 391.2 (MU), analysis 92 |B-methoxy 2-fluorophenyl lysis: calculated for С26Но5ЕМ2гОв: С, 64.99; H, 5.24; M, 5.83, established: C, 65.06; H, 5.23; M, 5.85 square meters 206-208"C, mass spectroscopy: t/72 361.1 (MU), analysis of 93 N 2-fluorophenyl: calculated for C25NozEM2gOv: C, 66.66; H, 5.15; M, 6.22 , determined: C, 66.30; H, 4.97; M, 6.21 mp 184-1867C, mass spectroscopy: t/72 391.2 (MU), ana- 94 |5B-methoxy 4 -fluorophenyl lyse: calculated for C2bNo5EM2gOv: C, 64.99; H, 5.24; M, 5.83, found: C, 63.99; H, 4.95; M, 5.75 mp 222 -2247С, mass spectroscopy: t/72 361.1 (MU), analysis of 95 N 4-fluorophenyl lysis: calculated for С25НозЕМ2гОв: С, 66.66; Н, 5.15; M, 6.22, established: C, 65.74; H, 4.81; M, 6.13 mp 198-2007C, mass spectroscopy: t/72 423.1 (MU), analytical

B-methoxy naphth-g-yl lyse: calculated for SzoNovM2gOv: C, 70.30; N, 5.51; M, 5.47, established: C, 68.97; H, 5.43; M, 5.44 square meters 219-22RS, mass spectroscopy: t/2 393.2 (MU), analysis of 97 n naphth-g-yl lysis: calculated for SgoNgaM2gOv: C, 72.19; H, 5.43; M, 5.81, established: C, 71.65; H, 5.32; M, 5.91 square meters 204-2067С, mass spectroscopy: t/72 387.2 (MU), analytical

B-methoxy benzyl lyse: calculated for О27НовМ2гОв: C, 68.05; H, 5.92; M, 5.87, established: C, 67.26; H, 5.80; M, 5.86 square meters 211-2137C, mass spectroscopy: t/72 357.3 (MU), analysis

H benzyl lyse: calculated for SobNovM2gO5: C, 69.94; H, 5.86; M, 6.27, established: C, 69.46; H, 5.75; M, 6.16 square meters 188-1907C, mass spectroscopy: t/72 359.2 (MU), analytical 100 | 5-hydroxy lyse: calculated for Co5NgaMgOv: C, 66.95; H, 5.39; M, 6.24, established: C, 63.56; N, 5.01; M, 5.86 101 | B-methoxy-o-pyrimid-5-yl m.p. 191-1937C, mass spectroscopy: t/72 375.2 (MU), analysis: calculated for Sga|NgaMaOvye: C, 62.06; H, 5.20; M,

77777717 011206, established; C, 6166; H, 541 M, 1087... t.pl. 188-1907C, mass spectroscopy t/72 345.1 (MU), analysis 12.89, determined: C, 62.52; H, 5.28; M, 11.58 square meters 124-1267С, mass spectroscopy: t/72 374.2 (MU), analysis and analysis: calculated for С2зН25Си2МзО»: С, 61.88; H, 5.64; M, 103 | 5-methoxy pyridyl 9.41, established: C, 61.26; H, 5.70; M, 9.14, (isolated as hydrochloride) m.p. 147-1497С, mass spectroscopy: t/72 344.2 (MU), analysis and analysis: calculated for С22НозСи»МзО: С, 63.46; H, 5.56; M, 104 H pyrid-4-yl 10.09, determined: C, 61.47; H, 5.33; M, 9.43, (isolated as hydrochloride) sereyae| about | yanani nn 105 | b-chloro pyrid-4-yl lyse: calculated for C22Hg2SizMzO: C, 58.61; N, 4.91; M, 9.32, established: C, 57.28; N, 4.61; M, 8.85 square meters 178-1807С, mass spectroscopy: t/72 374.2 (MU), and the rest of the samples were determined: С, 63.02; H, 5.30; M, 8.87 sq. m. 190-1927С, mass spectroscopy: t/72 344.1 (MU), analysis of 1 edoi ovettia established: С, 65.69; H, 5.21; M, 9.20 square meters 135-1377С, mass spectroscopy: t/72 362.3 (MU), analysis and analysis: calculated for Сг2Нг2Си2ЕМзО: С, 60.83; H, 510; M, 108) 5-fluoropyrid-3-yl 9.67, determined: C, 61.49; H, 5.31; M, 9.70, (isolated as hydrochloride) m.p. 160-1627С, mass spectroscopy: t/72 378.1 (MU), analysis and analysis: calculated for С22Нг2СизМзО: С, 58.61; N, 4.91; M, 109) bchloro pyrid-3-yl 9.32, determined: C, 58.18; N, 4.89; M, 9.01, (isolated as hydrochloride, m.p. 202-2047С, mass spectroscopy: t/72 374.2 (MU), analysis and lysis: calculated for С2зНо5Си»МзО): С, 61.88 ; H, 5.64; M, 110 | 5-methoxy pyrid-2-yl 9.41, found: C, 60.57; H, 6.35; M, 10.89, (isolated as hydrochloride) m. pl. 196-1987C, mass spectroscopy: t/72 344.2 (MU), analysis and analysis: calculated for С22НозСи»МзО: С, 63.46; Н, 5.56; M, 1 Н pyrid- a-il 10.09, determined: C, 63.69; H, 6.09; M, 11.62, (isolated as hydrochloride m.p. 149-1517C, mass spectroscopy: t/72 378.1 ( MU), analysis and lysis: calculated for Cg22Hg2SiIzMzO: C, 58.61; H, 4.91; M, 112 | b'chlor pyrid-2-yl 9.32, determined: C, 61.96; H . ; M, 8.94, determined: C, 58.11; H, 4.79; M, 8.84 pH || tones and 114 N thiazol-2-yl lyse: calculated for Cg22HgiMz3O55: C, 60, 12; H, 4.81; M, 9.56, determined: C, 59.73; H, 4.83; M, 9.36 pB B 2 v- t.pl. ia pasopectrovko hie svv -methoxy , «| lyse: calculated for SobNg«P2M2Ove: C, 55.51; H, 4.30; M, difluorophenylsulfonyl; 97, established: C, 55.90; N, 4.47; M, 512 in ts 26- t.pl. in pasopectrokogiy St., | Lyse: calculated for С25Нгг2Р2М2О75: С, 56.38; H, 4.16; M, difluorophenylsulfonyl 5 26, established: C, 56.96; N, 4.39; M, 5.31 square meters 174-176"С, mass spectroscopy: t/72 373.1 (MU), analysis and analysis: calculated for Сг2зНовСи"МаОв: С, 62.02; H, 5.88; M, 117 |5-methoxy| "MN. pyrid-a-yl 12.57, established: C, 61.45; H, 5.91; M, 12.22, (isolated as hydrochloride) m.p. 168-1707C, mass spectroscopy: t/72 343.1 (MU), analysis and analysis: calculated for С22НгаСи2Май: С, 63.61; H, 5.82; M, 118 N "Mn. pyrid-a-yl 13.48, determined: C, 62.18; H, 6.12; M, 12.11, (isolated as hydrochloride m.p. 164-1667C, mass spectroscopy: t/72 377.1 (MU), analysis and lysis: calculated for Cg22NozSizMa: C, 58.74; H, 5.15; M, 119 | bchlor | -MH- pyrid-2-yl 12, 45, determined: C, 57.75; H, 5.07; M, 11.94, (isolated as hydrochloride)

t.pl. 150-1547С, mass spectroscopy: t/72 373.2 (MU), analysis and analysis: calculated for С2зНовСи2МаОв: С, 62.02; H, 5.88; M, 120 |5-methoxy| "MN. pyrid-Z'il 12.57, established: C, 61.30; H, 6.58; M, 10.87, (isolated as hydrochloride, m.p. 140-1427C, mass spectroscopy: t/72 343.2 (MU), analysis and lysis: calculated for Cg22No2Ma: C, 77.16; H, 6.47; M, 16.36, 121 N "Mn. pyrid-Z-yl determined: C, 75.73; H, 6.54; M, 15.58, (isolated as a base) m.p. 172-1747С, mass spectroscopy: t/2 377.2 (MU), analysis and analysis: calculated for Сg22НозСизМа: С, 58.74; Н, 5.15; М, 122| bochlor | "МН. pyrid-Z-yl 12.45, determined: C, 57.05; H, 5.16; M, 11.84, (isolated as hydrochloride m.p. 170-1727С, mass spectroscopy: t/72 373, 3 (MU), analysis and analysis: calculated for C2zNovSi2MaOv: C, 62.02; H, 5.88; M, 123 61.05; H, 6.08; M, 11.97, (isolated as hydrochloride) mp 174-1767С, mass spectroscopy: t/72 343.4 (MU), analysis and lysis: calculated for С22НгаСи2Май: C, 63.61; H, 5.82; M, 124 N "Mn. pyrid-cycle 13.48, established: C, 62.32; H, 6.20; M, 12.44, ( isolated as hydrochloride) mp 158-1607С, mass spectroscopy: t/72 377.2 (MU), analysis and lysis: calculated for Сg22НгзСизМа: С, 58 .74; H, 5.15; M, 125| bchlor | "MN. pyrid-4-yl 12.45, established: C, 57.17; H, 5.19; M, 11.69, (isolated as hydrochloride m.p. 151-1537С, mass spectroscopy: t/72 397.2 (MU), anal.

B-methoxylysis: calculated for С24Но«BaМ2Ов: С, 56.25; N, 4.72; M, 126| vrtor | MN- | 2. trifluoroethyl | 5 46 established: C, 56.38; N, 4.76; M, 5.53, (isolated as maleate) m.p. 145-1477C, mass spectroscopy: t/72 447.2 (MU), analysis of 127 B-methoxy- -Mmn- 2,2,3,3,3- lysis: calculated for C25NoaEeM2gOv: C, 53.38; H, 4.30; M, b-fluorine pentafluoropropyl 4.98, established: C, 53.36; H, 4.29; M, 5.00, (highlighted maleate) t.pl. 143-1457С, mass spectroscopy: t/72 429.2 (MU), 128 B-methoxy-2,2,3,3-lysis analysis: calculated for С25Но5Е5М2Ов: С, 55.14; N, 4.62; M, b-fluorine tetrafluoropropyl 5.14, established: C, 55.10; N, 4.62; M, 5.18, (isolated as maleate) m.p. 163-166", mass spectroscopy: t/2 385.2 (MU), analysis: 129 |5-methoxy | -C(0)- calculated for C27NovM2gOv: C, 68.34; H, 5.52; M . -b(0)- lyse: calculated for SobNgaM2gOv: C, 70.26; H, 5.44; M, 6.30, established: C, 69.51; H, 5.52; M, 6.22 t .pl.: 123.4-124.97С, mass spectroscopy (EbBzh: t/2

Y I SHE 363.0(М--1), analysis: calculated for Сг2Нгог MзО: С, 73.11; 130A| b-fluorine pyridyl H, 5.58; M, 11.63, established: C, 73.36; H, 5.41; M, 11.57 (isolated as a free base) t.pl. 169.0-170.87"C, mass spectroscopy (ARSI): t/

І и ва 362.1(МА1), analysis: calculated for 1308| b-fluorine pyrid-Z-yl CgoNgogyM3O-1.0C4NaOa: C, 65.40; N, 5.07; M, 8.80, established: C, 65.45; H, 5.12; M, 8.70 (isolated as maleate, m.p. 151-1537С mass spectroscopy: t/2 397.2 (MU), anal.

B-methoxylysis: calculated for С24Но«BaМ2Ов: С, 56.25; N, 4.72; M, 13001. β-fluorine 2.2.2-trifluoroethyl | 5 46, established: C, 56.38; N, 4.76; M, 5.53 (isolated as maleate)

According to the method of Example 67, the following compounds were obtained, isolated in the form of oxalate, with the exception of the indicated:

her K ro Kk ve a nya hl

And m! 12 GB of them are 1777777717171717171717171717171717//7/7/7/7/7/7/7/7/7//77711 t.pl. 222-224"7C, mass spectroscopy: t/2 338.2 (MU, 131 C-chlorine analysis: calculated for CgzHg2SIMO): C, 64.56; H, 5.18;

M, 3.27, established: C, 64.24; H, 5.02; M, 3.89,

Z-trifluoro- m.p. 220-2227"C, mass spectroscopy: t/2 372.2 (MU, 132 methyl analysis: calculated for Cg4NooEzMO): C, 62.47; H, 4.81;

M, 3.04, established: C, 62.69; N, 4.78; M, 3.10 square meters 221-2237"C, mass spectroscopy: t/2 334.2 (MU, 133 | 4-methoxy analysis: calculated for Сг4Но5МОв: С, 68.07; Н, 5.95; M, 3.31, established: C, 67.98; H, 5.92; M, 3.29 mp 209-2117C, mass spectroscopy: t/2 364.2 (MU, 134 IZ,4-dimethoxy analysis: calculated for С25Н27МО» ;: C, 66.21; NN, 6.00; M, 3.09, established: C, 66.28; NN, 6.07; M, 3.27 t.pl. 210-2127"C, mass -spectroscopy: t/2 334.1 (MU, 1351 C-methoxy analysis: calculated for Сг4Но5МОв: C, 68.07; H, 5.95; M, 3.31, established: C, 68.31; H, 5.78; M, 3.36 mp 219-2217C, mass spectroscopy: t/2 372.1 (MU, 136 | 3,4-dichloro analysis: calculated for SgzNai Si2MO5: C, 59.75; H, 4.58;

M, 3.03, established: C, 58.98; N, 4.63; M, 3.66 square meters 214-2167С, mass spectroscopy: t/2 406.4 (MU, 137 З-chloro З--rifluoromethylphenyl | analysis: calculated for СгаНгиСИЕзМО»: С, 58.13; Н, 4.27; М, 2.82 , determined: C, 58.28; H, 4.53; M, 2.86 mp. 221-2237"C, mass spectroscopy: t/2 394.2 (MU, 138 analysis: calculated for С27НзоСИМО: С, 67.00; Н, 6.25;

M, 2.89, established: C, 66.36; H, 5.83; M, 2.94 square meters 212-2147C, mass spectroscopy: t/2 372.1 (MU, 139 C-chloro 4-chlorophenyl analysis: calculated for SgzNai Si2MO5: C, 59.75; H, 4.58;

M, 3.03, established: C, 61.50; H, 4.77; M, 3.20 square meters 207-2097C, mass spectroscopy: t/2 368.2 (MU, 140 C-chloro 4-methoxyphenyl analysis: calculated for SgaHg«SIMOv: C, 62.95; H, 5.28;

M, 3.06, established: C, 63.17; H, 5.32; M, 3.19 square meters 206-208"C, mass spectroscopy: t/2 352.4 (MU, 141 C-chloro 4-methylphenyl analysis: calculated for SgaHg"SIMO): C, 65.23; H, 5.47;

M, 3.17, established: C, 67.52; H, 5.68; M, 3.30 sq.m. 223-2257С, mass spectroscopy: t/2 406.3 (MU, 142 3-chlorine 3,5-dichlorophenyl analysis: calculated for Сг2гзНгоСиИзМО»: С, 55.61; Н, 4.06;

M, 2.82, established: C, 56.08; H, 3.83; M, 2.26 square meters 217-2197С, mass spectroscopy: t/2 406.4 (MU, 143 3-chlorine 3,4-dichlorophenyl analysis: calculated for СгзНгоСизМО»: С, 55.61; Н, 4.06;

M, 2.82, established: C, 55.73; N, 4.38; M, 3.02 square meters 162-1647С, mass spectroscopy: t/2 304.2 (MU, 144 Н analysis: calculated for Сг2зН2зМО»5: С, 70.22; Н, 5.89; М, 3.56, established: С, 70 ,70; H, 5.38; M, 3.78 m.p. 222-224"7C, mass spectroscopy: t/2 338.2 (MU, 145 4-chloro analysis: calculated for SgzNaoSIMO: C, 64.56, H, 5.18;

M, 3.27, established: C, 63.65; H, 5.18; M, 3.25 square meters 122-124"С, mass spectroscopy: t/2 354.3 (MU, 146 З-chloro -5- analysis: calculated for С2зН22СИМО45: С, 62.23; Н, 4.99; M, 3.15, determined: C, 63.08; H, 5.09; M, 3.15 mp 110-1127C, mass spectroscopy: t/2 386.1 (MU, 147 З-chlorine -5О2- analysis: calculated for C2zH22SIMOv5: C, 58.04; H, 4.66; M, 2.94, determined: C, 58.91; H, 4.78; M, 3.05 mp 111-1137С, mass spectroscopy: t/2 320.1 (MU, 148 n -5- analysis: calculated for С2зН2зМО45: С, 67.46; Н, 5.66;

M, 3.42, established: C, 67.66; N, 5.77; M, 3.41 square meters 127-1297С, mass spectroscopy: t/2 352.4 (MU, 149 Н -5О2- analysis: calculated for С2зН2зМОв5: С, 62.57; Н, 5.25;

M, 3.17, established: C, 62.75; H, 5.16; M, 3.26 150 3-chloro-5-4-methylphenyl m.p. 222-2247C, mass spectroscopy: t/2 368.1 (MU,

11121771 floor 5.28; M, 3.06, established: C, 63.11; H, 5.35; M, 3.11 square meters 226-228"C, mass spectroscopy: t/2 400.1 (MU, 151 C-chloro-5O2- 4-methylphenyl analysis: calculated for C24Hg"SIMOve5: C, 58.83; H, 4.94; M , 2.86, determined: C, 58.79; H, 4.94; M, 2.93 mp. 206-208"C, mass spectroscopy: t/2 351.5 (MU, 152 Z- chlorine -MH- benzyl analysis: calculated for Сг2г4Но5СИМ2О»l: C, 65.38; H, 5.72;

M, 6.35, established: C, 65.23; H, 5.86; M, 6.29 square meters 196-1987C, mass spectroscopy: t/2 337.2 (MU, 153 З-chlorine -MH- analysis: calculated for СгзНазСИМг2гОх: С, 64.71; Н, 5.43;

M, 6.56, established: C, 56.60; H, 4.90; M, 5.64 square meters 193-1957C, mass spectroscopy: t/2 352.4 (MU, 154 C-chlorine sn(one)- analysis: calculated for SgaNga«SIM2Ov: C, 65.23; H, 5.47;

M, 3.17, established: C, 64.96; H, 5.60; M, 3.32 square meters 220-222"C, mass spectroscopy: t/2 336.1 (MU, 155 C-chloro -SNeo- analysis: calculated For SgaNga"SIMO4: C, 67.68; H, 5.68;

M, 3.29, established: C, 67.65; H, 5.83; M, 3.42 square meters 182-1847"C, mass spectroscopy: t/2 354.3 (MU, 156 C-chlorine -CH(P)- analysis: calculated for С24НозСИЕМО4: С, 64.94; Н, 5.22; M, 3 ,16, determined: C, 65.21; H, 5.26; M, 3.09 mp 218-2207C, mass spectroscopy: t/2 356.2 (MU, 157 3-chloro 4-fluorophenyl analysis: calculated for C2zNaiSIEMO: C, 61.96; H, 4.75; M, 3.14, established: C, 60.56; H, 4.67; M, 3.17 3- mp. 221-2237"C, mass spectroscopy: t/2 390.2 (MU, 158 4-fluorophenyl analysis: calculated for Cg4NaB"MO5: C, 60.13; H, 4.42; riftomethyl M, 2.92, determined: C, 59.18; H, 4.30; M, 2.91 mp 214-2167C, mass spectroscopy: t/2 356.2 (MU, 159 C-chloro 2-fluorophenyl analysis: calculated for Sg2zNa(SIEMO): C, 61.96; H, 4.75; M, 3.14, established: C, 61.42; H, 4.68; M, 3.21 3- mp. 218 -2207"C, mass spectroscopy: t/2 390.2 (MU, 160 2-fluorophenyl analysis: calculated for Cg4NaB"MO5: C, 60.13; H, 4.42; riftomethyl M, 2.92, established : C, 59.83; H, 4.34; M, 2.96 mp 219-2217C, mass spectroscopy: t/2 356.2 (MU, 161 3-chloro 3-fluorophenyl analysis: calculated for C2zNaiSI EMO": C, 61.96; N, 4.75; M, 3.14, established: C, 61.26; H, 4.74; M, 3.11 3- t.pl. 221-2237"C, mass spectroscopy: t/2 390.2 (MU, 162 C-fluorophenyl analysis: calculated for Cg4NaB"MO5: C, 60.13; H, 4.42; riftomethyl M, 2.92, determined: C, 58.79; H, 4.28; M, 2.88 mp 229-2317C, mass spectroscopy: t/2 388.1 (MU, 163 C-chloro naphth-2-yl analysis : calculated for C27Ng"SIMO": C, 67.85; H, 5.06;

M, 2.93, established: C, 67.71; H, 5.02; M, 3.03 3- t.pl. 225-227"C, mass spectroscopy: t/2 422.0 (MU, 164 oil-g-il analysis: calculated for SovNgheEzMO"5: C, 65.75; H, 4.73; riftomethyl M, 2, 74, determined: C, 65.72; H, 4.84; M, 2.88 mp 208-2107C, mass spectroscopy: t/2 388.1 (MU, 165 C-chlorine naphth-1- il analysis: calculated for C27Hg"SIMO": C, 67.85; H, 5.06;

M, 2.93, established: C, 66.71; H, 5.11; M, 3.26 3- t.pl. 211-2137C, mass spectroscopy: t/2 422.0 (MU, 166 naphth-1-yl analysis: calculated for SgvNgaEzMO): C, 65.75; H, 4.73; riftomethyl M, 2.74, established : C, 64.30; H, 4.76; M, 2.90 mp 96-987C, mass spectroscopy: t/2 262.0 (MU), analysis: calculated for Si5H15SIMO: C, 68.83; H, 6.16; M, 167 | chlorine H 5.35, determined: C, 68.59; H, 5.99; M, 5.37, (isolated as bases, m.p. 101-1037C, mass spectroscopy: t/2 296.3 (MU, 168 3-H analysis: calculated for SibNieEzMO: C, 65.07; H, 5.46; riftomethyl M, 4.74, established: C, 65.06; H, 5.42; M, 4.80, (isolated as a base) 3- mp 223-2257С, mass spectroscopy: t/2 386.1 (MU, 169 benzyl analysis: calculated for C25NhaEzMO»5: C, 63.15; H, 5.08; riftomethyl M, 2.94, established: C, 63.22; H, 4.97; M, 3.02 o 2 d-t. pl. antifreeze mass spectroscotia tya 438.0 (MU, 170 Z-chloro -0- z. - Analysis: calculated for С2зНгоСИБ2МО75: C, 52.32; H, difluorophenylsulfonyl | 3 81; M, 2.65, determined: С, 52.26; H, 3.80: M, 2.71

3- 2 d- t.pl. 202-2047"С, mass spectroscopy: t/2 472.2 (MU, 171 riftomethyl difluorophenylsulfonyl analysis: calculated for Сг2аНгоб5МО75: С, 51.34; Н, 3.59; М, 2.49, established: С, 51.61; H, 3.65; M, 2.54 m.p. 216-2187C, mass spectroscopy: t/2 345.0 (MU, 172 3-chlorothiazol-2-yl analysis: calculated for SgoNizoSiIM2O55 : C, 55.23; H, 4.40; M, 6.44, determined: C, 55.15; H, 4.16; M, 6.43 3- mp 222-2247С, mass spectroscopy: t/2 379.4 (MU, 173 rifluoromethyl thiazol-2-yl analysis: calculated for Cg2iNioEzM2O55: C, 53.84; H, 4.08; M, 5.98, established: C, 53.71; H, 3.95; M, 5.96, mp 213-2157C, mass spectroscopy: t/2 339.1 (MU, 174 3-chloro pyrid-3-yl analysis: calculated for Сг2Наи SIM2Ов: С, 61.61, H, 4.93;

M, 6.53, established: C, 60.40; N, 4.89; M, 6.74 3- t.pl. 221-2237"C, mass spectroscopy: t/2 373.1 (MU, 175 pyrid-3-yl analysis: calculated for SgzNai EzMgOv: C, 59.74; H, 4.57; riftomethyl M, 6.05 , determined: С, 59.17; Н, 4.47; M, 6.93 mp 101-1037С, mass spectroscopy: t/2 335.2 (MU, . . analysis: calculated for Сг21иНгаСи2.М2О »: C, 61.92; H, 176 | 3-methoxy pyrid-Z-yl 5.93; M, 6.87, determined: C, 61.43; H, 6.07; M, 6.25, (isolated as hydrochloride) mp 154-1567C, mass spectroscopy: t/2 339.1 (MU, yth analysis: calculated for SgoNai SiIzM2gO: С, 58.34; Н, 5.14; 177| with -chloro pyrid---yl M, 6.80, determined: C, 58.35; H, 5.18; M, 6.69, (isolated as hydrochloride m.p. 208-2107C, mass spectroscopy : t/2 373.1 (MU, 178 3-pyrid-4-yl analysis: calculated for Cg2hyHgSioEzM2O: C, 56.64; H, riftomethyl 4.75; M, 6.29, established: C, 56.57 ; H, 4.68; M, 6.20, (isolated as hydrochloride) m.p. 205-207"C, mass spectroscopy: t/2 340.1 (MU, 179 3-chloropyrimid-5-yl analysis: calculated for C2g1iNgoSIMzOv: C, 58.67; H, 4.68;

M, 9.77, established: C, 57.66; N, 4.70; M, 8.17 3- t.pl. 218-2207C, mass spectroscopy: t/2 374.1 (MU, 180 pyrimidbyl analysis: calculated for Cg22HgoEzMzOv: C, 57.02; H, 4.35; riftomethyl M, 9.06, established: C, 56.55; H, 4.44; M, 8.89 mp 93-957C, mass spectroscopy: t/2 339.1 (MU), analysis and lysis: calculated for SgoNgiSizM2gO: C, 58 .34; H, 5.14; M, 181) pyrid-2-yl chloride 6.80, determined: C, 62.31; H, 5.30; M, 7.36, (isolated as hydrochloride, m.p. 86-88"С, mass spectroscopy: t/2 373.1 (MU), analysis 182 3-pyrid-2-ylolysis: calculated for Sg2iNaiSiO2EzM2gO: C, 56.64; H, 4.75; riftomethyl M, 6.29, determined: C, 60.00; H, 4.92; M, 6.76, (isolated as hydrochloride) t. pl. 158-1607C, mass spectroscopy: t/2 338.3 (MU, 183 C-chloro-MH-pyrid-3-yl analysis: calculated for Cg2NagSIM2Oa: C, 61.75; H, 5.18;

M, 9.82, established: C, 58.90; N, 4.64; M, 8.87 3- t.pl. 182-1847"C, mass spectroscopy: t/2 372.3 (MU, 184 -MH-pyrid-3-yl analysis: calculated for СгзНог2ЕзМзОа: С, 59.86; H, 4.80; riftomethyl M, 9 ,10, determined: C, 58.33; H, 4.44; M, 8.60 mp 156-1587C, mass spectroscopy: t/2 338.3 (MU, yth analysis: calculated for SgoNg2SyzMa : C, 58.48; H, 5.39; 185 chlorine "MH. pyrid-4-yl M, 10.22, determined: C, 57.13; H, 5.49; M, 9.80, ( isolated as hydrochloride) m.p. 142-1447"C, mass spectroscopy: t/2 372.3 (MU,

C-trifluoride analysis: calculated for C21Hg2Si2EzMaz: C, 56.76; H, 186 methyl "MH. pyrid-"-yl 4.99; M, 9.45, determined: C, 55.05; H, 4.88; M, 9.33, isolated as hydrochloride m.p. 142 -1447"C, mass spectroscopy: t/2 338.0 (MU, yth analysis: calculated for СгоНг2СизМа: С, 58.48; Н, 5.39; 187| B'chlor "MN. pyrid-2- il M, 10.22, determined: C, 58.12; H, 5.39; M, 10.08, (isolated as hydrochloride) mp 144-1467С, mass spectroscopy: t/2 372 ,1 (MU, 3- I I analysis: calculated for C21Hg22Si2EZMa: C, 56.76; H, 188 bifluoromethyl 7" pyrid-2-yl 4.99; M, 9.45, established: C, 56.60; H, 5.04; M, 9.32, (isolated as hydrochloride) l189| 3-chloro, | -0- | benzyl |MbZpuezbib(ty)

3- Oh. Oh, Sh

According to the method of Example 67, the following compounds were obtained, isolated in the form of oxalate, with the exception of the indicated:

Zh ss ov byu Be

Ka GB)

NITEY PI: CHIN PON a TT NN 194 pyrid-y-ilo | Tl. 176-178"С, mass spectroscopy: t/2 305.2 (MU), analysis: calculated for Сг22Нг2М2О5: Рид С, 66.99; Н, 5.62; М, 7.10, established: С, 67 .55; H, 5.70; M, 7.24 192 | pyrid-Z-yl, mp 198-2007C, mass spectroscopy: t/7 305.2 (MU), analysis: calculated for Cg2No2MgObv: rid C, 66.99; H, 5.62; M, 7.10, determined: C, 64.98; H, 5.43; M, 6.86 193 thien-?-yl, mp 234-236 "С, mass spectroscopy: t/7 310.2 (MU), analysis: calculated for С21иНги1МО55:

C, 63.14; H, 5.29; M, 3.50, established: C, 62.25; H, 5.18; M, 3.53 194 | imidazop-4-yl m.p. 194-1967C, mass spectroscopy: t/72 294.2 (MU), analysis: calculated for SgoNgoMzO5: d С, 62.65; H, 5.52; M, 10.95, established: C, 59.94; H, 5.30; M, 10.12 195 naphth-2-yl m.p. 223-2257С, mass spectroscopy: t/2 354.4 (MU), analysis: calculated for С27Но5МО5:

C, 73.12; H, 5.68; M, 3.16, established: C, 73.38; H, 5.94; M, 3.40 196 naphth-1-yl m.p. 223-2257С, mass spectroscopy: t/2 354.4 (MU), analysis: calculated for С27Но5МО5:

C, 73.12; H, 5.68; M, 3.16, established: C, 73.18; H, 5.52; M, 3.23

According to the method of Example 67, the following compounds were obtained, isolated in the form of oxalate, with the exception of the indicated: --

X so kA r

VIT PM: CHON PON and SU NO t.pl. 240-242", mass spectroscopy: t/72 336.0 (MU), analysis: calculated for 197 3-chlorophenyl C2zHgoSIMO: C, 55.23; H, 4.40; M, 6.44, established: C, 55.15; H, 4.16; M, 6.43 mp 255-257"C, mass spectroscopy: t/72 370.0 (MU), analysis: calculated for 198 | C-trifluoromethylphenyl | SgaNgobzMO"5: C, 62.74; N, 4.38; M, 3.04, established: C, 62.95; H, 4.27; M, 3.08 199 | 5-methoxy-1H-indole-3-yl m.p. 232-2347С, mass spectroscopy: t/72 371.1 (MU), analysis: calculated for d С2вНгаМ2гОв: С, 67.81; H, 5.25; M, 6.08, established: C, 67.46; N, 4.44; M, 5.44 square meters 221-2232С, mass spectroscopy: t/2 341.1 (MU), analysis: calculated for d С25Нг2М2Ов: С, 69.75; H, 5.15; M, 6.50, established: C, 71.99; N, 4.48; M, 6.40

According to the method of Example 67, the following compounds were obtained, isolated in the form of oxalate, with the exception of the indicated:

In the east; vyti i tu vk

NITEI PI Z POLON PO RU UNO ET NI t.pl. 225-227"C, mass spectroscopy: t/72 361.1 (Mu), analysis: calculated 201 Z-chlorophenyl for C25NazSIM2gOyal: C, 66.59; H, 5.14; M, 6.21, determined: С, 66.21; Н, 5.02; М, 6.14 mp. -rifluoromethylphenyl for C25Na5EzM2Ol: C, 64.45; H, 4.78; M, 5.78, determined: C, 63.98; H, 4.67; M, 5.76 mp 208-2107С , mass spectroscopy: t/72 394.2 (Mc, analysis: calculated 203 , 8.62, established: C, 67.78;

H, 5.29; M, 8.42 square meters 227-2297C, mass spectroscopy: t/72 364.3 (Mu), analysis: calculated 204 1H-indol-3-yl for C27Na25MzOa: C, 71.19; N, 5.53; M, 9.22, established: C, 70.02;

H, 5.33; M, 8.95 square meters 170-172"C, mass spectroscopy: t/2 318.2 (Mu), analysis: calculated 205 I5-methoxy-1H-indole-3-ylII NN for Cg22H2zMzO5: C, 64.53; H, 5 ,62; M, 10.26, established: C, 56.16;

N, 4.98; M, 8.75

According to the method of Example 67, the following compounds were obtained, isolated in the form of oxalate, with the exception of the marked: syu and n

VYT poly SONYA KO RO NO ET NO t.pl. 237-239", mass spectroscopy: t/2 361.1 (MU), analysis: calculated zosynny en EONIV KTKNE I 5.16; M, 6.20 t.pl. 239-24RS, mass spectroscopy: t/ 2 395.1 (MU), analysis: calculated 207 | 3--trifluoromethylphenyl for C25NaEzM2gOchl: C, 64.45; H, 4.78; M, 5.78, found: C, 64.59; H, 4, 83; M, 5.83 m.p. 194-1967C, mass spectroscopy: t/72 396.2 (MU), analysis: calculated 208 |5-methoxy-1H-indol-3-yl for Cg8H27MzOv5: C, 69.26; H, 5.60; M, 8.62, determined: C, 68.33; H, 5.37; M, 8.52 mp 206-208"C, mass spectroscopy: t /7 366.2 (MU), analysis: calculated 209 1H-indol-3-yl for С27Но5Мзоа: С, 71.19; N, 5.53; M, 9.22, established: C, 69.23; H, 5.42; M, 8.86 square meters 186-188"C, mass spectroscopy: t/72 318.2 (MU), analysis: calculated 210 |B-methoxy-1H-indol-3-yl| H | for Cg2Hg2zMzO5: C, 64.53; H, 5.66; M, 10.26, found: C, 62.88; H, 4.61; M, 9.27

Example 220

M-(2-(3-chlorophenyl)ethyl)-3-benzoylbenzylamine "g s - rin M soro n y I S t Sha y y ; with B: 1. o Mix 3-ethoxybenzaldehyde (3.38 g, 22.5 mmol), 2-(3-chlorophenyl)ethylamine / (2.33 g,

Mix 3-benzoylbenzaldehyde (0.45g, 15.0mol) and ZA molecular sieves (2.88g) in eth-2.1mmol), (3-chlorophenyl)ethylamine (0.3ml, nil (230ml). Stir the reaction mixture at 2.1 mmol) and ZA molecular sieves (1.0 g) in MEOH distillation temperature for 4 hours. Vidfilt- (ZOml). Heat under reflux. dig molecular sieves, then to the filtrate

After cooling, filter and slowly add sodium borohydride (1.70 g, titrate to obtain a residue. Dissolve 45.00 mmol) and stir at room temperature in dichloroethane (20 ml), add acetic acid. After 15 hours, concentrate (0.12 ml, 2.1 mmol) and the reaction mixture to obtain a residue, dissolve sodium triacetoxyborohydride (0.6 g, 2.94 mmol) and dissolve the residue in 1 M Mahon solution and extract, mix at ambient temperature with dichloromethane. Combine organic extracts, seeds. After 2 hours, concentrate the reaction mixture, wash it with brine, dry it over Ma»bO»x and con- the mixture, add dichloromethane (90 ml) and successively concentrate to obtain a residue. Chromatography - extract with distilled water (50 ml), then filter the residue on silica gel eluted with brine (50 ml). Dry the organic layer over ethyl acetate to give the target compound.

Ma»zO4 and get a residue. Chromatograph The hydrogen chloride salt was obtained in ethyl acetate from the residue on silica gel with EAs elution, followed by obtaining the target compound: m.p. obtaining the target compound in the form of a base. 178-1807C; M5 (ASRI): t/e 290.1 (M-1); analysis

According to the method of Example 67, oxalate was obtained for Si17H2 and Si2Mo: calculated: C, 62.58; H, 6.49; M, chew the target compound: m.p. 196-1987C, mass 4.29; established: C, 62.65; N, 6.53; M, 4.32. spectroscopy: t/72 350.4 (M, analysis: calculated According to the method of Example 221, the following were obtained for SgaHg2SIMO): C, 65.53; H, 5.04; M, 3.18, compounds isolated in the form of maleate , it was excluded: C, 65.27; H, 5.20; M, 3.13.

Example 221

M-(2-(3-chlorophenyl)ethyl)-3-ethoxybenzylamine

S wl -V. вн гу - ме! 77 | in HER 77777/79071717171 data//7/7/7/7/7/7/7/7/7/7/7777777771111111111 t.pl. 138-140", M5 (ASRI): m/e 304.1 (M-n1), analysis for CivHgzSi2MO: 222 C-chlorine calculated: C, 63.53; H, 6.81; M, 4.12; determined: C, 63.74; H, 6.81; M, 4.22, (isolated as hydrochloride) 3- mp 145-147", M5 (ASRI): m/e 338.1 (Ma1) , analysis for SgzNovbEzMO5: 223 riftomethyl calculated: C, 60.92; H, 5.78; M, 3.09; established: C, 60.77; H, 5.60; M, 312 3- t.pl. 164-166"C, M5 (ASRI): m/e 324.2 (Mat), analysis for SivNai SIEzZMO: 224 riftomethyl ethyl calculated: C, 60.09; H, 5.88; M, 3.89; established : C, 60.42; H, 5.80; M, 3.93, (isolated as hydrochloride) 2995. mp 181-1837"C, M5 (ASRI): m/e 386.2 (Mch) , analysis for C27NovEzMO5: 225 2-phenyl trifluoroethyl was found: C, 64.67; H, 5.23; M, 2.79; established: C, 64.52; N, 5.01; M, t.pl. 392, M5 (ASRI): t/e 386.2 (M-41), (Exception - one equivalent of trifluoroethyl | triethylamine in the reaction mixture) (isolated as a free base)

According to the method of Example 221, the following compounds were obtained, isolated in the form of maleate, with the exception of the indicated:

Dean of the School of Economics

HM I and ef an

M

N

YOU ARE Z PI : RN MON 5 ET OO t.pl. 153-156"C, M5 (ASRI): m/e 329.1 (Ma1), analysis for 227 B-chloroethyl CgzNa5CIM2O"v: calculated: C, 62.09; H, 5.66; M, 6, 30; established:

C, 62.27; H, 5.38; M, 6.19 square meters 163-166"C, M5 (ASRI): m/e 343.1 (Ma), analysis for 228 5-chloro СgaН27СИМ2Оv: calculated: C, 62.81; H, 5.93; M, 6.10; established :

C, 63.07; H, 5.80; M, 6.07 299. t.pl. 178-181"C, M5 (ASRI): mp 383.1 (Ma), analysis for 223 5-chloro trifluoroethyl C2zHg2SiIezM2O5: calculated: C, 55.37; H, 4.44; M, 5.62; installed:

C, 55.71; N, 4.39; M, 5.66 square meters 167-170"C, M5 (ASRI): m/e 361.1 (Ma), analysis for 230 B-chlorine 3-fluoropropyl | SgaNovSIEM2gO": calculated: C, 60.44; H, 5.49; M, 5.87; established:

C, 60.30; H, 5.25; M, 5.78 2233 8- t.pl. 170-173"СМ5 (ASRI) m/e 433.1 (Ma1), analysis for 231 5-chloropentafluoropropyl CgaHg2СИЕ5М2О5: calculated: C, 52.52; H, 4.04; M, 5.10; established:

C, 52.49; H, 4.06; M, 5.16 223583. t.pl. 163-167"C, M5 (ASRI): m/e 415.1 (Ma), analysis for 232 5-chlorotetrafluoropropyl SgaHgzSihaM2O5: calculated: C, 54.30; H, 4.37; M, 5.28; installed:

C, 54.47; N, 4.36; M, 5.33 299. t.pl. 179-182"C, M5 (ASRI): m/e 379.1 (Ma1), analysis for 233 B-methoxy trifluoroethyl CgaNo5EzM2Ov: calculated: C, 58.30; H, 5.10; M, 5.67; installed:

C, 58.26; H, 5.09; M, 5.69 223583. t.pl. 156-160"C, M5 (ASRI): m/e 415.1 (Ma), analysis for 234 b-chlorotetrafluoropropyl SgaHgzSIgaM2O5: calculated: C, 54.30; H, 4.37; M, 5.28; installed:

C, 54.31; N, 4.34; M, 5.31 299. t.pl. 176-178"C, M5 (ASRI): m/e 374.0 (Ma), analysis for 235 5-cyanotrifluoroethyl CgoNioSiEzMzO: calculated: C, 58.61; H, 4.67; M, 10.25; determined: C, 58.52; H, 4.61; M, 10.17, (isolated as hydrochloride

B- 299. t.pl. 193-1957C, M5 (ASRI) m/e 429.9 (MaA1), analysis for 236 methylsulfonyl trifluoroethyl itself C, 53.13; N, 4.64; M, 5.16; installed: 353-t.p.l. 150-154"C, M5 (ASRI): m/e 387.9 (Ma), analysis for 237 5-cyanotrifluoropropyl C2vNa"EzMzO5: calculated: C, 59.64; H, 4.80; M, 8, 35; established:

C, 59.55; H, 4.77; M, 8.38 238 5- 3,3,3- t.pl. 178-1817C, M5 (ASRI) t/e 440.9 (MA1), analysis for methylsulfonyl| trifluoropropyl | Со5На7ЕзМмм2О 75: calculated: C, 53.95; N, 4.89; M, 5.03; installed

17777711 (nose, 5387 NI 486 MOG 111 299. mp. 199-2027"C, M5 (ASRI) m/e 367.2 (Ma1), analysis for 239 4-fluoro trifluoroethyl Sche9NioSIRaM2O: calculated: C, 56, 65; H, 4.75; M, 6.95; established:

C, 56.82; N, 4.65; M, 6.84, (isolated as hydrochloride 2233583- mp. 118-121"C, M5 (ASRI): m/e 417.2 (Ma), analysis for 240 4-fluoropentafluoropropyl CgaHg2EvM2O»v: calculated: C, 54.14; H, 4.16; M, 5.26; established:

C, 54.39; H, 4.25; M, 5.30 22383. t.pl. 188-1917C, M5 (ASRI) t/e 399.0 (Ma1), analysis for 2A41 4-fluoroetrafluoropropyl SgoNgoSivR5M2O: calculated: C, 55.24; N, 4.64; M, 6.44; installed:

C, 55.03; H, 4.53; M, 6.34, (isolated as hydrochloride 299. mp. 157-160"C, M5 (ASRI): m/e 367.2 (Ma), analysis for 242 7-fluoro trifluoroethyl CgzNg2EB«M2O»v: calculated: C, 57.26; H, 4.60; M, 5.81; established:

C, 57.34; N, 4.39; M, 6,11 2233 8- t.pl. 166-168"C, M5 (ASRI): m/e 417.2 (Ma), analysis for 243 7-fluoropentafluoropropyl CgaHg2EvM2O»v: calculated: C, 54.14; H, 4.16; M, 5, 26; established:

C, 53.99; N, 3.98; M, 5.61 223583. t.pl. 170-173"C, M5 (ASRI): m/e 399.2 (Ma), analysis for 244 7-fluoroetrafluoropropyl CgaNgaE5M2O": calculated: C, 56.03; H, 4.51; M, 5.45 is set:

C, 55.73; H, 4.30; M, 5.66 353- t.pl. 143-147"C, M5 (ASRI): m/e 406.1 (Ma1), analysis for 245 B-amido trifluoropropyl Ca Hg2EzMzO": calculated: C, 62.22; H, 5.47; M, 10, 36; established:

C, 61.96; H, 5.42; M, 10.13, (isolated as bases 299. mp. 125-130"C, M5 (ASRI) m/e 392.1 (MaA1), analysis for 246 B-amido trifluoroethyl SgoNai SiEzMzO": calculated: С , 56.15; H, 4.95; M, 9.82; established:

C, 55.80; N, 4.93; M, 9.71, (isolated as hydrochloride) 299. m.p. 117-120"C, M5 (ASRI): mp 425.1 (MA1), analysis for 247 b-phenyl trifluoroethyl C2vHgzEzM2gO: calculated: C, 70.74; H, 5.46; M, 6.60; determined: C, 70.75; H, 5.42; M, 6.66, (allocated as bases 22333. t.p. 168-170"S, M5 (ASRI): t/e 413.2 (Ma) , analysis for 248 b-methyl pentafluoropropyl Ca Hgg2E5M2O: calculated: C, 56.82; H, 4.77; M, 5.30; found: C, 57.21; H, 4.46; M, 5.33 2233583- mp. 110.5-113.5"C, M5 (ASRI): m/e 475.1 (MaA1), analysis for 249 b-phenyl pentafluoropropyl C2vHgzE5M2O: calculated: C, 65.82; H, 4.89; M, 5.90; determined: C, 65.70; H, 4.84; M, 5.93, (isolated as bases 223583. t.pl. 94-987C, M5 (ASRI): t /e 457.1 (Mt), analysis for SovNgaBaMgO: 250 b-phenyl tetrafluoropropyl calculated: C, 68.41; H, 5.30; M, 6.14; found: C, 68.18; H, 5, 28; M, 6.06 (isolated as base) 299. mp. 176-178"C, M5 (ASRI) m/e 363.1 (MA1), analysis for 251 b-methyl trifluoroethyl CgoHg2gSiEzM2O: calculated: C , 60.23; H, 5.56; M, 7.02; established:

C, 60.16; H, 5.43; M, 6.98, (isolated as hydrochloride 223583. mp. 156-158"C, M5 (ASRI) m/e 395.1 (MaA1), analysis for 252 b-methyl tetrafluoropropyl Si NazSig2M2O: calculated: C, 58.54; H, 5.38; M, 6.50; established:

C, 58.60; H, 5.32; M, 6.55, (isolated as hydrochloride) v- 22383. m.p. 166-168"C, M5 (ASRI) m/e 453.1 (MaA1), analysis for 253 ethoxycarbonyl tetrafluoropropyl C2gzNa5SiRaM2Oz: calculated: C, 56.50; H, 5.15; M, 5.73; established:

C, 56.18; H, 5.00; M, 5.66, (isolated as hydrochloride in 299. mp. 169.5-171.5"C, M5 (ASRI): m/e 421.2 (MaA1), analysis for 254 ethoxycarbonyl trifluoroethyl SgvNatEzM2O" ;: calculated: C, 58.21; H, 5.07; M, 5.22; established:

C, 58.43; N, 4.85; M, 5.27 299. t.pl. 175-177"C, M5 (ASRI): m/e 374.1 (Ma), analysis for 255 b-cyano trifluoroethyl CgaHg2EzMzO5: calculated: C, 58.90; H, 4.53; M, 8.59; installed:

C, 58.62; N, 4.48; M, 8.50 223583. t.pl. 167-169"C, M5 (ASRI): m/e 406.1 (Ma1), analysis for 256 b-cyanotetrafluoropropyl SgvNazE"MzO5: calculated: C, 57.58; H, 4.45; M, 8, 06; established:

C, 57.31; N, 4.35; M, 8.08 299. t.pl. 10270, M5 (ASRI): m/e 392.2 (Ma1), analysis for SgoNgobzMzO2: 257 b-amido tetrafluoroethyl calculated: C, 61.38; H, 5.15; M, 10.74; established: C, 61.68; H, 5.11; M, 10.65, (isolated as bases 223583. m.p. 120"C, M5 (ASRI): m/e 424.3 (Ma1), analysis for SgiHgi1R"MzO5: 258 b-amido tetrafluoropropyl calculated: C, 59.57; H, 5.00; M, 9.92; determined: C, 59.33; H, 4.82; M, 9.79, (isolated as a base) in- 22383. t.p. 132 -134"C, M5 (АСРИ) m/e 465.1 (МА1), analysis for 259 riftomethoxy tetrafluoropropyl CgiNgoSIE?M2O": calculated: C, 50.36; H, 4.03; M, 5.59; established :

C, 50.25; N, 3.96; M, 5.58, (isolated as hydrochloride)

in- 299. t.pl. 160-164"C, M5 (ASRI): m/e 433.1 (Ma), analysis for 260 riftomethoxy trifluoroethyl CgoNiOSiBvM2O": calculated: C, 51.24; H, 4.08; M, 5.98; established :

C, 51.26; H, 3.99; M, 5.96, (isolated as hydrochloride) 223583. m.p. 153.6-154.47C, M5 (ARSI): m/e 415.1 (Ma1), analysis: calculated 260А 7-chloro tetrafluoropropyl for SgoNizoSIRRaM20-1.0HCII: C, 53.23; N, 4.47; M, 6.21, established:

C, 52.89; N, 4.40; M, 6.18, (isolated as hydrochloride) m.p. 193.4-194.97C, mass spectroscopy (Ebya): t/72 383.17 (Ma), 2608 7-khpor 2,2.,2- analysis: calculated for Sti9NivSiezM2gO-1.0HCl: C, 54.43; H, 4.57; M, trifluoroethyl |6.68, established: C, 54.66; N, 4.39; M, 6.66, (isolated as hydrochloride

Example 261 Y(cartrate o M-(2-(7-fluoro-1H-indol-3-yl)ethyl)-

Hydrochloride M-(2-(7-fluoro-1H-indol-3-3-(2,2,2-trifluoroethoxy)benzylamine yl)ethyl)-3-(2,2,3,3- Add solution I1-( -)-tartaric acid (295 mg, tetrafluoropropoxy)benzylamine 1.96 mmol) in methanol to a solution of M-(2-(7-fluoro-

Add dropwise acetyl chloride 1H-indol-3-yl)ethyl)-3-(2,2,2- (24ml, 338mmol) to anhydrous ethanol trifluoroethoxy)benzylamine (720mg, 1.96mmol) in (5Oml), stir the solution for 10 min with ethyl acetate. Concentrate the resulting solution at ambient temperature, add under reduced pressure to obtain a transparent to solution /-M-(2-(7-fluoro-1H-indol-3-yl)ethyl)-3- colorless oil. Crystallize the oil from di-(2,2,3,3-tetrafluoropropoxy)benzylamine (12.0 g, ethyl ether to give the target compound: 30.1 mmol) in ethyl acetate. Concentrate oder-t.pl. 118-11970. M5 (t/e): 367 (Ma), 365 (M-1). solution under reduced pressure to obtain Analysis for Si9NivR«M2OSaNevOv: calculated: C, yellow solid. Perekrysta - 53.49; N, 4.68; M, 5.42, established: C, 53.21; H, dissolve a solid yellow substance from a solution of 4.55; M, 5.41. mixture of ethyl acetate/ethanol/diethyl ether with Example 270 obtaining the target compound: m.p. 142-14376. Hydrochloride M-(2-(5-fluoro-1H-indole-3-

M5 (t/e): 399 (Maya), 397 (M-1). Analysis for yl)ethyl)-3-propoxybenzylamine

SgoNizE5M2O SI: calculated: C, 55.24; N, 4.64; M, 6.44, established: C, 55.44; H, 4.66; M, 6.46. IS

Example 262 "g

(M-(2-(7-fluoro-1H-M.ol indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropoxy"benzyl amine)

Add 1-(--)-tartaric acid (49mg, 0.333mmol) and methanol to the solution (M-(2-(7-fluoro-1H-indole-3- Mix 3-propoxybenzaldehyde/(2.96Hg, il) ethyl)-3-(2,2,3,3- | 18.0 mmol), 5-fluorotryptamine hydrochloride (2.58 g, tetrafluoropropoxy) benzylamine (130 mg, 12.00 mol), triethylamine (1.15 g) and ZA molecular

0.33 mmol) in ethyl acetate. Evaporate the solvent from a sieve (2.27g) in ethanol (200ml). Mix with resin recovery. Crystallize the resin from the reaction mixture at the distillation temperature in a mixture of diethyl ether/(ethyl acetate) with the resulting

Example 263 | sodium hydroxide (1.36 g, 36.0 mmol) and stir at ambient temperature. Hydrochloride M-(2-(7-fluoro-1H-indol-3- -tributorethoxy)benzylamine for 15 hours to concentrate the reaction mixture from the obtained

Add acetyl chloride dropwise to the residue, dissolve the residue in a 1M solution (2.3ml, 32.4mmMol) in anhydrous Mahon ethanol and extract with dichloromethane. Combine (50 ml), stir the solution for 10 minutes with organic extracts, wash with brine, dry at ambient temperature, add over Ma»bOx and concentrate to obtain a solution M-(2-(7-fluoro-1H-indole-Z) -yl)ethyl)-3-(2,2,2- sh. Chromatograph the residue on silica gel with trifluoroethoxy)benzylamine (10.7 g, 29.2 mmol) eluting with ethyl acetate to give 3.31 g of diethyl ether. Concentrate the obtained oil. Obtain hydrogen chloride salt in diethyl solution under reduced pressure to obtain twerov ether: m.p. 197-1992C; M5 (ASRI): t/e milky substances of yellow color. Recrystallizes - 327.2 (Ma); analysis for Sgong"SIEM2O: calculated: a yellow solid from mixture C, 66.20; H, 6.67; M, 7.72; established: C, 66.06; ethyl acetate/methanol to obtain the target N, 6.63; M, 7.76. compounds: t.pl. 163-1647C; M5 (t/e); 367 (We), according to the method of Example 270, the following 365 (M-1) were obtained; analysis for Si9NivEaM2O NS: calculated compounds isolated in the form of maleate, excluding: C, 56.65; N, 4.75; M, 6.95, established: C, reading of the marked: 56.45; H, 4.54; M, 6.90.

Example 264 from Y che ! "SA Sk

M - U o" sa.

M

NISTEMY o Z PI X ROL PON TE NN t.pl. 196-1987C, M5 (ASRI): m/e 313.1 (Ma), analysis for 271 5-fluoro ethyl SiOHg2SIEM2O: calculated: C, 65.42; H, 6.36; M, 8.03; installed:

C, 65.48; H, 6.30; M, 8.04, (isolated as hydrochloride)

B- t.pl. 156-1607C, M5 (ASRI): m/e 363.1 (Ma1), analysis for 272 ethyl CgaHg5EzM2O»: calculated: C, 60.25; H, 5.27; M, 5.85; established: riftomethyl C, 60.47; H, 5.26; M, 5.79

B- t.pl. 169-1727C, M5 (ASRI): m/e 377.1 (Ma), analysis for 273 со5Н2т7ЕЗзМго5: Calculated: C, 60.97; N, 5.53; M, 5.69; established: C, riftomethyl 60.95; H, 5.54; M, 5.70

B- t.pl. 180-1847C, M5 (ASRI): t/e 417.1 (Ma), analysis for 274 2,2,2-trifluoroethyl | SgaHg2EvM2gO5: calculated: C, 54.14; H, 4.16; M, 5.26; established: riftomethyl C, 53.99; H, 4.07; M, 5.61

B- 353- t.pl. 158-16RS, M5 (ASRI): m/e 431.1 (Mat), analysis for 275 iffluoromethyl and ifto zp opyl C25NgaEvM2O5: calculated: C, 54.95; N, 4.43; M, 5.13; established: riftor riftorpr C, 54.84; N, 4.46; M, 5.03 22588- t.pl. 144-147"C, M5 (ASRI): m/e 411.1 (Ma1), analysis for 276 | 4-methoxy tet aphthog ash C25NavE"M2Ov: calculated: C, 57.03; H, 4.98; M . ), analysis for 277 5-cyano tet aphtog poropyl Cg5NazE«MzO5: calculated: C, 57.58; H, 4.45; M, 8.06; it was established: баланпр С, 57.91; H, 4.13; M, 8.34 228838- t.pl. 168-1707C, M5 (ASRI): t/e 424.1 (Ma), analysis for 278 5-cyanopentaphto zp; opOXI C25Na2E5MzO5: calculated: C, 55.66; H, 4.11; M, 7.79; established: rpr C, 55,54; H, 4.16; M, 7.71

B-(4- 22383. P 161-165"C, M5 (ASRI) m/e 4751 (Ma), analysis for 279 fluorophenyl) | tet aftorpropyl С2вНгаСИЕ5М2О: calculated: C, 61.12; H, 4.73 ; M, 5.48; established p-value: C, 61.18; H, 4.64; M, 5.50, (isolated as hydrochloride) (isolated as hydrochloride) mp 168-1717С, M5 ( ASRI): t/e 493.1 280 5-(4- 2,2,3,3,3- (Ma), analysis for SobNozSiReM2O: calculated: C, 59.04; H, 4.38; M, fluorophenyl ) Ipentafluoropropoxy) | 5.30; determined: C, 59.15; H, 4.28; M, 5.30, (isolated as hydrochloride 22588- mp. 148-1517C, M5 (ASRI): tu/ ue 457.1 (Ma1), analysis for 281 5-phenyl tet aphtoropropyl С2вНг5СИРаМ2О: calculated: C, 63.35; H, 5.11; M, 5.68; established behavior: C, 63.16; H , 4.99; M, 5.67, (isolated as hydrochloride) 22383 3- mp 65-707C, with decomposition, M5 (ASRI): m/e 475.1 (Ma), analysis 282 5-phenyl pentaphto v. opyl | FOR С2вНгаСИЕ5М2О: calculated: С, 61.12; Н, 4.73; М, 5.48; рпр was established: С, 60.98; Н, 4.66; М, 5.41, (isolated as hydrochloride

B-4- t.pl. 214-216"C, M5 (ASRI): m/e 443.1 (Ma), analysis for 283 fluorophenyl) 2.2,2-trifluoroethyl | Со5НозСИРаМ2гО: calculated: C, 62.70; H, 4.84; M . e 425.1 (M41), analysis 284 5-phenyl 2,2,2-trifluoroethyl | for С25НгаСИезМ2О: calculated: C, 65.15; H, 5.25; M, 6.08; found: C, 65.46; H . ash С2вНгаСИЕ5М2О: calculated: C, 61.12; H, 4.73; M, 5.48; established rpr no: C, 61.11; H, 4.83; M, 5.40, (isolated as hydrochloride ) m.p. 60"C, with decomposition, M5 (ASRI): m/e 425.1 (Mat), analysis for 286 4-phenyl 2,2,2-trifluoroethyl | Co5Hg«SiEzM2gO: calculated: C, 65.15 ; H, 5.25; M, 6.08; determined: C, 65.08; H, 5.42; M, 5.93, (isolated as hydrochloride 22383. mp. 56"C, with decomposition . C, 63.35; H, 5.11; M, 5.68; established behavior: C, 63.60; H, 5.35; M, 5.48, (isolated as hydrochloride)

Tl. 212-2147C, M5 (ASRI): t/e 362.2 (M--1), (allocated as oxa tll. 167-1692С, M5 (ASRI): t/e 362.3 (Ma), (allocated as oxa, m.p. 116-120"C, M5 (ASRI): m/e 425.3 (M1), analysis for 299 7-phenyl 2,2,2-trifluoroethyl | CoH27EzM2O5: calculated: C, 64.44; H, 5.03; M, 5.18; established:

C, 64.47; H, 4.96; M, 5.24

22383. t.pl. 108-111"C, M5 (ASRI) m/e 457.3 (MA1), analysis for 300 7-phenyl tetrafluoropropyl CzoHgvE"M2O5: calculated: C, 62.93; H, 4.93; M, 4.89 is set:

C, 63.02; N, 4.91; M, 4.96

Example 301 at ambient temperature.

Maleate /M-(2-(b-chloro-1H-indol-3-yl)ethyl)-M- After 24 hours, evaporate to obtain a residue and dissolve the residue in methyl-3-(2,2,3,3-tetrafluoropropoxy)benzylamine in 1M Mahon solution with further extraction with dichloromethane. Unite-

SHU E ti organic extracts, washed with brine, dried

Al sew (Ma»5O»4), filter and evaporate from

Y E obtaining the remainder. Chromatograph the residue on silica gel eluting with ethyl acetate to obtain the target compound. Maleate was obtained in diethyl ether: m.p. 125-128"0. M5 (ASRI):

Add | C-(2,2,3,3-t/e 429.3 (Ma). Analysis for Co«NovSiBaMgOv: ob-tetrafluoropropoxy)benzaldehyde (232.6 mg, calculated: C, 55.10; H, 4.62 ; M, 5.14; determined: 0.98 mmol) to a solution of M-(2-(6b-chloro-1H-indole-3-C, 55.13; H, 4.59; M, 5.09. il) )ethyl)-M-methylamine (205.6 mg, 0.98 mmol) and sodium triacetoxyborohydride (305.3 mg, compound: 1.37 mmol) in dichloroethane (500 ml) was obtained by the method of Example 301. Mix

Si dl chut me n me! 2 Her Her 7777777777771717171717171717yu7yuodani7777777777771111 t.pl. 144-147"C. M5 (ASRI) m/e 393.1 (MA1). Analysis for 302 | B-methoxy | 2,2,2-trifluoroethyl | СgozNa5EzM2Ov: calculated: C, 57.26; H, 5, 22; M, 5.81; established:

C, 56.89; H, 5.16; M, 5.82, (isolated as oxalate 2238. mp. 104-1097"S. M5 (ASRI) m/e 425.2 (Ma1). Analysis for 303 | 4-methoxy tetrafluoropropyl SgaNovEB"M2gOv: calculated: C, 56.03; H, 5.09; M, 5.45; established:

C, 55.85; H, 5.05; M, 5.43, (isolated as oxalate) m.p. 199-202"C. M5 (ASRI): m/e 367.2 (Ma). Analysis for 304 | 4-fluoro 2,2,2-trifluoroethyl | Si9NiSiEM2O: calculated: C, 56.65; H, 4.75; M, 6.95; established:

C, 56.82; N, 4.65; M, 6.84, (isolated as hydrochloride 2238. mp. 94-98"C. M5 (ASRI) m/e 457.1 (Ma1). Analysis for 3051 b-phenyl tetrafluoropropyl SovNgaBaM2gO: calculated: C, 68 ,41; H, 5.30; M, 6.14; established:

C, 68.18; H, 5.28; M, 6.06, (highlighted as a basis)

Example 306

M-(2-(6-carboxy-1H-indol-3-yl)ethyl)-3-a theo, sa (2,2,3,3-tetrafluoropropoxy)benzylamine Z h BN. - | Well, I am too

The target compound is prepared according to the method of Example 306, m.p. 232-235" S. M5 (ASRI): t/e 393.2 (M--1).

Mix /M-(2-(b-ethoxycarbonyl-1H-Indole-3- Example 310 yl)ethyl)-M-(2,2,3,3-5-phenoxy-1H-indole tetrafluoropropoxybenzyl)amine (1, 09g, 2.4mmol) Mix potassium hydroxide (Zg, 0.054mol) and a 2M Mahon solution (4.8ml) in ethanol (4.8ml). phenol (15 g, 0.1 bmol) and heat at room temperature

Heat under reflux. Through 1107C until the dissolution of potassium hydroxide. Cool - cool the reaction mixture to room temperature and the environment for 2 hours, evaporate under vacuum to remove - add 5-fluoro-2-nitrotoluene in one aliquot, and then neutralize 5M solution (7.75g, O0.05mol) . Heat the reaction mixture in the manner of NSII (1.92 ml) with the formation of a solid, the temperature of which is 130 "C for 30 minutes, cool to the wine. Filter the solid substance and dry it at room temperature, then pour it at 1090 under vacuum to obtain the target compound in the Mahon solution ( 200ml). Extract with water to form a white powder: m.p. 186"C, with simple ether (2x100ml), combine with organic decomposition, M5 (ASRI): m/e 425.1 (M--1) . layers, washed with 10956 Mmaon solution

Example 307 (2x100ml), water (2x100ml), dry over

M-(2-(6-carboxy-1H-indol-3-yl)ethyl)-3-(2,2,2-Mag50" and concentrate in mass. Chromatograph- trifluoroethoxy)benzylamine on silica gel eluting with a mixture of hexa-

n/ethyl acetate With the preparation of 2-nitro-5- According to the method of Example 311, the following phenoxytoluene was obtained in the form of a solid substance: "H compounds:

NMR (300 MHz, SOCIv) 2.59 (5, 3H), 6.81-6.85 (t, a) 2-oxo-(5-p-tolyloxy-1H-indole-3-2), 7.06 -7.09 (t, 2H), 7.22-7.26 (t, Sh), 7.40-7.45 yl)yaacetyl chloride; (t, 2H), 8.03-8.06 (t, 1H). p) 2-oxo-(5-o-tolyloxy-1H-indole-3-

Mix 2-nitro-5-phenoxytoluene (1.15 g, yl)acetyl chloride: H NMR (300 MHz, SOCl3) 2.83 5.00 mmol) and tris(dimethylamino)methane (0.87 g, (5, 3H) . 1H), 7.40-7.44 (t, 1H), 7.87 (t, 1H), 8.20 - by a mouth refrigerator in a nitrogen atmosphere. After 8.32 (t, 2H), 8.90 (Big , 1H); cool the reaction mixture to room temperature for 2 hours and 2-oxo-(5-t-tolyloxy-1H-indole-3-mperature) and evaporate toluene under reduced thysolacetyl chloride; and give a residue. Dissolve the residue in a) 2-oxo-(4-fluorophenoxy)-1H-indole-3- 15 ml of E(Ac, mix with Ra/C (1095, 100 mg), peryl acetyl chloride. stir at room temperature under pressure Example 312 of hydrogen in Tatm for 1.5 days. Filter off the 2-oxo-2-(5-phenoxy-1H-indol-3-yl)acetamide catalyst and concentrate the filtrate. Chromatog- Mix 2-oxo-(5-phenoxy-1H-indole-3- raffinate on silica gel eluting with a mixture of isoacetyl chloride (2.15 g, 7.18 mmol) and hexane hydroxide u/EgOAc to obtain the target compound in ammonium (28-3095, 32 ml, bvOmmol) and stir in the form of a solid substance: "H NMR (300 MHz, for 2 hours. Pour the reaction mixture into 1090

SOCI3) 6.49-6.50 (t, 1H), 6.93-7.03 (t, 4H), 7.22- aqueous solution of HCI, extract with dichloromethane, 7.27 (t, 5H), 8, 15 (B, 1H). combine the organic layers, dry over Mag5Ohm,

According to the method of Example 310, the following was obtained by evaporating the solvent in bulk with obtaining 1.94 g of the compound: (9695) of the target compound: "H NMR (300 MHz, SOCI3) a) 4-(p-tolyloxy)-2-methylnitrobenzene: "H 4.87 (85, 2H), 7.51-7.91 (t, 7H), 8.13-8.24 (t, ZN).

NMR (300 MHz, SOS") 2.35 (5, ЗН), 2.57 (5, ЗН), According to the method of Example 312, the following compounds were obtained: 6.77-6.80 (t, 2Н), 6.93- 7.03 (t, 2H), 7.18-7.24 (t, Ky: 2H), 8.00-8.03 (t, 1H); a) 2-oxo-2-(5-p-tolyloxy-1H-indole-3-

B) B5-p-tolyloxy-1H-indole: "H NMR (300 MHz, yl)lacetamide;

SOCI3) 2.31 (5, 3H), 6.48-6.49 (t, 1H), 6.87-6.96 r) 2-oxo-2-(5-o-tolyloxy-1H-indole- 3- (t, ЗН), 7.07-7.10 (t, 2Н), 7.20-7.35 (t, ЗН), 8.15 il) acetamide; and (r, tn); c) 2-oxo-2-(5-t-tolyloxy-1H-indole-3-c)4-(o-tolyloxy)-2-methylnitrobenzene: "H yl)lacetamide.

NMR (400 MHz, SOS") 2.16 (in, ЗН), 2.57 (in, НН), Example 314 6.50-6.78 (t, 2Н), 6.93-7.03 (t, ZN), 7.18-7.35 (t, B5-phenoxytryptamine oxalate 1H), 8.00-8.03 (t, 1H); Add drop by drop a solution of 2-oxo-2-a) 5-o-tolyloxy-1H-indole: "H NMR (400 MHz, (5-phenoxy-1H-indol-3-yl)acetamide (1.9 g,

SOCI3) 2.31 (5, ZH), 6.45-6.46 (t, 1H), 6.78-6.80 b6.8bmmol) in tetrahydrofuran (bOml) to the solution (t, 1H), 6, 90-6.00 (t, 2H), 7.01-7.10 (t, 2H), 7.13- PAIN-tetrahydrofuran (1.0M, 41ml, 41.0mmol) 7.24 (t, 2H) , 7.32-7.34 (t, 1H), 8.11 (BI, 1H); in tetrahydrofuran at room temperature. f) 4-(t-tolyloxy)-2-methylnitrobenzene: "H Heat the reaction mixture with reflux

NMR (Z00MHZc, SOSIv) 2.37 (5, ЗН), 2.60 (5, ЗН), lynic for 4 hours, cool to room temperature 6.80-6.88 (t, 4Н), 7.03-7, 06 (t, 1H), 7.27-7.32 (t, temperature. Quickly stop the reaction by adding 1H), 8.03-8.06 (t, 1H); yum first cold water (bml), then the solution

In 5-t-tolyloxy-1H-indole: Mmaone (2M, 3ml) was obtained. Filter the precipitate and wash b,Og (5495) (red oil), "H NMR with simple ether (3x5Oml). Dry the filtrate (zOO0MHz, SOCIv) 2.25 (in, 3H), 6.51-6.52 (t , 1H), over Mag5O4, concentrate and mass, purify 6.76-6.98 (t, 4H), 7.14-7.39 (t, 4H), 8.17 (Bg, 1H); by chromatography (dichloromethane 9) 4-(4-fluorophenoxy)-2-methylnitrobenzene: "H tan/Mmeon/mnaon) to obtain 1.0 g (59965) of vil-

NMR (ZO0MHz, SOSIv) 2.60 (5, ЗН), 6.80-6.82 (t, amine of the target compound. Oxalate of the target 2), 7.03-7.12 (t, 4Н), 8, 03-8.06 (t, 1H); and the compound gives: m.pl. 156-157"; "H NMR (300 MHz, n). 5-(4-fluorophenoxy)-1H-indole: OM5O-yv) 2.94 ( 2H, 9y-7.3Hz), 3.00 ( 2H, 2.68g (2695) (red oil) was obtained , "H ue7,ZHz), 5.00 (Bg, 2H), 6.83-7.04 (t, 4H), 7.26-7.41

NMR (300 MHz, SOS") 6.50-6.52 (t, 1H), 6.91-7.01 (t, 5H), 11.05 (rg, 1H); mass spectrometry with electro- (t, 5H), 7.24-7.38 (t, ZN), 8.18 (Bi, 1H). by sputtering, t/e: 341.1 (M-1); analysis: calculating

Example 311: SivNivM2Ov: C, 63.15; H, 5.30; M, 8.18, 2-oxo-(5-phenoxy-1H-indol-3- was established: C, 62.97; H, 5.25; M, 8.20. yl acetyl chloride According to the method of Example 314, and kinds of

Mix 5-phenoxyindole (1.57g, 7.5mmol) and lila in the form of oxalate (unless otherwise indicated) anhydrous ether (Zb5ml), add a solution of the following compounds: lyl chloride (1.07g, 8.25mmol) in dZml of simple a) B-p-tolyloxytryptamine: "H NMR (300 MHz, ether. A precipitate falls out. Stir the reaction SOCI3) 2.31 (5, 3H), 2.83 (, 2H, 9U-6.4Hz), 2.98 ( mixture during the night. compounds: "H NMR 7.24-7.33 (t, 2H), 8.02 (Brg, 1H) (isolated as basic , 7.37-7.42 vu); (t, 2H), 7.60 (a, yn, 9u-8.7Hz), 7.75 (a, tn, b) 5-o-tolyloxytryptamine: m.p. 187-1882C, NN 9-2 AHC), 8.47 (0, 1H, 9U-3.2Hz), 12.49, (rg, 1H). NMR (300 MHz, ЮМ5О-в) 2.27 (5, ЗН), 2.90-3.05

(t, 4H), 6.66-6.68 (t, 1H), 6.76-6.79 (t, 1H), 6.93- spectrometry with electrospraying t/e: 6.98 (t, 1H ), 7.06-7.16 (t, 2H), 7.24-7.39 (t, ZN), 170.0 (M-1). 7.66 (g, 2H), 11.05 (rg, 1H); mass spectrometry with f) 4,7-difluoro-1H-indole. "H NMR (400 MHz, electrospraying, t/e: 265.1 (M-1-С-HgOx); OM5O-av): 11.91 (Brg 8, 1H), 7.44 (i, 1H, 9-2 ,8Hz), analysis: calculated: С1и9Нг2М2Ов: С, 64.04; Н, 5.66; 6.84-6.90 (t, 1Н), 6.69-6.74 (t, 1Н), 6, 54-6.56 (t,

M, 7.86, established: C, 63.90; H, 5.72; M, 7.83; and 1H); M5 (E5-): t/e 152.0 (M-1). c) 5-t-tolyloxytryptamine: m.p. 164-165"; Example 316

IN NMR (250 MHz, OM5O-adv) 2.26 (5, ZN), 2.89-3.07 3-formyl-b-chloro-7-fluoro-1H-indole (t, 4H), 4.52 (Bi, 2H), 6.68-6.72 (t, 2H), 6.82-6.86 Add with vigorous stirring oxy- (t, 2H), 7.17-7.42 (t, 4H), 11, 06 (Bg, 1H); mass of phosphorus chloride (0.94g, b.1bmmol) to dime- spectrometry with electrospray t/e: 265.1 tylformamide (12ml, cooled in an ice (M-1-C2HgOx) bath). After approximately 1 hour, add solution 6-

Example 315 chloro-7-fluoroindole (0.93 g, 5.6 mmol) in anhydrous b-chloro-7-fluoro-1H-indole dimethylformamide (4 ml), stir at

Mix a solution of boron trichloride (36.0 ml, at a temperature of 0 °C for an hour, warm to room temperature - a 1.0 M solution in heptane, Zb mmol) and a temperature of 1.2 t and stir overnight with dichloroethane (40 ml) and cool to a temperature of at room temperature (16 hours). Process at 5"C. Drop by drop, add a solution of 2-fluoro-3- 14.0 ml of 2M Mahon solution (4 eq.) with vigorous chloraniline (4.36 g, 30 mmol) in 20 ml of 1,2- stirring. Heat the reaction mixture with dichloroethane. Heat the reaction mixture to room temperature of 80"C for half an hour, then cool to room temperature and stir while stirring. Pour the reaction mixture into cold water with

Add chloroacetonitrile to the reaction mixture with vigorous stirring to obtain solid (2.71g, 36b, mol), then TiSi. (6.83g, 3.84ml, solids. Filter off the solids and 36.Ommol). Heat the reaction mixture with reverse - dry overnight in a vacuum oven with a room refrigerator overnight. Cool to room temperature to obtain the target compound: the reaction mixture to room temperature, add IN NMR (z00MHz, СОзСОсСО3/СОСИ3) 7.09 (u, 1Н, 55.0 ml of 2.5 M HCl solution, heat at a temperature of 9-7 ,7Gu), 7.83-7.86 (t, 2H), 9.89 (5, 1H). After heating at 85 °C for 30 min. Cool to room temperature. Example 316 obtained the following compounds: combine the organic layers, wash with (zOO0Mhz, СОзСОсСО») 6.98-7.06 (t, 1H), 7.71-7.75 salt, dry over Mag5O»4, concentrate ip (t, 1H), 8.35 (5, 1H), 10.04 (5, 1H); oil with 5.1 g of 1-(2-amino-2-fluoro-3-B) 3-formyl-b,7-difluoro-1H-indole. "H NMR of chlorophenyl)-2-chloroethanone; "H NMR (Z3O00Mhz, (z30OMhz, SOCI3) 7.10-7.19 (t, 1H), 7.86-7.88 (t,

SOCI3) 4.63 (5, 2H), 6.49 (rg, 2H), 6.62-6.69 (t, 1H), 7.98-8.03 (t, 1H), 8.95 ( rg, 1H), 10.06 (in, 1H); 1H), 7.36-7.39 (t, 1H). c) 3-formyl-5,6,7-trifluoro-1H-indole: "H NMR

Dissolve 1-(2-amino-2-fluoro-3-chlorophenyl)-2-(zOOMHz, COzSOSO»z) 7.87-7.93 (t, 1H), 8.42 (5, chloroethanone in 500 ml (1095 of water in 1,4-dioxane, in 1H), 10.07 (5.1H); and volume ratio) and carefully add MavNa a) 3-formyl-4,5,7-trifluoro-1H-indole: " H NMR (0.86 g, 22.8 mmol) at room temperature (300 MHz, OM5O-v) 7.46-7.55 (t, 1H), 8.49 (5, 1H),

Heat the reaction mixture under reflux - 10.02 (a, 1H, 2-3.7 Hz), 13.19 (rg, 1H). lyner for about 4 hours, cool to e) 3-formyl-4,7-difluoro-1H-indole: "H NMR at room temperature. Add 35 ml of 1M solution (400 Mhz, OM50-av): 6 13.03 (rg 5, 1H ), 10.00 (a,

NSI and stir at room temperature 1H, 2-3.2Hz), 8.36 (5, 1H), 7.07-7.13 (t, 1H), 6.94- for half an hour, extract with dichloromethane- 7.00 (t, 1H); M5 (ARSI): t/e 182.0 (M--1). nom (3x20ml), combine the organic layers, wash with 3-formyl-4,5,6,7-tetrafluoro-1H-indole: "NN

NgO and brine, dry over Mag50Ox and concen- NMR (400MHz, OM5O-av): 5 13.33 (ri 5, 1H), 9.94 ir massio. Chromatograph on silica gel (0, 1H, 9u-4,4Gu), 8.49 (5, 1H); M5 (E5-): m/e 216.0 with elution with a mixture of EtAs/hexane from the der- (M-1). extraction of the target compound, 0.94 g (2495): "H NMR Example 317 (300 MHz, SOCI3) 6.55-6.58 (t, 1H), 7.04-7.10 (t, 3-(2-nitrovinyl )-b-chloro-7-fluoro-1H-indole 1H), 7.22-7.33 (t, 2H), 8.38 (Bi, 1H). Mix 3-formyl-b-chloro-7-fluoro -1H-indole

According to the method of Example 315, the following (1.00g, 5.0bmmol), ammonium acetate (292mgG, compounds: C, 8mmol, 0.75eq.) were obtained (dried with the help of a) 5,7-difluoro-1H-indole. "H NMR (300 MHz, lpuol and remove toluene ip massio) and nitromethane

SOCI3) 6.55-6.56 (t, 1H), 6.71-6.78 (t, 1H), 7.01- (6.17g, 101.2mmol, 20eq.). Heat to temperature - 7.11 (t, 1), 7.26-7.28 (t, 1H), 8.34 (Bbg, 1H); after completion of the reaction (according to p) 6,7-difluoro-1H-indole. "H NMR (300 MHz, thin-layer chromatography), add

SOCI3) 6.53-6.56 (t, 1H), 6.90-6.99 (t, 1H), 7.22- likagel and remove nitromethane ip massio. Enter 7.31 (t, 2H), 8.39 (Running, 1H); silica gel to the upper part of short silica-c) 5,6,7-trifluoro-1H-indole: "H NMR (300 MHC, left column and elute 2595 with acetone solution

SOCI3) 6.52-6.55 (t, 1H), 7.13-7.20 (t, 1H), 7.26- in hexane to obtain, after evaporation, these- 7.27 (t, 1H) , 8.35 (bg, 1H); and left compound. a) 4,5,7-trifluoro-1H-indole: "H NMR (300 MHz, According to the method of Example 317, the following

ОМ5О-ав) 6.68-6.71 (t, 1H), 7.20-7.29 (t, 1H), compounds: 7.57-1.59 (t, 1H), 12.07 (bg , 1); mass-a) 3-(2-nitrovinyl)-5,7-difluoro-1H-indole: "NN

NMR (300 MHz, SOSI") 6.68-6.81 (t, 1H), 7.16-7.21

(t, 7), 7.60 (a, tn, O-13.5Hz), 7.73 (a, MH, a) 4,5,7-trifluorotryptamine: "H NMR (30OMHC, y2.7Gu), 8.18 (9, 1H, 9U-13.5Hz), 10.95 (Bg, 1H); СосСИз) 2.93 (i, 2H, 9U-6.6Hz), 3.03 (i, 2H, uU -6.4Gu), p) 3-(2-nitrovinyl)-6,7-difluoro-1H-indole: -"H 6.73-6.82 (t, 1H), 7.02 (5, 1H) , 8.58 (bg, 1H); mass

NMR (300 MHz, SOS") 6.93-7.00 (t, 1H), 7.30-7.35 spectrometry with electrospraying, t/e: (t, 7), 7.58 (a, tn, O -13.5Hz), 7.69 (a, 1nH, 215.0 (M-A1), 213.0 (M-1). y-2.9Hz), 8.10 (y, 1H, y-13 .5 Hz), 11.18 (Og, 1H): e) 4,7-difluorotryptamine: "H NMR (400 MHz, mass spectrometry with electrospraying t/e: OM50O-av): 11.57 (rg 5, 1H) , 7.19 (5, 1H), 6.80-6.85 225 (MA1), 223 (M-1); (t, 1H), 6.61-6.67 (t, 1H), 2, 79 (z, 4H), M5 (E5-): c) 3-(2-nitrovinyl)-5,6,7-trifluoro-1H-indole, m/e 197.0 (M--1) 180.0 (M-MH"). a) 3-(2-nitrovinyl)-4,5,7-trifluoro-1H-indole. In 4,5,6,7-tetrafluorotryptamine: 1H NMR e) 3-(2- nitrovinyl)-4,7-difluoro-1H-indole: M5 (400MHz, OM5O-av): 5 7.31 (85, 1H), 2.78 (5, 4H); (E5-): t/e 223 ,0 (M-1). M5 (Eb-yu): t/e 233.0 (M-a-1) 216.0 (M-16).

In 3-(2-nitrovinyl)-4,5,6,7-tetrafluoro-1H-indole: Example 319

M5(E5-): t/e 259.0 (M-1). M-(2-(5-phenoxy-1H-indol-3-yl)ethyl)-3-

Example 318 phenoxybenzylamine b-chloro-7-fluorotryptamine

Add drop by drop a solution of 3-(2-nitrovinyl)-6-chloro-7-fluoro-1H-indole (1.20 g, TU 5.06 mmol) in anhydrous tetrahydrofuran to 3 g of lithium aluminum hydride solution (30.Oml, 30, Ommol, M. about a 1.0M solution in tetrahydrofuran). Heat under reflux for 2 hours, then cool to room temperature. Quickly stop the reaction by carefully adding 5-phenoxytryptamine (0.400g, aqueous 1M Mahon solution to obtain a suspension of 1.59mmol), 3-phenoxybenzaldehyde /(0.377g, zies. Filter the suspension through a layer of celite and 1.90mmol) and molecular sieves 4A (0.40 g) in me- wash again with ether. Evaporate tanol (15 ml) and stir for 4 hours. filtrate and mass to obtain a residue. Chroma- Filter and wash several times, molecularly photograph the residue on silica gel with MeonN eluting sieves. In portions, add Movna with dichloromethane, methanol and hydroxide (61.5 mg, 1.59 mmol) to the filtrate and mix ammonium (10:1:01) with the product, after evaporation at room temperature for an hour. Edition, the target compound: "H NMR (300 MHz, SOS with) pouring MeonN under vacuum to obtain a residue, 2.87 (6 2Н, uU-6.6Hz), 3.02 (I, 2Н, 9-6, 7Hz), 7.03- dilute the residue with a dichloromethane/water mixture, 7.08 (t, 2H), 7.26-7.29 (t, 1H), 8.51 (Yug, 1H). | separate the layers, extract aqueous layer of respiratory

According to the method of Example 318, the following were obtained with lormethane, combine the organic layers and dry the compounds: | above Mag50»4. Concentrate ip massio and chromatog- a) 5,7-difluorotryptamine: "H NMR (300 Mgtsu, run on silica gel with elution with a mixture

CObIz) 2.46 (6 2H, 9-6.5Hz), 3.01 (, 2H, 9U-6.4Hz), dichloromethane/Meon with obtaining the target sp- 6.69-6.77 (t, 1H) , 7.03-7.11 (t, 2H), 8.29 (bg, 1H); meadows Obtain oxalate from the target compound: m.p.

B) 6,7-difluorotryptamine: "H NMR (300 MHz, 196-1982С; "H NMR (300 MHz, OM5O-av) 2.95-3.15

SOCI3) 2.87 (b 2H, 9U-6.6Hz), 3.02 (, 2H, 9-6.7Gu), (t, 4H), 4.15 (5, 2H), 6.85-7 .46 (t, 18H), 11.06 (bg, 6.88-6.97 (t, 1H), 7.04 (t, 1H), 7.20-7.25 (t, 1H), 1H ); electrospray mass spectrometry 8.64 (B, 1); t/e: 435.3 (Ma1); НЕМ5 (Eb- calculated for c) 5,6,7-trifluorotryptamine: "H NMR. (300MHC, SgoNo7M»O" (MeH) 435.2084 established

SOSIz) 2.83 (B 2H, 92-6.6Hz), 3.00 (1, 2H, 9U-6.7Gu), 435.2073. 7.08-7.14 (t, 2H), 8.71 (rg, 1H); mass spectrometry According to the method of Example 319, the following were obtained with electrospraying, t/e: 215.0 (Ma); and compounds isolated in the form of oxalate, with the exception of the one marked: p B ; sx still n

NITEY pom YOU PO x ROLLING POLONA and TECH UN t.pl. 204-2062C; "H NMR (250MHz, OM5O-dv) 2.25 (5, ЗН), 2.97-3.12 (t, 4Н), 4.01 (BI, 2Н), 4.16 (5, 2Н), mass -spectrometry with electro 320 |5-p-tolyloxy sputtering m/e: 449.1 (My1-C2Hg2O4); analysis: calculated for

Cz2NzoM2gOv: C, 71.36; H, 5.61; M, 5.20, established: C, 71.22; H, 5.59;

M, 5.28 square meters 191-1922C; "H NMR (300MHz, OM5O-dv) 2.28 (5, ЗН), 2.99-3.15 (t, 4Н), 4.17 (5, 2Н), 6.63-6.66 (t , 1H), 6.756.79 (t, 1H), 6.92-7.42 (t, 321 |5-o-tolyloxy phenyl 15H), 9.50 (bg, 2H), 11.05 (rg, 1H ); electrospray mass spectrometry t/e: 449.1 (Ma1-C2HgO»x); analysis: calculated for Cz2HzoMgOv:

C, 71.36; H, 5.61; M, 5.20, established C, 71.11; H, 5.59; M, 5.18 square meters 174-1752C, "H NMR (250 MHz, OM50O-dv) 2.51 (5, ЗН), 3.00-3.13 322 5-t- (t, 4H), 4.15 (v, 2H), 6.81-7.03 (t, 7H), 7.11-7.42 (t, 11), 11.05 (B, tolyloxy 1H): electrospray mass spectrometry t/e: 449.1 (Ma1 -

C2gHgOH m.p. 186-187"C, "H NMR (300MHz, OM50O-av) 3.13 (5, 4H), 4.15 in, 2H), 4.78 (a, 2H, 9-8.7Hz), 7, 07-7.12 (t, 2H), 7.21-7.24 (t, 1H), 7.37-7.45 323 b-chloro-7- 2,2,2- (t, 4H), 9.44 (rg, 1H), 11.72 (rg, 1H): mass spectrometry with trifluoroethyl electrophoresis, t/e: 401.2 (Ma-1-HC1), 399.2 (M-1 -NSI): analysis: calculated:

Sche9Ni?SIgaM2gO- NOSI: S, 52,19; H, 4.15; M, 6.41, established: C, 52.15;

H, 4.14; M, 6.38 (isolated as hydrochloride) m.p. 155-1562C; "H NMR (300MHz, OM50-av) 3.13 (5, 4H), 4.16 (in, 2H), 4.61 (B 2H, 9-13.5Hz), 6.70 (H, 1H, 9U-51.9Hz, 9U-5.5Hz), 7.08-7.10 (t, b-chloro-7- 22383. 2H), 7.11-7.12 (t, 1H), 7.21 -7.45 (t, 4H), 9.41 (Bg, 1H), 11.72 (bBg, 1H); 324 fluoroetrafluoropropyl electrospray mass spectrometry t/e: 433.2 (M-1-NSІ) , 431.2. (M-1-NSІ); analysis: calculated: SgoNivСИР5М2ОНСІ: C, 51.19; H, 4.08; M, 5.97, established: C, 51.27; H, 4.10 ; M, 6.07 (isolated as hydrochloride) m.p. 179-1802С; "H NMR (Z3O0MgCz, OM50-av) 3.11 (5, 4H), 4.16 (5, 2H), 4, 77 (a, 2H, 9-8.7Hz), 6.93-6.97 (t, 1H), 7.00-7.14 (t, 1H), 7.21-7.43 call | B,7-difluoro 2.2.2- (t, 5H), 9.41 (rg, 1H), 11.61 (Bg, 1H); mass spectrometry with trifluoroethyl electrodispersion m/e: 385.2 (Ma-1-HCI), 383.0 (M-1-HCI); analysis: calculated for Si9Ni7E5M2O-NOSI 0, 1H2gO: C, 54.00; H, 4.34; M, 6.63, determined: C, 53.71; H, 4.24; M, 6.70 (isolated as hydrochloride) mp 109-1102С; "H NMR (300 MHz, OM50O-av) 2.71-2.84 (t, 4H), 3.71 (5, 2H), 4.53 (I, 2H, 9-13.5Hz), 6.67 (NK, 1H, 9U-51.9Hz, 9U-5.5Hz), 6.87 calls | 5,7-difluoro 2,2,3,3- 7.02 (t, 4H), 7.12-7.28 (t, ZN), 11.40 (rg, 1H); mass spectrometry with tetrafluoropropyl electrospraying m/e: 417.0 (Mn), 415.0 (M-1); analysis: calculated for SgoNivEvM2O:0.1H2O: C, 57.45; H, 4.39 ; M, 6.70, established:

C, 57.24; N, 4.08; M, 6.68 square meters 164-1652C; IN NMR (300 MHz, OM50O-adv) 3.13 (5, 4H), 4.16 (5, 2H), 4.77 (a, 2H, 9-9.1Hz), 7.00-7.13 ( t, 2H), 7.20-7.23 (t, 1H), 7.33-7.43 327 | 6,7-difluoro 2.2.2- (t, 4H), 9.36 (rg, 1H), 11.57 (Bg, 1H); mass spectrometry with trifluoroethyl electrodispersion m/e: 385.2 (Ma-1-HCI), 383.3 (M-1-HCI); analysis: calculated for Сч19Ни7Е5М2ОНСЙ: C, 54.23; H . 3.02-3.17 (t, 4H), 4.16 (5, 2H), 4.59 (II, 2H, 9-13.5Gu), 6.68 (H, 1H, 9U- 51.9Hz, 9U-5.5Hz), 7.00- 328 | 6,7-difluoro 2,2,3,3- 7.17 (t, 5H), 7.21-7.42 (t, 4H ), 11.65 (rg, 1H); mass spectrometry with "tetrafluoropropyl by electrospraying tu/e: 417.0 (Ma-1-C4NaOz4), 415.0 (M-1-C4NaOx); analysis: calculated: SgoNivEeM2O:SaNaOl: 0.920: C, 52.54; N, 4.37; M, 5.11, established: C, 52.14; H, 3.95; M, 5.49 (isolated as maleate, m.p. 111-1122C; 1N NMR (300 MgCz, OM5O-yv) 2.72-2.81 (t, 4H), 3.71 (5, 2H), 4, 68 (а, 2Н, У-8.8Hz), 6.87-7.00 (t, ЗН), 7.22-7.40 (t, ЗН), 329 5.6.7- 2.2, 2- 11.58 (g, 1H); electrospray mass spectrometry t/e: 403.1 trifluoro trifluoroethyl |(M1), 401.2 (M-1), analysis: calculated for Si9NiReM2gO: С, 56.72 ; H, 4.01; M, 6.96, determined: C, 56.61; H, 3.92; M, 6.96 (separated as the basis of m.p. 223-224"C; "H NMR (300MHz, OM50O-av) 3.11 (5, 4H), 4.15 (5, 2H), 4.61 (5 2H, 9-13.5 Hz), 6.70 (B, 1H, 9- 51.9Hz, 9U-5.5Hz), 7.08-7.12 (t,

Bvt- 22383. 1H), 7.19-7.25 (t, 1H), 7.36-7.43 (t, ЗН), 7.52-7.58 (t, 1H), 9.50 ( B, 330 t ifto et aftog propyl 1H), 11.78 (Bg, 1H); mass spectrometry with electrospraying, t/e: riftor of propylene 351 (Ma1-NSII), 433.1 (M-1-NSII); analysis: calculated for

SgoNivEvM2gO-NSI-O,1H2O: C, 50.83; H, 3.88; M, 5.93, established: C, 50.60; H, 3.74; M, 6.07 (isolated as hydrochloride, m.p. 243-244"C; "H NMR (30MHz, OM50-av) 3.16-3.21 (t, 4H), 4.18 (5, 2H) , 4.75 (а, 2Н, 9-8.8Hz), 7.11-7.25 (t, ЗН), 7.39-7.45 (t, ЗН), 9.37 331 4.5, 7- 2,2,2- (g, TTN), 11.90 (Bg, 1H); mass spectrometry with electrospray trifluoro trifluoroethyl |t/e: 403.1 (MA1-HCI) 401.0 (M-1 -NSЙ); analysis: calculated:

Sze9NivBvM2gO NOSE: C, 52.00; N, 3.91; M, 6.38, established: C, 51.83; H, 3.62; M, 6.55 (isolated as hydrochloride, m.p. 261-262"C; "H NMR (300 MHz, OM50O-av) 3.18 (5, 4H), 4.17 (5, 2H), t- 223583 . aphtoi poropil 1H), 7.17-7.26 (t, 2H), 7.32-7.42 (t, ZN), 9.37 (Bg, 1H), 11.92 (Bri, 1H); p р р рпр mass spectrometry with electrospraying m/e: 435.1 (Ma-1-НСІ), 433.1 (М-1-НСІ); analysis: calculated: СгоНі7Е7М2О:-НСІ, С, 51.02; H ,

NO PI NNYA B ii iii rochloride) m.pl. 241-242"C; "H NMR (300 MHz, OM50O-av) 3.15 (5, AN), 4.17 (5, 2H), 4.78 (a, 2H, uU-8.7 Hz), 7 ,10-7.22 (t, ZN), 7.33-7.43 (t, ZN), 7.60-7.62 333 7-cyano 2,2,2- (t, 71), 7, 95-7.97 (t, 1), 9.29 (rg, 2H), 11.90 (VH, 1H); mas- trifluoroethyl | spectrometry with electrospraying t/e: 374.2 (Ma-1-NSI), 372.0 (M-1-NSI); analysis: calculated: SgoNivEzMzO:HCl-0.2H2gO: C, 58.10; N, 4.73; M, 10.16, established: C, 57.91; N, 4.56; M, 10.08, t.pl. 212-2132C; IN NMR (300 MHz, OM50O-dv) 3.16 (5, 4H), 4.16 (5, 2H), 4.61 (6 2H, 9U-13.6Gu), 6.69 (H, 1H, 9U -51.9Hz, 9U-5.5Hz), 7.09-7.22 (t, 223583. ZN), 7.33-7.43 (t, ZN), 7.60-7.63 (t, 1H), 7.96-7.98 (t, 1H), 9.34 (Bg, 334 7-cyanotetrafluoroethyl 2H), 11.92 (Brg, 1H); mass spectrometry with electrospraying t/e: 406.2 (Mya1-NSI), 404.0 (M-1-NSI); analysis: calculated for

C21NioBa«MzZONSII, S, 57.08; N, 4.56; M, 9.51, established: C, 57.12; N, 4.61; M, 9.53

Example 335 7.41 (t, 2H), 7.36-7.35 (t, 1H), 7.16-7.13 (t, 1H), 2-fluoro-3-phenoxybenzaldehyde 4,10-4, 04 (d, 2H), 1.64-1.40 (I, ZN).

Cool the solution of 2,2,6,6- According to the method of Example 336, the following tetramethylpiperidine (5.1 ml, 30.00 mmol) was obtained in the following compounds: a) 3-propoxybenzaldehyde: "H NMR rahydrofuran (40 ml) to a temperature of -787C. - (SOCIv) 9.95 (5, 1H), 7.43-7.41 (t, 2H), 7.37-7.36 then add p-butyllithium dropwise (18.7 ml, (t, 1H) ,7.17-7.14 (t, 1H), 9.98-3.95 (i, 2H), 1.84-30, Ommol, 1.6M solution in hexane) and stir 1.79 (t, 2Н), 1.05-1.02 (I, ЗН). for 10 minutes at a temperature of -78"С. Add phenyl ether of 2-fluorophenyl p-toluene-3-(2,2,3,3 - (4.7 g, 25.0 mmol) according to Example 337 drop by drop, stir for 2 hours tetrafluoropropoxy)tosylate at a temperature of -78"C. Drop Add M,M-dimethylformamide (2.3 ml, a sphere equipped with a mechanical stirrer, 30, mol) to a round-bottomed flask (5 L) with an inert atmosphere for 15 minutes. Stir the resulting mixture, add pyridine (1.9 L) (dried on the molecular length of the temperature of -787C, and aged sieves 4A) and add propanol (604.5g, 4.58mol) with heating to ambient temperature of 2,2,3,3-tetrafluoro-1-th. Cool the reactions - medium for 1 hour. Quickly stop the mixture in an ice bath to a temperature of 0"C. the reaction by adding cold water (5 Oml), extracting 4 to the reaction mixture for 20 minutes, adding ethyl acetate, drying over Ma»5Ox, portions of p-toluenesulfonyl chloride (960 g, filter and concentrating under reduced pressure 5.04 mol) and mix. After 20 minutes, with cooling and pressure to obtain oil. Crystallize the marmalade in an ice bath, a precipitate forms. Wash with hexane to obtain a solid, stir the reaction mixture for 1 hour, collect and recrystallize from the mixture of hexane at a temperature of 0"C and for 2 hours at a temperature of n/ethyl acetate/umethylene chloride to obtain 2076. Pour off the reaction mixture with stirring of the target compound: t. pl. 75-777С; MB(t/e): 216 to a mixture of water with ice (1.44 l) and stand (Mk); analysis for SizNeoBO»:: calculated: С, 72.22; during the night (18 hours) at temperature of 2070. No-

H, 4.20, established: C, 72.41; N, 4.23. Purification The purified tosylate derivative is separated from the mother liquors by chromatography of the aqueous mixture as an oily material on silica gel (2-3906 ethyl acetate/hexane mixture) (1.34 kg) containing 1495 (by mass) gives an additional amount of the target compound: M5 pyridine, which corresponds to 1.15 kg of tosylate (87.890). (t/e): 216 (MU). Unrefined material is used for

According to the method of Example 335, the following compounds were obtained in the reaction stage without additional purification: compounds: a) 6-fluoro-33-phenoxybenzaldehyde: M5 1TIN-YAME is suitable. (t/e): 216 (MU). Example 338

Example 336 3-(2,2,3,3.3-pentafluoropropoxy)benzaldehyde

C-ethoxybenzaldehyde Mix C-hydroxybenzaldehyde (137.6g,

Mix 3-hydroxybenzaldehyde (5.6 g, 1.127 mol), p-toluene-3-(2,2,3,3,3-46 mmol) and 1-iodoethane (10.7 g, 9 mmol) in dimepentafluoropropoxy)tosylate ( 243g, 0.799mol), thylsulfoxide (25ml) and heat potassium carbonate (220g, 1.597mol) and dimethylformamide to a temperature of 80°C. Process cesium carbonate rmamide (2451ml) in portions in a 4L reactor with double walls (22.Ag, bumol ).During the addition, the temperature of the kama equipped with a partial condenser begins to rise, so the bath is removed. hot irrigation and a mechanical stirrer, and

Stir the reaction mixture at a temperature of 110"C for 80"C for an hour, pour into 200ml of brine and for 46.5 hours in an argon atmosphere. Cool the reaction mixture and extract twice with 150 ml of diethyl ether. Bring the mixture to room temperature twice and filter, wash the combined extracts with 200 ml of brine, pass through a layer (400 g) of silica gel. Elute the layer, dry over Mdzoh and concentrate under vacuum on licagel with 2451 ml of ethyl acetate. Infusions are combined to obtain oil. Purification by chromium-organic layers in 7.000 ml of a mixture of water and ice. Dotography (51052; 2.595 solution of EtOAc in hexane) add to this mixture a TOM solution of sodium hydroxide gives 5.73 g (Zvmmol; 8395) of the target compound in (500 ml) and stir for an hour. Separation of oil: "H NMR (SOCI3) 9.94 (5.1H), 7.42 - wash the aqueous phase and extract with ethyl acetate

(1000 ml). Combine the organic phase, wash the reaction mixture to a temperature of 65-7C with the obtained water (10000 ml) and brine (750 ml). and heat under pressure to obtain 159.79 g of an oily mother- at the temperature of distillation for 5 hours. A cool, brownish color, which includes the unpurified reaction mixture to a temperature around the target compound. Thanks to the fractional distillation of the excess medium, and add borohydride to (two consecutive cycles ) under reduced pressure (2 MmmM triium (267 mg, 7.immol). Stir the reaction Hg.) using a distiller, equipped - the mixture for 18 hours at ambient temperature with an adiabatic column with a length of 30 cm, a medium. Cool the reaction mixture 52.4 g fraction of the expected product (96.290 in a water bath, quickly stop the reaction do- area according to the data of a highly efficient liquid by giving cold acetone, dilute eta by chromatography). and acetone, and filter through molecular sieves.

Example 339 Concentrate the filtrate under reduced pressure, dilute 3-(3,3,3-trifluoropropoxy)benzaldehyde with 1M Mahon solution, extract with ethyl

Mix 3-hydroxybenzaldehyde (130 2 g, with acetate, wash with brine, dry 1.066 mol), 3,3,3-trifluoropropoxytosylate (143 Hg, (Mag2504), filter and concentrate under 0.53 3 mol), potassium carbonate (147.35 g, 1.066 b mol ) under reduced pressure to obtain 1.0 g of oil. Chro- and absolute ethanol (1430 ml) in a three-neck matograph on silica gel with elution 1905, round-bottom flask equipped with a partial 496 2M solution of ammonia in a mixture of methane- hot irrigation condenser and magnetic lu/methylene chloride with a clear stirrer, and heated at the temperature of the distillation of colorless oil . Preparation of hydrogen chloride - for 4 hours in an argon atmosphere. of the concentrated salt in a mixture of ethyl acetate/methanol to ensure the reaction mixture under reduced pressure. Pour the preparation of the hydrochloride of the target compound: the concentrated mixture into a 1M hydroxide solution at room temperature. 173-174,570; M5 (t/e): 379 (Mn), 377 (M-1); tritium (2145ml), stir for 30 minutes and analyze for Cg2zNgob2M2OHnSiI: calculated: C, 66.59; extract with dichloromethane (2145 ml). Drain H, 5.10; M, 6.75, established: C, 66.50; H, 5.09; M, organic layer, washed with 1 M hydroxide solution 6.73. of sodium (2145 ml). After separation, sequentially Example 341, wash the organic layer twice with 1 l of water (pH of aqueous M-(2-(6-fluoro-1H-indol-3-yl)uethyl)-6-fluoro-3-phase-7), dry over 30 g of sulfate magnesium, phenoxy-benzylamine, evaporate dichloromethane, dry the organic layer under reduced pressure to obtain 55.4 g of the target E compound (0.254 mol, 47.695 yield) in the form of a light-yellow fibrous material. and about

Example 340 M

M-(2-(6-fluoro-1H-indol-3-yl)ethyl)-2-fluoro-3-n phenoxy-benzylamine I I

The hydrochloride of the target compound is obtained by the method of Example 340: m.p. 183.5-185.57С2; M5

There are these, F (t/e): 379 (Ma1), 377 (M-1); analysis for

Y Ge) С2гзНгог2М2гО Her: calculated: С, 66.59; H, 5.10; M,

ME 6.75, established: C, 66.54; H, 5.11; M, 6.68. According to the method of Example 340, the following were obtained

Mix 6β-fluorotryptamine (419mg, 2.35mmol) in sodium chloride, and 2-fluoro-3-phenoxybenzaldehyde (610mg, 2.82mmol) in absolute ethanol (bml). Heat up

M-

N me! 2 | In | 77777777777yusodan//777777711111111c1

IZM5 325 (Ma1); analysis for СгоНг5СИМ2О» 0.2ЕУН 0.1Н2О: calculated:

C, 65.88; H, 7.16; M, 9.53; established: C, 65.90; H, 6.97; M, 7.16; "NN 342 | 5-methoxy ethyl NMR (0M50-av) 10.85 (5, 1H), 9.43 (p5, 2H), 7.42-7.22 (t, AN), 7.18-710 (t, 2H), 7.05-7.0 (t, 1H), 6.32-6.15 (t, 1H), 4.3-4.15 (t, 2H), 4.15-4 .05 (а, 2), 3.85 (c, ЗН), 3.15 (5, 4Н), 1.45-1.35 (I, ЗН

IBM5 339 (Mch); analysis for Сг2иН27СИМ2О»: calculated: C, 67.28; H, 7.23;

M, 7.47; established: С, 67,28; H, 7.30; M, 7.13; "H NMR. (0M50O-d0v) 343 | 5-methoxy 10.85 (5, 1H), 9.43 (p5, 2H), 7.35-7.15 (t, 4H), 7.1-7 .05 (t, 2H), 7.0-6.92 (t, 1H), 6.7-6.6 (t, 1H), 4.3-4.16 (t, 1H), 4.15 -4.05 (d, 2H), 3.85 (5, ЗН), 3.15 (5, 4Н), 1.45-1.35 (I, ЗН trifluoroethyl |/|4.75; M, 6 .95; found: C, 56.37; H, 4.83; M, 6.81 (base 345 | 5-methoxy 2,2,2- Analysis for ChoHg2SiEzM2O): calculated: C, 57.91; H, 5.34; M, 6.75; standing

0 | trifluoroethyl |novleno:;С,57,72;Н, 517; M, 66 I5M5379(MY).S7777111 2,2,3,8,3- IZM5 417 (M--1); analysis for SgoNivEeM2gO C2HgOx: calculated: C, 51.18; 346 5-fluoropentafluoropropyl Nelnav; M, 5.53; established: C, 51.18; N, 3.91; M, 5.51 (allocated as ca. 225583- IBM5 429 (Mat); analysis for CgiNa1P5M2O» 1.2C2H2Oz 0.8HgO: calculated: 347 | 5-methoxy pentafluoropropyl C, 51.02; H, 4.57; M , 5.09; determined: C, 50.64; H, 4.23; M, 5.15 (separated as oxalate) seed | ot sne SA M VL maple 348 | 5-methoxy otc 55.0; H, 4.86; M, 5.58; established: C, 54.74; H, 4.74; M, 5.58 (separated tetrafluoropropyl as trifluoropropyl oxalate | established: C, 58.42; H, 5, 44; M, 6.51; IZM5 393 (Ma1) tetrafluoropropyl | established: C, 57.49; H, 5.04; M, 6.76; IZM5 381 (Ma methoxy trifluoroethyl | established: C, 53.33; H, 4.65; M, 6.21; IZM5 413 (Ma-1 methoxy |tetrafluoropropyl| determined: C, 52.25; H, 4.50; M, 5.80; IZM5 445 (Ma1) methoxy | trifluoropropyl found: C, 54.18; H, 4.86; M, 6.06; IZM5 427 (Ma1

According to the method of Example 340, the following compounds were obtained, isolated in the form of hydrochloride, with the exception of the indicated: and

K r K - f --, thing d-

TI Me ZL PI: PH MON 5 ST TON trifluoroethyl /|4.77; M, 3.68; established: C, 53.61; H, 4.96; M, 3.66 3- 299. IZM5 378 (Ma1); analysis for SgoNioReMO»5: calculated: C, 51.40; H, 361 1" 4.10; M, 3.0; determined: C, 51.26; H, 4.06; M, 3.07 (isolated as oxyfluoromethyl trifluoroethyl salate) pentafluoropropyl 4.22; M, 3.26; determined: C, 50.38; H, 4.03; M, 3.45 3- 22333- IZM5 428 (Ma1); analysis for С19Н17Е8МО С2Нхох: calculated: С, 48.75; 363 riftomethylipentafluoropropyl sisal 2.710 ; determined: C, 48.76; H, 3.67; M, 2.79 (isolated as tetrafluoropropyl | 3.01; determined: C, 51.92; H, 4.29; M, 3.08; IZM5 376 (Mat) 3- 2,2 8,8- Analysis for C1i9NivE7MO C2NgOl: calculated: C, 50.51; H, 4.04; M, 2.81; 365 riftomethyltetrafluoropropyl established: C, 50.48; H, 4.02; M, 2.85; IZM5 410 (M) (isolated as rifluoromethyl trifluoropropyl | determined: C, 53.23; H, 4.73; M, 3.28; IZM5 392 (Ma-1) trifluoropropyl | established: C, 54.74; H, 5.02; M, 3.11; IBM5 358 (Ma-1

Example 370 would also process Mavna (148 mg, 3.9 mol). Alternately

M-(2-(6-fluoro-1H-indol-3-yl)ethyl)-3-(2,2,2-stir for 1 hour, concentrate the reaction trifluoroethoxy)benzylamine mixture in oil to obtain a residue. Divide the residue between 25 ml of 5M Mahon solution and 25 ml of dichloromethane. Extract the aqueous layer

A E 25 ml of dichloromethane, combine the organic layers,

Her | dry over Md5Ox and concentrate to approx.

And g zno 20 ml volume. Chromatograph on silica gel with 195 elution with MeonN solution in SNI", changed. . treated with a concentrated solution of MNAOH, with

Mix 6-fluorotryptamine oxalate (350 mg, obtaining the target compound. Mix a solution of 345.2 zmmol of d-trifluoroethoxy)benzaldene of the target compound in EtOAc with a solution of one equivalent of oxalic acid in E(Ac from the obtained (2bBbmg, 1, mmol) and molecular sieves (47) In the absence of solid, filter the solid

EUN (Zoml) and heat with the reverse refrigerant, the substance and dry under vacuum with the formation of lumps for 7 hours. Drain the liquid into a separate container

oxalate of the target compound: IZM5 367 (M-1); Analyzing by the method of Example 370, the following lyzes were obtained for Sti9NiOSIBaAM2O: calculated: C, 55.27; H, compounds isolated in the form of hydrochloride, according to 4.42; M, 6.14; established: C, 55.17; N, 4.38; M, connecting the indicated: 6.09.

OA

AND

NI TE field Sl PO s RON KOOOOOOOOOONNY x TE OOOOOOOOOOOOO 22383. ИЗМ5 399 (Ма1); analysis for C19H17E8MO C2HgO4 HgO: calculated: C, 372 5-fluorotetrafluoropropyl 53.51; H, 4.41; M, 5.67; established: C, 53.12; H, 4.21; M, 5.63 (separated as oxalate) pentafluoropropyl was determined: C, 52.88; H, 4.05; M, 6.12; IZM5 417 (Ma1

Analysis for SgoNgoSIEzM2O» NOI: calculated: C, 53.47; N, 4.71; M, 374 b-chloro-5-2,2,2-6,24; established: C, 53.65; N, 4.85; M, 6.45; IZM5 413 (Ma) methoxy trifluoroethyl | (Forms a salt in 50 ml of a mixture (50/50) of tetrahydrofuran/E(OH with the use of polyvinylpyridine hydrochloride) methoxy tetrafluoropropyl 5.82; determined: C, 52.15; H, 4.51; M, 5.69; IZM5 445 (Ma-1 tetrafluoropropyl | established: C, 55.06; H, 4.63; M, 6.44; IZM5Z 399 (M--1) trifluoropropyl | established: C, 54.74; H, 5.02 ; M, 3.11; IZM5 381 (MaA1) riftomethoxy|Ipentafluoropropyl| established: C, 48.55; H, 3.48; M, 5.33; IZM5 483 (Ma-1 riftomethoxy|tetrafluoropropyl| established: C, 50.27; H, 3.92; M, 5.63; IZM5Z 465 (M--1) riftomethoxy! trifluoroethyl | established: C, 51.33; H, 4.09; M, 6.26; IZM5 433 (M--1

Example 381 142-144"C; "H NMR (250MHz, OM50-av) 2.24 (in,

M-tert-butoxycarbonyl-2-(5-t-tolyloxy-1H-ZH), 2.634 (5, ZH), 3.01-3.12 (t, 4H), 3.92 (ri, 2H)) , indole-3-yl)ethylamine 4.16 (in, 2H), 6.65-6.70 (t, 2H), 6.81-6.84 (t, 2H),

The target compound is obtained by the method 6.99-7.03 (t, ЗН), 7.12-7.26 (t, 6Н), 7.34-7.43 (t,

Example 20: "H NMR (300 MHz, SOSIz) 1.41 (5, AN), 11.00 (Brg, 1H); mass spectrometry with electro-

ОН), 2.30 (5, ЗН), 2.89 (i, 2Н, 9-6.7Hz), 3.41 (t, 2Н), sputtering t/e: 463.4 (М-1-С2НгОх ); analysis: 6.74-6.85 (t, ЗН), 6.93-6.99 (t, 1Н), 7.07-7.35 (t, calculated for СззиНзаМ2Ов: С, 71.72; Н, 5.84; M, 4H), 8.05 (Bi, 1H). 5.07, established: С, 71.44; H, 5.89; M, 4.99.

Example 382 Example 384

M-methyl-2-(5-t-tolyl)tryptamine B-nitrotryptamine

The target compound is obtained by heating a mixture of 5-nitroindole (10g, b2mmol) and

Example 21; oxalate preparation gave: m.p. 200 ml of glacial acetic acid to a temperature of 182-1832C; "H NMR (250MHz, OM50-av) 2.26 (v, t0"s and treated with Eschenmoser salt

ZN), 2.59 (5, ZN), 2.98-3.18 (t, 4H), 6.68-6.72 (t, (Ezspeptoseg5 for!) (12g, b5mmol). After 1h g) , 6.82-6.86 (t, 2H), 7.17-7.22 (t, 1H), 7.29-7.42 concentrate the reaction mixture under vacuum to (t, Н), 11.06 ( Bg, 1H); mass spectrometry from elec. dryness. Mix the residue with 200 ml of toluene, atomizing, m/e: 281.2 (Ma-1-C2HgOx); analysis: concentrate again to dryness, after which it was calculated for СгоН2г2М2Ов5: C, 64.85; H, 5.99; M, divide between 200 ml of a concentrated solution of 7.56, set: C, 65.01; H, 5.74; M, 7.71. ammonium hydroxide and 200 ml EtOAc. After calculating

Example 383 of all solids, separate the layers and

M-methyl-Im-(2-(5-t-tolyloxy-1H-indol-3-) extract the aqueous layer with 200 ml of EtOAc. Dry the yl)ethyl)-3-benoxybenzylamine. - concentrate to obtain /M,M-dimethyl-5-nitrotryptamine as a solid.

U Dissolve the obtained M,M-dimethyl-5-nitrotryptamine in 200 ml of dry dimethyl sulfoxide

C is sidu, treated with iodomethane (7.7 ml, 17.5 g,

M about 124 mmol) and stir for an hour at m | ambient temperature. Add

H KSM (40 g, 621 mmol) and 18-crown-b (0.5 g). Heat the reaction mixture at a temperature of 11070

The target compound is obtained by the method within 45 minutes, cool, pour on ice, after

Example 301; oxalate preparation gave: m.p. what to feed Masi. Extract the cooled reaction mixture with EtOAc, combine the extracts and wash the b-nitrotryptamine three times with brine. Dry over Ma5ox and (b-nitro-1H-indol-3-yl)y-acetonitrile is obtained, concentrate under vacuum, chromatograph according to the method of Example 384: IZM5 200 (M-1); on silica gel eluting with 195 solution of meon analysis for SchioH7MzO" 0.120: calculated: C, in CHcSiIz with obtaining (5-nitro-1H-indole-3- 59.17; H, 3.58; M, 20.70; determined: C, 59.04; H, yllacetonitrile in the form of a solid substance: 3.28; M, 20.39, which ensures the preparation of the entire

EOM5 201 (Mk); analysis for С1иоН7УМзО»: calculated compound: IZM5 206 (Ma); "H NMR (0M50O-dv) found: C, 59.70; H, 3.51; M, 20.89; determined: C, 11.5 (65, 2H), 8.26 (5, 1H), 7.84-7.81 (t, 1H), 7.68-59.32; H, 3.52; M, 20.56. 7.66 (t, 1H), 7.57 (85, 1H) , 2.80-74 (t, 4H) (indole M-

Dissolve (5-nitro-1H-indol-3-yl)acetonitrile H is not observed). (9g, 44.7mmol) in 250ml of anhydrous tetrahydrofuran Example 390 and treat 90ml of a 1M solution of ВНз in tetra-M-(2-(5-nitro-1H-indol-3-yl)ethyl)-3-hydrofuran at of the surrounding se-phenoxybenzylamine row. Stir overnight and quickly stop the reaction by carefully adding 10ml of cold water dropwise. Concentrate to dryness under vacuum and distribute the residue between a 5M solution of HCl and EtOAc. Extract the aqueous layer with EAs and combine with the original EtOAc layer. Treat the aqueous layer with a 5M Mmaon solution and extract it three times with a 1095 solution. Purify the extracts by using Example 340; formation of salt in 0.0000000000000000000000000000000000000000000000000 of 0.00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000010

ЗСХ, wash 2 liters of MeOH, which was poured off, after further concentration with obtaining a solid, which is washed with a 2 M solution of MHz in MeOH and the concen- tance ensures the receipt of dark-colored hydrogen chloride solid substance: C, 64.62; N, (Math); analysis for SgoNivReMgOg2:0.3NgO0.1C7Nv: 5.17; M, 9.75; established: C, 64.89; H, 5.40; M, calculated: C, 57.34; H, 5.74; M, 19.29; set - 9.75; IZM5 388 (Ma1). but: C, 57.30; H, 5.38; M, 19.08; "H NMR (OM5O-yv) According to the method of Example 390, the following 11.9-11.2 (re, 1H), 8.50-8.49 (y, 1H), 7.95-7.92 (t, compounds isolated in the form of hydrochloride, according to 1H), 7.47-7.45 (t, 1H), 7.98 (85, 1H), 2.79 (in, 4H), excluding the indicated: 2.2 -1.3 (re, 2H).

Example 385

He is waiting for the right as a member of the NN

NI T-MY R PO: RON PON ST UNO trifluoroethyl |Н, 4.48; M, 9.74; established: С, 52,63; N, 4.34; M, 9.67 tetrafluoropropyl M, 9.10; established: C, 51.94; H, 4.19; M, 8.93

IZM5 394 (M-1); "H NMR (SOCIz-free base) 8.47 (5, 1H), 8.31-8.30 (t, 393 | v-nitro 2.2,2- 1H), 8.01-7.98 (t, 1H), 7.63-7.61 (t, 1H), 7.32-7.31 (t, 1H), 7.24-7.21 (t, trifluoroethyl|1H), 6.94-6, 92 (t, 1H), 6.88 (5, 1H), 6.80-6.77 (t, 1H), 4.33-4.26 (t, 2H), 3.79 (5, 2H) , 3.00-2.93 (t, 4H), 1.54 (5, 1H) tetrafluoropropyl 9.10; determined: C, 51.96; H, 4.16; M, 8.76 76, established: C, 49.76; H, 3.86; M, 8.67

Example 396 O,b4mmol) and MiSi»-6NgO (460mg, 1.9mmol) in

M-(2-(5-amino-1H-indol-3-yl)ethyl)-3-ZOml Meon and treated Mavna (7Zmg, 1.9mmol). phenoxybenzylamine After 1 hour, concentrate to dryness, distribute between EAs and concentrated MNAOH solution.

No Extract the aqueous layer of EOASs, combine organic

Fe night layer, dry over Md5O»h and concentrate

M g to dryness. Chromatograph on silica gel with 9) step gradient elution (20/75/5)

I tetrahydrofuran/hexane/EVvvM, followed by (40/55/5) tetrahydrofuran/hexane/EizM, with the receipt of this

Mix /-M-(2-(5-nitro-1H-indol-3-yl)ethyl)-3-ol compound in the form of oil. Additional chlorophenoxybenzylamine hydrochloride (250 mg, matography on silica gel eluting with a 195 solution of Meo9nH in СНеСі», mixed with concentrated С2зНгзМ30О:2.6НСІ-О.6ЕУН: calculated: C, 59.66; МНАОН solution gives the target compound in H, 5.83; M, 9.07; established: C, 59.30; H, 5.48; M, in the form of oil. Treatment of 100 ml of EN with 0.25 ml of 5M 8.82; IZM5 358 (M1). solution NCI and 40 ml of toluene followed by con- According to the method of Example 396, the following centration gives the target compound in the form of hydro- compounds, isolated in the form of hydrochloride, in the form of hydrochloride: analysis for the connection indicated by: then pu,

Al

M

N

Mmm 2 | В» І7777777777І7ІюІІІІІІІодани77777777777777111111111с1 and Analysis for Си9НГоезМзО 2НІІ 0.2СНСіИз 0.З3СНзОН: calculated: C, 49.85; .2-trifluoroethyl| at 5.02: M, 8.94: established: C, 50.05; H, 4.99: M, 8.73: IZM5 364 (Ma

IN NMR (0M50-yv) 11.3 (05, 1Н), 10.25 (р5, ЗН), 9.6 (re, 2Н), 7.6 (5, 1Н), 398 | B-amino 2,2,3,3- 7.5-7.35 (t, 4H), 7.3-7.2 (t, 1H), 7.2-7.0 (t, 2H), 6.9-6.5 (0, 1H), 4.65-4.5 (i, tetrafluoropropyl | 2H), 4.25 (5, 2H), 3.3 (5, 4H); analysis for SgoNaiB«MzO 2NOI: calculated: C, 51.29; H, 4.95; M, 8.97; established: C, 51.26; N, 4.98; M, 8.26

IZM5 363 (Me); SteHng2Si2EzimzO-0.4H20: calculated: C, 51.45; H, 5.18; M, 393 | β-amino |p,2.2-trifluoroethyl 9.48; established: C, 51.45; H, 5.10; M, 9.63 400 2,2,3,3- IZM5 393 (Me); SgoNgzSi»2RaMzO:0.2H2O0: calculated: C, 50.90; H, 5.00; M, tetrafluoropropyl | 8.90; established: C, 50.73; N, 4.82; M, 8.65

Example 401 at a temperature of 4573 to obtain chloride-b-fluorotryptamine day salt of the target compound.

Mix 6-fluoroindole (108g, 0.8mol) and dichloromethane (324ml). Cool in an ice bath. M-(2-(6-fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-

Add trifluoroacetic-tetrafluoropropoxy)benzylamino acid (308 ml) over several minutes (exothermic reaction).

Over 40 minutes, add a solution of 727-1-dimethylamine-E 2-nitroethylene (94.7 g, 0.816 bmol) in dichloromethane M (b0O0 ml) while simultaneously maintaining the temperature at the level of approximately 0-57C. After 45 minutes, heat the mixture to a temperature of approximately 20°C. After 2 hours, pour into 1.2 liters of water and ice mixture and stir overnight with the addition of seed for the preparation of diodes and odors (SO substances. Filter the solid Mahon (gm, 230 ml) and dichloromethane (900 ml) substance, wash first with 100 ml of a mixture of dichloromethane and methane-cyclohexane (PL, then 750 ml of water and wash the wavy layer with dichloromethane, combine and dry at a temperature of 4076 with obtained 3- organic layers, washed with water, dried over the dilutions of KN, SHOV. 1ovbmol, side) and 0 MOB and filtered to remove the residue. mixture: tetrahydrofuran (vavml) and cooled on ice - 0 one Theo, the bridge of Zunate color. The mixture of water bath to a temperature of approximately 6" while simultaneously maintaining the temperature below the above by obtaining the first portion of 3276. Add a solution of 3-(2-nitrovinyl)-6-fluoroindole (53g, 0.257mol, Eq.) in tetrahydrozal borty and 2233. taperanury tsa with the relevant SUBTRI Zes you tetrafluoropr propylbenzaldehyde (176 g, keep in the oven with stirring at a temperature of 100 °C for a day, cool to room temperature after 10 days. After 2.5 hours, quickly add MaVNa (35.2 g, 0.93 mol, stop the reaction by adding 49 ml of cold water 1. Beq.). After an hour, filter through a layer of 49 ml of cold tetrahydrofuran, then 43 ml of celite and wash with 500 ml of ethanol. Evaporate the cold 1576 solution of Masonry and, finally, 4 ml of the literate under reduced pressure to obtain oil-cold water. During the termination of the reaction, the following: Divide the residue between adding cold product, maintain with water and dichloromethane. in 750 ml of diethyl ether and cool in an ice-water bath. Add under reduced pressure to obtain the title compound" solution. NesSi/diethyl ether to obtain nom: Mix M-(2-(8-fluoro-1H-indole-Z- yl)ethyl)-3- solid. Stir for 1 hour, (2,2,3,3-tetrafluoropropyl)benzylamine (387, filter the solid, wash with diethyl ether (3.95 L) at room temperature ether and dry under reduced pressure at that temperature. During 15 minutes drop by drop

add NCI/ESO solution (298 ml) until the pH of the 5-methoxycarbonyl-1H-indole solution in portions reaches a level of approximately 3 with obtaining a solid 30 ml of dimethylformamide with maintenance of the substance. Stir for an hour and collect the precipitates below 20°C. Remove the cooling solid, wash with ether, wash and stir the reaction mixture at room temperature, dry under reduced pressure at ambient temperature for 40°C to obtain the target compound in the form of 1h , then pour over ice. During the addition of the hydrochloride. 5 Oml of 5M solution of Mahon to the precipitate precipitates solid

Example 410 substance, which is filtered off and washed with vo-(5-bromo-1H-indol-3-yl)acetonitrile and EIOAcC to obtain the target compound: "H

The target compound was obtained by NMR (OM50-α) 9.95 (5, 1Н), 8.76 (5, 1Н), 8.4 (5,

Example 384 with the use of 5-bromoindole: 1H), 7.9-7.8 (t, 1H), 7.5-7.7 (y, 1H), 3.85 (5, ЗН), 1.7

IZM5 234 (M-1); analysis for SioNUVIM2 0.1H20: (5, 18); ИЗМ5 204 (М-А1). calculated: C, 50.70; H, 3.06; M, 11.83; established Example 415: C, 50.69; H, 2.90; M, 11.64; "H NMR (SOCI3) 3-(2-nitroethyl)-5-methoxycarbonyl-1H-indole 8.22 (5, 1), 7.70-7.69 (t, 1), 7.33-7, 31 (t, The target compound is obtained by the 1H method), 7.24 (5, 1H), 7.23-7.22 (t, 1H), 3.78-3.77 (t, Example 317: "H NMR (0М50-ав) 12.5 (re, 1Н), 4Н). 8.38-8.37 (t, 1H), 8.37-8.34 (t, 1H), 8.23 (v, 1H),

Example 411 7.87-7.84 (t, 1H), 7.80-7.77 (t, 1), 7.57-7.55 (y, 5-bromotryptamine Ш), 3.85 (5, ZN); IZM5 246 (M'n1).

Dissolve 5-bromo-1H-indole-3-carbonitrile Example 416 (9.5g, 40.4mmol) in 200ml of anhydrous tetrahydro-3-(2-nitroethyl)-5-methoxycarbonyl-1H-indolefuran and treat with 8O0ml of a 1M solution Treat a solution of 3-(2-nitrovinyl)-5-hydrofuran at ambient temperature of methoxycarbonyl-1H-indole (57mg, 0.233mmol) in the medium. Stir overnight, add 9ml of tetrahydrofuran and 2ml of Meon, and stop the reaction by carefully adding Goi Mavna (26mg, 0.b9mmol). Mix 5 ml of cold water drop by drop. Concentrate at ambient temperature to dryness under vacuum overnight, concentrate to dryness and distribute the residue. Divide the residue between a 1M solution between a concentrated solution of MNAOH (10ml) and

NSI and EUAs. Extract the organic layer with copper dichloromethane. Extract the respirable aqueous layer with the original aqueous layer, a 1M solution of lormethane, acidify with a concentrated solution of

NOSE Treat the aqueous layer with a 5M solution of Mahon and nom NOSI and extract twice with dichloromethane. Extract E(OAc. Saturate the mass and extract the organic layers again, concentrate (I treat with EOAc. Combine the extracts, dry, chromatograph on silica gel with elution over Ma5Ox, and concentrate to dryness with the resulting Meon solution in SnClII" with the aim of obtaining 4.72 g (19.7 mmol, 4995) of oil, which is a crystalline compound in the form of a solid: , 1H), 7.92-7.90 (t,

Conversion to oxalate is carried out by treating a solution of the mentioned compound in EAsC ( , 2H), 3.93 (5, ЗН), 3.51-3.48 (I, 2H); IBM5 248 with a solution of one equivalent of oxalic acid. (Ma).

Filter the resulting solid and dry it under vacuum. Example 417: Analysis for SiONi1VI/M2

SoNgO» NgO: calculated: C, 43.08; H, 4.10; M, 8.37; Mix 3-(2-nitroethyl)-5-methoxycarbonyl- established: C, 43.26; N, 3.91; M, 8.20; IBM5 240 TN-indole (280 mg, 1.1 mmol), RIO" (200 mg) and 15 ml (MA). Mmeon and hydrogenate under atmospheric pressure

Example 413 during the night. Filter the reaction mixture

B5-methoxycarbonyl-1H-indole through a layer of celite, concentrate the filtrate and

Mix a solution of 5-carboxyindole (7.2 g, chromatographed on silica gel with an elution of 44.7 mmol) in 400 ml of dichloromethane and 100 ml of Meon solution in SNI", mixed with concen-

OH and treat by adding drop by drop 35 ml of a poisoned solution of MNAOH, with the preparation of a complete 2M solution of tetramethylsilanediazomethane in the form of oil: IZM5 219 (Mai1); "H sled. Stir overnight at ambient tempera- NMR (SOSI") 9.01 (5, 1H), 8.36 (5, 1H), 7.88-7.85 ambient temperature. Concentrate (t, 1H) ,7.32-7.24 (t, 1H), 7.05 (t, 1H), 3.91 (t, 3H), under vacuum to obtain the target compound at ), 2.93-2.89 (t, 2H), 1.22 (p5, 2H). in the form of a solid substance: analysis for SiONeMO» Example 418 0 1HgO: calculated: C, 67.86; H, 5.24 ; M, 7.91; 2-(2-(5-benzyloxy-1H-indole-3- determined: C, 68.03; H, 5.15; M, 7.98; "H NMR yl)ethyl) isoindole-1,3-dione (SOCIv) 8.44 (05, 1H), 8.412-8.409 (t, 1H), 7.91- Mix 5-benzyloxytryptamine hydrochloride 7.88 (t, 1H), 7.46- 7.38 (t, 1H), 7.26-7.24 (t, 1H), (g, 3,3mmol), phthalic anhydride (0.56g, 6.64-6.63 (t, 1H), 3.92 (5, ZN); IZM5 176 (M--1). 4, O0mmol) and M,M-diisopropylethylamine (0.86g,

Example 414 b,bmmol) in 25 ml of anhydrous pyridine and heat

C-formyl-5-methoxycarbonyl-1H-indole under reflux for 1 hour,

Add anhydrous dimethylformamide (25ml), warm to room temperature and process 4g into a flask under a nitrogen atmosphere, cool to room temperature. Heating with reverse temperature to 107"C and processing by adding a drop under the refrigerator is carried out for two days, with a drop of ROSIz (8.22g, 54mmol) with simultaneous cooling, the reaction mixture is filtered. Thanks to maintaining the temperature below 15"C. Add to the concentration under vacuum to obtain the residue

shock, which is mixed with 25 ml of SNCI3»z and filtered with 3.96 (t, 4H), 3.12-3.08 (t, 2H), 1.86-1.81 (t 2H), obtaining a solid substance. The filtrate is purified - 1.64-1.57 (t, ЗН), 1.08-1.04 (t, 21Н). are chromatographed on silica gel with elution Example 421 196 Meon solution in CHCl with obtained 5-propoxy-1-triisopropylsilanyltryptamine additional amount of the target compound: IZM5 Mix 2-(2-(5-propoxy-1-397) (Mat); analysis for C25HgM2Oz 0.3HgO SoNv: triisopropylsilanyl-1H-indol-3-yl)ethyl)isoindole- calculated: C, 75.09; H, 5.25; M, 6.82; established- 1,3-dione (41bmg, 0.vmmol) in 20 ml of EYN and ml no: C, 75.00; H, 5.22; M, 6.96. hydrazine hydrate. Heat with reverse cooling

According to the method of Example 418, the following compounds were obtained by filtering through a layer of compounds: a) 2-(2-(5-hydroxy-1H-indol-3-celite) and concentrating to obtain a residue. yl)ethyl)isoindole-1,3- dione: (4.5 mmol, 95965); "H Dissolve the residue in 100 ml of Meon, add to 12g

NMR (OM50-dv) 10.47 (5, 1Н), 8.59 (5, 1Н), 7.84- ion exchange column ZСХ and sequentially washed 7.78 (t, 4Н), 7.09-7, 06 (a, 1), 7.03-7.02 (a, 1Hn), Meon, dimethylformamide, then MeonH. Elute - 6.85-6.84 (9, 1), 6.56-6.54 (t, 1H), 3.79-3.75 (i, wash the product with a 2M solution of MHz in Meon from the extract - 2H) , 2.91-2.87 (t, 2H). extraction of the target compound in the form of oil: IZM5

Example 419 375 (Ma); "H NMR (SOCI3) 7.34-7.32 (y, 1), 7.02 2-(2-(5-hydroxy-1-triisopropylsilanyl-1H- (5, 1H), 7.00-6 .99 (a, 1H), 6.80-6.77 (t, 1H), 3.97-indol-3-yl)ethyl)isoindole-1,3-dione 3.94 (t, 2H), 3 ,01-2.98 (t, 2H), 2.86-2.83 (t, 2H),

Combine in portions a mixture of oil dispersion 1.88-1.76 (t 2H), 1.70-1.58 (t, ЗН), 1.3 (р5, 2Н),

KH (4095, 1 g) in ZoOml of anhydrous tetrahydrofuran 1.14-1.08 (t, 18H), 1.06-1.02 (i, ZN). and a suspension of 2-(2-(5-benzyloxy-1H-indol-3- Example 422 yl)ethyl)isoindole-1,3-dione (1.2 g, 3 mmol) in 30 ml of b-benzyloxytryptamine tetrahydrofuran. Stir for 1 hour. Add to the mixture lithium aluminum hydride (6.2 g, at ambient temperature, 163 mmol) and 30 ml of dry tetrahydrofuran, cool to a temperature of 0 °C, add triisops solution of 3-(2-nitrovinyl)-b-benzyloxy-1H -indole ropylsilyltrifluoromethanesulfonate (1.85 g, (9 g, 30, mmol) in 200 ml of tetrahydrofuran. Heat, mmol) and additionally stir the reaction mixture with a reflux refrigerator for 1 hour at ambient temperature overnight, after which cool to room temperature. Pour the reaction mixture into a rapidly stirred room temperature of 0"C and quickly stop the reaction of the saturated solution of MansSoz and extract by sequentially adding 2.2 ml of cold water,

EUAs (2x50ml). Combine the organic layer, remove 2 ml of cold 1595 Mahon aqueous solution and dry over Md5O", concentrate to dryness and 18.6 ml of cold water. After mixing, chromatograph on silica gel with elution for 2 hours, filter through a layer of celite 196 with a solution of MeonN in CHS to obtain 2-(2-) and concentrate to obtain 7.9 g (9695) of the target (B-benzyloxy-1-triisopropylsilanyl-1H-indole -3- compounds in the form of oil: "H NMR (SOCI3) 8.06 (rve, yl)ethyl)isoindole-1,3-dione in the form of oil. 1H), 7.47-7.43 (t, ЗН) , 7.38-7.35 (t, 2H), 7.32-7.28

Mix 2-(2-(5-benzyloxy-1- (t, 1H), 6.88-6.84 (t, 3H), 5.08 (v, 2H), 3.01-2.97 triisopropylsilanyl- 1 H-indol-3-yl)ethyl)isoindole- (t, 2H), 2.87-2.83 (t, 2H), 1.6 (p5, 2H). 1,3-dione and EOAc (4 Oml) and hydrogenate with Example 423 overnight with 1 g at 595 Pa/C under atmospheric pressure. M-tert-butoxycarbonyl-2-(6-benzyloxy-1 H-

Filter through a layer of celite, concentrate to dryness indole-3-yl)ethylamine and chromatograph on silica gel with elution. , 9.36

ECOAc in hexane to 3095 solution of ECOAc in hexane with (5, 2H), 8.91 (5, 1H), 7.38-7.33 (t, 2H), 7.28-7.26 obtaining the target compound in the form solid (t, 1H), 7.20-7.18 (t, 1H), 7.09-7.07 (t, 1H), 6.94- substance: BROM5 462 (Ma1), analysis for 6.93 (t, 1H), 6.68-6.67 (t, 1H), 6.50-6.47 (t, 1H),

C27NgaM2gOzvi Ng2gO: calculated: C, 69.55; N, 7.44; 4.79-4.72 (t, 2H), 4.13 (5, 2H), 3.05-3.02 (t, 4H).

M, 6.01; established: C, 69.44; H, 7.17; M, 6.00. Example 425

Example 420 M-tert-butoxycarbonyl-2-(6b-hydroxy-1H-2-(2-(5-propoxy-1-triisopropylsilanyl-1H-indole-3-iluethylamine indol-3-yl)ethyl)isoindol- 1,3-dione The target compound is prepared according to the method

Mix 2-(2-(5-hydroxy-1-Example 471.triisopropylsilanyl-1H-indol-3-yl)ethyl)isoindole-Example 428 1,3-dione (0.7g, 1.5mmol), cesium carbonate (g, 2-(2-(5-ethoxy-1H-indol-3-yl)ethyl)isoindole-1,3-

zmmol) and 1-iodopropane (0.4g, 2.3mmol) in didion methylformamide (25ml) and stir at ambient temperature for )ethyl)isoindole-1,3-dione (900mg, 2.9mmol), carnochi. Pour the reaction mixture into 5095 EUAs solution of cesium bonate (960 mg, 2.9 mmol) and 1-iodoethane in hexane and wash three times with brine. Dry (920mg, 5.9mmol) in M-methylpyrrolidinone (5ml) and the organic layer over Md5oOx and concentrate under stirring at ambient temperature under vacuum to give an oil. Chromatography medium for 4 hours, pour into roseol and oil on silica gel with elution 595 dilution, extract E(OAc) twice. Wash the combined nom EIHUAcS in hexane three times to obtain the target solution, extract with brine, dry over Md5Oa and conclu- IZM5 505 (Ma); "H NMR (SOCIz). 7.80-7.78 center under vacuum to give an oil. (t, 2H), 7.67-7.65 (t, 2H), 7.30- 7.27 (0, 1H), 7.12- Chromatograph the oil on silica gel with eluent - 7.11 (a, tn), 7.02 (5, 1H), 6.77-6.74 (t, 1H) , 4.01- by treating 2095 with a solution of EtOAc in hexane to obtain

extracting the target compound in the form of a solid solution with hexane, wash with brine, and then dry the white wines: ИЗМ5 335 (Ма1); analysis for over Mao.' Concentrate under vacuum and chrome-

SgoNivM2Oz: calculated: C, 71.84; H, 5.43; M, 8.38; tograph on silica gel with elution 195 was determined: C, 71.97; H, 5.47; M, 8.36. by EOAc in hexane to obtain 5-bromo-1-

According to the method of Example 428, the following triisopropylsilanyl-1H-indole was obtained in the form of a colorless compound: oil: "H NMR (SOCI3) 7.73-7.72 (y, 1H), a) 2-(2-(5- isopropoxy-1H-indole-3- 7.36-7.34 (a, 1H), 7.24-7.23 (0, 1H), 7.21-7.19 (t, yl)ethyl) isoindole-1,3-dione: IZM5 348 (MU) "H NMR 1H), 6.55-6.54 (t, 1H), 1.72-1.61 (t, ЗН), 1.13-1 .10 (SOSI") 7.94 (p5, 1H), 7.82-7.80 (t, 2H), 7.70-7.67 (t, 18H). (t, 2H), 7.21-7.19 (j, 1), 7.18 (c, 1H), 7.05-7.04 Cool the solution of 5-bromo-1- (a, tn), 6 .82-6.79 (t, 1H), 4.55-4.49 (t, 1H), 3.99-triisopropylsilanyl-1H-indole (9g, 25.5 mmol) in 3.95 (t, 2H ), 3.11-3.07 (t, 2H), 1.64-1.33 (y, 6H); 550 ml of anhydrous tetrahydrofuran to temperature

B) 0 2-(2-(5-(2,2,2-trifluoroethoxy)-1H-indole-3- ture -757C in an argon atmosphere and treat 1.7M yl)ethyl)isoindole-1,3-dione: ИЗИМ5 389 (МА1); analysis with a solution of tert-butylene (33 ml, 56.2 mmol) with od- for SgoNi5EzM2gOz: calculated: C, 61.86; H, 3.89; M, by keeping the temperature below - 7.21 at night; established: C, 61.77; H, 3.83; M, 7.20; 60"C. After the addition is complete, re-heat the reaction mixture to a temperature of approx. 1,93-dione: ИЗМ5 363 (Ma1); analysis for Сg22Но2М2гоз: zno -73"С before adding the phenylsul solution - calculated: С, 72.91; H, 6.11; M, 7.73; phenylfluoride (4.6g, 28./mmol) in Zbml no: C, 72.76; H, 6.09; M, 7.42; "H NMR (SOCI3) of tetrahydrofuran. Stir the reaction mixture. at a temperature of -78"C for an hour, after 1H), 7.16-7.15 (t, 1H), 7.08-7.07 (t, 1H), 6.85-6.84, so stop the reaction quickly by adding rest- (t, 1H), 6.4.02-3.98 (t, 4H), 3.13-3.09 (t, 2H), tku of a cold saturated solution of MansSoO»z, then 1.83- 1.76 (t, 2H), 1.56-148 (t, 2H), 1.01-0.98 (i, cold brine. Separate the layers and extract

ZN); vat water layer of EIUAs. Treat the combined organic 94) 002-(2-(5-nitro-1H-indol-3-yl)ethyl)isoindol- organic layers with a 1M solution of tetrabutylammonium 1,9-dione: IZM5 334 (M-1); analysis for Si8NizMzO4 fluoride (35 ml) in tetrahydrofuran for 0.1 NgO: calculated: C, 64.13; H, 3.95; M, 12.47; 1Th at the ambient temperature, it was found: C, 64.05; H, 3.82; M, 12.27. after which concentrate to dryness. United

According to the method of Example 421, the following residues were obtained from EIOAcS, washed twice with a 1M solution of the compound: NOCI, dried over Mo5Ox and concentrated in mass- a) 5-ethoxytryptamine: IZM5 205 (M.1); Lee's analysis. Chromatograph the oil on silica gel with eluent for C12Ni6eM2O HgO: calculated: C, 69.33; H, 7.95; by a step gradient (5095 solution

M, 13.48; established: C, 69.62; H, 7.75; M, 13.30; SNI" in hexane, then 5095 solution of SNCI3 in MeOH)

B) 5-isopropoxytryptamine: IZM5 219 (Mn); "H from an oily solid substance. Grind mass

NMR (SOCI»z) 8.57 (re, 1H), 7.20-7.18 (a, 1H), 7.08 - a crystalline solid from SNCIz to obtain 7.07 (a, 1), 6 .95 (5, 1H), 6.84-6.82 (t, 1H), 4.54- the target compound in the form of a solid substance: 4.48 (t, 1H), 3.01-2.98 (t , 2H), 2.86-2.83 (t, 2H), analysis for C1i4H11:MO»5 HgO: calculated: C, 64.89; 1.38 (p5, 2H), 1.35-1.33 (9, 6H); N, 4.36; M, 5.41; established: C, 64.76; H, 4.45; M, c) 5-(2,2,2-trifluoroethoxy)tryptamine: ИЗМ5 5.33; IZM5 257 (Mk). 258 (Ma); "H NMR (SOCI»z) 8.33 (re, 1H), 7.26-7.24 Example 430 (a, 1H), 7.09-7.08 (a, 1), 7.03- 7.02 (t, 1H), 6.90- 2-(2-(5-amino-1H-indol-3-yl)ethyl)isoindol-1,3- 6.87 (t, 1H), 4, 40-4.34 (t, 2H), 3.03-3.00 (t, 2H), dione 2.87-2.84 (t, 2H), 1.44 (p, 2H); Combine a mixture of /2-(2-(5-nitro-1H-indole-3-a)B-butyloxytryptamine: "H NMR of (SOCIiz)yl)ethyl)isoindole-1,3-dione (1.68g, 5.4mmol) , RYU» 8.08 (p5, 1), 723-721 (a, tn), 7.03-7.02 (a, tn), (500 mg), 100 ml MeonH and 100 ml tetrahydrofuran 7.03-7.02 (t, 1H), 6.98-6.83 (t, 1H), 4.01-3.98 (t, and hydrogenate under atmospheric pressure vpro- 2H), 3.02-2.99 (t, 2H ), 2.87-2.84 (t, 2H), 1.82-1.74 throughout the night. Filter the reaction mixture through (t, 2H), 1.56-1.50 (t, 2H), 1.32 (re, 2H), 1.00-0.96 a layer of celite and concentrate to dryness. Repeatedly ( ЗН); dissolve the residue in a mixture (50/50) of chlorophor-

Example 429 mu/dichloromethane and filter again through 5-benzenesulfonyl-1H-indole through a layer of celite. Concentrate under vacuum with

Add 3596 oil dispersion KH (bg) to obtain the target compound in the form of a solid flask in a nitrogen atmosphere, wash with 50 ml of hexane and dark-colored substances: IZM5 306 (М--1); ana- dry under vacuum. Cool the suspension of lyses for SivNizMzOa4 0.1С7Н8 0.2 dichloromethane: the solid substance in 10000 ml of anhydrous dime- calculated: C, 68.70; N, 4.89; M, 12.58; established: tylformamide to a temperature of 0"C. During C, 69.08; H, 4.75; M, 12.69; H NMR (SOCI3) 7.9-7.8 10 min drop by drop add a solution of 5- (t ) ,0 (t, 2H), 6.7-6.6 (t, 1H), 4.0-3.9 (t, 2H), 3.4 of tylformamide. Stir the mixture during (p5, 2H), 3, 1-3.0 (t, 2H). 1T1h at a temperature of 0"C, then treat Example 431 with triisopropylsilyltrifluoromethanesulfonate 2-(2-(5-benzoylamino-1H-indole-3-) (32.2g, 105.1mmol). Remove the cooling yl)ethyl)isoindole-1,3-dione bath and stir the reaction mixture for 72 hours before pouring into 500 ml of water and ethyl)ethyl )isoindole-1,3-dione (0.5 g, 1.64 mmol) and 4-treated EAs. Dilute the combined extracts of dimethylaminopyridine (0.3 g, 2.5 mmol), dissolve in 30 ml of dichloromethane and cool to temperature - the form of oil: "H NMR (SOCI3) 8.54 (p5, 1H), 8.07 - р 0" WITH. Treat the reaction mixture with benzoyl chloride - 8.06 (t, 1H), 7.63-7.61 (t, 1H), 7.39-7.37 (t, 1H), dom (27 mg, 1.96 mmol) and mix during 7.26-7.24 (t, 1H), 6.60-6.59 (t, 1H), 6.14 (p5, 1H), nights; during this time, the reaction mixture is heated to 3.5-3.45 (t, 2H), 1.64-1.57 (t, 2H), 1.47-1.37 (t, room temperature. Concentrate from 2), .97-0.93 (t, ZN); EIM5 217 (M--1). harvesting the residue and chromatographing the residue on Example 434 silica gel eluting with 0.595 Meon solution in 5-(M-propylamido)-1H-indole

SNeSiiz with obtaining the target compound in the form The target compound is obtained by the method of a solid substance: ИЗМ5 410 (Ма); "H NMR of Example 433: "H NMR (SOCI") 8.07 (p5, 1H), 8.07 (SOCI3) 7.86-7.85 (t, 2H), 7.79 (5, 1H), 7.72-7.68 (5, 1H), 7.63-7.60 (t, 1H), 7.38-7.36 (t, 1H), 7.25- (t, 2H), 7 .60-7.57 (t, 2H), 7.46-7.42 (t, 1H), 7.4-7.24 (t, 1H), 6.59-6.58 (t, 1H) . .41 (t, 2H), 1.69-1.60 (t, 2H), 1.00-0.96 (t, ZN); 3.88-3.84 (I, 2H), 3.00-2.97 (I, 2H). EIM5 203 (M-1).

The following compounds were obtained by the method of Example 431. The following compounds were obtained by the method of Example 414: compounds: a) 2-(2-(5-methanesulfonylamino-1H-indole-3-a) 3-formyl-5-benzenesulfonyl-1H-indole: yl)ethyl)isoindole-1,3-dione: IZM5 384 (Ma1); "H NMR IBM5 286 (Mat); "H NMR (0M50-two) 9.83 (5, 1H), (SOSIv) 10.84 (5, 1H), 9.21 (5, 1H), 7.83 -7.76 (t, 8.55 (5, 1 H), 7.89-7.86 (t, 2H), 7.61 (v, 2H), 7.59- 4H), 7.39- 7.38 (t, 1 H), 7.27-7.24 (t, 1H), 7.17-7.52 (t, ZN), 1.70 (5, ZN). 7.16 (t, 1), 6.96-6.93 (t, 1H), 3.83-3.80 (t, p) 3-formyl-5-ethoxycarbonyl-1H-indole: ana- 2H) ... ; 2H), 3.00-2.97 (i, 2H). M, 6.45; established: C, 65.97; H, 5.17; M, 6.46;

According to the method of Example 421, the following IZM5 218 (Mt) were obtained; compounds: c) 3-formyl-M-butylamido-1H-indole: analysis a) 5-benzoylaminotryptamine: "H NMR (CO3O) for Si4NiM2O" 0.1H2O: calculated: C, 68.33; H, 7.94-7, 92 (t, 2H), 7.85 (5, 1H), 7.54-7.47 (t, ЗН), 6.64; M, 11.38; determined: C, 68.35; H, 6.24; M , 7.34-7.29 (t, 2 H), 7.08 (5, 1H), 4.86 (5, 2H), 3.33 (5, 11.30; IBM5 245 (M-n1) ; 2), 2.95-2.86 (t, 4H); and a) 3-formyl-5-(M-propylamido)-1H-indole: ana-

B) 5-methanesulfonylaminotryptamine: IZM5 lyses for CizNi"M2gO": calculated: C, 67.81; H, 6.13; 253 (M.k); "H NMR (SOzOB) 7.46-7.45 (y, 1H), 7.31- M, 12.16; established: C, 67.42; H, 6.04; M, 12.10; 7 .28 (a, 1H), 7.08 (5, 1H), 7.04-7.01 (t, 1H), 4.86 (c, IN NMR (OM50-a4c) 9.95 (5, 1H ), 8.6 (z, 1H), 8.48- 4H), 2.89-2.83 (t, 7H). 8.45 (Ii, 1Hn), 8.36-8.35 (t, 1H), 7.76-7.73 (t, 1H),

Example 432 7.52-7.50 (9, 1H), 3.32 (p5, 1H), 3.24-3.19 (t, 2H),

B-ethoxycarbonyl-1H-indole 1.58-1.48 (t, 2H), 0.90-0.86 (t, ЗН); EIM5 230

Mix a solution of 5-carboxyindole (4.8g, (Me); 29.8mmol) in 150ml of tetrahydrofuran and carbo-e) 3-formyl-b6-benzyloxy-1H-indole: "H NMR nidimidazole (9.7g, 59.bmmol) ) and mix (0M50-ydv) 11.93 (5, 1Н), 9.83 (5, 1Н), 8.12-8.11 (t, overnight at ambient temperature 1Н), 7.92-7, 90 (t, 1H), 7.45-7.27 (t, 5H), 7.04-7.03 medium. Treat the reaction mixture with 25 ml (t, 1H), 6.92-6.89 (t, 1H ), 5.11 (5.2H).

EUN and 1.2 g (29.8 mmol) of 6095 oil dispersion According to the method of Example 415, the following were obtained

Man and stir for 2 hours. Concentrate compounds: cotton under vacuum to obtain a residue. Disposition a) 5-benzenesulfonyl-3-(2-nitrovinyl)-1H- divide the residue between 150 ml of EIUAs and 100 ml of rosindole: analysis for Si6Ni2M2O45 0.1H20: calculated salt. Separate the layers, dry organic but: C, 58.42; H, 3.83; M, 8.31; established: C, layer above Md5O»m, filter and concentrate - 58.63; H, 3.52; M, 8.02; ИЗМ5 229 (М-А1); you with obtaining oil. Chromatograph on B). 3-(2-nitrovinyl)-5-ethoxycarbonyl-1H-indole: silica gels eluting with 195 Meon solution in the analysis for Si6Ni2M2O45 0.1H20: calculated: C,

SneSyiz with obtaining 7.2 g of oil. Crystallize 58.42; H, 3.83; M, 8.31; established: C, 58.63; H, oil from toluene to obtain the target compound: 3.52; M, 8.02; IBM5 229 (M-1); analysis for С1ии1НииМО»:: calculated: С, 69.83; H, c) C3-(2-nitrovinyl)-N-butylamido-1H-indole: 5.86; M, 7.40; established: C, 69.82; N, 5.90; M, analysis for Schi5Ni7MzOz: calculated: C, 62.71; N, 7.38; IBM5 190 (MA1). 5.96; M, 14.62; established: C, 62.46; H, 5.81; M,

Example 433 14.38; IBM5 288 (MA1); 5-(M-butylamido)-1H-indole 9) 3-(2-nitrovinyl)-M-propylamido 1H-indole:

Dissolve a mixture of 5-carboxyindole /(5g, IZM5 273 M(1); "H NMR (OM50O-d9v) 12.38 (5, 1H),

Zimmol) in 150 ml of tetrahydrofuran, treated with 8.62-8.59 (I, 1H), 8.43-8.39 (j, 1), 8.37 (5, 1H), carbonyldiimidazole (5g, Zimmol) and mixed - 8.31-8.30 (a, 1H), 8.18-8.15 (9, 1), 7.84-7.82 (t, you during the night at ambient temperature 1H), 7.55- 7.53 (A, 1), 3.31-3.24 (t, 2H), 1.61-1.52 medium. Process the reaction mixture /n- (t, 2H), 0.92-0.89 (i, ЗН); analysis for C14Ni5MzOz with butylamine (4.5g, b2mmol) and heat with reverse - 0.1HgO: calculated: C, 61.12; H, 5.57; M, 15.28; him in the refrigerator for an hour. The concentration was determined: C, 61.06; H, 5.38; M, 15.05; under vacuum to obtain a residue, calculate e). 3-(2-nitrovinyl)-b-benzyloxy-1H-indole: "H thread the residue in EUDAs. Wash successively 5M NMR (0M50-4av) 11.85 (5, 1H), 8.32-8.29 (t . Dry the organic layer over Md5Ox and 7.45-7.43 (t, 2H), 7.38-7.91 (t, 2H), 7.29-7.27 (t, concentrate to obtain the target compound in 1H) , 7.05-7.04 (t, 1H), 6.92-6.89 (t, 1H), 5.13 (in,

2H). extraction of the target compound in the form of a solid

According to the method of Example 416, the following wines were obtained: IZM5 333 (Ma-1); analysis for St9HgvM2gOz: compounds: calculated: C, 68.65; H, 8.49; M, 8.43; established a) 5-benzenesulfonyl-3-(2-nitroethyl)-1H-no: C, 68.83; H, 8.18; M, 8.33. indole: analysis for SivNi4M2O25 0.1H20: calculated by the method of Example 435, the following values were obtained: C, 57.85; N, 4.31; M, 8.43; established: C, compounds: a) M-tert-butoxycarbonyl-2-(6b-ethoxy-57.72; H, 4.22; M, 8.25; IZM5 329 (M-1); 1H-indole-3 -yl)oethylamine: IZM5 305 (Ma1); analysis p) 3-(2-nitroethyl)-5-ethoxycarbonyl-1H-indole: for Si17H2aM2Oz: calculated: C, 67.08; H, 7.95; M, analysis for CizNi«M2Ol: calculated: C, 59.54; H, 9.20; established: C, 66.85; N, 7.79; M, 9,14. 5.38; M, 10.68; established: C, 59.23; H, 5.25; M, Example 436 10.53; IZM5 263 (M1); b-butoxytryptamine c) 3-(2-nitroethyl)-N-butylamido-1H-indole: Mix M-tert-butoxycarbonyl-2-(6- analysis for Schi5NioMzOz: calculated: C, 62.27; H, butoxy- 1H-indole-3-yl)ethylamine (430 mg, 6.62; M, 14.52; determined: C, 61.98; H, 6.39; M, 1.3 mmol), Thiml of anisole and 5 ml of trifluoroacetate 14, 42: IBM5 290 (Mt) ; and acids and stir at room temperature a) 3-(2-nitroethyl)-M-propylamido-1H-indole: "H for 2 hours. Concentrate the reaction mixture

NMR (SOCI3) 8.52 (p5, 1H), 8.06 (5, 1H), 7.58-7.55 to dryness under vacuum, mix with tOml conc- (t, 1H), 7.35-7 .33 (t, 1H), 7.10-7.09 (t, 1H), 6.23 of a diluted MNAOH solution and extract 20 ml (re, 1H), 4.65-4.61 (I, 2H), 3 ,48-3,43 (t, 4H), 1,71-dichloromethane. Dry the extract over Md5oh and 1.62 (t, 2H), 1.01-0.98 (Yii, ZN); analysis to concentrate to obtain 300 mg of oil

Si4Ni?MzOz 0.1H20: calculated: C, 60.68; H, 6.26; (1, Zmmol, 10090).

M, 15,16; established: C, 60.88; H, 6.05; M, 15.07. According to the method of Example 436, the following were obtained

According to the method of Example 421, the following compounds were obtained: a) b-ethoxytryptamine: IZM5 305 (Ma1); compounds: analysis for Сч17НгаМ2Оз: calculated: C, 67.08; H, a) 5-benzenesulfonyltryptamine: I5M5 301 7.95; M, 9.20; established: C, 66.85; N, 7.79; M, (Ma); "H NMR (NSI-OM5O-adbv) (5, 1H), 8.3 (5, 1H), 9.14. 8.2 (re, 2H), 8.0-8.9 (t, 2H) , 7.4-7.2 (t, 5H), 7.1- Example 437 7.0 (t, 1H), 3.2-3.0 (v, 4H); M-tert-butoxycarbonyl-2- (6-p) B-ethoxycarbonyltryptamine (isolated as phenylsulfonate-1H-indol-3-yl)ethylamine oxalate: analysis for CizNieM2Og C»HgO4: calculation Mix M-tert-butoxycarbonyl-2-(6- lene: C , 55.90; H, 5.63; M, 8.69; determined: C, hydroxy-1H-indole-3-yl)ethylamine (750 mg, 56.07; H, 5.54; M, 8.29 ; IZM5 233 (Ma1) ; and 2.tmmol) and pyridine (43Omg, 5.4mmol) in dichloro-c) 5-M-butylamidotryptamine: analysis for rmethane (30ml), cool to a temperature of 0"C and

Si5NaiMzO 0.3H2gO: calculated: C, 68.05; H, 8.22; treat with benzenesulfonyl chloride (480mg,

M, 15.87; established: C, 68.36; H, 8.11; M, 15.49; 2.7 mmol). Keep the reaction mixture with heating

IBM5 260 (M-1) ; and stirring to room temperature and stir a) 5-M-propylamidotryptamine: (isolated as oc- during the night. Concentrate the reaction mixture salad): analysis for С14НиоМзО С2Нг2О4 ОЛ1ЕХАСС: under vacuum to dryness, mix with dichlorometha- calculated: С, 57, 23; H, 6.38; M, 12.21; established and chromatographed on silica gel with eluent: C, 57.48; N, 6.53; M, 12,12; "H NMR (0OM50O-dv) by 3095 with a solution of EtOAc in hexane yielded 11.2 (5, 1H), 8.4 (I, 1H), 8.2 (5, 1H), 7.75-7, 65 (t, by harvesting M-tert-butoxycarbonyl-2-(6-1H), 7.6 (re, 4H), 7.4-7.35 (t, 1H), 7.3-7.25 (y . 45 (t, 2H), look of oil: IZM5 415 (M-1); "H NMR (SOCIz) 8.14 0.9-0.8 (i, ZN); IZM5 246 (M.-1). (p5, 1H), 7.66-7.62 (t, 2H), 7.51-7.47 (t, 1H), 7.40-

Example 435 7.38 (t, 2H), 7.10 (v, 1H), 7.04-7.03 (t, 2H), 6.59-

M-tert-butoxycarbonyl-2-(6-butoxy-1 H- 6.57 (t, 1H), 4.57 (p5, 1H), 3.40-3.80 (t, 2H), 2.89 - indol-3-yl)ethylamine 2.86 (t, 2H), 1.41 (5, 9H).

Mix M-tert-butoxycarbonyl-2-(6- Place M-tert-butoxycarbonyl-2-(6-hydroxy-1H-indol-3-yl)ethylamine (250mg, phenylsulfonate-1H-indol-3-yl)ethylamine (0.5g, 0O.9mmol), cesium carbonate (295mg, 0.9mmol), 1- 1.2mmol) into a flask through which a flow of Me» passes, iodobutane (200mg, 1.1mmol) and M- heat at temperature 200"C overnight and methylpyrrolidinone (1O0ml), stir at room temperature - cool to room temperature. Dissolve the residue in dichloromethane at ambient temperature and chromatograph for 2 hours and pour into 75ml of brine. Extract the silica gel twice with elution with 290 MeonN solution into a mixture of 25ml of EtOAc Wash the combined extracts of SneSiIzZ-MNaAOH to obtain the target compound in brine (2x50 ml), dry over Mdzoh and concentrate the oil. Incubate under vacuum to obtain an oil. According to the method of Example 425, the following were obtained

Chromatograph the oil on silica gel eluting with the compounds isolated as hydrochloride, eluting with a 3095 solution of EOAc in hexane with the exclusion of the indicated:

board Also:

Oh, and more

NO PE ZY PI: RO PON x ET UN

IZM5 401 (Ma); analysis for SgoNivM2Oz 0.1H2O: calculated: C, 71.17; H, 6.71; M, 6.38; established: C, 71.02; H, 6.54; M, 6.33; "H NMR (free base-SOCI3) 7.93 438 | b-propoxy (p5, 1H), 7.34-7.30 (t, 2H), 7.35-7.28 (t, 2H), 7 ,12-707 (t, 1H), 7.06-6.96 (t, B6H), 6.89-6.84 (t, 2H), 3.97-3.94 (t, 2H), 3 .79 (5, 2H), 2.97-2.94 (t, 4H), 1.89-1.7 (t, 2H), 1.51 (b5, 1H), 1.07-1.04 (, ZN

Example 440 for 1 hour, treat 0.74 mmol of tetrabutyl

M-(2-(5-propoxy-1H-indol-3-iluethyl)-3-ammonium fluoride and additionally stir (2,2,3,3-tetrafluoropropoxy)benzylamine for an hour. Concentrate under vacuum to obtain a residue. Chromatograph the solids -

It9 shock on silica gel eluting with 1095 solution of t-tu melts N i ce E Meon in SNSIIiz to obtain the target compound. Process the target compound with 10 ml of EUN, 0.25 ml of 5M and 100 ml of HCI solution and 40 ml of toluene, then concentrate to obtain the hydrogen chloride salt

And the target compound: IZM5 439 (Ma1); "H NMR (free base-SOSiIz) 7.89 (p5, 1), 7.23-7.21 (t, 1H), triisopropylsilanyltryptamine also about zvmt 7.03-7.02 (0, 1H), 6.99 -6.98 (0, 1H), 6.94-6.92 (t, 0.37mmol) 3-2.23 3. 1H), 6.89-6.83 (t, 2H), 6.78 -6.75 (t, 1H), 6.18-5.90 (t, 1H), 4.29-4.23 (t, 2H), 3.95-3.91 (t, 2H), 3.78 tetrafluoropropoxy)benzaldehyde (87mg, on), 295 AN) 185-175 (t. 28). 1.51 (6 1.8mmol) and Ig ZA of molecular sieves in 25mL (5, ). 2.95 (in, 7, 5 (t, t (bv, y y 1H), 1.06-1.03 (I, ЗН).

EUN and heated under reflux According to the method of Example 440, the following were obtained during the night. Pour the liquid into a separate flask, according to U. ot: the compounds isolated in the form of hydrochloride, after cooling to a temperature of 0"C and treating 42 mg of the indicated: (1.immol) MnNe. Stir the reaction mixture at the temperature environment

To go

IN

NITEMS pesl PO H ROD POLON E UN . . IZM5 434 (MT); СгзНовЕзМзО»: НСИ-0.8НгО.0.1С7Нв: calculated: C, ethoxycarbonyl | tetrafluoropropyl | 5.73; established: C, 56.26; H, 5.04; M, 5.76 sheaves! osn Sonia vol ethoxycarbonyl 6.06; M, 6.19; established: C, 68.78; N, 5.87; M, 6.19 2238. IZM5 473 (Ma); SovNa5SiRaM2O2:0.5H20: calculated: C, 60.29; H, 445 5-phenoxyny - 15.06; M, 5.41; established: C, 60.27; N, 4.81; M, 5.33 (the tetrafluoropropyl base was isolated)

IZBM5 349 (M1); StieNgoSIRzM2O-0.2H2O: calculated: C, 58.75; H, pentafluoropropyl | 4.37; M, 6.60; established: C, 53.81; H, 4.19; M, 6.59 cm vane | dreams PRY sem vov nak s snya

M, 6, 11; established: C, 76.01; H, 5.92; M, 5.97 IZM5 419 (Mt) and Analysis for SgoHg5EM2gO:-HCI-0.2HgO: calculated: C, 73.08; H, 5.58; zve |viaFtorfenya) Feny Mov established. P. 729; H, 88 M Z IEME YAZ MO

B-(M- Analysis for Сg24НгвЕзМз3зО»2:НОСИ-О0.7Н2О: calculated: C, 58.05; H, 460 b and 2,2,2-trifluoroethyl 6.17; M, 8.46; determined: C , 57.86; H, 5.98; M, 8.39 IBM5 448 utilamido) (Me)

IZM5 365 (MT) "H NMR (OM50O-av) 10.6 (5, 1H), 9.4 (p5, 2H), 8.75 461 B-hydroxy /I2,2,2-trifluoroethyl (5, 1H ), 7.45-6.6 (t, 7H), 4.9-4.7 (t, 2H), 4.2 (p5, 2H), 3.2-2.9 (t, 4H 462 | B-benzyloxy 2,2,3,3,3- Analysis for C27Na25E5M2O»: NOSI: calculated: C, 58.87; H, 4.95; M,

77777777 |pentafluoropropyl | 5.09; established: C, 759.02; N, 4.76; M, 5115М5505(МА1)4

IBM5 455 (Mat) "H NMR (SOCIz-free base) 7.88 (B5, 1Н), 7.48-7.45 (t, ЗН), 7.41-7.34 (t, 2Н), 7 .35-7.30 (t, 1H), 7.25-7.23 (t, 463 | b-benzyloxy |2.2,2-trifluoroethyl 1H), 6.95-6.93 (t, 1H), 6 ,91-6.90 (t, 2H), 6.88-6.86 (t, 2H), 6.814 6.79 (t, 1H), 5.10 (5, 2H), 4.31-4, 25 (t, 2H), 3.79 (v, 2H), 2.96 (v, 4H), 1.65 (b5, 1H 2,2,3,3- IZM5 487 (M--1) Analysis for С27Н27РаМ2О2:"НСИ: calculated: С,

IN NMR (SOS-free base) 7.86 (05, 1H), 7.45-7.43 (t, 1H), 7.23-7.19 (t, 1H), 6.94-6.92 (t, 1H), 6.89-6.88 (t, 1H), 6.84-6.75 t, 4H), 4.29-4.23 (t, 2H), 3.99-3, 96 (t, 2H), 3.78 (5, 2H), 2.94 (5, 465| b-butyloxy P,2,2-trifluoroethyl c, pa (t, zv TEBE (t, iv; 099-095 (p zu; known for Сг2зН2а7ЕзМ2О» NS: calculated: C, 60.46; H, 6.18; M, 6.13; established: C, 60.23; H, 5.99; M, 6, 01 2,2,3,3- Analysis for SgaNaovE"M2O"-HCI: calculated: C, 58.96; H, 5.98; M,

IZM5 393 (Ma1); analysis for C2g1iNozEzM2gO2: NOSI: calculated: C, 6-IZM5 505 (Ma1); analysis for С25НгзЕзМ2О25: CARRIERS: calculated: C, phenylsulfonate!| tetrafluoropropyl | 54.50; N, 4.40; M, 4.89; established: C, 54.63; H, 4.41; M, 4.86

IZM5 419 (Ma1); analysis for SovNgaBaM2O45:HCI-0,ZN2gO: calculated 470 b-phenyl: C, 75.65; H, 6.04; M, 6.08; established: C, 75.63; H, 5.89; M, 6.07 2,2,3,3- Analysis for SgziNa7EzM2O2: NOSI-NSIII: calculated: C, 58.52; H, 6.02; M,

Example 471 mix 0.3 ml of a 5M solution of NSI and Z0Omg 595 Ra/С and

M-(2-(5-hydroxy-1H-indol-3-yl)ethyl)-3-(2,2,2- hydrogenate under atmospheric pressure against trifluoroethoxy)benzylamine overnight. Filter the reaction mixture through a layer of celite and concentrate to dryness, after which

chromatograph on silica gel to obtain the target compound: ИЗМ5 365 (Ма1); "H NMR x x Y N u y a (0M50-ydv) 10.6 (rve, 1H), 9.4 (re, 2H), 8.75 (v, 1H), absorption TC 7.45-6 .6 (t, 7H), 4.9-4.7 (t, 2H), 4.2 (re, 2H), 8.2-

More ! C 2.9 (t, 4H).

Н According to the method of Example 471, the following compounds were obtained, isolated in the form of hydrochloride, according to

Mix M-(2-(5-benzyloxy-1H-indol-3- yl)ethyl)-3-(2,2,2-trifluoroethoxy)benzylamine hydrochloride (295mg, 0.bmmol) and 25ml EN, traffic j r "IN ; M vena thing ! ; ; e i

I am; and | vVyYa | 7777777777777 given tetrafluoropropyl| 53.28; H, 5.14; M, 6.21; established: C, 53.31; N, 4.91; M, 6.33

IBM5 487 (Ma); "H NMR (0M50-dv) 5 10.52 (re, 1H), 9.36 (5, 2H), 8.91 473 | β-hydroxy 2,2,2- (5, 1H), 7.38 -7.33 (t, 2H), 7.28-7.26 (t, 1H), 7.20-7.18 (tn), 7.09-7.0 trifluoroethyl | (t, 1H), 6 ,94-6.93 (t, 1H), 6.68-6.67 (t, 1H), 6.50-6.47 (t, 1H), 4.79-4.72 t, 2H), 4.13 (5, 2H), 3.05-3.02 (t, 4H tetrafluoropropyl| 53.28; H, 5.14; M, 6.21; determined: C, 53.33; H, 4, 76; M, 6,12

Example 475

M-(2-(5-carboxy-1H-indol-3-yl)ethyl)-3-(2,2,2-trifluoroethoxy)benzylamine and NMR (300 MHz, COS"): 7.82 (9, 2H, 9-9.0Gu), 7.40 yu-i (A, 2H, 9-9.0Hz), 5.92 (y, 1H, 9U-55.0, 0.4Gu), 4.19 that r ( I, 2H, 912.6, 4.0Hz), 2.48 (5, ZN). Example 482 is 3-(2,2-difluoroethoxy)benzaldehyde.

Mix M-(2-(5-methoxycarbonyl-1H-indol-3-one), pulto)obainovo, diyl)ethyl)-3-(2,2,2-trifluoroethoxy)benzylamine 1.2Hz ), you (n, tn, ue55.0, 4 OHC), 424 (8, 2H, (200 mg, O0.5 mmol) in 500 ml of tetrahydrofuran and 9e12.6, 4.0 OHC). 1 ml of 3M Mahon solution. Heat the reaction mixture of Example 483 under reflux overnight, add M-(2-(β-chloro-1H-indol-3-yl)ethyl)-3-(3-) to 0.7 ml of a 5M solution of NOSI and concentrate to fluoropropoxy )benzylamine dryness. Chromatograph to obtain the target compound: IZM5 393 (Ma1); analysis for

SgoNioEzM2Oz SEZSOON 1.2С7Н8 2.1Н20: calculated: C, 55.76; H, 5.20; M, 4.28; established: C, M 7 55.51; H, 5.47; M, 4.50. AND

Example 480 M 3-(3-fluoropropoxy)benzaldehyde n

Mix 1-bromo-3-fluoropropane (10.0 g, ... 77.1 mmol) and 3-hydroxybenzaldehyde (10.4 g, Mix b-chlorotryptamine (1.4 g, T.2 mmol), 3-92.5 mmol) in dimethylformamide (220 mL) and per-(3-fluoropropoxy)benzaldehyde (1.g, 7.2 mmol) and stirred at room temperature. Portions of molecular sieves U, ethanol (15 Oml) and heat treated with potassium carbonate (21.3 g, 144.2 mmol). at a temperature of 18 Mi during the night. Profile-

Heat the reaction mixture at a temperature of 1007C, pour the reaction mixture through a layer of Celite, stir for 10 minutes, then pour into the mixture (1:1), beat the resulting filtrate with sodium borohydride, water with ice and dichloromethane. Separate (817mg, 21.bmol) ! stir the phases overnight and extract the aqueous layer with an additional kel- at room temperature. Evaporate the solvent with dichloromethane. Wash the body mass successively to obtain a residue. Chromatograph these organic extracts with a 1.0 M solution of Toly hydroxide on a melting point, eluting with a mixture of sodium, a saturated solution of sodium bicarbonate, (9: ) dichloromethane, and a solution of ammonia in meta-brine, after which it is dried over sodium sulfate to obtain a residue. Chromatograph sodium. By filtering and removing, dissolve the residue on a ZOH column (10 g) (wash the column and massio to obtain a residue. Chromatograph with methanol, then elute and decolorize the residue on silica gel eluting with ammonia in methanol) and concentrate the massio with a 4095 solution of ethyl acetate in hexane to obtain a light yellow oil. To separate the target compound in the form of a yellow oil, dissolve the oil in methanol and treat with a color solution. "H NMR (400 MHz, SOCI3) 9.98 (5, 1H), ammonium chloride in methanol (112 mg, 2, Tmmol). 7.50-7.42 (t, 2H), 7.42-7.38 ( t, 1H), 7.22-7.16 (t, Treat the resulting mixture with ultrasound in experiment 1), 466 (F, OH, 0e46.8, 5.8Hz), 417 (5 2H, for 10 min, remove the solvent butter and mix

Ch-6.0Hz), 2.19 (double quintuplets, 2H, 926.0, obtained residue with simple ether, including 6.0Hz); M5 (ARSI): t/e 183.1 (Ma). adds a few drops of acetonitrile, with the result

Example 481 solid. Filter the solid 2,2-difluoroethyltosylate wine to obtain the target compound in the form of

Mix p-toluenesulfonyl chloride (12.9 g, OMBO, 67.4 mmol) in pyridine (15 ml) at room temperature (c) 75 (4 1H. 5 og ) I "Ko them at 5 temperature and treat by adding drop by drop 7 32 (5 IN Chet 8gu) 7 in (a. IN un? au) 7 ov; with the help of a syringe of 2,2-difluoroethanol (5.0 g, 724 (t 18) 714 (4 IN dev oghts) 701 (aa tn 60.9 mmol). Stir the reaction mixture in 28.8 2 g.) 697 (cha IN vo, with og) 480 (CHE, nitrogen atmosphere for 72 hours, distribute 2H dna in v. ogz) 413 (og v. 2n) 4 08 (a ?n between water (20ml) and dichloromethane (20ml) Vido-CH-6,АЦС), 3.10 (ог 5, 4Н), 2.11 (double quintuple-lime the aqueous phase and extract with an additional thy), 2H, 2-28.0, 8.0 Hz); MO (Ebu): t/e 361.3 (Ma); with the amount of dichloromethane (2x40 ml). Combine or-SNM (for SgoHgSIEM»2O-HC) calculated: C 60.46 organic extracts and successively wash with 1 M solution 583 M 705: established: C 60.48 H 5 86 M hydrochloric acid (2x5O0ml), sodium bicarbonate (2x50ml) and brine (2 x 50 ml). hoard 483 was received by the following

Dry the organic layer over sodium sulfate and the compounds isolated in the form of hydrochloride, after concentrating the mass to obtain the target compound indicated by the following: compound in the form of a yellowish oil: "Н

Ek p: N r.

Obruryii!

IN.

N

WE TEY DE ZI PO x ROD PON ET NO t.pl. 174.8-176.02С; "H NMR (400MHz, OM50O-av): 11.03 (rg 5, 1H), 9.35 (p 5, 2H), 7.52 (ai, 1H, 9U-8.8, 5.2Hz), 7.30 (y, 1H, 9U-7.8Hz), 7.22-7.17 (t, 2H), 7.13-7.06 (t, 2H), 6.95 (da, 1H, uU -7.8, 2.2Hz), 6.83 (ada, yin, 2-9.6, 8.8, 484 | b-fluorine | Z-fluoropropyl | 2.4Hz), 4.58 (0, 2Н , 9U-47.2, 5.8Hz), 4.11 (5, 2H), 4.06 (i, 2H, 9-6.2Hz), 3.08 (rg 5, 4H), 2.08 ( double quintuplets, 2H, 9U-26.0, 6.0Gsh); M5 (EbBzh): m/e 345.3 (Ma1); SNM (for SgoNggB2M2O NOI) calculated: C 63.07, H 6.09, M 7.36; determined: C 62.82, H 6.13, M 7.57 mp 165.0-166.57С, "H NMR (400MHz, OM5O-dv): 11.08 (Big 5, 1H), 7.56 (yes, 1H, 0-8.7, 5.2Hz), 7.39-7.31 (t, 2H), 7.21 (9, 1H, 9u-2.0Hz), 7.18 (a, tn, 485 | b-fluorine | 2,2-difluoroethyl | У-6.9Hz), 7.12 (ai, 1Н, 9У-10.4, 1.7Hz), 7.04 ( yes, 1nH, 9u-8.7, 1.7 Gu), 6.89-6.81 (t, 1H), 6.42 (B. 1H, 9-53.9, 3.5Hz), 4, 32 (Id, 2H, 9U-11.3, 3.2Gu), 4.14 (5, 2), 3.20-3.00 (t, 4H); M5: (Eb--): m/e 349.0 (M-1 mp. 131.6-1332С: "H NMR (400 MHz, OM5O-dv): 11.15 (horn 5, 1H), 9 ... ,2Hz), 7.32 (bg 5, 1), 7.26 (a, 1H, 9U-2.0Hz), 7.17 (a, 1H, 9U-7.6Hz), 7.04 (aa, 1H, 9-78, 486 | b-chloro | 2,2-difluoroethyl | 2.2Hz), 7.01 (a49, 1H, 9-84, 2.0Hz), 6.41 (B 1H, 9-54 4, 3.4Gu), 4.32 (a, 2H, y-14.8, 3.6Hz), 4.14 (rg 5, 2H), 3.11 (rg 5, 4H); M5 (EbB, ): t/e 365.3 (MA1);

SNM (for StioNioR2SIM2O: HCI-O,3HgO) calculated: C 56.11; H 5.11; M 6.89; established: C 56.03; H 4.95; M 7.18 t.pl. 199.8-201.12С; "H NMR (400MHz, OM50O-adbv): 11.15 (ri 5, 1H), 9.35 (6 8, 2H), 7.57 (y, 1H, uU-8.4Hz), 7.44- 7.32 (t, ZN), 7.26 (y, 1H, 9U-2.0Gu), 7.22 487 | b-chloro 2.2,3,3,3- (a, yin, 9-8.0Hu ), 7.10 (aa, 1H, 9-84, 2.0Hz), 7.00 (ad, 1H, 9-86, 1.8Gu), pentafluoropropyl 4.85 (y 2H, 9-13.2Hz) . , H 4.08, M 5.98; established: C 51.61, H 4.07, M 6.00

B- 2233 8- t.pl. 168.5-171.07C; M5 (EbBu: t/e 4411 (Ma1);, SNM (for 488 isopropyl pentafluoropropyl СгзНа5Е5М2гО: НСИ-О, ЗН2гО) calculated: С 57.28, Н 5.56, М 5.81; established: С 57 ,10, H 5.21, M 6.03, mp 167.0-168.27С; "H NMR (400 MHz, OM5O-dv): 10.72 (g 5, 1H), 7.44 ( 1H , 0-7.8Hz), 7.34 (g 5, 1H), 7.22-7.15 (t, 2H), 7.14 (rg 5, 1H Hu), 7.06 (a, 489 5 - 2,2,3,3- 1H, y-7.6Hz), 7.01 (ai, 1H, 9U-8.4, 1.6Hz), 6.69 (H, 1H, 9U-51.6 . ,17- 3.05 (t, 1H), 3.05-2.91 (t, 2H), 1.24 (y, 6H, 2-6.8Hz); M5 (Eb-): t/e 422 ,1

M

Example 490 shock in methanol and add directly to the column

M-(2-(b-chloro-1H-indol-3-yl)ethyl)-M-methyl-3-ky ZSH (10g). After thorough washing of chloro-(2,2-difluoroethoxy)benzylamine with methanol, elute with a 2M solution of ammonia in methanol. Concentrate the mass to obtain sn, the target compound in the form of an oil. Dissolve the mass layer (239mg, 0.4mmol) in methanol (20ml) and add ammonium chloride solution (Zbmg, 0.67mmol)

And in methanol (ml). Treat the reaction mixture with sonication and sonication for 10 min before removing the solvent and mass to obtain the target compound

Mix /M-(2-(β-chloro-1H-indol-3-yl)ethyl)-3- in the form of a hydrogen chloride salt. Dissolve the salt in (2,2-difluoroethoxy)benzylamine (276 mg, 10 ml of a mixture (1:1) of acetonitrile-water and lyophilized 0.76 mmol) and formaldehyde (55.5 μl of 38905 water overnight to obtain a loose solid solution , 0.7 mmol) in dichloroethane (15 ml) and a white substance. Mix the solid substance - mix with diethyl ether (Toml) and acetonitride at room temperature for 10 minutes; after that, for 10 minutes, add a mixture of sodium chloride salt, see a column, and slowly stir: mp: 63.8-65.82C; IN NMR 1, . stir up the reactionary su- ! mish at room temperature overnight, (400MHz, OM5O-yv): 11.10 (rg 5, 1H), 7.52 (9, TN, : y-8.4Hz) 7.36 (a, 1H, 9- 2.0 Hz), 7.40-7.26 (t, 2H), dilute with methanol (1 Oml) and stop quickly. reaction by adding one drop of glacial acetic acid 7.22 (d, TN, ut2.4Hz), 720-711 (t, TN), 7.04 (rga, . 1Н, 0-7.6Hz), 6.96 (ai, 1H, 9y-8.6, 1.4Hz), 6.38 (y, acid. Remove the solvent and oil, obtain a residue, redissolve the crude residue - 1H, ue54.4, 3.6Hz), 4.50- 4.02 (horn t, 2H), 4.30 (yu, ! 2H, 9uU-14.4, 3.2HZ), 3.15 (rg 5, AN), 2.68 (Brg 5, ZN);

M5 (E5-): t/e 378.9 (M--1). compounds isolated in the form of hydrochloride, according to

According to the method of Example 490, the following were obtained by joining the indicated:

Beetle sleep, Eh

OA x re | and I and

NI T-Y MR II PO x ROD PON a S UN t.pl. 70.8-73.0"С; "H NMR (400 MHz, SOSI»z): 9.01 (g in, 1H), 7.40-7.35 (t, 1H), 7.35 (da, 1H, uU-8.8, 5.6Hz), 7.31-7.25 (t, 1H), 7.10-7.02 (t, 2H), 6.97-6.91 (t, 491 |6b-fluorine | 2,2-difluoroethyl | 2H), 6.77 (19, 1H, 9-9.2, 2.0Hz), 6.05 (y, 1H, 9U-54.8, 4.0Hz ), 4.21 (9, 2H, 9-13, 0, 4.0Hz), 4.08 (rg 5, 2H), 3.30-3.18 (t, 2H), 3.18-3, 05 (t, 2H), 2.66 (z, ZN); M5

ARSI): tue 363.1 (Ma-1 m.p. 66.4-69.32C; "IN NMR (ZO0MHZc, OM5O-dv): 11.04 (5, 1H), 11.20-10.70 (p 5, 1), 7.52 (ai, 1H, U-8.8, 5.5Hz), 7.34 (I, 1H, 9-7.9Hz), 7.30-7.20 (t . -fluoro|Z-fluoropropyl |)-8.4Gu), 6.84 (444, 1H, 4-9.9, 8.8, 2.2Hz), 4.61 (di, 2H, 4-47.2, 5.9Hz), 444 4.03 (g t, 2H), 4.08 (Yi, 2H, 9U-6.4Hz), 3.17 (rg 5, 4H), 2.68 (rg 5, ЗН) . ; "H NMR (400 MHz, OM5O-dv): 11.14 (in, 1H), 7.54 (9, 1H, y-8, AHC), 7.40 (a, 1H, 9U-2.4HC) , 7.35 (i, 1H, 9U-8.0Hz), 7.32-7.23 (t, 2H), 7.13 7.00 (t, 1H), 6.99 (aa, 1H, 9-86, 1.8Hz), 4.60 (41, 2H, 493 |b-chloro| Z-fluoropropyl | /-46 8.5 ,8Hz), 4.50-4.15 (g t, 2H), 4.08 (I, 2H, U-6, AGC), 3.18 (g 5, 4H), 2.72 (bg 5, ZH), 2.11 (double quintuplets, 2H, 9U-26.0, 6.4Hz); M5 (ARSI): m/e 375.1 (Ma mp. 206.6-207.52C; "H NMR (400 MHz, methanol-dia): 7.97 (y, 1H, 9-8.0Hz 7.93- 7.85 (t, 2H), 7.75-7.68 (t, 2H), 7.65 (rg a, 1n, 9U- 7.2Gu), 7.58 (bBg a, 1n, 494 | y-chloro 2.2,3,3,3- y-8.0Htsu), 7.47 (rga, 1H, 9U-9.2Htsu), 5.21 (y, 2H, 9U-13.0Htsu), 4, 60 (rg 5, 2H), 3.61 pentafluoropropyl (bg 5, 4H), 3.14 (rg 5, ЗН); MB (Ebya): t/e 4471 (My); SNM (for

C21NhoSiIv5M20.: NOI) calculated: C 52.19; H 4.38; M 5.80; established: C 52.16; H 4.29; M 5.82

Example 495 by harvesting the target compound as colorless

IM-(1-(b-chloro-1H-indol-3-yl)ethyl)-M-isopropyl oil. Dissolve the oil (237mg, 0.49mmol) in 3-(2,2,3,3,3-pentafluoropropoxy)benzylamine methanol (15ml) and treat with a solution of ammonium chloride (27mg, 0.49mmol) in methanol (5ml) . Obvy ( | Where to make the reaction mixture with ultrasound during

From that time, not 10 minutes before concentration with obtaining lip-

Its BOS is a white solid. Dissolve the sticky solid in 1 ml of a mixture (1:1) of aceto-

Mix /- M-(2-(b-chloro-1H-indol-3-yl)ethyl)-3-nitrile-water and lyophilize to obtain 241 mg of (2,2.3,3,3-pentafluoropropoxy)benzylamine (254 mg, ( 9695) of the target compound in the form of hydrochloride

O.5Omol) in 20 ml of a mixture (95:5) of methanolic salt: mp: 77.0-80.22С; "H NMR (400 MHz, meso-acetic acid, treat (portions) with acetone, ethanol-da): 7.31 (g, MH, 9U-7.8 Hz), 7.26-7.21 (t, (441 μl, 5 ,9mmol), then with cyanoborohydride 1n)U, 7.16 (bog a, yin, 9-84), 7.15-7.07 (t, 2H), sodium (148mg, 2.3mmol). Mix the reaction- 7 .05-6.95 (t, 2H), 6.83 (aa, 1H, 9U-8.0, 2.0Hz), 4.52 well mixture at a temperature of 50"C during the night; (, 2H, 9U-12.8Gu), 4.12 (rg 5, 2H), 3.53 (Brg 5, 1H), then additionally stir for 2 3.11 (rg 5, 2H), 2.89 (rg 5, 2H), 1.27 (horn 5, 6H); M5 days at room temperature. Remove dis- (ARSI): t/e 475.1 (M--1). factor ip mass with obtaining the remainder. Chromatography- According to the method of Example 495, the following compounds were obtained by graphing the residue on silica gel with elution, isolated in the form of maleate: 495 with a solution of methanol in dichloromethane with a

X y puttya is E hu no

M E n and E me; 2 | in. Y 7777777С7С7ю7ю7ю0odani7///777777771111111111111111111111с11 t.pl. 92.4-94.67С. mass spectroscopy (Ebzh): t/72 475.0 (M--1). Elemental analysis of PEN TATI no: C, 53.00; H, 4.55; M, 4.86 square meters 101.0-1-104.02С. Mass spectroscopy (E.Yu): t/2 461.0 (Ma)

Example 500 sodium hydroxide (37.83 mg, 1.0 mmol) in 1-methyl-2-

M-(2-(b-chloro-5-methoxy-1H-indol-3-yl)ethyl)-3-pyrrolidinone (1 ml). After stirring with rotating (2,2,3,3-tetrafluoropropoxybenzylamine) melting for 2 hours, dilute the reaction mixture with ml of methanol and transfer the resulting solution

And directly to column 5СХ (2g). Carefully

To wash the column with methanol, elute with 2M solution! in the form of ammonia-methanol and concentrate with Odersi SAaih sky E

Shk and n | harvesting the remainder. After that, clean on the column p: ше, ХХ: ра 5I. Elute with pure ethyl acetate. Characteristic

She and | ok, compounds were determined by liquid chromatography

What is the method 1 or 2. | CM5 (mass spectrometry with liquid chromatography) R: 2.749 min at

Mix a solution of 5-methoxy-b-chlorotryptamine 254 nm, 2,800 min at 220 nm; t/e 445(M1)... (O0.2mmol) in dichloromethane (1ml) and solution 3- General methods of liquid chromatography: (2,2,3,3-tetrapropylfluoropropoxy)benzaldehyde Method 1: (Zpitaygi oPVOOO) 10- 90 continuously (0.32 mmol) in dichloromethane (1 ml) and stir for 4.5 min. Solvent A: water 0.195 trifluoroacetate with rotation. After 2 hours, add concentrated acid, solvent B: acetonitrile 0.195 tryftone solution of sodium borohydride / (37.8 Zmg, acetic acid. Column: C18 Mesaspet, 1.0 mmol) in dichloromethane (1 ml). After mixing - topospgot Zmkm, 2.5x25. with rotation during the night, dilute Method 2: (Zpitaid2y) 10-80 during min. Dilute the reaction mixture with methanol and transfer solvent A: water 0.195 trifluoroacetic acid, concentrated solution directly onto the 5СХ column Solvent B: acetonitrile 0.0895 trifluoroacetic acid (27). Thoroughly wash the column with methanol, eluic acid. Column: С18 Meiaspet, top-preparation with 2M ammonia-methanol solution and concentration - 5 µm, 4.6x50. cotton wool to obtain the remainder. In the event that the following compounds were obtained by a method similar to the method of Example 500 and isolated in the eluent, it turns out that the reaction is not complete, in the form of a base, unless otherwise indicated: dilute the residue with dichloromethane (ml) and add the second portion of a concentrated solution of borohids and rashe a -kE

NETEI PON NN PON RON KON ONNU «T, ONONO

Because the call 00 agolriftoretilo | Method 2: Liquid chromatography (LC) retention time (B) 501 3-SEz ge, trifluoroethyl |390min at 220nm, 3.908min at 2b4nmM 2.2 2-trifluoroethyl Motokh pe P 3.620min at 254nm, 3.62min at 220nm, t/e . . - | Method 1: mass spectrometry with liquid chromatography. 03-SEz 0/0 |2,2,3,3-tetrafluoropropyl| Method 1: ISM5 RI 2.885 min at 254nm, t/e 410 (Ma

Method 2: C RI 3.420 min at 254 nm, 3.42 min at 220 nm

Z-trifluoromethyl Method 2: IR IR 3.580 min at 254 nm, 3.58 min at 220 nm

Method 2: IS Rg 3.212 min at 254 nm, 3.22 min at 220 nm 509| C-trifluoromethyl| avenue /// |Method 2: IC BI 3.892 min at 254 nm, 3.89 min at 220 nm 510 00002-chloro 00 | 0000 phenyl 0/0 |Method 1: CM5 B 2.479 min at 2854 nm, t/e 338 (Man1

C-trifluoromethyl| Phenyl.

N me! 27711111 Vve1Ї111111111111111111111 dan 2.2,2-trifluoroethyl | Method 1: GSM5 RI 2.651 min at 220nm, t/e 413 (Mat) 5i3| boron | a2oltrifluoroethyl | Method 1: /CM5 RI 2.618 min at 254 nm, 2.700 min at 220 m, 513 b-fluorine 2,2,2-trifluoroethyl t/e 367 (Ma . Y . Method 1: GSM5 KG 2.683 min at 254 nm, 2.661 min at 220nm, 514 | 4-chloro 5-methoxy 2,2,2-trifluoroethyl t/e 399 (Ma) 515 | 5-methoxy 6-chloro |2,2,3,3-tetrafluoropropyl| Method 1: GSM5 RI 2.749 min at 254nm, 2,800min at 220nm,

11111111 dark - |Method 1: GSM5 KI 2.683min at 254nm, 2.661min at 220nm, - | Method 1: GSM5 CI 2.682 min at 254 nm, 2.663 min at 220 nm,

Example 523 medium for column 5СХ (2g). Rinse thoroughly

M-(2-(b-trifluoromethyl-1H-indol-3-yl)ethyl)-3- column with methanol, elute with a 2M solution of ami-phenoxybenzylamine in methanol and concentrate to obtain a residue. After that, clean on column 5I with eluent

EE by dilation with ethyl acetate to obtain the necessary compound. The characteristics of the compound were determined according to method 1. ISM5 VI 2.954 min at 254 nm, 2.954 min

EM at 220nm, t/e 411 (M.-1). n Liquid chromatography method:

Method 1: (Response ОР8000) 10-90 continuously

Mix a solution of 5-trifluoromethyltryptamine 4, Bhv. Solvent A: water 0.195 trifluoroacetate (0 mmol) in methanol (ml) and 3-acid solution, solvent B: acetonitrile 0.195 trifluorophenoxybenzaldehyde (0.2 mmol) in methanol acetic acid. Column: C18 Meiaspet, (Iml) and mix with rotation. Through Zgod topospgot Zmkm, 2.5x25. add a concentrated solution of borohydride to the following compounds were obtained by the method, tri (18mg, 0.5mmol). In 1-methyl-2-pyrrolidinone similar to the method of Example 523 and isolated in (0.5 ml). After stirring with rotation of the form of the base, unless otherwise indicated: during the night, dilute the reaction mixture with 1 ml of methanol and transfer the resulting solution without water and

Kiya ped ody V me o ch I

And me; 0727777 She is in | 77777771 Dan///7/7/7////77777111111111 524 |b-trifluoromethyl| phenyl |Method 1: -SM5 V 2.954 min at 254 nm, 2.954 min at 220 nm, t/e 411 (Ma) 525| b-fluorine | phenyl | Method 1: GSM5 RGg2.712 min at 254 nm, 2.712 min at 220 nm, t/e 361 (M1) 526 |5-methoxy b-chloro| phenyl |Method 1: -SM5 V/2.757 min at 254nM, 2.757 min at 220nm, t/e 407 (Met) 527 |4-xpro 5-methoxy| propyl | Method 1: -SM5 V/2.578 min at 254 nm, 2.577 min at 220 nm, t/e 373 (May) 528 |b-trifluoromethyl) propyl | Method 1: -SM5 V 2.850 min at 254 nm, 2.849 min at 220 nm, t/e 377 (Mya1) 529| b-fluorine | propyl | Method 1: GSM5 Рg2.576min at 254nm, 2.576min at 220nm, t/e 327 (Ma1) 530 | -methoxy b-chloro| propyl |Method /i: (CM /2637min at 220nm, i.e. ZY7Z(MY)YIL/:(UU./С:(//

Example 531 mixture of 1 ml of methanol and transfer the resulting solution

M-(2-(4-sulfonamidophenyl)ethyl)-3-(2,2,3,3,3-chin) directly on the column of ZCH (2g). After pentafluoropropoxybenzylamine is thoroughly washed with methanol, elute the column with a 2M ammonia-methanol solution and conc. - remove the eluent to obtain a residue. An additional step where purification on the UV preparative system Siib5op Zaxx, Mito E ensures the preparation of the required compound. The characteristics and characteristics of the compound were determined by method 1. VI 2.345 min at 254 NnMm, 2.347 min at 220 nm, in xx t/e 439 (Mat) 461 (M22). o Liquid chromatographic method:

And Method 1: (Response ОР8000) 10-90 continuously

Mix the solution for 4-4.5 minutes. Solvent A: water 0.195 sulfonamidophenylethylamine trifluoroacetate (0.2 mmol) in meta-acid, solvent B: acetonitrile 0.195 triphtonol (ml) and a solution of 3-(2,2,3,3,3-acetic acid). Column: C18 Meiaspet , pentapropylfluoropropoxy)benzaldehyde toposphgot Zmkm, 2.5x25. (0.32 mmol) in methanol (1 ml) and mix with The following compounds were obtained by the method, rotation. After 1 hour, add concentrated similar to the method of Example 531 and isolate in a solution of sodium borohydride (18 mg, 1.0 mmol) in the 1-form of the base, unless otherwise indicated: methyl-2-pyrrolidinone (ml). After mixing with rotation during the night, dilute the reaction mixture: V scha t aiva BU nia a! sia

LEAKAGE MON MON MON UNN KOOOONNNNY x ET O - |Method 1: GSM5 KG2.816min at 254nm, 2.815min at 220nm, 532| 2,5-dimethoxy | 2,2,3,3,3-pentafluoropropyl t/e 420 (Ma)

Y Y - |Method 1: GSM5 KG2.634 min at 254 nm, 2.637 min at 220 nm, 533 3,4-dimethoxy | 2,2,3,3,3-pentafluoropropyl t/e 420 (M

And and. and Method 1: GSM5 K2.155min at 254nm, 2.156min at 220nm, 534 | 4-sulfonamide | 2,2,3,3-tetrafluoropropyl t/e 421 (Ma)

Y y Y y Method 1: HOM5 KI 1.816 min at 254 nm, 1.818 min at 220 nm, 535 | 4-sulfonamide Z-fluoropropyl m/e 367 (Me-1), 389 (M-22)

Y y Y Method 1: HOM5 KI 1.606 bhv at 254nm, 1.606 bhv at 220nm, 537 | 4-sulfonamide 2-fluoroethyl t/e 375 (M?

And Method 1: GSOM5 K2.511min at 254nm, 2.511min at 220nm, and Method 1: GOM5 KI 1.782min at 254nm, 1.782min at 220nm, 539 | 4-sulfonamide 2,2-difluoroethyl m/e 371 (Me), 393 (Ma22)

Method 1: GSM5 P2.359min at 254nm, t/e 352 (Ma

Y Y Method 1: HOM5 KI 2.085 min at 254 nm, 2.070 min at 220 nm,

BA1| 3,4-dimethoxy 2,2-difluoroethyl m/e 335 (Ma), 352 (Ma22)

Y and Y Method 1: GSM5 KI 1.816 min at 254 nm, 1.818 min at 220 nm, 542 | 4-sulfonamide 2,2-difluoroethyl m/e 367 (Me-1), 389 (M-22) 543| 2B-dimethoxy | Z-fluoropropyl | Method 1: CM5 RIG2.387min at 254nm, 2.381min at 220nm, 543 | 2,5-dimethoxy Z-fluoropropyl t/e 348 (M

Example 545 transfer the resulting solution directly to

M-(2-(b-methoxy-1H-indol-3-yl)ethyl)-3- column CH (2g). After thorough washing of (2,2,3,3,3-pentafluoropropoxy)benzylamine with methanol, elute the column with a 2M ammonia-methanol solution and concentrate the eluent from the obtained residue, which was additionally purified by UV t : . not to the preparative system of siizop. Features above. - and: ek compounds were determined according to method 1. /!СМ5 КГ і in 3.752 min at 254 nm, 3.753 min at 220 nm, t/e 429 і (Ma). "Mix a solution of amine (02mmol) in 1-methyl- Method 1. (Epitayai OROS) 10.90 during g-pyrrolidinone (ml) and aldehyde (0.32mmol) In 4.5min. Solvent A: water 0.196 trifluoroacetate dichloromethane (1ml) and mix with rotation acid, solvent B: acetonitrile 0.195 triphto-

After 1 hour, add a concentrated solution of Rispota KoponKA boron. Add sodium hydride (18mg, 1.0mmol) in 1-methyl-2-pyrrolidinone (1ml). After mixing with rotation, N MKM, 2 ex. by melting overnight, dilute the reaction mixture according to the method of Example

Doultte m : ! and it melts

And what

N

NO PR LY POLONI ROK NOT NO

BAYE 4-chloro 2,2,3,3,3- Method 1: GSM5 KI 3.87С3min at 254nm, 3.877min at 220nm, t/e 433 g pentafluoropropyl | (M--1) 2,2,3,3,3- Method 1: ISM5 RU 3.828min at 254nm, 3.833min at 220nm, t/e 429 pentafluoropropyl | (Ma1

BAV B-methoxy 2- 2,2,3,3,3- Method 1: GSM5 KI 3.802min at 254nm, 3.805min at 220nm, t/e 433 methyl pentafluoropropyl | (M--1) 2,2,3,3,3- Method 1: GSM5 RI 3,800 min at 254 nm, 3,806 min at 220 nm, t/e 429 pentafluoropropyl | (Ma1 5BO in-chlo 2,2,3,3,3- Method 1: GSM5 KI 3.947 min at 254 nm, 3.952 min at 220 nm, t/e 433 g pentafluoropropyl | (M--1)

Y 2,2,3,3- Method 1: GSM5 KI 3.695 min at 254nm, 3.695 min at 220nm, t/e 411 551| 4-methoxy tetrafluoropropyl | (Ma1) 2,2,3,3- Method 1: ISM5 RU 3.654 min at 254 nm, 3.654 min at 220 nm, t/e 425 methyl tetrafluoropropyl | (Ma-1

Y 2,2,3,3- Method 1: HOM KI 3.659 min at 254 nm, 3.661 min at 220 nm, t/e 411 553| 7-methoxy tetrafluoropropyl | (Ma1)

BBA in-chlo 2,2,3,3- Method 1: GSM5 KI 3.821min at 254nm, 3.821min at 220nm, t/e 415 r tetrafluoropropyl | (Ma1)

Method 1: GSEM5 VI 3.169min at 254nm, 3.169min at 220nm, t/e 345 method 1: GSEM5 VI 3.411min at 254nm, 3.412min at 220nm, t/e 347

Method 1: EM5 in 3.303min at 254nm, 3.304min at 220nm, t/e 343 5BV8 B-methoxy 2-2-fluoroethyl Method 1: GSM5 KI 3.236min at 254nm, 3.236b6min at 220nm, t/e 357 methyl (Ma ) i 1: GEM5 r 3.263 min at 254 nm, 3.264 min at 220 nm, t/e 343

Method 1: GSEM5 VI 3.465min at 254nm, 3.466bhv at 220nm, t/e 347 2,2-difluoroethyl | Method 1: ISM5 RI 3.190 min at 254 nm, 3.190 min at 220 nm

Method 1: GSM5 KI 3.795 min at 254 nm, 3.795 min at 220 nm, t/e 377 562 b-chlorine (Man)

Method 1: GSEM5 V 3.305min at 254nm, 3.306bhv at 220nm, t/e 331

B oachlor | own method 1: GSM5 in 3.668 min at 254 nm, 3.668 min at 220 nm, t/e 343

B72| 4methoxy | Propl 1: ЕМ5 in 3.581 min at 254nm, 3.582 min at 220nm, t/e 339 mists 0 prolia Method 1: ИСМ5 РИ 3.524 min at 254nm, 3.524 min at 220nm, t/e 353 methyl ImM1 574 tomatoes | propl method 1: GSEM5 VI 3.553 min at 254 nm, 3.554 min at 220 nm, t/e 339

B75| chlorine | propl 1: eM5 in 3.736 min at 254nm, 3.736 bkhv at 220nm, t/e 343 verb difto 5 ofenya | Method 1: ISM5 RU 3.830 min at 254 nm, 3.832 min at 220 nm, t/e 423 methoxy ImM1 577 bometok | hair dryer method 1: GSEM5 VI 3.527 min at 254 nm, 3.531 min at 220 nm, t/e 373

BTW 4chlor | pheno Method 1: eM5 in 3.749 min at 254 nm, 3.749 min at 220 nm, t/e 377 579 ametok | Phen method 1: HEM5 VI 3.657min at 254nm, 3.658min at 220nm, t/e 373 5VO B-methoxy 2- Method 1: GSM5 KI 3.609min at 254nm, 3.609min at 220nm, t/e 3387 methyl (MA) wt ) 7-methoxy | hair dryer Method 1: GSEM5 VI 3.622 min at 254 nm, 3.622 min at 220 nm, t/e 373

Ba bhlor | pheno method 1: GSEM5 VI 3.795 min at 254nm, 3.795 min at 220nm, t/e 377 4,6-difluoro 5-Y Method 1: GSM5 KI 3.514 min at 254nm, 3.519 min at 220nm, t/e 411 583 methoxy 2 ,2-difluoroethyl (Man) 2.2-difluoroethyl Method 1: GSEM5 VI 3.418min at 254nm, 3.419min at 220nm, t/e 365 2 2-difluoroethyl method 1: GHEM5 in 3.30min at 254nm, 3.305min at nm, t /e 361 2.2-difluoroethyl Method 1: GSM5 RI 3.269 min at 254nm, 3.269 min at 220nm, t/e 375 methyl ImM1 2.2-difluoroethyl method 1: GSM5 VI 3.265 min at 254nm, 3.271 min at 22 nm, t/e 361 2.2-difluoroethyl I 1: ЕМ5 р 3.476 bhv at 254nm, 3.476 bhv at 220nm, t/e 365 2.2-difluoroethyl Method 1: GSEM5 VI 3.326 bhv at 254nm, 3.326 bhv at 220nm, t/e 349

Z-fluoropropyl | Method 1: GSM5 RI 3.170 min at 254 nm, 3.176 min at 220 nm, t/e 357

11111111 m) 8-fluoropropyl Method 1: EM5 in 3.400 min at 254nm, 3.407 min at 220nm, t/e 361 8-fluoropropyl Method 1: GSEM5 VI 3.326 min at 254nm, 3.327 min at 220nm, t/e 357

B-Methoxy 2-Y and Method 1: GSM5 KI 3.277 min at 254 nm, 3.277 min at 220 nm, t/e 371 595 methyl 3-fluoropropyl (Man) 8-fluoropropyl Method 1: HYSEM5 VI 3.290 min at 254 nm, 3.291 min at 220nm, t/e 357 8-fluoropropyl Metoy 1: GSEM5 VI 3.498min at 254nm, 3.499min at 220nm, t/e 361 8-fluoropropyl eto 1: ЕМ5 in 3.329min at 254nm, 3.330min at 220nm, t/e 345 600 b-methoxy | 2.2 2-trifluoroethyl Method 1: GSEM5 VI 3.288 min at 254nm, 3.228 min at 220nm, t/e 379 2.2 2-trifluoroethyl Method 1: GSEM5 VI 3.518 min at 254nm, 3.518 min at 220nm, t/e 382- 2.2 trifluoroethyl Method 1: EM5 in 3.427 min at 254 nm, 3.428 min at 220 nm, t/e 379 in B-methoxy 2- 2,2 2-trifluoroethyl Method 1: GSM5 KI 3.378 min at 254 nm, 3.378 min at 220 nm, t/e 393 methyl (Ma) 2.2 2-trifluoroethyl eto 1: EM5 r 3.234 min at 254nm, 3.255 min at 220nm, t/e 379 2.2 2-trifluoroethyl Method 1: GSEM5 VI 3.587 min at 254nm, 3.587 min at 220nm, t/e 383

The following compounds were obtained by a method similar to the method of Example 545: x ! z che go M re "in A

What- and not

NETE Pme sl MON « ACCOUNTING CON ET NO 606| b-methoxy |2,2-difluoroethyl| Method 1: ISM5 VI 3.190 min at 254 nm, 3.190 min at 220 nm here! 4-fluoro-5- Method 1: GSM5 VI 3.390 min at 254 nm, 3.395 min at 220 nm, t/e 401 607 methoxy-6-fluoro 3-fluoropropyl MA1

OB 4-fluorine b-fluorine 2.2.2- Method 1: GSM5 KI 3.442min at 254nm, 3.453min at 220nm, t/e 429 5-methoxy trifluoroethyl | (Ma)

Example 620, add 1 ml of methanol to the reaction mixture and transfer

M-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3- directly on the ZCH column (2g). After thorough (2,2,3,3,3-pentafluoropropoxy)benzylamine washing with methanol, elute the column with a 2M ammonia-methanol solution and concentrate the non-o eluent to obtain a residue, which was additionally purified on a UfFf preparative system oiЙ5op. and M Ya ka | EE E The characteristics of the compound were determined by method 3. Shi zy kosh Zhrya ' ISM5 A 4.823 min at 254 nm, 4.823 min at 220 nm, s orat R t/e 443 (May).

M in Liquid chromatographic method: n Method 3: (Zpitad2y ОР8О000) 5-90 during

I I 4.5 min. Solvent A: water 0.196 trifluoroacetate

Mix a solution of amine (0.2 mmol) in dichloro-acid, solvent B: acetonitrile 0.195 tryphto-methane (0.5 ml) and aldehyde (0.4 mmol) in dichloro-acetic acid. Column: C18 Meiaspet, methane (1 ml) and mix with rotation. Through topospgot Zmkm, 2.5x25. hours, add a concentrated solution of borohydride. The following compounds were obtained by the method, sodium (82mg, 0.8mmol) in 1-methyl-2-pyrrolidinone similar to the method of Example 620: (Iml) and mix with rotation. After mixing with rotation overnight, dilute

no

You will drink -

N

VETEI O x SON NOOOOOOONNNN ES, ONNNONOOOOOOOO 2,2,3,3-tetrafluoropropyl | Method 3: ISM5 RI 4.681min at 254nm, 4.692min at 220nm, m/e 425 (Ma1 2,2,2-trifluoroethyl Method 3: GSM5 R 4.639min at 254nm, 4.64Zh at 220nm, m/e 393 (Mat. )

Example 624 (1.0 mmol) in 1-methyl-2-pyrrolidinone (0.5 ml) and pe-

M-(2-(6-fluoro-1-methyl-1H-indol-3-yl)ethyl)-M- stir with rotation. After stirring with methyl-3-propoxybenzylamine by rotation for 30 minutes, dilute the reaction mixture with Tml 1095 acetic acid/methanol mixture and

E: сн, sei transfer the obtained solution directly to i | | | column of ZSh (2g). After thorough washing of diks with pev and methanol, elute the column with a 2M solution of amine

I and acu-methanol and concentrate the eluent from the obtained

There was a residue, which was additionally purified on the Ufshche preparative system SiYib5op.

Liquid chromatographic method: : J Med. 4. Method 1: (Questions ОР8О0О00) 10-90 during

Mix the solution M methyl M-(2-(6-fluoro-4.5 min. Solvent A: water 0.196 trifluoroacetate methyl-1H-indol-3-yl)ethylamine (0.2 mmol) in 1. , solvent B: acetonitrile 0.195 triphto-methyl-2-pyrrolidinone (00.5 ml) and 3- , and I succinic acid. Column: C18 Mesaspet, propyloxybenzaldehyde (0.32 mmol) in dichloro- n 2 BxO5 methane (ml) and mix with rotation. After sweating on the hot ZMKM, 2, okho. b mixing with rotation during the night, until the tosob By the same method, give a concentrated solution of sodium borohydride podionim to the method of the example, etc.

VETECYA Pe SPON KON s UNI PON UNN KON t . Y Y Method 1: SM5 CI 3.214 min at 254nm, 3.213 min - |Method 1: GSM5 CI 3.042 min at 254 nm, 3.042 min

3-fluoromethyl 4-fluoro 3,3,3-trifluoropropyl at 220 nm, m/e 410 (MA). Y Y Method 1: CM5 KI 2.828min at 254nm, 2.828xV

3--rifluoromethyl 4-fluoro|./ NN 2,2-difluoroethyl at 220nm, m/e 378 (Ma 2,2,3,3,3- Method 1: СМ5 КИ 3.196min at 254nm, 3.196min

Method 1: CM5 CI 2.984min at 254nm, 2.984xVv

3-trifluoromethyl 4-fluoro 2,2.2-trifluoroethyl at 220 nm, m/e 396 (Ma). Y Y y Method 1: SM5 KI 2.855 min at 254 nm, 2.855 min

3-trifluoromethyl 4-fluoro|. NN Z-fluoropropyl at 220nm, t/e 374 (M) ropfrenia oh cheeks H | in. it's the same: i Y rya a hi m

N me | /7y 7 | her name is 7777 HER 77777771 Dan

Y Y 4- Method 1: SM5 KI 3.14 minutes at 254 nm, 3.140 minutes at 632 | 5-fluoro b-chloro | uetud ooprolia 220nm, t/e 375 (MA) 633 b-tri-H 3,3,3- Method 1: CM5 KI 3.065 min at 254nm, 3.06bbh at fluoromethyl trifluoropropyl |220Onm, t/e 431 (Ma1) 634 | fluorochlorin NOI oti Method 1: ISM5 RI 2.977min at 254, 2.977min at 220nm, 634 | 5-fluoro b-chloro and trifluoropropyl | t/e 415nm (Ma-1 5,8-difluoro Method 1: (SM5 V 2.871 min at 254 nm, 2.872 min at

77777171 | trifluoropropyl (Mat)

Y Y Y Method 1: CM5 VI 2.782 min at 254 nm, 2.782 min at 637 | 5-fluoro b-chloro n 2,2-difluoroethyl 220 nm, t/e 383 (Ma)

Y Y Method 1: (SM5 V 2.655 min at 254 nm, 2.655 min at 638 | 5,b-difluoro n 2,2-difluoroethyl 220 nm, t/e 367 (Ma) 6- I Method 1: 1SM5 VI 2.876 min at 254 nm ... t/e 417 (Ma)

Y Y 2,2,3,3,3- Method 1: HOM5EI 3.135 min at 254 nm, 3.135 min at 220 nm, ba1) 5 fluorob'chlor| NOI pentafluoropropyl | t/e 451 (Ma)

Y 2,2,3,3,3- Method 1: 1 CM5 V 3.027 min at 254nm, 3.027 min at b12 | 5budiftor NOI pentafluoropropyl | 22o0nm, t/e 435 (Me 643 6- Н 2,2,3,3,3- Method 1: СМ5 В 3.202 min at 254nm, 3.202 min at trifluoromethyl pentafluoropropyl | 22Onm, t/e 467 (М--1)

Y. Method 1: CM5 B 2.982 min at 254nm, 2.982 min at 645 at 646 rifluoromethyl| 00 | 2ee-trifluoroethyl| 550um, tu 417 (Ma)

Y Y Y Y Method 1: CM5 VI 2.796 min at 254 nm, 2.796 min at 647 | 5-fluoro b-chloro n Z-fluoropropyl 220nm, t/e 379 (Ma)

Y Y y Method 1: I CM5 ВИ 2.644 min at 254 nm, 2.646 bhv at 648 .

I don't

Mme/ 2 HER in HER 77 Vve | 77777771 Dan 631 Sh|6-fluoro| 4-methyl | propl, |Method 1: SSM5 RI Z, 152 min at 220nm, t/e 355 (Ma1)

And 3,3,3- Method 1: CM5 KI 2.949min at 254nm, 2.953min at 220nm, b33A|b- fluorine! H trifluoropropyl | t/e 395 (Ma)

Y 223 3 3- Method 1: ISM5 KI 3.112 min at 254 nm, 3.117 min at 220 nm, bod) b'fluorine and pentafluoropropyl | t/e 431. (Mch . Method 1: SM5 KI 2.895 min at 254nm, 2.898 min at 220nm, 649 16 fluoro n 2,2,2-trifluoroethyl t/e 381 (Ma)

Example 650 wash the aqueous layer with dichloromethane (5Oml). About-

M-2-(3-chlorophenyl)ethyl-3-hydroxybenzylamine, wash the combined organic layers with saturated brine (3x), dry over Md5oOa and concentrate with it to obtain the target compound. N ! Example 650A pod i tt t M-tert-butoxycarbonyl-M-2-(3-chlorophenyl)ethyl-3-hydroxybenzylamine - Mix M-2-(3-chlorophenyl)ethyl-3-hydroxybenzylamine, dichloromethane (40 ml), di-

Si tert-butyldicarbonate (1.556g; 7.131mmol) and

With triethylamine (1.0 ml; 7.2 mmol). After 18 hours, mix 2-(3-chlorophenyl)ethylamine (1.866 g; pour into water (50 ml), separate the layers and extract 15.28 mmol) and 3-hydroxybenzaldehyde (1.567 g; wash the aqueous layer with dichloromethane. Wash with - 10.07 mmol) in 40 ml of methanol, mix the organic layers with water, dry over MdSO4 at room temperature for 20 min, process and concentrate. Chromatograph on silica gel with sodium borohydride (0.950g; 25.1mmol) one eluting with 595 ethyl acetate solution in hexaportion. Stir the mixture at room darkness to obtain the target compound. surgery After 15 hours, add water (10 ml) and extract the methanol using a rotary evaporator. dichloromethane (50 ml), separate the layers and add 5095 solution of sodium hydroxide in water

(O0.dml) to a solution of M-tert-butoxycarbonyl-M-2-Ex (3-chlorophenyl)ethyl-3-hydroxybenzylamine (46.7 mg, n 0.129 mmol), p-propyl iodide (0.17 g, 1.00 mmol ) diamine and tetrabutylammonium bromide (18 mg, 0.057 mmol) g in toluene (Iml). Stir the mixture at 1200 rpm and heat at a temperature of 50-54260.

After 64.5 hours, pour the mixture into 5 ml of water, wash the phases separately and extract the aqueous phase twice with dichloromethane. Combine the organic phases, wash. Add methanesulfonic acid (7 µl) to a saturated solution of sodium bicarbonate, then a solution of M-tert-butoxycarbonyl-M-2-(3- saturated brine, dry (Ma5O") and concen- xporphenyl)ethyl-Z -propoxybenzylamine in dichlonate to obtain a residue. Chromatography-methane (4 ml) and stir the resulting mixture, and the residue on silica gel to obtain the whole - for 10 minutes at room temperature. Add compounds M5 (EbBzh) t/e (Mya1) 404. 1095 aqueous solution of Mag2CO3 (2 ml), separate

Thin-layer chromatography. (2095 EUAs in hex-layers and concentrate the organic layer in a sled flow, MK 0.54). of nitrogen to obtain a residue. Dissolve the residue

Example 652 in 4 ml of 595 solution of acetic acid in methanol and

M-(2-(3-chlorophenyl)ethyl)-3- pass through a ZSC column (1g) eluting with propoxybenzylamine 1M solution of ammonia in methanol to obtain the target compound: M5 (Eb'zh): t/e (M'-1 ). NRI C (10-90905 water/acetonitrile over 7.5 min, T/-4.490 min).

The following compounds were prepared by a method similar to that of Example 651 and Example 652:

What is it?

TE poh RON PON TU UN 658 | all |MethodsSM5R4,37Zkhvpri254/220nm; te 3019 (ME) 660 | pyridine-2-ylmethyl |Method'/: I CM5A3, 547 xvpri 254/220nm; t/e 352.9(MY)../:ХИиС/Ю

Example 665 O.ZOmole) in dichloromethane (Iml). After 44 hours

M-(2-(5-methoxy-1-ethyl-1H-indole-3-iluethyl)-M- quickly stop the reaction by adding cold ethyl-33-phenoxybenzylamine methanol (0.5 ml) and concentrate in a stream of nitrogen to obtain a residue. Dissolve the residue in 4 ml

Neo 595 solution of acetic acid in methanol and partially; I purify by passing through a column

HOW AND ; and ZSH (1g) with elution with 1M ammonia solution

X M | methanol to obtain a residue. The chromatograph was used to separate the residue using preparative high-performance liquid chromatography (column C-18,

NN flow rate 20 ml/min, 5-9095 mixture of water/acetonitrile for 12 min) to obtain

Add acetaldehyde (0.08Oml; 0.77mmol) to the target compound: MB (EbZzh): t/e (Mat); NRI.S: solution // M-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3- (10-9095 water/acetonitrile over 10 min, Ti-5.25 MinV). of phenoxybenzylamine (free base, 55.5 mgH, The following compounds were obtained by the method, 0.149 mmol) in dichloromethane (1 ml), then a suspension similar to the method of Example 665: sodium triacetoxyborohydride (b4 mg;

g ve village what else ay nyty shshi nshih S TT 666 | methyl, |(SMethod2 at 254/220nm; TUE Z51.9(M).L/: SG

May

From AHA

What is on and in this

N threads of our ST PO

Example 670 to dig. Chromatograph on silica gel (0-2095

3-propoxybenzaldehyde solution of ethyl acetate in hexane) to obtain this

Mix 3-hydroxybenzaldehyde (7.50g; oil product. 61.4mmol), p-propyliodide (17.3g; 102mmol) and Example 672 potassium carbonate (16.90g; 122mmol) in 2-butanone 3-(2-fluoroethoxy) benzaldehyde (100 ml) and heat under reflux. Mix 1-bromo-2-fluoroethane (4.575g;

After 17 hours, cool the mixture to room temperature - 36, mol), 3-hydroxybenzaldehyde (4103Hg; temperatures, drain the solution and concentrate on a rotor - 33.60mmol) and CaCO3 (7.05g; 51.0mmol) in a 2-layer evaporator. Distribute the resulting solution in butanone (100 ml) and heat under reflux between diethyl ether (150 ml) and water. After 18 hours, cool the mixture to room temperature (15 Oml), separate the layers and extract the aqueous solution of the environment, concentrate the layer with diethyl ether (2 x 100 ml). Combine cotton wool and distribute between 100ml of water and 100ml of organic layers and wash with water, 1M solution of dichloromethane. Separate the layers and extract

Mahon, then with water, dry over Md5oOx and the aqueous layer with dichloromethane (2x75 ml). Combine to center to obtain the remainder. Dissolve the organic layers and successively wash the residue with brine to obtain the target compound: tempeh (2x150ml), 1M Mahon solution (2x10Oml), boiling range: 122-1257C (15mm); thin-layer NaClSOOz (saturated, 100 ml) and brine chromatography (1095 ESO/hexane; Me 0.35). (15O0ml), dry (Md5O5), concentrate and chro-

Example 671 to be matographed on silica gel (0-25905 solution of diethyl ether 3-(3,3,3-trifluoropropoxy)benzaldehyde in hexane) to obtain the target

Cool the mixture of toluenesulfonyl chloride compounds. (7.43g; 39.0mmol) and pyridine (50ml) to a temperature of 0"C, add 3,3,3-3,3,3-trifluoropropanol M-(2-(5-fluoro-1H- indol-3-yl)ethyl)-3-(2.23g; 19.5mmol) and store the mixture at a temperature of 3°C. After 48 hours, pour the reaction mixture into

35 ml of a mixture of water and ice and extract with diethyl ether (3 x 125 ml). Combine the organic layers and wash with 5M HCl solution, water, saturated sodium bicarbonate solution and brine, dry over Md5OH and concentrate to give 3,3,3-trifluoropropyltosylate. The obtained M material was used at the next stage without further purification. And I

Mix 3,3,3-trifluoropropyltosylate (4.057; Mix 3-propoxybenzaldehyde (29.6 mg; 15.12 mmol), 3-hydroxybenzaldehyde / (1.85 g; 0.1 mmol) and 5-fluorotryptamine // (14.2 mg; 15 .12 mmol) and CoCO3 (4.15 g; 30.00 mmol) in dimeth- 0.080 mmol) in methanol (2 mL). Add a solution of tylformamide (8 Oml) and heat at the temperature of sodium borohydride in diglyme (1 ml of a 0.5M solution; 1002C. After 18 hours, cool to room temperature - 0.50 mmol) and mix. After 6 hours at room temperature, dilute with water (200 ml) and concentrate in a stream of nitrogen at the extraction temperature. dichloromethane (2 x 200 ml). Combine the organic compounds. sodium bicarbonate (100 ml) and saturated product. of the target compound Me. metal salts with brine (100 ml), dry (Md5Oai) and concentrate (Me1); NRIS (10-9095 water/acetonitrile over

10 min, Ti/-4.08 min. topospgot Zmkm, 2.5x25.

General methods of liquid chromatography (LC): Method 3: (High-performance liquid chromatography

Method 1: (High-performance liquid chromatograph M/asgeg5 MiPepit and liquid chromatograph bpitad?y MR class and liquid chromatograph Misgotavz5 Riakogt with liquid chromatograph Misgotav55 Riakogt with liquid chromatog system NRI1100) 10-100 for 10 min. by the NRI100 raphic system) 10-90 continuously Solvent A: 0.195 trifluoroacetic acid, Sol- 7.5 min. Solvent A: water 0.195 trifluoroacetic acid factor B: acetonitrile 0.0895 trifluoroacetic acid, solvent B: acetonitrile 0.195 trifluoroacetic acid. Column: UMS, 5μm, 2.5x25. tartaric acid. Column: C18 Meiaspet, Method 4: (Liquid chromatograph Zpitaidly toposphot Zmkm, 2.5x25. ORVOOO) 10-90 for 4.5 min. Solvent A: in

Method 2: (High-performance liquid chromatograph 0.195 trifluoroacetic acid, Solvent B: chromatograph MR class and liquid chroma-acetonitrile 0.195 trifluoroacetic acid. Colotograph Misgotavz5 Riazgot from liquid chromatography: С18 Measpet, toposphot Zmkm, 2.5x25 by the NRI100 raphic system) 10-90 for 10 min. Solvent A: water 0.195 trifluoroacetic acid similar to the method of Example 673: acid, Solvent B: acetonitrile 0.195 trifluoroacetic acid. Column: C18 Meijaspet, ex t, K v g

In each

Still shizhiashn live tires 690 | 4-sulfonamide | Method 3 RgZ4bhvpri 254/220nm; m.p. 383.0 (MNM).

The following compounds were obtained by a method similar to the method of Example 673:

E resoeknkh she dO i Zh bitu yati -

Tires 699 | B-chlor | SSMethod ki2,893hvpri254/220nm.tue 377(My).-/://:/:/

; in (in Mytny lov, still shizhishinyzhininnnnnnnshsh nn

The following compounds were obtained by a method similar to the method of Example 673:

She

S sn an -th Hall Z shin: chn shin tn

The following compounds were obtained by a method similar to the method of Example 673:

Or vyy - n sht SHE and y: ROL PI a ET OO

The following compounds were obtained by a method similar to the method of Example 673: c : And where

KOH and at oh

Me! and 11111111 dan/////7777777111111С1

Example 760 cremate the aqueous layer, neutralize 2M solution

C-trifluoromethoxyphenethylamine nom Mahon (100 ml), extract with ether, process

Mix nitromethane (1.8g, 30mmol), ethanol, wash over Ma»5O»x, filter, then (A4ml) and TOM Mahon solution (0.1ml). Add 3- concentrate to give the target compound, trifluoromethoxybenzaldehyde (5.0g, 28.6mmol) and which can be used without additional stirring. After 20 hours, pour into ethyl acetate, clean. M5 (MN) 206; "H NMR (SOSIz) 7.32 washed with water, dried over Mag5O", profile (IN, its 9U-7.6 Hz), 7.18-7.06 (ZH, t), 2.98 (2Н, its .

Chromatograph the residue on silica gel to obtain Example 761 2-nitro-1-(3-M-(2-(3-trifluoromethoxyphenyl)ethyl)-3-(2,2,2-trifluoroethoxyphenyl)ethanol: M (M-1 ) 250; "H trifluoroethyl) benzylamine

NMR (SOCIz") 7.45 (1Н, и, U-84Hz), 7.36-7.30 (2Н, т), 7.24-7.20 (1Н, т), 5.51 (1Н, ai, 9U-8.8 and 4.0Gu), 4.62-4.51 (2H, t).

Mix 2-nitro-1-(3-H E trifluoroethoxyphenyl)ethanol (6.1 g, 24.2 mmol) and Kk methanesulfonyl chloride (2.02 mL) in dichloromethane E (5 O mL) and cool in an ice bath. Add triethylamine (7.28 ml) drop by drop while maintaining the temperature at a level close to 0°C. After 2 hours pour into ethyl acetate, wash with water, dry over Mag50O»4, filter and then concentrate Chromatograph the residue on silica gel with Mix trifluoromethoxyphenethylamine to give 3-(2-nitrovinyl)-1-(400 mg, 1.95 mmol), 3-(2- trifluoroethoxybenzene: M5 (MH) 234; "H NMR trifluoroethoxy) benzaldehyde (596mg, 2.92mmol) (SOCI3) 7.97 (1H, a, 9-13.6Hz), 7.57 (1H, a, and 4A molecular sieve (4.0g) in ethanol (30ml) and 13 ,6Hz), 7.53-7.48 (2H, t), 7.40-7.35 (2H, t). heat under reflux. By

Mix 3-(2-nitrovinyl)-1- for 4.5 hours, drain and treat with MaVNia (221 mg, trifluoroethoxybenzene (3.0 g, 12.88 mmol), meta- 5.85 mmol). After an hour, evaporate and distribute the zero (50 ml) and concentrated NH (5 ml) and hydrogen between 5 M Mahon solution and dichloromethane. Deionize at ambient temperature, incinerate the organic layer, dry over Ma»5Ox, higher under a pressure of 5Olb/in2 (340kPa) and filter and concentrate to obtain the presence of RIO» (0.6g). After 5 hours, the residue is filtered. Chromatograph the residue using a catalyst, dilute the filtrate with a 1M solution of high-efficiency liquid chromatography

HCl (5 mmol) and washed twice with ethyl acetate. It is combined with obtaining the target compound. chloride

the neva salt of the target compound gives a colored solid. Recrystallize from ethyl acetate from white color: М5 (МН.ю 394; "Н (ООМ5О-дв) 9.48 obtaining the hydrogen chloride salt of the target sp- (2Н, рго5), 7.48 (1Н, its 9у-7.6Hz), 7.40 (1H, i, bows: m.p. 208.5-210.0С; "H NMR (400 MHz, u8, OGC), 7.34 (1H, 5), 7.32-7.21 ( 4H, t), 7.11 (IN, OM50O-av): 11.79 (horn in, 1H), 9.21 (Bg in, 2H), 7.39 (i, da, 9U-8.4 and 2.8Hz), 4.79 (2H, ad, U9-8.8Hz), 4.15 (2H, 1H, y-7.8Hz), 7.32 (9, 1H, 9U-2.0Hz) 7 .30 (5, 1H), 5), 3.22-3.12 (2H, t), 3.11-3.04 (2H, t). 7.18 (a, yin, 20-8.0Hz ), 7.11 (da, yin, 9U-2.6, 8.2Gu),

Example 762 6.85-6.91 (t, 1H), 6.67-6.73 (t, 1H), 4.77 (a, 2H,

M-(2-(3--trifluoromethoxyphenyl)ethyl)-3-9-8.8HC), 4.16 (5, 4H), 3.12-3.16 (t, 4H); M5 (2,2,3,3-tetrafluoropropyl)benzylamine (ARSI): m/e 385.1 (Mat); sleep (for

SteNi7R5M2O-NOI) calculated: C 54.23, H 4.31, M g E 6.66; established: C 54.20, H 4.30, M 6.66.

Example 764

M-(2-(4,5,6,7-tetrafluoro-1H-indol-3-yl)ethyl)-3-

Uh (2,2,2-trifluoroethoxy)benzylamine

IS

E Azh -k i vo t i i o E

E and E

The target compound is obtained according to the method

Example 761. The hydrogen chloride salt of the target compound by a method similar to the method of Example gives a white solid substance: M5 763, using 2-(4,5,6,7-tetrafluoro-1 H-(MNU) 426; -dv) 9.42 (2H, Bg 5), 7.48 (1H, indol-3-yl)ethylamine (484mg, 2.08mmol), ethanol 1, 9-7.6Hz), 7.40 (1H, y, 9U-7.6Hz), 7.32-7.26 (ZH, t), (45 ml), 3-(2,2,2-trifluoroethoxy)benzaldehyde 7.201 1nH,a,ut7.2Hz), 7, 11 (1H, aa, y-8.4 and 2.8, (425mg, 2.08mmol), anhydrous sodium sulfate 6.70 (1H, H, Y 2-52 and 5.2Hz), 4.62 (2H , 5 9U-13.6Gu), (3.5g) and sodium borohydride (236mg, 6.24mmol), 4.15(2H, 5), 3.22-3.12 (2H, t), 3.10 -3.02 (2Н, M). obtain the free base of the target compound in the

Example 763 looks like a straw-colored solid. Pe-

M-(2-(4,7-difluoro-1H-indol-3-yl)ethyl)-3-(2,2,2- recrystallized from methylene chloride to obtain the target compound: m.p. 107.2-108.22C, "N

NMR (400MHz, OM5O-iv): 11.92 (horn 5, 1H), 7.32 (85,

E 2H), 6.95-6.99 (t, 2H), 6.87 (ai, 1H, 9U-2.4, 8.0Hz) i E 4.68 (94, 2H, 9-8.8Hz ), 3.70 (5, 2H), 2.88 (I, 2H, i.e. 9U-7.2Hz) 2.75 (, 2H, 9-7.2Hz), M5 (EbBk): t/e 421, 1

R M y (Ma), SNM (for StioNizE7M2O-1HCII0.20H20) total: C 53.83, H 3.66, M 6.61; established: S

I I 53.75, H 3.33, M 6.

Mix 2-(4,7-difluoro-1H-indole-3- Example 765 yl)ethylamine (48 mg, 2.4 mmol) and ethanol (45 ml) and B-trifluoromethyltryptamine and mix. After 10 min, treat 3-(2,2,2- Mix 4-trifluoromethylaniline (32.2g, trifluoroethoxy)benzaldehyde (502mg, 199.8mmol) and dichloromethane (6b00ml) in hl 2.4bmmol) and anhydrous sodium sulfate in a round-bottom flask under atmosphere of nitrogen and cool (3.5 g), mix in a nitrogen atmosphere and heat to a temperature of -702C. Add a solution of tert- at a temperature of 70". After 2 hours, cool re-butyl hypochlorite (protected from light) (22.8 g, cation mixture, filter under vacuum for 210 mmol) in dichloromethane (150 ml) and stir- removal of sodium sulfate and treat the for a total of 45 minutes at a temperature of 500 ml of sodium chloride (279 mg, 7.38 mmol) in a circular manner from -652 C to -702 C. After 35 minutes, add methylthioacetaldehyde dimethyl acetal (Zog,

Keep the solution with stirring for 220 .2 mmol) in dichloromethane (150 ml). After 45 minutes and 2 hours at room temperature, after which, at a temperature of -70C, add the solution of triethylamine, treat with three drops of glacial acetic acid (31.2 ml, 22.78 g, 225.1 mmol) in dichloromethane to quickly stop the reaction with ( VOml). Adjust the temperature of the reaction mixture with an excess of hydride. Remove the solvent and bring the mass to room temperature. Wash with water and evaporate to and redissolve the crude material in dryness to obtain 72g of oil. methanol. Purify on a 10g column of ZHCH by Dissolving the oil in toluene (b00ml) and adding thorough washing with methanol, elution with triethylamine (bOml). Heat to reflux with a 2M solution of ammonia in methanol and concentrate with a separator. After 24 hours, evaporate the solvent and ip masso to obtain the target compound in the form of dry the residue under vacuum to obtain 7 g of straw-colored oil. Obtain a chloride residue. Mix the residue, diethyl ether hydrogen salt By dissolving the FREE base (6b00ml) and 2M HCl solution (500ml) and stir (800mg, 2.08mmol) in methanol (15ml) and treat for 24h at room temperature. Add ammonium chloride solution (111 mg, 2.08 mmol) to the aqueous layer, successively wash with organo-methanol (ml). Treat the reaction mixture with water and a saturated solution for 10 minutes before concentrating Mansoz, dry over MozOx, filter and evaporate to obtain a white solid. Chromatograph-

cotton wool on silica gel eluting with a mixture of cyclo- (1627) and dimethylformamide (dl). Add 1-hexane-ethyl acetate (8/2, in the volume ratio- iodopropane (1000g), heat to temperature no), combine the fractions including the expected 10572 and stir for 4 hours. Cool the product, evaporate with the receipt of 33.8 g of 2- to a temperature of approximately 50"C and add methylthio-5-trifluoromethyl-1H-indole water. (15 l), continue cooling to approximately

Mix wet Raney nickel (330g), 2-room temperature and add toluene (Ol). Bi-methylthio-5-trifluoromethyl-1H-indole (33.8 g, skim the organic layer and extract with aqueous 146.2 mmol) and absolute ethanol (850 ml) and the second phase with toluene (2x10 l), combine the organic phases and stir. After 1.5 hours, filter the reaction and wash with 1 M Mahon solution (2 x 5.8 l), the concentration mixture through a layer of Celite and wash the combined organic layers with ethanol (500 ml). Evaporate the filtrate to dryness, harvesting the target compound. add toluene (20 ml), evaporate and dry with Example 777 obtaining 5-trifluoromethylindole: m.p.-55- M-(2-(B-methoxy-1H-indol-3-yl)ethyl)-3- 60. propoxybenzylamine

Dissolve 5-trifluoromethylindole (24g, mix 3-propoxybenzaldehyde /(14.05g, 130mmol) in anhydrous diethyl ether 0.0856mol) and 5-methoxytryptamine /(13.64g, (288ml), cool to a temperature of 10"С, drop 0 .0717 mol) in 390 ml of absolute EN. Add dropwise over 10 minutes, add oxalyl chloride molecular sieves (19.2 g), and heat the obtained (12 ml) (exothermic reaction) and stir the suspension under reflux. After room temperature for 4 hours. Add and cool for 4 hours to room temperature and with an additional amount of oxalyl chloride (3 ml) and pepper, add Mavna (37.32 g, 0.2146 vmol). Stir overnight at room temperature; stir the mixture for an hour at room temperature to obtain a solid Collect the substance. fluoromethyl-1H-indol-3-yl)-2-oxormethane, combine the organic layers, dry with acetyl chloride. over Md5o", filter, evaporate the solvent

Mix 2-(5-(trifluoromethyl-1H-indol-3-yl)-2-yl maso to obtain the target compound. oxo-acetyl chloride with 1 M solution /MNAOHn Mix the target compound and isopropanol (700 ml) and intensively stir the obtained (250 ml) and slowly add a solution of NCI to the suspension of EUN. After about 10 minutes, collect //2-(5- (33 ml, 2.5 M). Heat with reflux- (trifluoromethyl)-1H-indol-3-yl)-2-oxo- of acetamide and stir for 30 minutes Cool to

Add PAINAe (37.95 g, 1.00 mol) to tetrahydrogen at room temperature and stir continuously with rofuran (b50 ml) with cooling on ice for 2 h to obtain a solid. Filter baths. Obtain a solution of AiSiz (50g, 375mmol) in a solid substance, wash with isopropanol tetrahydrofuran (bbOml) and drop by drop and dry to obtain a hydrogen chloride salt, add over 45 minutes to a solution of HIAIN at the target compound. at a temperature of 5-107C. Add a solution of /-2-(5- Example 778 (trifluoromethyl)-1H-indol-3-yl)-2-oxoacetamide 2,2,3,3,3-pentafluoropropyltosylate (21.4 g, 83.5 mmol) in tetrahydrofuran ( 600ml) with Mix 2,2,3,3,3-pentafluoropropan-1-ol keeping the temperature at about (9.7ml) and pyridine. Cool to a temperature of 5"C and stir overnight with heating ranging from 0"C to 107C, adding p- to ambient temperature in portions. toluenesulfonyl chloride (6.2g) and mix with

Cool the resulting mixture with a mixture of water and ice-heating to room temperature. Through the house and treat 3095 with a Mahon solution (100 ml) from Zhod at room temperature, pour the reaction mixture into a mixture of water and ice and stir at a temperature not lower than about 30 "C. filter for about 30 minutes, filter the solid, wash with water, wash with tetrahydrofuran (2 L) and evaporate the filter and dry to give the target compound. Add 3,3,3-trifluoropropan-1-ol (61.8 ml) and NaOH in diethyl ether (until acidic pyridine (224 ml) is reached. Cool to reaction temperature. Filter solid substance, washed between 0"С and 10"С, added in portions with diethyl ether and dried under reduced toluenesulfonyl chloride (147g). Keep under pressure to obtain the hydrogen chloride salt heating to room temperature and mixing compound. wate throughout the night. Add 0.5M solution of NOSI

The target compound can be further purified (16 L), extracted with ethyl acetate, combine the organic layers by main extraction of hydrogen chloride salt, dry over Ma5Box, filter with ethyl acetate, dry over MazO", filter and evaporate to obtain the target by sporulation and evaporation to dryness from afar - Ky. by obtaining the hydrogen chloride salt in diethyl ether. b-Fluorotryptamine

Example 766 Add drop by drop over 40 minutes

Z-propoxybenzaldehyde 422ml glacial acetic acid to 4095 aqueous

Mix 3-hydroxybenzaldehyde (790g), CaCO3 solution of dimethylamine (408ml) with simultaneous sub-

keeping the temperature at a level lower than (100g, 0.437mol), 290 solution (in a mass ratio of approximately 1570. Cool to a temperature of 0"С.) Mahon (2.5kg) and dichloromethane (1.5L) and powder

After stirring for 20 minutes at room temperature, stir. After 15 minutes, pour off the organic layer, extract at 0"C, slowly add 3795 aqueous solution, treat the aqueous layer with dichloromethane, combine formaldehyde (289 ml, 1.3 equiv.) over the course of the preparation of the organic layers and concentrate to obtain a liquid for 15 minutes. In four portions over approx. of the residue. Mix the residue and isopropanol and after 15 minutes add a solution of b-fluorindole (400 g, dissolve in oil to obtain the target compound. 2.96 bmol, Eq.). After 30 minutes, divide the reaction Example 782 mixture into two portions. One portion - 1149g (7595 from M-(2-(6-fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3- total mass) - slowly, over 30 minutes, tetrafluoropropoxy was added) benzylamine to Zl 1095 of Mahon solution and stir at room temperature. After 18 hours, filter off the obtained solid substance, wash three times with 200 ml of water, dry with suction from a cloth, and dry with wet 3 -(M,M-dimethylaminomethyl)-6-sh-KE fluorindole

Dilute another portion of the reaction mixture (383g, 2595 of the total weight) with an aqueous solution. Mix Isopropanol (500g), 2,2,3,3-

Mahon to pH 12-13 to obtain a solid - tetrafluoropropylbenzaldehyde (16.87) and 6-ni. Filter the solid, fluorotryptamine (1.15 eq.) through Zohv. Heat with backwash with water, dry at a temperature of 502C in a refrigerator for about 1.5 hours. Pis- during the night to obtain 3-(M- la ZOkhv heating with reflux dimethylaminomethyl)-6-Fluorindole. " beat and during ZO0 minutes collect approx

Mix KSM (50.8, 0.78 mol), 3-(MM-380 g of distillate. Cool the reaction mixture to dimethylaminomethyl)-6-fluoroindole (100 g, temperature 50 "C and add 0.52 mol of mauve in one portion), dimethylformamide (400 ml ) and water (19.71 g). After 1 hour at a temperature of 507C, slowly (200 ml). Heat with a reflux refrigerator. but during 15 minutes add water and stand

The release of gas begins at the temperature of the heated solution with cooling to room temperature - approximately 70"C. Continue heating from the vapor temperature during the night. Evaporate isopropanol with a mouth refrigerator for 4 hours. Cool - under reduced pressure to obtain a residue, and bring the reaction mixture to room temperature , extract M beans, combine yours, dilute with water and toluene and mix with water and mix with water for 10 minutes. Pour off the organic layer and follow- (th ml) With the formation of a solid substance. Wash again with a saturated aqueous solution, thick suspension for 2 hours with sodium tembonate and 2M aqueous chlorine solution at a temperature of 20-2570. Filter off the solid hydrofluoric acid. Concentrate the organic layer, wash with dichloromethane and dry to dryness to obtain 2-(6-fluoro-1H- indole-3- at a temperature of 50"C under vacuum overnight with il)acetonitrile to obtain the target compound.

Mix 2-(6-fluoro-1H-indol-3-yl)acetonitrile (1657, 0.925 mmol) and tetrahydrofuran (1.32 L). Ch2,2,2-trifluoroethoxy)benzaldehyde

Over approximately 40 minutes, slowly add 1M Mix 3-dihydroxybenzaldehyde (134.3g), carbo solution of VN (2.042l, 1.832kg, 0.131 mol) in potassium tetragibonate oo in 2.2.2-trifluoroethyl p-drofuran. After the addition is complete, heat topoopsulfonate ( and C) and dimethylformamide under reflux for 1 hour. Pis- (hl). Heat the reaction mixture at a temperature of 1 hour under reflux at 9070. After T5 hours, cool to room temperature, cool to room temperature and during the rature, pour into ice and extract and add dichloromethane to a well-stirred cotton wool for about 25 min. combine the organic layers, 1595 of Mahon's aqueous solution (1 9 L, 9.5 mol). After washing first with 1 L of sodium hydroxide solution, the addition is completed, slowly and gradually heat - then with water. Dry the organic phase over salt to a temperature of 502. After an hour, heat to a fathom of magnesium, filter and concentrate from a temperature of 60"C. After 30 minutes, heat to return the residue. Dissolve the residue in a toluene refrigerator for 1 hour. Cool the oils (200 ml), chromatograph on silica gel with to room temperature and mix in the process by successive elution with toluene and ethyl acetate e- during the night, drain the alkaline aqueous layer and replace with tatam to obtain the residue. Dissolve the residue with water. Heat to 302C under reduced pressure using a 200mbar tetrahydrofuran distillation flask until Claisen equipped with a Midgench column, approximately 2.5kg of distillate will be removed from the ode. Extraction of the target compound: boil the reaction mixture with dichloromethane. Vpro- at 0, mm Hg, 8424-8570. Konizen repeatedly, for 25 minutes, slowly add some fractions to the combined organics. , filled with Rashiga rings, made of a solid substance. After an hour, filter out the target compound: boiling point of the solid substance, wash with dichloromethane and dry with a mixture of TtA-T6o. dry overnight with the formation of chlorine deposits. hydrogen salt of the target compound. 3-(2,2,3,3-tetrafluoropropoxy)benzaldehyde

Combine b-fluorotryptamine hydrochloride Mix 3-(2,2,3,3-

tetrafluoropropoxy)tosylate (200g, 0.bb4mol), 3- stir overnight, then heat to room temperature- ) and powdered carbonate (342g, 4.28mol). After stirring continuously, potassium (192g). Heat with stirring at about 1h. filter the suspension through a layer of celite. You-

Cool the reaction mixture to a temperature of 40°C, evaporate the filtrate to dryness to obtain an oil. Pour into the mixture ice water and extract ethyl alcohol. EBO/HCI (15 ml) at room temperature with a solution of sodium hydroxide (Tl and 0.5 L), then with the formation of a solid. rinse with 5 Oml of ESO, dry and evaporate to dryness to obtain an oily solution under vacuum at a temperature of 50"7C from the residue. Evaporate the oily residue under the addition of hydrochloride of the target compound. under reduced pressure in a Claisen flask to obtain Add 5-chlorotryptamine hydrochloride (15g, the first fraction of the target compound: temperature 0.Obmol), water (150ml), 1M Mahon solution (75ml) boiling 108-1107С at 0.4-0.5 mm Hg Art. and the second and dichloromethane (350 ml). Stir the mixture of fractions at a temperature of 110-1117C at 0.4-0.5 mm at room temperature for 30 minutes and ref. cremit phases. Wash the aqueous phase with dichloromethane

Example 784 nom, combine the organic phases, dry over 3-(2,2,3,3-tetrafluoropropoxy)benzaldehyde Ma5o", filter and evaporate to dryness under

Mix 3-(2,2,3,3- under vacuum to obtain the target compound. tetrafluoropropoxy)tosylate (5.72g, 17.2mol), 3- Example 789 hydroxybenzaldehyde (2.44g, 20.0mmol), dimeth- M- (5-chloro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-thylformamide (Zbml) and powdered potassium carbo-tetrafluoro-propoxy)benzylamine (3.03 g) and heat at at a temperature of 1107C for 10 hours. Cool to a temperature of 20"C. Pass through a layer of aluminum oxide-90 c E eE (57.2 g, mesh 700-230 (0.210-0.06Z3 mm), class 11-P, M -y»

VhosKktapp: Megsk Me1.01097) and elute with toluene (120 ml). Wash the eluted organic phase E with a 1M solution of NSII (Zbml), then with water. Evaporate the organic layer under reduced pressure with Mix 5-chlorotryptamine (12.1g, 0.0621mol) to give the target compound. and 3-(2,2,3,3-tetrafluoropropoxybenzaldehyde

Example 785. (17.6 g, 0.0821 mol) In EUN (340 ml). Add molecular sieves and heat with reflux

Mix 5-chloroindole (20 g, 0.1 mol) and dibucom for 4 hours. Cool the mixture to room temperature - ethyl ether (230ml), cool to room temperature and add MaVna in portions (7Tg, 5"7C and over 15 minutes slowly add oxalyl chloride - 0.1876mol). Stir continuously at room temperature (20.08g, 0 .16 bmol) with simultaneous maintenance at room temperature. Filter the substance by solidification at a temperature in the range from 5C to 1070. and evaporate the filtrate to a mass of approximately

Warm to room temperature and mix 90g, add water and extract with dichloromethane. within hours with receipt firmly! substances Dry the combined organic layers over Mo5o».

Cool to a temperature of 57C and stir, filter and remove the solvent under reduced pressure for 15 minutes, filter the solid under pressure to obtain the target compound. wash with dibutyl ether and dry under vacuum. Mix the target compound (27.6 g) and isopropacuum to obtain the target compound. zero (300 ml). Add a solution of oxalic acid

Example 786. | | (bg) in isopropanol (bOml) to obtain a suspension. (2-(5-chloro-1H-indol-3-yl)-2-oxoacetamide Heat the suspension under reflux

Mix 2-(5-chloro-1H-indol-3-yl)-oxo- and stir for 30 h, then cool acetyl chloride (28.97, 0.2 mol) and 1 M solution to room temperature. Stir the try-

MNaOH (720 ml) to obtain a suspension. After a long hour at room temperature. After filtering, filter for 18 hours, wash with water and dry with cotton wool, wash with isopropanol and under vacuum to obtain the target compound. dry under vacuum to obtain oxalate

Example 787... of the target compound.

B-chlortryptamine | | Example 790

Cool the suspension of HyAlNaea (40.97 g) in tetra-1-tartrate /M-2-(5-chloro-1H-indol-3-yl)ethyl)-3-hydrofuran (700 ml) to a temperature of 57. of 3,3-tetrafluoropropoxy)benzylamine for about 30 minutes, add a solution of AIISiz (53.9 g, I "Mix oxalate /M-2-(5-chloro-1H-indole-3- 0.40 mol) to tetrahydrofuran (645 ml) with one yl)ethyl)-(3-(2,2,3,3-) by temporarily maintaining the temperature in the range from tetrafluoropropoxy)benzylamine and dichloromethane approximately 5'C to TO C. Add a solution of (2-(5- (700 ml) and add 1M Mahon's solution (1500ml), water xpro-1H-indole-3-yl)-2-oxoacetamide sot, (450ml) and Meon (190ml). Stir the reaction- 0.09mol) in tetrahydrofuran (900ml) with a simultaneous mixture for hours at room temperature, maintaining the temperature within the range of 0. Separate the layers. Add water (200 ml) approximately 57C to 7.5"C. After completion, add to the aqueous phase and extract with dichloromethane, allowing to warm to room temperature. Mix "combine organic layers, dry over Mo5o",

filter and evaporate under vacuum with stirring to obtain a solid. By straining 19.4 g of M-2-(5-chloro-1H-indol-3-yl)ethyl)-3-res for 2.5 hours, filter the solid substance, pro-(2,2,3,3-tetrafluoropropoxy)benzylamine . wash with isopropanol and dry under vacuum at

Mix M-2-(5-chloro-1H-indol-3-yl)ethyl)-3- at a temperature of 4572 to obtain the target compound. (2,2,3,3-tetrafluoropropoxy)benzylamine (19.4 g) in According to the method of Example 221, the following isopropanols (125 ml) were obtained and heated until dissolution. compounds isolated in the form of maleate, with the exception of

Add a solution of I-tartaric acid (7.02 g) in the isopropionate indicated: panol (/Oml). Add seed crystals and pe-

Jelly eh and ; I ; ! H x W | From the holy

NO PE ZY POLON: YEARS NO U NO tetrafluoropropyl |Н, 4.03; M, 4.87; established: C, 50.24; H, 4.02; M, 4.87 square meters 168-17170S. Analysis for Cg2zHg22VIEzM2gOv: calculated: C, 50.84; in- 223583. t.pl. 233-235"C. M5 (ASRI): m/e 459.1 (Ma1). Analysis for 793 methanesulfonyl tetrafluoropropyl Ca НгзСИРаМ2Оз5: calculated: C, 50.96; H, 4.68; M, 5.66; established : C, 50.87; H, 4.65; M, 5.64, (isolated as hydrochloride) 794 ethane lronti Ro tokitoretna mp 234-2362 C. M5 (ASRI): t/e 427.0 (Ma1). Analysis for 794 -12,2,2-trifluoroethyl|ChoNgoSiEzM2Oz5: calculated: C, 51.89; H, 4.79; M, 6.05; established methanesulfonyl: C, 51.84; H, 4.79 ; M, 6.10, (isolated as hydrochloride b-benzene-2,2,33- m.p. 213-21570. M (ASRI); m/e 521.0 (Me7). Analysis for 795 sulfonyl tetrafluoropropyl СгвНа5СИБаМ2Оз35 : calculated: C, 56.07; H, 4.52; M, 5.03; determined: C, 55.81; H, 4.66; M, 4.96, (isolated as hydrochloride) in benzop - m.p. 231-233.5"C. M5 (ASRI): m/e 489.0 (Ma1). Analysis for 796 sulfonyl 2,2,2-trifluoroethyl | Co5Hha«SiEzM2Oz5: calculated: C, 57.20; H , 4.61; M, 5.34; established: C, 56.98; H, 4.63; M, 5.21, (isolated as hydrochloride

Example 799 Cool a solution of b-bromo-1-b-methanesulfonyl-1H-indole triisopropylsilanyl-1H-indole (5.5g, 15.7mmol) in

Dissolve b-methanesulfonylindol-1-ol (5.0 g, 100 ml of anhydrous tetrahydrofuran to temperature - 23.7 mmol) in triethyl phosphite (35 ml) and heat to -78"C in a nitrogen atmosphere and treat 1.7M at a temperature of 1607"C for 5 hours . Cool the solution to ambient temperature with a solution of tert-butyllithium (20.5 ml, 34.5 mmol) while simultaneously maintaining the temperature of the reservoir and dilute with diethyl ether. Wash at -78°C. After completion, slowly add the ether solution with brine and water, followed by nylsulfonyl fluoride (2.1ml, 17.3mmol) and overdrying (sodium sulfate) and stirring for 30h at -7876 to give of the residue. Crystallize the residue. Heat the mixture to ambient temperature from warm ethyl acetate to obtain the target medium and stir for 1 hour. Seam compounds in the form of colorless hexahedra: mp dko cool the excess tert-butyllithium with ice 149-152700. M5 (ASRI): t /e 196.0 (Ma1).. Analysis and dilute the mixture with water followed by extraction for SeNeMO»5: calculated: C, 55.37; H, 4.65; M, by dissolving with ethyl acetate. Mix, wash (dissolve 7 ,17; determined: C, 55.14; H, 4.71; M, 7.20. ol), dry (sodium sulfate) and concentrate

Example 800 extracts with a residue. Purify excess p-benzenesulfonyl-1H-indole on silica gel using 5095 mixture

Dissolve b-bromoindole (6.0g, 30.bmmol) in hexane/dichloromethane to give the product in tetrahydrofuran (1000ml) and cool the mixture to a white solid. at a temperature of -10"C. Slowly add the 6095 solution. Dissolve the resulting white manna solid in mineral oil (3.67g). After 1 hour of color in tetrahydrofuran (5Oml) and treat, slowly add triisopropylsilyltrifluorome- solution with a 1M solution of tetrabutylammonium fluoride tansulfonate (9.9ml, 36.7 mmol), remove alcohol (18.1 ml) and 1M solution of boric acid (18.1 ml). lye bath and stir for 24 hours. and remove the tetrahydrofuran under vacuum. Dilute the mixture with water and extract with ethyl acetate. Wash the residue with water and extract with dichloromethane, wash (roseol), dry (sulfate nano. Mix, wash (roseol), dry (sutria) and concentrate the extracts to obtain sodium sulfate) and concentrate the extracts from the residue. gels with the use of a mixture of hexa- obtaining the target compound in the form of a solid nu/dichloromethane with obtaining an oil of a yellow substance of white color: m.p. 141-14476. M5 color. (ASRI): t/e 258.0 (Ma-1). Analysis for С1и4Н11МО»95:

calculated: C, 65.35; N, 4.31; M, 5.44; established compounds isolated in the form of hydrochloride, for wine: C, 64.99; N, 4.31; M, 5.39. by connecting the indicated:

According to the method of Example 440, the following were obtained

A. M. From life in her and I 7 ch

M me | and | IN IT 777777777717707000 given777777777771111111c1 223583. IBM5 415 (Ma); "H NMR (OM5O-dev-hydrochloride) 11.3 (5, 1H), 9.4 (p5, 802 | 7-chloro tet aphtoi poropyl 2H), 7.6-7.5 (t, 1H), 7 ... .2 (05, 2H), 3.25 (08, AN)

IN NMR (SOCI3-free base) 7.99 (p5, 1Н), 7.47-7.44 (а, 1Н), 723-719 803 | β-methoxy 2.2,3,3- (t, 1H), 6.94-6.92 (y, 1H), 6.89-6.88 (t, 1H), 6.83-6.82 (t , 2H), 6.79-6.75 tetrafluoropropyl (t, 2H), 6.19-5.90 (t, 1H), 4.29-4.22 (t, 2H), 3.82 (5, ЗН), 3.78 (t, 2Н), 2.95 (5, 4Н), M-Н not detected

According to the method of Example 270, the following compounds were obtained, isolated in the form of maleate, with the exception of the marked: »

And also: about | in

M

N

SHUI: IZM5 437 (MA-1); SgeNovesi-M2O:0.2H2gO: calculated: C, 73.08; H, 5.58; M, 5-(4-fluorophenyl) Phen. 5.88; established: C, 72.99; H, 5.38; M, 5.83

Divide Example 811 between 50ml of 1M Mahon solution and 25ml

M-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-(3-(3,3,3-dichloromethane). Extract the aqueous layer with 25 mL of trifluoropropoxy)benzyl)amine dichloromethane, combine the organic layers and concentrate to dryness. Clean the obtained oil

NE--oa means of radial chromatography (5105;

X is a 190 solution of Meon in SNSI", mixed with a concentration of Her LE, diluted with a solution of MNAOH) with the production of 705 mg and: p NYA Soche (1.mmol; 10095) of the necessary compound in the form

X and Y a: "into oils. The conversion to the hydrogen chloride salt is carried out by mixing a solution of the compound in 5 ml of tetrahydrofuran/EUN (50/50) with 1 g of polyvinylpyridine hydrochloride overnight, filter

Mix /350 mg (1.6 mmol) by trituration and concentration to obtain trimethoxytryptamine, 401 mg of the 3rd substance. Recrystallize the product from trifluoropropoxybenzaldehyde (1.9 mmol) and 4 g of COAs: analysis for CgiHgzEzM2O»:HCI: calculated: 4A of molecular sieves in 35 ml of EUN and heat with C, 58.81; H, 5.64; M, 6.53; established: C, 58.42; reflux overnight. Drain H, 5.44; M, 6.51; IZM5 393 (M-n1). liquid to a separate flask and process 209 mg According to the method of Example 811, the following (5.5 mmol) MaVNa was obtained. Mix the reaction compound isolated in the form of hydrochloride with a mixture at ambient temperature by adding the indicated: within an hour. Concentrate under vacuum and det / in i y y chn to 7 i

Mhi

NTR Pe IL PO Z ROD PON NO 812 B-fto 3,3,3- Analysis for SgoNgobaM2O:- NOSI: calculated: C, 57.63; H, 5.08; M, 6.72; r trifluoropropyl | established: C, 57.49; H, 5.04; M, 6.76; IZM5 381 (MA1) v'4| oBbrom | Hairdryer Analysis for SgzNhi VGM2O: NCI-0.5H2O: calculated: C, 59.18; H, 4.97; M, r 6.00; established: C, 59.18; H, 4.80; M, 5.92 IZM5 422 (Ma-1 815 5-bromo 2.2,3,3- Analysis for SgoNi«VgRaM2O: CARRIERS: calculated: C, 48.46; H, 4.07; M, 5.65; p tetrafluoropropyl| established: C, 48.39; H, 3.95; M, 5.55; IZM5 459 (M.

pentafluoropropyl| established: C, 46,47; H, 3.67; M, 5.46; ИЗМ5 478 (МА1)

Analysis for SgoNizVIE5M2gO: NCI-0.5H20.:0.4С7Nev: calculated: C, 64.01; 817 5-502CH3 H, 5.85; M, 5.57; established: C, 64.09; H, 5.64; M, 5.48 IBM5 421

MA

ES NOSY NN sn CAS 10.27; established: C, 70.55; H, 5.41; M, 10.25 IZM5 368 (M--1) methyl 819 complex ester Analysis for Cg25HgaMgOz:HCl-0.3ZH2gO: calculated: C, 68.04; H, 5.62; M,

B-carbon 6.35; established: C, 68.06; H, 5.64; M, 6.43 IZM5 401 (Mt) acid methyl 8g2o complex ester 2,2,2- Analysis for C2iNai1EzM2gOz: NOSI 0.120: calculated: C, 56.72; H, 5.03;

B-carbon | trifluoroethyl | M, 6.30; established: C, 56.46; H, 4.77; M, 6.04 IZM5 407 (Ma1) acid

IZM5 385 (Mk); analysis for SgaNgzMzO2:HCI-0.9H2O0:0.1С7Nav: amide 5- was calculated: С, 66.32; H, 5.99; M, 9.39; established: C, 66.07; H, 5.68; M, 821 | carbon 9.01; NMR NMR (free base SOCI3) 6 8.56 (5, 1H), 8.13 (5, 1H), 7.64- acid 7.62 (t, 1H), 7.33-7.22 ( t, 4H), 7.10-6.94 (t, 6H), 6.87-6.84 (t, 1H), 6.2 (5, 1H), 5.8 (05, 1H), 3 .77 (85, 2H), 2.99-2.94 (t, 4H), 1.7 (05, 1H

Example 825 distribute the residue between 25 ml of 1M solution of MaOH

M-2-(5-nitro-1H-indol-3-yl)-ethyl)-3- and 25 ml of dichloromethane. Extract the aqueous layer of phenoxybenzylamine with 25 ml of dichloromethane, dry the combined organic layers over M950O4 and concentrate to dryness. om Purify the obtained oil by means of radial chromatography (5102; 295 solution of MeOH in weight of SNeIIz) to obtain the required compound in the form of

M and butter. Convert to hydrogen chloride salt

And by treating a solution of the compound with 10 ml of EUN with 0.25 ml of a 5 M solution of NSI and 40 ml of toluene, after

What to concentrate to obtain a solid substance. Analysis for Cg2zHg1MzOz:HCI-0.2 EN: calculated

Mix 5-nitrotryptamine (500 mg, 2.4 mmol), salt: C, 64.62; H, 5.17; M, 9.75; installed: C,

Z-phenoxybenzaldehyde (480mg, 2.4mmol) and 4g 64.89; H, 5.40; M, 9.75; IZM5 388 (M-1). 4A of molecular sieves in ZOml EUN and heated with According to the method of Example 825, these were obtained under reflux during the night. Pour the compounds isolated as hydrochloride into a separate flask and treat with Mavna (280 mg, compound labeled: 7.2 mmol) at ambient temperature. After 1 hour, concentrate under vacuum and

Ah hee

IN

N

NT PIV LIN PY x ROK CON ET MON

Analysis for C27NzoM2gO2: HCI-0.4H2O: calculated: C, 70.77; H, 7.00; was Bullshit | fen TM is established S. 7081: H, buva M, BMYA M 415 (MO and Analysis for SzoNag7MzO): NCI-0.2H2O: calculated: C, 71.83; H, 5.71; 27 Bbenamd | Fen Mov established: P. 7163, 535; M 809 1EM 462 (My) trifluoroethyl |8.33; determined: C, 61.78; H, 5.16; M, 7.97; IZM5 468 (M-1) tetrafluoropropyl | 7, 84; established: C, 60.47; H, 4.95; M, 7.49; IZM5 500 (Ma-1

B- Analysis for SgaHg5MzOz5: NOSI О.5Н20-0.5С7Нв: calculated: C, 63.53; 830 and H, 5.86; M, 8.08; established: C, 63.57; N, 5.77; M, 7.81; IBM5 436 methanesulfonamide (Ma)

B- 299. Analysis for SgoNggEzMzOz5: NOSI 0.1H20-0.5C7H8v: calculated: C, 831 methanesulfonamide trifluoroethyl 53.68; H, 5.21; M, 7.99; established: C, 53.48; H, 5.19; M, 7.72;

IZM5 442 (Ma

B- 22383. Analysis for Cg2g1NgzEaMzOz5: NCI-O 1 EUNI0.8C7Nav: calculated: C, 832 methanesulfonamide tetrafluoropropyl 54.72; H, 5.31; M, 7.14; established: C, 54.63; H, 5.25; M, 6.99;

ИЗМ5 474 (May 1)

Analysis for Сг2вНгвМ2О»:1.1НЧ1И-0.1Н2О: calculated: C, 70.58; H, 833| 5-isopropoxy 6.68; M, 6.33; established: C, 70.37; H, 6.31; M, 6.35; ИЗМ5 401 (МА) 2295. Analysis for Сг22На5ЕзМ2гО»:НСИ-ОО, ЗН2гО: calculated: C, 58.94; H, 834| 5-isopropoxy shea 5.98; M, 6.25; established: C, 59.08; H, 5.78; M, 6.25; IM 407 trifluoroethyl (Man) 22383. Analysis for Cg2gzNovE«M2gO»:HCI-0O,ZH2O: calculated: C, 57.51; H, 835| 5-isopropoxy NI - 15.79; M, 5.83; established: C, 57.66; H, 5.55; M, 5.80; IBM5 439 tetrafluoropropyl (Ma) 836 B-ethoxy Analysis for C25NovM2O»2: HCI-0.2HgO: calculated: C, 70.39; H, 6.47;

M, 6.57; established: C, 70.40; H, 6.32; M, 6.68; IZM5 387 (M-1 837 B-ethoxy 2,2,2- Analysis for C21H2zEzM2O2: NOSI: calculated: C, 58.81; H, 5.64; M, trifluoroethyl /|6.53; established: C, 58 .61; H, 5.61; M, 6.52; IZM5 393 (M--1) 838 B-ethoxy 2,2,3,3- Analysis for Cg22NgaBaM2O2: CARRIERS: calculated: C, 57.33; H . : calculated: C, 62.96; H, 5.07; M, trifluoroethoxy 5.87; determined: C, 62.76; H, 4.93; M, 5.88; IZM5 441 (Mt) 840 2, 2,2- 2,2,2- Analysis for С21НгобеМ2О2: NOSI: calculated: C, 52.24; H, 4.38; M, trifluoroethoxy trifluoroethyl |5.80; found: C, 52.21; H, 4 ,28; M, 6.18; IZM5 447 (M-A1) 2995. 22383. Analysis for SggNaiE7M2O2: HCI-0.2H20:0.2C7Nav: calculated: C, 52.35; 841 trifluoroethoxy|tetrafluoropropyl py; M, 5.22; established: C, 52.15; H, 4.30; M, 5.58; IZM5 479

Analysis for Cg2vNhoMzO2:2HCI-0O,5BEYUN.:O,3SUNv: calculated: C, 842 B-butyloxy pyridin-2-yl 64.83; H, 6.81; M, 7.79; established: C, 64.99; H, 6.48; M, 7.47;

IZM5 416 (Mat) and 2,2,2- Analysis for Сg2Но5ЕзМ2О: CARRIERS: calculated: C, 61.90; H, 6.14; M, 6.56; y y Analysis for С2вНгвМ2гО: NOSI: calculated: С, 74.18; H, 6.94; M, 6.65; 845 5B- Analysis for СгоНовМ2О25:2НСИ: calculated: C, 67.11; H, 5.24; M, benzenesulfonyl 5.40; established: C, 67.46; H, 5.37; M, 5.09; ИЗМ5 483 (М-А1)

B- 22383. Analysis for Sg2vNgaBaM2Oz35:NSI-O, ZE. 0, 2С7Nav: calculated: С, 846 I ots 157.07; N, 4.86; M, 4.75; established: C, 56.95; N, 4.68; M, 4.77; benzenesulfonyl |tetrafluoropropyl I5M5 521 (Ma 847 5B- 2,2,2- Analysis for СовНоМозО2: НСИ-0.6Н2гО: calculated: C, 56.04; H, 4.74; benzenesulfonyl | trifluoroethyl |М, 5.23; determined: C, 56.05; H, 4.71; M, 5.12; IZM5 489 (M-n1) ethyl compound 848 ether 5- 2,2,2- Analysis for C22NaozEzM2Oz: NOSI: calculated: С . 5- 22383. Analysis for С2зНовЕзМзО»2 CARRIER 0.6Н2гО:0.1С7Н8а: calculated: C, 849 carboxylic acid, aphtorp opyl 56.84; H, 5.79; M, 8.05; determined: C, 56 .65; Н, 5.63; М, 7.71; t-isopropyl| (em 466 (Ma) propylamide 5- Analysis for C27NhoMzO»2: HCI-0.4H20:0.2С7Nav: calculated: C, 69.66 ; 8501 carboxylic acid - H, 6.67; M, 8.58; determined: C, 69.75; H, 6.57; M, 8.38; IZM5 428 and ImM1 propylamide 5- 299. Analysis for C2zNovEzMzO" 2: HCI-0.8H2gO.: 0.1C7H8a: calculated: C, 851 | carboxylic acid-tiftoethyl 57.67; H, 6.00; M, 8.51; determined: C, 57.55; H , 5.77; M, 8 ,43; you riftor IZM5 434 (MA) butylamide 5th. Analysis for SgvNaiMzO2: HCI-0.7H2gO: calculated: C, 68.54; H, 6.86; you PD M, 8.56; established: C, 68.41; H, 6.60; M, 8.37; IZM5 442 (Ma1) vBZ ka butylamide 5 o-| 22.33- / |Analysis for SoNoRaMzO» NSI-NYO: calculated: C, 56.23; H, 6.04; p ti tetrafluoropropyl/i M, 7.87; established: C, 56.23; N, 5.79; M, 7.84; IZM5 480 (M-1) 8BA H 2,2,3,3- Analysis for SgoNgoiaM2gO: NSI-0.5H2gO: calculated: C, 56.41; H, 5.21; tetrafluoropropyl) M, 6.58; established: C, 56.98; N, 4.93; M, 6.53; IZM5 381 (Mat 2,2,2- Analysis for SovbNo5EzM2O2: NOSI: calculated: C, 63.61; H, 5.34; M, 2,2,3,3- Analysis for С27NovEaM2O2: NOSI: calculated: С, 62.01; H, 5.20; M, b56 | B-benzyloxy | terropropyl 5.36; established: C, 62.04; H, 5.16; M, 5.36; IZM5 487 (Ma-1 )

And IZM5 435 (MA1);. СгоНг7СИ-М2О»:0.1Н20: calculated: C, 73.67; H, 857) b-phenoxy phenoxy | 5.80; M, 5.93; established: C, 73.49; H, 5.49; M, 5.82 2.2.,3.3- IZM5 473 (Ma-1); SoviNe5RaSIMO»: calculated: C, 61.36; H, 4.95; M,

77777111 (tetrafluoropropyl | 5.50; established: C, 6102; H, 4.67; M, 542.:/.::.:// trifluoroethyl | 5.12; M, 5.83; established: C, 62 ,27; H, 4.78; M, 5.74. 2.2,3,3-IZM5 474 (Ma1); Cg5NavBaSi»-M3zO2:0.5H2O: calculated: C, 54.06; H,

IZM5 442 (Mt); "H NMR (SOCI3) 8.37-8.36 (t, 1H), 8.27-8.26 (t, vB-(pyridinyl-3-299. 1H), 8.01 (65, 1H), 7.35-7.32 (t, 1H), 7.26-7.24 (t, 3H), 7.22-7.18 861 oxy) trifluoroethyl (t, 2H), 7.08-7.07 (t, 1H), 6.93-6.91 (t, 2H), 6.9-6.86 (t, 1H), 6.79-6.76 (t, 1H), 4.31-4 .25 (t, 2H), 3.77 (5, 2H), 3.77 (5, 4H). Isolated as dihydrochloride

Example 863 (4bmmol) and 10.7g of 1-iodoethane (b9mmol) in di-b-phenoxytryptamine methylsulfoxide (25ml), heated to temperature

The target compound was obtained according to the method, at 80 °C, treat 22.4 g of carbonate in portions with the method of Example 422: IZM5 253 zium (b9 mmol) and mix. After 1 hour, pour into (Ma); "H NMR (SOCI3) 8.1 (65, 1H), 7.56-7.54 (t, 200 ml of brine and extract twice with 150 ml of diet- 1H), 7.32-7.28 (t, ZN), 7.07-6.98 (t, 4H), 6.89-6.86 of ether. Combine the extracts and wash twice (t, 1H), 3.06-3.02 (t, 2H), 2.92-2.88 (t, 2H), 1.68 200 ml of brine, dry over Mdzoa and conc. - (re, 2H). boil under vacuum to obtain oil. Way-

Example 864 chromatographic purification (5102; 2.595 2-(5-(pyridin-3-yloxy)-1H-indol-3-yl)- EtOAc solution in hexane) yielded 5.73 g of ethylamine (2 mmol, 8395) of the required compound in in the form of ma-

The target compound was obtained by the following method: "H NMR (SOCI3) 9.94 (5.1H), 7.42-7.A1 (t, similar to the method of Example 422: IZM5 254 2), 7.36- 7.35 (t, 1H), 7.16-7.13 (t, 1H), 4.10-4.04 (Ma1); ), 1.64-1.40 (i, ZN).

C, 58.04; N, 4.98; M, 11.81; established: C, 58.17; Example 870

N, 4.62; M, 11.45. C-propoxybenzaldehyde

Example 865 The target compound was obtained by a method for b-phenoxy-1H-indole-3-carbaldehyde similar to the method of Example 869: "H NMR (SOCI3)

The target compound was obtained according to the method, 9.95 (5, 1H), 7.43-7.А41 (t, 2H), 7.37-7.36 (t, similar to the method of Example 414: IZM5 238 1H) ,7.17-7.14 (t, 1H), 9.98-3.95 (i, 2H), 1.84-1.79 (Ma); "H NMR (SOCI3) 10.78 (65, 1H), 9.95 (5, 1H), (t, 2H), 1.05-1.02 (i, ЗН). 8.20-8.18 (t, 1H), 7.76-7.75 (t, 1H), 7.30-7.26 (t, Example 872 2), 7.06-7.02 (t, 2H), 7.00 -6.95 (t, ЗН) 4-phenoxy-1-methyl-2-nitrobenzene

Example 866 Mix phenylboronic acid (7.32 g, 5-(pyridin-3-yloxy)-1 H-indole-3-carbaldehyde, 1 mmol), 4-methyl-3-nitrophenyl (4.5 g, 3 mmol) and

The target compound was obtained according to the method, according to the method of SschoAS)2-HgO (6bg, ZOmmol) in ZOml SNes? and similar to the method of Example 414: IZM5 239 to make 6bg 4A of powdered molecular sieves. (Mate); Si4NioM2O»2:0.3H2gO: calculated: C, 69.01; H, dropwise add EBM (15.18Hg, 4.39; M, 11.50; found: C, 68.91; H, 4.16; M, 150mmol), and stir the reaction mixture at 11.39. ambient temperature,

Example 867 for 8 days. Dilute 100 ml of NaCl, filter 3-(3-methyl-4-nitrophenoxy)pyridine through a layer of Celite and concentrate to dryness

Wash the 3595 KH oil dispersion twice. Purify by chromatography from (12g, 1immol) 100ml of hexane and dry under vacuum using a 295 solution of EAsC in hexane with vacuum before cooling in an ice bath. by grinding the necessary product in the form of oil

Add 100 ml of dry dimethylformamide, then yellow. drop by drop a solution of 3-hydroxypyridine Example 873 (10 g, 105 mmol) in 100 ml of dimethylformamide. b-phenoxy-1H-indole

Treat with a solution of 5-fluoro-2-nitrotoluene. Mix 4-phenoxy-1-methyl-2-nitrobenzene (16.3g, 115mmol) in 50ml of dimethylformamide with (bg, 26.2mmol) and dimethylformamidedimethyla - obtaining a dark colored solution. Dimise peremycetal (15.6g, 13immol) in bOml of dry medium at ambient temperature and heat at a temperature of 17070 higher for 1 hour, pour the mixture into 1 liter of brine and for 1 hour. Cool to room temperature - extract twice with 200 ml of EIUAs. Combine the extracts and concentrate to dryness. Dissolve the crystals, wash twice with 500 ml of brine, dry the residue in 500 ml of E(FAs) and hydrogenate with 2 g of 590 over Ma5O054 and concentrate to obtain 24 g of Ra/C for 10 hours under atmospheric pressure. dark oil. Clean the chromatograph - filter through a layer of celite and concentrate - by elution with 2095 EUAs solution to obtain an oil. Purify by chromatography hexanes to obtain the target compound in the form of fuming using a mixture of hexane/Eds oil: IZM5 231 (MA1); C1i2NioM2Oz: calculated: with the obtaining of a solid substance /- yellow-

C, 62.61; N, 4.38; M, 12.17; established: C, 62,63; brown color: IZM5 210 (Mat), "H NMR

N, 4.58; M, 12.06. (SOSI") 8.08 (5, 1H), 7.61-7.59 (t, 1H), 7.34-7.29

Example 869 (t, 2H), 7.18-7.17 (t, 1H), 7.18-7.0 (t, 4H), 6.92-

C-ethoxybenzaldehyde 6.89 (t, 1H), 6.56-6.54 (t, 1H).

Mix 5.6 g of 3-hydroxybenzaldehyde Example 874

5-pyridin-3-yl-1-methyl-2-nitro-benzene Z-phenoxybenzylamine

The target compound was obtained by a method similar to the method of Example 872.

Example 875 SU 5-(pyridine-3-yloxy)-1H-indole o

The target compound was obtained by a method similar to the method of Example 873: IZM5 211 |Ї with (Mat); CizNioM2gO:0.1H2O: calculated: C, 73.64; H, n 4.85; M, 13.21; established: C, 73.76; H, 4.80; M, and at 13.09. M

Example 877

M-2-(5-phenoxy-1H-indol-3-yl)-ethyl)-3- Slowly add a 1.0 M solution of HyAIN in tetra-phenoxybenzylamine hydrofuran (5.5 ml, 5.5 mmol) to a solution of tert-butyl ether (3-phenoxybenzyl)-(2-(5-phenoxy-1H-indol-3-yl)ethyl)ucarbamic acid (0.60 g, 1.12 mmol) in 100 ml of dry tetrahydrofuran. After the addition, heat the reaction mixture under reflux. After 2 hours, cool it to room temperature, quickly stop the reaction by carefully adding 1.5 ml of cold water, then 2 M Mahon solution (1.0 ml). Profile-

And dig up the suspension and wash it again with simple ether, dry the organic solution over Mag25O4

Mix 2-(5-phenoxy-1H-indol-3-yl)ethylamine and concentrate in mass. Purify on silica gel (0.400g, 1.59mmol), 3-phenoxybenzaldehyde using a CH2CIg/MeOnH mixture as an eluent (0.5377g, 1.90mmol) and molecular sieves 4A to obtain the free base of the target compound from (0.40g) and mix in methanol (15 ml). After further reaction with oxalic acid from 4 hours, filter through molecular sieves and obtain several salts: t.ol. 1174-1750; "NN NMR wash MeonH several times. To this solution MeOonH (250MHz, OM50-av) 2.51(5, ЗН), 3.00-3.13 (t, 4Н), add Mavnae (61.5mg, 1, 59 mmol), 4.15 (85, 2H), 6.81-7.03 (t, 7H), 7.11-7.42 (t, 11H), stir the resulting mixture at room temperature - 11.05 (Bg, 1H); mass spectrometry with electrolysis for 1 hour. Remove Mn under vacuum, m/e: 449.1 (Ma-1-С2НхОх). with water, dilute the residue with a mixture of SnSg/water, Example 880 extract SnSgSi », combine the organic layers and M-(2-(b-chloro-1H-indol-3-yl)ethyl)-(3-(2,2- dry over Mag5O4. Concentrate the solvent difluoroethoxy)benzyl)amine and fat Purify on silica gel (CH2Cl2/mMeon) to obtain the free base of the target compound.

Carry out the reaction of a free base with oxalic acid to obtain a salt: m.p. 196-19820; NN ME

NMR (С30ОМХ, ЮОМ5О-ав) 2.95-3.15 (t, 4Н), 4.15 and the same (5, 2Н), 6.85-7.46 (t, 18Н), 11.06 (rg , 1H); mass spectrometry with electrospray It/e: 435.3 m lava calculated for SgoNatM»O» Mix 2-(b-chloro-1H-indol-3-yl)ethylamine hy- ( ) , found 435.2073. hydrochloride (1.0g, 4.3mmol) and ethyldiisopropyl-

Example 878 - th min (900 μl, 5.2 mmol) in ethanol (15 Oml), re-

Tert-butyl ether (Z-phenoxybenzyl)-(2- mix at room temperature, treat with 3-(5-phenoxy-1H-indol-3-yl)-ethyl)-carbamic (2,2-difluoroethoxy)benzaldehyde (B56mg, acid 4, mmol) and anhydrous sodium sulfate (12g) and "Mix (3-phenoxybenzyl)-(2-(5-phenoxy- heat at a temperature of 78"C overnight. 1TH-indol-3-yl)ethyl)amine ( . Treat the obtained filtrate with borohydrofuran (Oml), stir at room temperature with sodium chloride (488 mg, 12.9 mmol) and stir at room temperature for 5 min. Add di-tert-mixture of milky white color at room temperature-butyldicarbonate (0.58g, 2.b4mmol) in tetrahydro-temperature during the night. Remove the ip rofuran solvent (TOml) and mix. After 2 hours, dissolve the fat, purify the crude residue to silicate the reaction mixture with water, extract EAs gel with elution with 1095 methanol solution in (Zht5ml), dry over Mag5O". Concentrate in dichloromethane to obtain the free base of this organic solvent under vacuum to obtain the left compound in the form of an oil of the light yellow target compound in the form of an oil: "H NMR color. Dissolve part of the oil (651 mg, (ZOOMHC, SOCIz) 1.36 (z, 9H), 2.85-2.91 (t, 2H), 1.78 mmol) in methanol (15 ml) and treated with homo- 3.89-3.65 (t, 2H), 4.26 (5, 1H) . - 1.78 mmol) in methanol (Zml). Treat the resulting solution with 534.9 t/e electrospray spectrometry with ultrasound for 10 minutes before (Ma). removal of the solvent and mass with obtaining

Example 879 | | solid substance not quite white in color. Dis-

M-methyl-m-2-(5-phenoxy-1H-indol-3-yl)-ethyl)-

rub with diethyl ether and a few drops with the addition of one drop of glacial acetic acid. acetonitrile. Filter and dry the precipitate with Remove the solvent from the mass, redissolve the target hydrochloride in the form of the unpurified residue in methanol and directly as a white solid: m.p. 131.6 should be added to 10 g of column C. After thorough 1332C; "H NMR (400 MHz, OM5O-iv): 11.15 (ri 5, washing with methanol, elute column 2M 1H), 9.50 (rg 5, 2H), 7.57 (9, 1H, 9U-8.8Hz ), 7.39 (a, with a solution of ammonia in methanol. Concentrate elu- 1Н, У-2.0Hz), 7.36 (І, 1Н, 9У-8.2Hz), 7.32 (rg 5, 1Н), ent ip masso with obtaining the free base of the target compound in the form of straw oil. (a9, 1H, 9U-7.8, 2.2Hz), 7.01 (aa, 1H, 9U-8.4, 2.0Gu), Dissolve the free base (239mg, 0.6b4mmol) in 6, 41. . SizNioR2SIM2gO-NSI 0.3 make the mixture with ultrasound for 10 minutes before

NgO) calculated: C 56.11; H 5.11; M 6.89; by removing the solvent, the mass was determined: С 56.03; H 4.95; M 7.18. hydrogen chloride salt in the form of a sticky oil

Example 881 is yellow. Dissolve the oil in 10 ml of the mixture

M-methyl-1-(2-(b-chloro-1H-indol-3-yl)ethyl)-3-(111) acetonitrile-water and lyophilized overnight with (2,2-difluoroethoxy)benzylamine to obtain a loose solid white substances; mix with diethyl ether (1 Oml) and acetonitrile (2 drops). Filter and dry the resulting precipitate to obtain hydrochloride

ME du in the form of an amorphous white solid

I She color: melting point: 63.8-65.8С; "H NMR (400 MHz,

ME OM5O-av): 11.10 (rg 5, 1), 7.52 (a, 1H, U-84Hz) n 7.36 (9, 1H, 9-2.0Hz), 7.40-7 ,26 (t, 2H), 7.22 (y, mix (Fibchlori nide titi OS ovve (2,2-difluoroethoxy)benzyl)amine (276bmg, - 0.7bmmol) and formaldehyde (55.5μl 38905 water- 54 ,4, 36 Hz), 4.50-4.02 (og t, 2), 4.30 (ju, gH, no solution, 0.7 mmol) in dichloroethane (15 ml) and h-144, 32 Hz), 3, 15 (rg 5, 4H), 2.68 (rg 5, ZN); M5 and b and n. (EbBu): t/e 378.9 (Mat); сн (to mix at room temperature in the process of СгоНаи СИБ2М2О-НСИ-0.7Н2О) calculated: C 56.14, H along Tohv; in two portions during Toh doda: 5.51, M 6.55; established: C 55.72, H 5.32, M 7.07. 1 Bimmol) and stir at a considerable rate According to the method of Example 319, the following ratios were obtained before diluting the meta-compounds isolated in the form of oxalate, with the exception of the one marked: zero (100 ml) and the rapid termination of the reaction

Mo from v

Or

And me! 717777 77711111 data/77777777771111111111111c1 t.pl. 208.5-210.02С; "H NMR (400 MHz, OM5O-adbv): 11.79 (Bg 5, 1H), 9.21 (bg 5, 2H), 7.39 (Y, 1H, 9U-7.8Hz), 7.32 ( y, 1H, 9-2.0Gu) 7.30 (5, 1H), 7.18 883 | 4,7-difluoro 2,2,2- (a, 1nH, 9U-8.0Hz), 7.11 (aa, 1H, U-2.6, 8.2Hz), 6.85-6.91 (t, 1H), 6.67- " trifluoroethyl |6.73 (t, 1H), 4.77 (d . ) calculated: C 54.23, H 4.31, M 6.66; established: C 54.20, H 4.30, M 6.66, t.pl. 107.2-108.27C; "H NMR (400 MHz, OM5O-dbv): 11.92 (Bg 5, 1H), 7.32 dBvt- 22909. (5, 2H), 6.95-6.99 (t, 2H), 6.87 (yes, 1H, 9-2.4, 8.0 Hz) 4.68 (4, 2H, 884 tetrafluoro trifluoroethyl y-8.8 Hz), 3.70 (5, 2H), 2.88 (Y, 2H, 9-7.2 Hz) 2.75 (1, 2H, 9U-7.2Hz), M5 (Eb-yu): t/e 421.1 (Ma), SNM (for SiZNizE7M2O1NCI-0.20H20) calculated : C 53.83, H 3.66, M 6.61; determined: C 53.75, H 3.33, M 6.54, mp 171.8-173.07С; "IN NMR (400 MHz, OM5O-dv): 11.80 (rg 5, 1H), 9.21 (5, 2H), 7.39 (Her, 1H, 9U-8.0Hz), 7.30-7.33 (t, 2H ), 7.18 (a, 1H, 9-7.6Gu), 885 | 4,7-difluoro 2.2,3,3- 7.10 (aa, 1H, 9-24, 8.0Gu), 6.85-6.91 (t, 1H), 6.54-6.83 (t . (M),

SNM (for SgoNivEvM2gO-1 HCI-0.25H20) calculated: C 52.53, H 4.30, M 6.13; established: C 52.75, H 4.24, M 5.76 t.pl. 262.5-263.8"C; "H NMR (400 MHz, OM5O-dv): 12.16 (rg 5, 1H), 9.43 w- 2238. (5, 2), 7.44 (a, 1H, 9-2.0Hz), 7.34-7.40 (t, 2H) 7.19-7.21(a, 1H, 886 tetrafluoroetrafluoropropyl y3.6Hz), 7.08-7.10 (aa , tn, 0-2.0, 8.0Hz), 6.69 (B, 1H, U-5.2, 52.0Hz) 4.59 (i, 2H, 9-13.4Hz), 4.15 (5, 2H), 3.16 (5, 4H), M5 (ARSI): m/e 453.1 (Ma), SNM (for SgoNivEvimgO-1HCI-O,10H20) calculated: С 48.96, Н

77777717 |353, M5 installed C48,74, H 333, Ministry of Internal Affairs t.pl. 173.8-175.62C, "H NMR (400MHz, OM5O-yv): 11.36 (Brg 5, 1H), 9.07 (Bg 5, 1), 7.87 (a, 1H, 9U-7 ,6Hz), 7.45 (a, 1H, U-7.6Hz) 7.38-7.42 (t, 1H), 887 7- 2.2,2- 7.36 (a, 1H, 9-2, 4Hz), 7.28-7.29 (t, 2H), 7.16-7.29 (t, 2H) 7.11 (yes, tn, riftomethyl trifluoroethyl /|-2.0, 8.0Hz), 4.77 (4, 2H, 9U-8.8Hz), 4.15 (5, 2H), 3.12-3.16 (t, 4H), M5 (ARSI): t/e 417.1 (Ma1 ), SNM (for SgoNivEvM2gO-1HCI-0.20H2O) calculated: C 52.63, H 4.28, M 6.14; determined: C 52.56, H 4.05, M 5.79 t. pl. 154.0-155.82С; IN NMR (400 MHz, OM5O-dv): 11.95 (rg 5, 1H), 9.51 (bg 5, 2H), 7.91 (a, 1H, U- 8.0Hz), 7.36-7.45 (t, 4H) 7.22 (a, 1H, U-8.0Hz) 888 7- 2,2,3,3- 7.17 (B 1H, 9 -7.6Hz), 7.09 (yes, 1H, 9U-2.2, 8.0Hz), 6.69 (H, 1H, 9-52, riftomethyltetrafluoropropyl 52.0Hz), 4.60 (Her, 2H . 10NgO) calculated: C 51.83, H 4.18, M 5.76; found: C 51.54, H 3.97, M 5.68 mp 133.0-134.82C; " H NMR (400 MHz, OM50O-av): 11.81 (5, 1H), 9.4 6 (rg 5, 2H) 8.14 (a, tn, 9-8.0Hz), 8.11 (a, yin, 9U-8.0Hz) 7.45 (a, 1H, 299. y-2, 0Hz) 7.39 (i, 1H, 9U-8.0Hz), 7.36-7.37 (t, 1H), 7.25 (I, 1H, Y-8.0Hz), 889 7-nitro trifluoroethyl 7.21 (a, 1H, 9U-8.0Hz), 7.10 (aa, 1H, 9-2.0, 8.0Hz), 4.78 (4, 2H, U-8.8Hz), 4 ,15 (5, 2H), 3.12-3.24 (t, 4H), M5 (ARSI): t/e 3941 (M-A1), SNM (for

SiONivEzMzOz:1HCl-0.80H2O) calculated: C 51.37, H 4.67, M 9.46; established: C 51.02, H 4.43, M 10.19 t.pl. 175.0-176.87C; "H NMR (400MHz, OM5O-dv): 11.81 (rg 5, 1H), 9.32 (bg 5, 2), 8.13 (a, yin, 9U-8.0Hz), 8.11 ( a, yin, U-8.0Hz) 7.45 (4, 1H, 2238. y-2.0Hz) 7.39 (Yii, 1H, 9U-8.0Hz), 7.31-7.32 (t . ,4, 8.4Hz), 6.69 (H, 1H, 9-52, 52.0Gu), 4.60 (i, 2H, 9U-13.2Hz), 4.16 (5, 2H), 3 ... established: C 49.98, H 4.38, M 9.47

Example 892 is yellow. Treat the crude 2-(7-trifluoromethyl-1H-indol-3-yl)-ethylamine material with 200 ml of ammonium hydroxide and extract

Mix in a 500 ml round-bottomed flask with ethyl acetate. Combine organic phases filtered with a magnetic stirrer, (2- wash over magnesium sulfate and concentrate i.p. trifluoromethylphenyl)hydrazine (5.0g, 28.4mmol) and mass to obtain an intermediate amine compound in 4-aminobutyraldehydedimethylacetal (4.54g, in the form of a solid yellow crystalline substance 34.1 mmol) and mix. After 5 minutes, the color slowly fades. Immediately dissolve the chemical intermediate, add a 1M solution of HCl (200 ml) and heat the reaction compound in 200 ml of dimethylsulfoxide, treat the reaction mixture at a temperature of 85°C for 2 hours with methyl iodide (4.55 ml, 56.2 mmol) and stir to obtain a solution of orange-red - you overnight at room temperature. Dolor. Raise the temperature to 100"C for 1 hour and give potassium cyanide (18.30g, 281mmol) and 18-crown - cool to room temperature. Pour 6 (226 mg), and stir the mixture at the temperature of the reaction mixture on ice and stir at 507C for 25 min. Pour the resulting suspension on ice for 10 minutes with subsequent pH adjustment to the level of 710 brown-yellow color, mix with ammonium hydroxide. Extract for 10 minutes, saturate with sodium chloride and the mixture with methylene chloride, combine organics, extract with ethyl acetate. Wash the combined phases, dry over sodium sulfate, and concentrate the extracts once with water, twice with brine, filter the mixture to obtain a dark oil, wash over sodium sulfate, and concentrate the orange-brown color. Purify on upamaso to obtain the target compound in the form of a forged silica gel column treated with hexa- solid yellow-brown color. Do-methyldisilazane, with the use of step-by-step purification was unnecessary. "H NMR of that gradient (9956-1795 methanol solution in (400Mhz, OM5O-yv): 11.92 (horn 5, 1H) 8.14 (a, tn, methylene chloride) with the receipt of pure target y-8.0Gsh), 8.12 (a, yin, 9u-8.0Hz) 7.53 (a, 1nH, compounds in the form of orange oil: "Н у2.0Hz) 7.31 (1H, 9-8.0Hz), 4, 16 (5, 2H), M5

NMR (400MHz, OM5O-av): 11.18 (rg 5, 1), 7.82 (a, (E5-): t/e 200.0 (M-1). 1H, 9U-7.6Hz) . .83 (t, 4H), 2-(7-nitro-1H-indol-3-yl)ethylamine

M5 (ARSI): t/e 229.0 (M.--1), 212.0 (M-MN"). In a 50 bml round-bottomed flask equipped with a

Example 893 with a pressure stirrer and an inlet for introducing nitrogen (7-nitro-1H-indol-3-yl)-acetonitrile, dissolve (7-nitro-1H-indol-3-yl)-

In 130 ml of glacial acetic acid in 500 ml of acetonitrile (5.27 g, 26 mmol) in an anhydrous tet round-bottom flask equipped with a magnetic stirrer - hydrofuran (150 ml). Dissolve 7-nitroindole (4.55g, 28.1mmol) and VNz in tetrahydrofuran (55ml, 55mmol) and heat to a temperature of 70°C. Add dimethyl me- stir at room temperature. Eschenmoser's salt) and stir for 20 hours, quickly stop the reaction by watering the mixture at a temperature of 70"C. After 45 minutes of adding cold water drop by drop, cool the reaction mixture, and remove the solvent (9 ml), and stir until the foam and foam mass stop, obtaining an unpurified solid resin formation. Concentrate the mixture until dry and thick. re-dissolve in a 1M solution of NOSI with it to the melting temperature of ice. Dry (300 ml) and extract with ethyl acetate. Increase the chloroform solution over sodium sulfate, the basicity of the aqueous phase with the help of a 5M solution, filter and concentrate under reduced pressure

Mahon is extracted with ethyl acetate. Combine com. Dissolve the residue in acetonitrile (5Oml) and ethyl acetate extracts, dry over sulfate, add 4-methylmorpholine-4-oxide (4 bg, sodium and concentrate ip massio to obtain 39.1mmol) and powdered 4AA sieves (200mgH). of the target compound in the form of a solid ora- Stir at ambient temperature njevish-brown color; "H NMR (400 MHz, medium for 20 hours, filter and

OM5O-av): 11.66 (Bg 5, 1H) 8.07 (6 2H, 9-7.6Hz), concentrate. Purify by chromatography 7.32 (85, 1H), 7.20 (1H, 2-8.0Hz) 2.79-2.83 (t, 4H), on silica gel (595, 3095 ethyl acetate/hexane) with ode-

M5 (ARSI): t/e 189.0 (M-MN"). by grinding 220 mg (895) of the target compound: M5 (t/e):

Example 895 216 (MU.

M-(2-(6-fluoro-1H-indol-3-yl)ethyl)-4-fluoro-3- Example 899 phenoxy-benzylamine 7-fluorotryptamine

Mix lithium aluminum hydride (12.6 g;

E E 336.1 mmol) and anhydrous tetrahydrofuran, which

Fe g has the melting point of ice (160 ml). As a result of c) cooling, there is an exothermic reaction to the

Temperature 0"C. Drop by drop add a solution of 7-fluoro-3-(2-nitrovinyl)-1H-indole (11.55 g,

The halochloride of the target compound is obtained by the method of Example 340: m.p. 173-175"; M5 ! (tu) 379 (Me), 377 (M-1); analysis for the environment. Cool after 4 hours

СозНгог2М2ОН- НС: calculated: C, 66.59: H. 510: M to a temperature of 0"С and add drop by drop then and then tya ' served visible: and iiiyu (35ml). From- 6.75, established: C, 66, 39; H, 5.05; M, 6.57. saturated sodium sulfate solution ( and

Example 896 filter the solids and wash with tetrahyd-

M-(2-(β-fluoro-1H-indol-3-yl)ethyl)-3-rofuran and ethyl acetate. Concentrate the filtrate and dissolve the residue in methylene chloride. phenoxybenzylamine.

Filter the precipitate to obtain 1.26 g of the product in the form of brown crystals. Con-

Centrifuge the filtrate and chromatograph on

M o kagels with elution of 595, 795, 1090 2M solution

M I of ammonia in methanol/methylene chloride to give

H of the product: M5 (t/e): 179 (Mt), 177 (M-1); analysis for SiONiIIEM2: calculated: C, 67.40; H, 6.22; M,

Hydrochloride of the target compound is obtained for 15.72, found: C, 67.06; H, 6.11; M, 15.48. by the method of Example 340: t.pl. 196-1997"С; M5 Example 900 (t/e): 361 (MA-1), 359 (М-1); analysis for 3-(2-nitrovinyl)-b-methanesulfonyl-1H-indole

C2z3Na EM2O: CARRIERS: calculated: C, 69.60; H, 5.59; M, Mix 1-dimethylamino-2-nitroethylene 7.06, found: C, 69.23; H, 5.58; M, 7.00. (892.1 mg, 7.68 mmol) and trifluoroacetic acid

Example 897 (9.Oml) and stir until dissolved. Add 6-4-fluoro-1-methyl-3-phenoxybenzene methanesulfonyl-1H-indole (1.5 g, 7 b8 mmol) and

Add triethylamine drop by drop, stirring at ambient temperature (28.bml, 205mmol) to the mixture of /2-fluoro-5-sedum. After 24 hours, pour the reaction mixture into methylphenol (5.18g, 41.1mmol), copper acetate (1I), a mixture of water and ice, extract with ethyl acetate, (7.46g, 41.1mmol), phenylboronic acid, then wash the ethyl acetate with brine and saturate 10.0g, 82.1mmol), powdered 4A sieves (7g) with sodium bicarbonate solution. Filter and methylene chloride (400 ml). Stir, wash and dry the precipitate to obtain a whole at ambient temperature. Through your compounds in the form of a yellow powder: 22h filter and concentrate the filtrate. t.pl. 225070. M5 (ASRI): t/e 267.0 (Ma1). Analysis

Purify the residue by chromatography on strength - for СНиоМ2гО45: calculated: C, 49.62; N, 3.79; M, kageli (5090 solution of methylene chloride in hexane), 10.52; established: C, 49.86; H, 3.97; M, 10.25. concentrate and purify again by chromatography on silica gel (10095 hexane) to obtain 3-(2-nitrovinyl)-6-benzenesulfonyl-1H-indole 2.4 g (29905) of the target compound: M5 (t/e): 202 (MU). Mix 1-dimethylamino-2-nitroethylene

Example 898 (676.9 mg, 5.83 mmol) and 4-fluoro-3-phenoxybenzaldehyde trifluoroacetic acid (9.0 mL) and stir until dissolved. Add 6-

Mix 4-fluoro-1-methyl-3-phenoxybenzene benzenesulfonyl-1H-indole (1.5g, 5.83mmol) and (2.43g, 12.0mmol), M-bromosuccinimide /(4.92g, stir at room temperature 27 mmol), benzoyl peroxide (408 mg, 1.68 mmol) medium. After 24 hours, pour off the reaction mixture and carbon tetrachloride (55 ml). Heat the mixture to a mixture of water and ice and bring it to pH 8. After refluxing for 6.5 hours and stirring, filter the precipitate, wash, cool to a temperature of 0"C for 4 hours with water and dry to obtain the target compound

Filter the solids and concentrate in the form of a yellow powder: m.p. 110"C, with filtrate. Dissolve the residue in chloroform and decompose. MB (ASRI): t/e 329.0 (Mat). Analysis washed with a solution of sodium carbonate, cooled - for SivNi2M2O45: calculated: С, 58.53; Н, 3.68; M,

8.53; established: C, 58.54; H, 3.83; M, 7.85. NCI solution (37.5 ml) and mix the solution

Example 902 at room temperature overnight. end-

(3-Phenoxybenzyl)-(2-pyridin-2-yl) oxalate, filter the reaction mixture, treat with water and ex-ethyl)amine, triturate with СНоСиИ». Wash the organic extract

Mix 2-pyridin-2-ylethylamine (Aygisy, water, dry (Mag504) and concentrate with ode-

O,Zbml, Z,Ommol), Z-phenoxybenzaldehyde by purging the crude product. Purify by (Alagis, 0.58ml, 3.66mmol), THROUGH molecular sieves, flash chromatography (hexane/k(OAc (0.5g) and methanol (300ml) and heat with reverse (7:3)) to give of the target compound in the form of a refrigerator for 4 hours. Filter off the yellow solids. molecular sieves. Slowly add sodium borohydride Example 905 (0.35g, 9, mol) and mix the reactions- M-(3-(2-(b-chloro-1H) -indole-3-yl)ethyl)-3-(pyrid-2-one mixture at room temperature. After 1 hour, ylamino)benzylamine, concentrate the reaction mixture, dissolve the residue in a mixture of TM solution of Maon and methylene chloride, and extract the mixture with methylene chloride. Wash the organic extract with water, dry ru MM M (Mag2504) and concentrate to obtain a pale yellow oil B. Obtain the salt with the help of oxalic acid and crystallize from ethylace- Mix b-chlorotryptamine (0, 22g, 1.1mMMmol) tat with obtaining a white solid Co-3-(pyridin-2-yl-amino)benzaldehyde shi (0.22g, lor: m.pl.-183-18 57C; mass spectrometry: ions 1.1 mmol), ZA molecular sieves (0.5 g) and methanol at 305.2. (25ml) and heat under reflux

Example 903 y y y y for 4 hours. Filter molecular sieves. (9-11,3Idioxolan-2-yl-phenyl)-pyridin-2-ylamine Slowly add sodium borohydride (0.16g,

Mix 2-aminopyridine (8.25g, 95mmol), 2-Z,Zmmol), and stir the reaction mixture at (Z bromophenyl) GP Zidiyuxolan (13,vml, 9Ommol), room temperature. After 1 h, concentrate sodium tertoxide (12.27, 126 mmol), VIMAR reaction mixture, dissolve the residue in a mixture of 1 M (2.2-bisidiphenylphosphine)-1,1-binaphthyl) (210 mg, Mahon solution and methylene chloride, and extract

O.6b2mmol), Raz(daby)z (63Omg, 0.21mmol) and the mixture with methylene chloride. Wash the organic luol (100 ml) and heat the extract with water under reflux, dry (Mag50") and concentrator for 48 hours. Cool the reaction mixture to obtain the crude product. Clean to room temperature, dissolve. To titrate by flash chromatography with simple ether, filter and concentrate (EOAS/MeeOH (9-1) with 295 concentrated solution. Purify by flash MNAOH) to obtain the required chromatography product (hexane/Euds (8.571.5) , then in the form of a colorless oil.Get dihydrohexane/ctOAc (7:3)) to obtain the target compound and crystallize from EIODc to obtain ki in the form of a yellow oil. of the required product: melting point -164-166"C; mass

Example 904. and spectrometry: ions at 377 1. in ee nsolane 2-p The following compounds were obtained by a method, phenyl)pyridin-2-yl-amine (10.32 g, 42.bmmol) in a similar way to the method of Example 673: tetrahydrofurans (15 Oml). Add concentrated

AHA my | in HER 7 Vb HER 77777717 Dan 906 | operid-2il | phenyl, iSMethod3: P2.83 min at 54/220nm; t/e 305.0(MYA1)../.O 907 | tiene-il | Phenyl |SSMethod3: v/4.00 hvpri254/220nm: t/e 3309.9(M).Y.-:// Z"

The following compounds were obtained by a method similar to the method of Example 673:

ШИ о пр: зще п with PI H RON PO ET PO 908 | ZV | avenue | Method: v/4.48hvpri254/220nm:t/e 349.9 (My!).-://АЯЙ.ЮСУ /)

M5-362 (t--1), IV; 1718.51, 158426, 1489.84, 1445.78, 1285.67, widow | zsosst | hair dryer | thousand

The following compounds were obtained by a method similar to the method of Example 665:

in zhu, bassom i yo

S AL

7th question from PO: UNN POLON EE KO 909 | - N | oisopropl |SSMethod3: Rg54Zkhvpri254/220nm; t/e 385.0(MYA1).-/:/(KHYN..-:Ch

According to the method of Example 221, the following compounds were obtained, isolated in the form of maleate, with the exception of the indicated:

What M

TE Pe Sl PO: RON CONONKO

Example 914 wash the resulting solid with ether

3-propoxybenzonitrile to give the target compound as a solid

Mix 3-hydroxybenzonitrile / (11.052 g; white solid. 92.8 mmol), p-propyl bromide (24.4 g; 198 mmol) and Example 916 potassium carbonate (38.65 g; 280 mmol) in 2-butanone 2-(3-bromophenyl )-M-(3- (175ml) and heat under reflux. propoxybenzyl)acetamide

After 17 hours, cool the reaction mixture to room temperature. Mix 3-propoxybenzylamine in 50 ml at room temperature, drain the solution and concentrate lormethane and add drop by drop to the mixture on a rotary evaporator. Distribute the remainder of 3-bromophenylacetyl chloride (4.90g; 21.0mmol) and triethylamine (3.60g; 35.9mmol) in 250ml of dichloromethane between diethyl ether (150ml) and water (150O0ml) - separate the layers and extract the aqueous layer with di-methane at a temperature of 0"C. Keep with reactive ether (2x100ml). Combine the organic layers with the mixture heated to room temperature and wash with water, 1M Mahon solution, and stir for 18 hours. Pour off the reaction mixture, dry over Mdazoh and concentrate. Dissolve the mixture in 100 ml of saturated brine, separate the residue to obtain the target, wash the layers and extract the aqueous layer with 100 ml of dichloromethane. Combine the organic layers, wash

Example 915 with brine, dry (M9d50O4) and concentrate.

Hydrochloride of 3-propoxybenzylamine Purify by chromatography on silica gel with

Mix 100 ml of lithium aluminum hydride (1M elution with 4095 EtOAc solution in hexane with 1 part in tetrahydrofuran) and 50 ml of tetrahydrofuran to obtain the target compound. and drop by drop add sulfuric acid Example 917 (10095) at a temperature of 10"C. Keep the reaction mixture of 2-(4-fluorobiphenyl-3-yl)-M-(3- propoxybenzyl)acetamide with heating to room temperature Mix bromamide ture and mix. Filter through berries (0.365g; 1.00v8mmol), 4-fluorophenylboronic acid- solids through a layer of diatomaceous earth under the lot (0.175g; 1.25mmol), cesium fluoride (0.360g; nitrogen pressure and purify solution by adding 2.37mMmMol) and dichloromethane drop by drop of a nitrile solution in 50ml of tetrachloro(bistriphenylphosphine)palladium (I) (0.062g; hydrofuran at a temperature of 0"C. Stir 0.088mmol) in MMP (M-methylpyrrolidone) (Zml) and the reaction mixture. After 1 hour at a temperature of 0"C, heat at a temperature of 104"C. After 13 hours, the reaction mixture is allowed to stand with heating until it cools down to the ambient temperature of the environment and the medium and diluted with dichloromethane (40 ml) and stirred for 2.5 hours. Cool the reaction with water (40 ml). Separate the layers and extract the mixture to a temperature of 0"C, drop by drop the aqueous layer with dichloromethane (2x20ml). Combine, add 1bml of solution (17) to the organic layers, wash four times with 1Oml porcide/gtetrahydrofuran and 2M mMon solution (boml ). pits of saturated brine, dry (Ma5o)") and

Filter the resulting reaction mixture, concentrate. Purify by chromatography, wash the solids with tetrahydrofuran on silica gel eluting with 4095 EA solution (2x100Oml), combine the organic layers, dry in hexanes to obtain the target compound. over sodium sulfate and concentrate. Solutions - Example 918 and the residue in dry ether (250 ml) and acidified with M-(2-(3-(4-fluorophenyl)phenyl)ethyl)-3- HCl/dioxane solution (20 ml of 4M solution). Pro-propoxybenzylamine o

IS

7 Oi g g y dany y o y

Mix 2-(2-fluorodiphenyl-3-yl)-M-(3- Mix M-(2-(5-benzyloxy-1H-indole-3-propocosybenzylacetamide) in 15 ml of tetrahydrofuryl)ethyl)-3-phenoxybenzylamine (1.61g, 3.59mmol) wound and drop by drop add a solution of VNz- and maon (143.6mg, 3.59mmol), dissolve in tet-

ZMeg (2M solution in tetrahydrofuran) at room temperature, hydrofuran (25 ml) and stir at room temperature of 0"C. Keep the reaction mixture at a heated temperature. After 15 minutes, add the solution by stirring to the temperature of the surrounding medium butyddicarbonate (1.57g, 7.18mmol) into the above and stir. After 5h carefully add tetrahydrofuran (20ml) and heat with reflux ethanol (1ml), and concentrate the reaction mixture. refrigerator for 4h. Remove the dis-

Dissolve the residue in ethanol (2ml), heat with a factor, dilute with water, extract СНоСиг with a reflux condenser for 2h and con- (Хх15ml), dry over Mag50" and concentrate, centrifuge. Purification gives the target compound in the mass fraction with the yield of a brownish-brown solid substance of yellow-brown color. The crude product was used without delay. Dissolve the substitute in 100 ml of the mixture (17) medium at the next stage without purification. of dichloromethane/methanol and add bb0Omg of polyvinyl- Mix a 1.0M solution of CAIN in tetrahydrofur- pyridine hydrochloride. Shake the reaction mixture (13 4 ml, 13.4 mmol) and tert-butyl ether mixture for 4 hours, filter the polymer, (3-phenoxybenzyl)-(2-(5-benzyloxy-1H-indole-3-) concentrate the residue and wash with simple ethyl of yl)ethyl)carbamic acid (1.83g, 3.34mmol) and rum to obtain the target compound in the form of slowly add 15ml of dry tetrahydrofuran. hydrochloride: M5 (Eb-yu): t/e 364 (M--1). After the addition is complete, heat the reaction vessel

Example 919 reflux mixture. After 4.5 hours

Cool M-(2-(5-benzyloxy-1H-indol-3-yl)-ethyl)-3- to room temperature. Quickly stop the reaction with phenoxybenzylamine by carefully adding cold water (1.5 ml), then 1095 Mahon solution. Then filter the suspension and wash again with ether. Dry the organic solution over

Mag5O5 and concentrate the solvent ip massio. eyes-

and purified by chromatography on silica gel with eluent

I ovation with a mixture of СНе2СиИг/МЕОНН with obtaining h free base: "H NMR (300 MHz, СОСИ3) 2.95 (v, n ЗН), 2.69-2.74 (t, 2Н), 2.91-2, 96 9t, 2H), 3.65 (5, 2H), 5.07 (5, 2H), 6.90-7.53 (t, 18H), 7.80 (5, 1H).

Mix 5-benzyloxytryptamine (/ (1.23 g, As a result of the further reaction of this compound with oxal- 4.bmmol), 3-phenoxybenzaldehyde (9795, 1.09Hg, a salt was obtained with levoic acid. 5.53 mmol) and molecular sieves 4A (1, 0 g) and stir Example 922 in methanol (15 ml) for 4 hours. From M-(2-(6,7-difluoro-1H-indol-3-yl)-ethyl)-3- wash Meon. To this solution Add Mavnae (174 mg, 4.60 mmol) in portions to Meon, and stir the resulting reaction mixture at room temperature for 1 hour. Remove Meon under vacuum, dilute the residue with mixture I o

SneoSi/water, extract SNeosi", combine the organic layers, dry over magnesium oxide and concentrate the solvent and mass. Purify by chromatography on silica gel (CH2Cl2/MeOH) with Mix 6,7-difluorotryptamine (0.285 g, obtaining the free base. Mix the free base 1.450 mmol), 3-pyridin-4-yloxybenzaldehyde new with oxalic acid to obtain a salt : (0.303g, 1.52mmol, 1.05eq.) and molecular sieves (ZO0MHz, OM5O-yv) 2.95-3.15 (t, AN), 3.93 (5, 2H), 4A (0, 30 g) and mix in methanol (12 ml). Che- 4.10 (og, 1H), 5.05 (5, 2H), 6.85-7.46 (t, 18H), rez 4h filter molecular sieves and deki- 10.67 (bg, 1H); mass spectrometry with electrodispersion, rinse with MEON several times. To this solution, by dusting, t/e: 449.2 (Ma-1). Add Mavna (55.0mg, 1.45mMMmolLl) to it in portions and

Example 921 should be stirred at room temperature for

M-(2-(5-benzyloxy-1H-1indol-3-yl)ethyl)-M- for hours. Delete MeonNip Masio. dilute the methyl-3-phenoxy-benzylamine residue with a SNeoSig/water mixture, extract

Sneosi", combine the organic layers, dry over

Mag25O4 and concentrate ip mass. Purify by flash chromatography on silica gel (CH2Cl2/Meon) to obtain the free base, which is converted to the hydrogen chloride salt: "H NMR

(Z0OMHz, OM5O-av) 3.13 (5, 4H), 4.20 (5, 2H), 6.85 - temperature control. 7.55 (t, 10H), 8.47-8.50 (t, 1H), 9.58 (bBg, 1H), To determine the characteristics of crystalline 11.57 (rg, 1H): mass spectrometry with electrodis- forms of organic compounds, a whole range of sawing t/e is available: 380.2 (Ma-1-HCI), 378.3 (M-1- methods. These methods include, for example, di-

NOSE). differential scanning calorimetry, NMR-

This invention also provides new intermediates for spectrometry of the crystalline state, infrared products of compounds of formula I. This invention provides prone spectroscopy and powder X-ray intermediates of formula PI: diffraction. Among these methods, powder X-ray diffraction and NMR spectrometry of the crystalline state are very suitable for identification

M tification and differentiation of crystalline forms. Powder X-ray diffraction analyzes are performed in a variety of ways known to those skilled in the art. These methods can change

Az is selected from the group consisting of hydrogen, to increase the sensitivity by sub-fluorine and methyl methods; preparation of samples and the use of more intensive

Ba - fluorinated Co-Ca alkyl. less radiation, smaller scanning steps

This invention also provides new crystal photo- and slower scanning speeds. One of these few compounds of formula I. Thus, for example, M-(2-(6- methods) is as follows. A sample (without grinding or from fluoro-1H-indol-3-yl)ethyl)-3-(2,2, 3,3- by minor grinding in an agate mortar with thick tetrafluoropropoxy)benzylamine hydrochloride by a duck) is introduced into the sample holder for the can be obtained by crystallization under the counter- value of powder X-ray diffraction. fused conditions with obtaining new crystalline Powder X-ray patterns are obtained with the help of forms. Methods of crystallization from a solution and a suspension of a powder X-ray diffractometer are provided within the scope of this invention. Under practical conditions, the form M-(2-(6-fluoro-1nH- (4-1.54056A), which is operated at 50 kV and indol-3-yl)ethyl)-3-(2,2,3,3- 40 mA with the size of the diffuser aperture in 1 mm, tetrafluoropropoxy)benzylamine hydrochloride, the input aperture in mm and the aperture of the detector which was obtained, can be affected by a whole of 0.1 mm. Samples can be scanned within a range of factors, including temperature and composition 42 to 352 (29) with a step size of 0.022 and maxi-solvent. While the exact conditions of formation with a low scanning speed of Cs/step. Data on crystalline M-(2-(6-fluoro-1H-indole-3-iluethyl)-3- are collected using the semiconducting (2.2,3,3-tetrafluoropropoxy)benzylamine hydro-silicon-lithium Kemech detector. to determine empirically, that option, the usual practice is to use a number of methods, which, as it was established, are suitable in practice.

Polymorphic form /M-(2-(6-fluoro-1H-indole-3-) It is well known in the field of crystallography that, yl)ethyl)-3-(2,2,9,3- for any given crystal form , relative to tetrafluoropropoxy)benzylamine hydrochloride, the intensity and width of the diffraction peaks, which is preferred, can be obtained by changing under the influence of a number of factors of crystallization of the suspension in diethyl ether. ditch, including as a result of the effects of the prevailing

Another polymorphic form of M-(2-(6-fluoro-1H-indole-3- orientation and/or particle size. In the case of the presence of yl)ethyl)-3-(2,2,3,3- effects of the predominant orientation and/or the size of tetrafluoropropoxy)benzylamine hydrochloride, ru particles, the intensity of the peaks can change, which is preferred, can be obtained, but the positions of the characteristic peaks of crystallization from an aqueous solution of dichlorometa-polymorph remain unchanged. (See, well, an aqueous solution of acetone, ethyl acetate, a mixture, for example, US Pharmacopoeia Mo24, Book of recep- ethyl acetate/cyclohexane, ethyl acetate/hexane, tour formulas issued by the American Pharmaceutical Association, Me19, p. 1843- ropanol/hexane, acetonitrile, mixtures of acetonit- 1844, 2000). ril/gluol, p- Grinding can be used for zvepropanol/isoamyl acetate/hexane, isopropylation to a minimum intensity of peaks. However, in tat/diethyl ether, methyl tert-butyl case, if grinding significantly changes the diffracto- ether/acetone, water, water/acetone, /- vogram or changes the crystalline state of the sample, trace of di/diethyl ether. use the diffractogram of the unbroken

Crystalline M-(2-(6-fluoro-1H-indole-3- sample. Grinding is carried out in a small yl)ethyl)-3-(2,2,3,3- agate mortar using a pestle. The tetrafluoropropoxy)benzylamine mortar can be obtained is retained during grinding, and a small pressure is applied to the pestle by direct crystallization under controlled conditions. conditions New crystalline forms according to the present invention Thus, in the X-ray pattern obtained by can also be obtained by dissolving M-(2- as described above, accordingly prepared- (b-fluoro-1H-indol-3-yl)ethyl)-3- ( The 2,2,3,3-th sample of the crystalline compound of the formula can be tetrafluoropropoxy)benzylamine in a solvent with one or more significant 29. by adding a solution containing hydrochloric acid, with subsequent crystallization, whether I can also be determined by means of NMR

spectrometry of the crystalline state. Chemical shifts and chemical properties of the selected compound, the selected crystalline state of the ZS reflect not only the molecular route of introduction and other relevant molecular structure, but also the electronic composition that is taken into account in the usual arrangement of molecules in the crystal. pharmaceutical practice. Vetipdyup'5

Analysis of the NMR spectrum of the crystalline state (13C) of RPpagptaseciis! Zsiepse5, 18 Eyop, Mask can be carried out by the combined use of meri- Rybiivpipdu So. (1990)|. then cross-polarization and rotation under the magic Pharmaceutical compositions are obtained by means of "ZS (SR/MA5). NMR spectra (NMR crystallibom, well known in the field of pharmaceuticals. carrier state or NMRKS) are obtained with the help of or the filler can be a solid, semi- 400 MHz Spectrometer Magiap Oppyu, which is a real or liquid material that can serve as this at the frequency of carbon (100.580 MHz), a carrier or medium for the active ingredi- equipped with a complete set of semiconductors. Suitable carriers or fillers are well-aged auxiliary equipment and 7mm Magiap probe homes in this field.Pharmaceutical composition

MT SR/MA5. The parameters of collection and accumulation can be adapted for oral. Inga- data are easily determined and include, as regulatory, parenteral or local administration, a width of 90" of high-frequency proton impulse and can be administered to the patient in the form of a tabulse (4.0 msec), the duration of contact (1.0 msec) , drops, capsules, aerosols, dosage forms for pulse frequency (5s), frequency of rotation of inhalation, suppositories, solutions, suspensions, etc. under the magic angle (7.0kHz), spectrum width Compounds according to this invention can be administered (50kHz) and collection time and accumulation of data orally, for example, with an inert diluent (5 Ohmsec). Chemical shifts are determined, as a rule, in the form of capsules or compressed in a tablet by comparison with the methyl group of the exterior. For oral therapeutic administration of a sample of hexamethylbenzene, i.e. by means of compounds can be included with fillers and simple replacement of the sample with hexamethylbenzene. be used in the form of tablets, lozenges,

Thus, crystalline compounds of the formula | capsules, elixirs, suspensions, syrups, wafers, can be characterized by one or more chewing gums, etc. These preparations should include at least 495 compounds of this invention-1360 obtained according to the above description by resonances in the NMR spectrum of the crystalline form. course, the active ingredient, however, this amount

The compounds of the present invention may be administered independently or in the form of a pharmaceutical compoform and may suitably be administered in combination with 495 to about 70,905 by weight of a unit doseable carriers or excipients. . Compounds The amount of compound present in the compositions is, according to this invention, effective in itself, so that the appropriate dose is obtained. Compositions that can be included in the compositions and administrations and preparations according to this invention, which are preferred in the form of their pharmaceutically acceptable salts, can be determined by a specialist in this salt for reasons of stability, convenience, development. validity, etc. Under practical conditions, the compounds of formula I and formula I are administered, as a rule, in can also include one or more of the pharmaceutical compositions, i.e. in the following adjuvants: astringent substances, mixed with pharmaceutically acceptable carriers or, for example, microcrystalline cellulose, tragacanth diluents. or gelatin; fillers, for example, starch

Thus, the present invention provides pharma- or lactose, disintegrants, tical compositions comprising a compound of the formula e.g., alginic acid, primogel

I or formulas II and pharmaceutically acceptable (Rgitodei), corn starch, etc.; lubricant-thinner. valuable substances, for example, magnesium stearate or

Compounds of the formula | and formulas Ii can sterotex (5iegoieh); slippery substances, for example, can be introduced in a variety of ways. For effects - colloidal silicon dioxide; can be added to the treatment of a patient affected by disorders, sweetening substances, for example, sucrose or the description of which is given, a compound of the formula | and phosaccharin or corrigents, for example, peppermint II can be administered in any form or va, methyl salicylate or orange flavoring- in any way by which the compound becomes a mash. In the case when the dosage form for mono-bioavailable in an effective amount, including single administration is a capsule, it can be administered orally and parenterally. Include, in addition to materials of the above-mentioned type, for example, compounds of formula I and a liquid carrier of formula I, for example, polyethylene glycol or orally, inhaled, subcutaneous fat oil. The composition of other medicinal forms, but, intramuscularly, intravenously, for one-time administration may include various transdermal, intranasal, rectal, intra-other materials that modify the physical form of the intraocular, local, sublingual, subbuccal dosage unit, for example, a shell. Yes, etc. For the treatment of disorders, the description of which navo- tablets or dragees can be coated with sugar, see, the preference is usually given to in- shellac or other coating substances. orally. Syrup may include, in addition to these compounds, sucrose,

A person skilled in the art of compositions such as sweeteners and certain preservatives can easily choose the appropriate form and method of colorants, dyes and corrigents. The mother-introduction, depending on the specific characteristics used to obtain such ristics of the selected compound, disorder or condition to various compositions, should be pharma- treatment, stage of the disorder or condition, solubility ceutically pure and non-toxic in use

these quantities. concentrations from 125 mM to 1.25 nm with a semi-log

For the purpose of parenteral therapeutic rhyming growth using 1095 di- administration of the compounds of this invention can methyl sulfoxide as a diluent. This operation should be included in a solution or suspension. These preparations are carried out with the help of an automatic and, as a rule, include at least 0.195 TESAM devices. The final content of dimethylsulphate according to this invention; this amount, however, can foxide at this stage is 21.2595. vary from 0.195 to about 90905 Ligand, labeled with a radioactive isotope, di- from their mass. The amount of the compound of formula I! and mixed in the analytical buffer to obtain the formula Ii, present in these compositions, is such that 125 nm of the solution and the contents of each membrane tube can be obtained the appropriate dose. Our solutions are diluted with experimental buffer or suspensions can also include one or up to 92 ml. The final analytical volume (250 μl) is several of the following adjuvants: sterile includes 210 μl of diluted membranes, 20 μl of solvents, for example, water for injections, physiological compounds or 21.2595 dimethyl sulfoxide for logic solution, non-volatile oils, polyethylene glycol of complete binding, and 20 μl of diluted ligand, glycerol, propylene glycol or other synthetic substances, labeled with a radioactive isotope. Solvent compounds; antibacterial agents, for example, are transferred from tablets for dilution of medicine - benzyl alcohol or methylparaben; antioxidants for angular 96-well analytical dents, for example, ascorbic acid or bisu-tablets using a 96-well device of sodium philite; chelating agents, for example, for simultaneous pipetting Myikitek. Ligand, clade, ethylenediaminetetraacetic acid; buffers, labeled with a radioactive isotope, and membranes, such as acetates, citrates, or phosphates, and added to analytical tablets using a tonicity-adjusting agent, such as a cryo- device for simultaneous pipetting of several sodium or dextrose readings. Parenteral preparations of samples. Non-specific binding can be determined in ampoules, disposable syringes containing serotonin with a final concentration or multi-dose vials made with a 10 μM concentration. To the final analytical volume of glass or plastic. Compositions and preparations include a preferred radiolabeled ligand (T1OnNM) and membrane protein (approximately 25 µg per well). Final semi-logarithmic concentration

The compounds of the present invention can also be administered topically in a dosage of from 10 μM to 1 nM. The final amount of dimethyl sulfoxide in the solution, ointment or gel base. The reference of the analytical mixture is 1.790. on the base, for example, may include one or After adding the medicinal product, the membrane several of the following components: vaseline, and the ligand, the tablets are incubated for 1 hour lanolin, polyethylene glycol, beeswax, mine- at room temperature. During this time, 96 wells of ral oil, diluents, for example, water or MiPiroge filter tablet alcohol, and emulsifiers and stabilizers. Compositions (MARVMOV5O) are infiltrated for at least as long as for local use may include ZOkhv 0.595 solution of polyethyleneimine (200 μl per compound of formula I and formula II or their formulation). Ceutic salt in the range of about 0.195 to 0.595 polyethyleneimine solution is removed from about 1095 (weight to volume). wells of the filter tablet using

Compounds of formula I or formula II are antagonists of the Tiegtek MAR aspirator and 200 μl of incubation with 5-HT receptor noses. Such antagonism can be transferred from the incubation plate to the filter plate after mixing. It's self. transfer is carried out using 96-

Example A of a tip device for simultaneous pipetting

5-HT binding analysis of several Mshiitek samples. After transferring

The analytical buffer that was used was applied to the filter tablets, the last ext. included a 50 mM Tris-HCI solution, pH 7.4, 120 mM raguated and washed twice with the mass solution, 5 mM KSI solution, 5 mM Masig solution with cold buffer ( 220 μl per well). Removable 1mm solution of ethylenediaminetetraacetic acid. bottom coverings from filter tablets

A ligand labeled with a radioactive isotope, which is added to each well with the help of ZN-Y50 from the Memstroy company, was used for simultaneous pipetting of several

Epdiapa Misieag, catalog number: MET 638 - samples are introduced with 100 μl of scintillation liquid 75.9Ki/mmol. Membranes from Tisgossypi 20 were used. Tablets are placed on the appropriate Keseriog Vioiodu companies, catalog number: KV- holders and kept at room temperature

Nh5Zv6. These are the membranes of the NEK-293 cell line, which ex- during the Zhod, after which the human 5-HT receptor is pressed. ЗН with the help of the counter of Umaiijas Misgoreia or

Experimental compounds were presented by Raskaga Torsoishpi. battle 10mM concentrated solutions in 10095 dime- According to one version of the embodiment, this invention of tylsulfoxide. they are diluted to 1 mM in 100905 provides methods of treating disorders related to dimethylsulfoxide by adding 18O0μl to the 5-HT receptor, which include: injecting dimethylsulfoxide up to 20μl of a concentrated day to a patient who needs it, an effective solution in 96-well tablets with the help of the amount of the compound of formula I. Thus, this device for simultaneous pipetting of several of the invention considers various disorders to treat- samples. After that, the 1 mM concentrated solutions described below and others that can be diluted to produce an 11-point series are treated with such antagonists as are properly appreciated by those skilled in the art. alternative nomenclatures, nosologies and classi-

In particular, due to their ability to antagonize the system of disorders, the description of which is the induction of the 5-HT receptor, it is recognized that the compounds, including those whose characteristics are suitable for the treatment of this field according to the present invention, are not precisely defined, as well as those, a description of disorders of cognitive ability, that is, disorders that are listed in OM5-IM and ISO-10, and which include disorders of cognitive ability. nology and classification systems are evolving

Thanks to the developed and accepted classifications, which change along with the development of medical knowledge, a number of disorders are known that can be treated with drugs. forging with the help of 5-HTv antagonists, in that According to one of the variants of embodiment of this invention, while others are unknown. provides treatments for disorders that choose

Some of the disorders to be treated according to this are from a group that includes: cognitive disorders are not very clearly categorized and classi- ability related to age, slightly impaired, because cognitive ability is not cognitive ability, depressive disorders (in a complex and, to some extent, poorly defined, including depression, mania, manic phenomenon. It is generally accepted, however, that depressive psychoses), psychoses (in particular, schizophrenia) cognitive ability includes different "areas". rhenium), disorders accompanied by anxiety of these areas belong to short-term memory, (including, in particular, generalized disorder, long-term memory, working memory, executive, accompanied by anxiety, a disorder that co-functions and attention. accompanied by panic fear and obsessive-

Despite the fact that the disorders that can be treated according to the present invention are not the same, Parkinson's disease and Parkinson's disease caused by medical description and classification in this field, of course, epilepsy, convulsions , migraine (for which the compounds of the present invention are suitable for including throbbing headache), syndrome treatment of disorders characterized by withdrawal from taking narcotic substances, impairment of any of the above areas (including substances such as opiates, nicotine , cognitive ability or other aspects of cognitive ability - tobacco products, alcohol, benzodiazepines, coca- cal ability. Thus, the term "Tn disorders, sedatives, hypnotics, etc.), cognitive ability" means any sleep disorder ( including narcolepsy), mood deficiency, characterized by a violation of one or attention/hyperactivity syndrome, behavioral disorders of several areas of cognitive ability, whereas learning disabilities, dementia including, but not limited to, short-term memory (including Alzheimer's disease and dementia-long-term memory, working memory, executive function caused by AIDS), Gentinton's chorea, function and attention. impairment of cognitive ability as a result of recon-

One of the cognitive disorders amenable to structural arterial surgery and treatment according to this invention is age-related transplant, stroke, cerebral ischemia, cognitive impairment. This disorder of damage to the spinal cord, damage to it does not have a precise definition, but includes the hypopharynx, perinatal hypoxemia, arrest of the areas of cognitive ability, in particular, the heart, and hypoglycemic damage to the neural areas of memory and attention, which accompanies sta- cells, dementia due to vascular diseases. Another disorder is a slight disturbance of impulses, polyinfarct dementia, lateral amiocognitive ability. And, again, this disorder trophic sclerosis and multiple sclerosis, which is not well defined in the art, but includes: administration to a patient in need of it, which includes deterioration of areas of cognitive ability, an effective amount of a compound of formula I or ness and, is thought to be characteristic of the patient group of formula II. That is, this invention provides a method for subjects, most of which have an initial stage of tailing the compound of formula I! and formula II or Alzheimer's disease. In addition, the result of their pharmaceutical composition for the treatment of a wide variety of strokes, including, "apop- disorders associated with the receptor 5-HTv. lexical stroke", ischemia, hypoxia, inflammation and It is recognized that the terms "treatment" and "drug - infectious processes, there may be disorders of vata" mean the improvement of impairment of cognitive-cognitive ability, which, as a result, may ability associated with each of the disorders, can be treated according to this invention. associated with the 5-NTee receptor, the description of which is

Disorders that can be treated with antagonists see. It is also recognized that an experienced fachi- 5-HTe, are known at this time in accordance with the findings can affect the disorders through treated and acceptable classifications; these classifications of a patient already affected by disorders or fixations can be found in various sources. Now, by prophylactic treatment of the patient, for example, in the fourth edition of the "Advisor, who is thought to be susceptible to such disorders and diagnosis of psychiatric disorders, with an effective amount of the compound of formula I. Mepiai Thus, the terms "treatment" and "treat" rizogaete (О5М-ИМм)) (1994, Ategisap Rzuspiaiis) mean all processes, the result of which can be

Avzosiainop, M/azpipdiop, O.S.) diagnostic slowing down, interruption, control, temporal methods for identifying many temporary or complete cessation of the progression of modes, the description of which is given in it, are provided. In addition, disorders, the description of which is given, but not necessarily

The International Classification of Diseases (ISO-10) provides a classification and also means preventive treatment of many disorders described in it. disorders For example, this invention specifically

It is clear to an experienced specialist that there are including treatment of cognitive impairments

ities associated with schizophrenia, stroke, disease, according to an embodiment of which treatment of Alzheimer's and other disorders that are op-weighted, this invention provides a method of treatment are spread. Thus, it is clear that this invention of modes of cognitive ability, which includes the introduction of methods of auxiliary treatment of the disorder to the patient in need of it, effective divas, which are described. In particular, compounds of the formula | amount of the compound of formula I. or formula II are suitable for the treatment of dementia. which includes the introduction of effective butyric acid in combination with adenylation potentiating agents to a patient who needs it; with typical and atypical antipsychotics, including olanzapine; with According to an embodiment, which is given by various agents, for example, agonists of revaga, this invention provides a method of treatment of shi-glutamic acid receptor, agonists of M-sophrenia, which includes the administration to a patient who methyl-O-aspartate, inhibitors of interleukins 1-6 of this requires, effective amount of compound, etc.; with cholinergic agents, including formula I. cholinesterase inhibitors, for example, tacrine In the fourth edition of the "Guide to Statistics and Donepezil, and Compounds that Suppress Tics and Diagnostics of Psychiatric Disorders" amyloid protein processing, including (О554-ЙМтм) ) (1994, Ateipsap Rvusniainis by inhibitors of the processing of amyloid precursors - Avzosiaiop, Uuazpipoiyup, 0.S.| provided diagnostic protein and antibodies directed against amyloid methods for identifying schizophrenia and day proteins; with antidepressants, including related disorders, all of which are believed to be selective inhibitors of serotonin reabsorption specifically included in the scope of this wine, and with anxiolytic agents, etc. It is believed that the above-mentioned combinations are synergistically beneficial. because they provide efficacy in doses, revaga, this invention provides a method of treating migra- which constitute only a small part of the doses that nothing involves administering to a patient, who would need it to achieve that particular need, an effective amount of the compound of the effect formula with the individual components. or formula II, or its pharmaceutical composition

The term "patient" as used herein. description, means a warm-blooded animal, for example, In one of the available diagnostic sources of a mammal affected by one or more disorders, Juopapae Meadiisa! Oispopagu |239 EaV., ladies associated with the 5-HTv receptor. Understand - 1982, M.V. bappayets Sotrapu, Rpiaie!rnia, RA), that examples of animals that are included in the scope of migraine defined as a symptom complex of the redefinition of this term are guinea pigs, dogs, odic headaches, as a rule, temporary cats, rats, mice , horses, cattle, one-sided and one-sided, often with irritability, boring- sheep, pigs and people. that, vomiting, constipation or diarrhea and

The term "effective amount" of the compound is photophobic. The term "migraine", which is used in this description, means the periodic main description, means the amount, i.e. the dose, which is effective, temporary and one-sided pain associated with it in the treatment disorders that are described. irritability, nausea, vomiting, constipation or dia-

An effective amount can easily determine rheumatism, photophobia and other related symptoms. staff physician of the hospital, as a specialist in this field, it is clear to the experienced specialist that there are alternative nomenclatures, nosologies and classifications using traditional methods and by observing the results that were obtained under the fixation systems of neurological and psychiatric similar circumstances. When determining the effective- disorders, including migraine, and that these systems ny amount of dose of the compound of the formula | staff develop and change along with the development, the hospital doctor takes into account a number of factual medical science. riv, including, but not limited to: compound According to an embodiment, which is given per- formula I or formula II before administration; At the same time, this invention provides a method of treatment of different administration of other drugs, in the case of their conditions accompanied by anxiety, in the case of their use; a species of mammal; its size, age and conditions, in particular, generalized disorder, general state of health; the specific involved is accompanied by anxiety, disorder, which super-disorder; degree of involvement or severity of the disorder; is driven by panic fear and obsessive- reaction of a specific patient; method of introduction; compulsive disorder, which includes the introduction of the characteristics of the bioavailability of the administered drug to a patient who needs it, an effective amount; the selected scheme of taking the drug of the compound of formula I. bu; use of other medical therapies; and others At this time, the fourth edition of the "Advisor on relevant circumstances. statistics and diagnostics of psychiatric disorders

The effective amount of the compound of the formula ! and shen" (O5M-IMtm) (1994, Ategisap Rvuspiaiis formula Ii, as expected, varies within Avvosiaiop, Umazpipdiop, O.S. provides diagnostic methods from approximately 0.1 milligram per kilogram of body weight to identify disorders that su- per day (mg/kg per day) up to about 100 mg/kg per day. Preferred amounts may include: a disorder accompanied by panic fear with/ without agoraphobia, agoraphobia

A number of disorders to be treated according to this invention, including panic disorder, are particularly preferred. hom, specific phobia, social phobia, obsessions

obsessive-compulsive disorder, light-noise and noise-only test-related disorder. post-traumatic stress, a disorder associated with The difference in the amplitude of the startle response was analyzed by acute stress, a generalized disorder, which with the help of the statistical program Utr with one student). Group differences were considered as a known state, a disorder accompanied by fear, more common at p<0.05. caused by narcotic substances and disorder, the model of the labyrinth with radial ramifications, which is accompanied by fear of the unknown, can be used as a model of cognition. The term "anxiety", as used in the general capacity and used to evaluate this description, includes the treatment of those disorders of the compounds of this invention. are accompanied by anxiety and related disorders. Example C disorders, the specific description of which is given in OZM-IM and Labyrinth with radial branches, the term "anxiety" means similar disorders that are described in other diagnostic sources. retention used a slow reaction

For the disorders, the description of which is given, a number of preclinical animal models were described due to inconsistency with the experimental task. ); Stobli U.

Example B (Ziashbii 0.) and others, Rgos Maya! Asai 5a 91: 777-

The fear-enhanced startle paradigm 781(1994)| in a labyrinth with eight radials

Male rats of the Zrgadoe-Oauleu line have many branches. 325-400g were purchased from the Napap company. Well-trained rats had the opportunity to

Zrgadie-Oauleu, Ips. (Sitbrepapa, Indiana); creation of a food reward from four arbitrarily before the tests, selected branches of the maze were obtained (selection phase, a one-week acclimatization period. Rats of samples). After some time, a vivarium with food was placed in front of the rats in separate cages, and eight open branches appeared; the ability of rats to remember and avoid light/darkness was tested with water and Irisht with a 12-hour light cycle; lighting was turned on from 6:00 a.m. to the branches they entered earlier in the morning until 6:00 p.m. in the evening. The compound of Example 16 for obtaining fodder. Re-penetration into the composition of the suspension, which included 5905 branching, which had a bait during a series of repulsive ethanol, 0.590 carboxymethyl cellulose, 0.595 ru samples, was counted as a control error,

Twin-80 and 9995 water. The solution of 25-2-amino-2-(15,25- while penetrating to the same branch- 2-carboxycyclopropan-1-yl)-3-(xanth-9-) more than once during the series of pro- yl) of propionic acid was prepared in sterile water, retention was counted as a work error. yes Control rats received a suitable Total (control rats) number of errors, vehicle. made during the retention test,

Tests according to the fear paradigm increased with increasing delay periods. Intensified by fear, carried out for three examples, young male rats did 0.66 (0.4) consecutive days. All three days began with 5 errors in the case of a 1-minute delay, a 2 (0.5) minute adaptation period before the start of an error in the case of a 1-hour delay, and 3.95 trials. On the first day (initial level (10.2) of errors in the case of a seven-day delay (scare) after the adaptation period of the guard animal of this laboratory). is subjected to thirty tests with an audible Zrgadoe-Samieu male rat holding noise (120dB). The average startle amplitude of foxes in separate cages with a 12-hour light cycle (Mmax) is used to divide the animals into non-dark (lights were turned on at 2h in the morning). Pa-groups with similar average indicators before the bales had free access to water and their mass, after the start of conditioning. The second day was spent conditioning the animals with the help of additional feed. Each Rygipa gar Spomu, maintained at a level of 8590 per animal received an electric shock (0.5mMA, mass in the case of free food consumption. 5b0Ohmsec) after a 5-second visual demonstration. At first, the rats were taught to search for food light, which was not excluded during the application at the end of each of eight branches. After that electric shock. Ten visual tests were performed, and the rats reached the criterion for no more than two light demonstrations and one electric shock. On the third day (that is, penetration to the same day, the experimental test is carried out more than once during the series of injections with the introduction of the drug before the experiments) during three consecutive days, the test. 24 hours after conditioning, a one-minute delay was introduced. Thanks to mental intimidation. At the beginning of the training series, complete familiarization of the animals was provided by subjecting the rats to ten auditory grinding with procedural aspects of intimidation (120dB) without visual demonstration of the act before the introduction of any medicinal light. After that, a 20-fold arbitrariness of the means is carried out. After achieving stable performance on the noise-only test and 20-time repetition of the delayed task (i.e., during the continuous noise test preceded by the gaze on three consecutive days, the rats did no more than the light demonstration. With the exception of the first one error), began conducting trials, the amplitudes of the startle response for the drugs and vehicles from the trials of each type are averaged for each seven-hour delay. A bait every day of the animal. Data are presented as the difference between for each rat placed in a new set of branches; maze during the delay in thorough- animal models, there is a maze with 8 radial but cleared. branches |Alton D.S. (Oyop 0.5.) Pe

During a series of experiments with the selection of zrazgadiai apt tale av a 0! ip Bepamioga! kiv, each rat was placed on the central rpaptasiod. Rpusioiodu « VeNamiog, 40: 793-797 platforms with closed all eight branches- (1986)). by the maze. Bait food was placed in four arbitrarily chosen branches. The door of the hippocampus disrupts the performance of this task. branches with food were raised and the rat had five. Moreover, old animals, as a rule, perform this task with errors in order to receive food at the end of the skin |Porsolt R.D. one of the four branches. After the rat (Rogzoi K.O.), Roux S. (Koih 5.), Wettstein JG. received fodder, it was removed, a carrier was introduced (UUeyvivip 9.5.) Apita! todei!5 oi dDetepia. Hydroxide or compounds at various doses, and returned to OemeIuortepi Nezeagsy, 35: 214-229(1995)|. his cells After 7 hours (a series of experiments on During this test for spatial retention), the rat was again placed on the central learning and memorization, a hungry rat well platform with closed access to all eight- was placed in the center of the maze and allowed direct branching. The bait-bait was placed again to walk through the maze in search of the food it found at the four branches in which it was located at the end of each divergent branch during a series of experiments with nya. In this version of the maze, the rat learns by sampling and opening all eight exits - a variable gain strategy in which the exits visited were raised. The rat had 5 minutes to ensure that the improvement was not replaced. In this way, the best effect is given to these four pieces of fodder. A more insightful behavior associated with searching for and ny to a branch that did not have a lure or to retrieve food is a single visit to re-penetrate a branch in which each branch. The rat has already visited this version of the maze, it was counted as an error. is also included in the conditions of the processes of general

Statistical significance (p«0.05) was determined by slagging, since the maze on the first day of the four-way analysis of variance with a repeat of the experiment was completely unknown, with the subsequent determination of the criterion for this rat.

Data for comparison with the results of control. rameu? placed in separate cages of the vivarium with

To compare the experimental compounds with a regular light cycle and provided possible standards, scopolamine and tacrine were administered for at least 4 hours of acclimatization subcutaneously immediately after the sampling phase. days before the tests. The weight of each patient

The effect of scopolamine, a well-known drug that causes memory loss, was reduced and maintained during the experiment. It was checked after a three-day drop to 8,595 times the usual level. The appropriate mass, while the effect of tacrine, an inhibitor of body su, was maintained by rationing cholinesterase, which is used in the treatment of laboratory feed, based on age and daily Alzheimer's disease, was checked after the sixth determination of the body weight of rats. one hour delay. Scopolamine eliminated the rete- A series of experiments was started with placement after a three-hour delay dose-dependently of an individual rat to the central part of the la- way. Tacrine significantly improved retention after birinth, after which all the doors of the guillotine six-hour delay at a dose of 1Omg/kg, not the type were raised with free access

Zmg/kg. to all areas of the labyrinth. Feed distributor

Example O bunker was located at the end of each of the 8 divergents

Collection and accumulation of data in a maze with 8 branches, and in each feed-dispensing hopper with radial branches, there was one feed ball. Every one

A remarkable characteristic feature of the sym- day series of experiments was completed after the initial stage of Alzheimer's disease was the vitiation of all 8 feeding bunkers or mayor (AB) is a pronounced violation of the declarative when the rats were eliminated from the time schedule of memory (R.V. Parke (K. MU. Ragk5), R.F. Zeck (EE (15 min on 1 day: 5 min on 2-4 days). Number of penetrations 27ee), R.S. Wilson (K.5. UMibop) (editors), before the branches were registered. There were errors

MeshyhorvuspoYodu oi AI2Peiteg5 aiizease and oiShteg repeated penetrations to branches or non-detepiases. MM: Okhtoga Opimegzyu Rgez5 p.3-80 of branching over time conducted- (1993))|. days of a series of experiments. The animal was excluded from

In the case of progression of the disease, severe disor- research, if it did not occur, at least other areas of cognitive ability are also affected - to one branch in 1 day, 2 branches. To areas of the brain that are disturbed on day 2 and at least 4 branches on Z and 4 at the initial stage of Alzheimer's disease development. mayor, belongs to the hippocampus, which is a critical neural substrate for declarative memory. Each rat was pseudorandomly assigned to a group that received a vehicle or a drug means, and during the experimental period he

R.O.), Flood D.G. (RiooYa 0.5.), Troncoso J.K. was subjected to the same treatment. The carrier consisted of (Ttopsovo 9.0.) Oiyegepse5 ip (She rayet oi 595 solution of gum arabic in sterile water.

Pyrrhosatra! paygopa! 055 ip popta! adipd apa Injections were carried out subcutaneously for 20-

AI2peiteg5 aiveaze. Iapsei, 344: 769-772 (1994)). Before each daily series of experiments

One of the behavioral tests that often used to assess the function of the hippocampus on During the performance of this task from the collected

nya and accumulation of data, animals that were administered 12. Voscheadde, S., ei ai. (2000). You 9. Rpaptasoi. media, did not demonstrate a constant significant na- 130(7): 1606. accumulation of data from the study of the maze, compare 13. Nigvi, MU.O., ей айЙ. (1999). Hg. 9. RNAptasoi. but with the number of mistakes made in 1 day. We are watching. ((ip rzhezv)). established that the effect of compounds that facilitate 14. Nigvi, MU.O., Yei Ai. (2000). Hg. U. Rnagtasoi. 130: Accumulation of Labyrinth Study Data, often 1597. observed only from the fourth day of training. 15. Voshghzop, A., ei a. (1995). In Rpagptasoi Ehr Tpeg

Thus, the results were 274(1): 173-800. the full number of errors on the 4th day for all expe- 16. Vepieu, 9.S., ей аЙ. (1999). Vg ) РNagptasoi! rimental groups. 126(7): 1537-42.

Main reference literature: 17. Voigzop, A., ей айі. (1998). Vg U RPagptasaoi 1. Vgapspek, T.A. her a). (2000). App Aem 125(7): 1562-6.

RPpagtasoi Tohisoi! 40: 319-34. 18. Vosheadde, S., ei a. (1999). Hg. 9. Rpaptasoi. 2. Mopzta, R.9., Ug., ei aI. (1993). My Rpagtasoi 127(Birri.): 21Р. 43(3): 320-7. 19. Soidregd, T.E., ei aI. (1993). Vg In Rzuspianu

Z. Aptsai, M., ei aI. (1993). Viospet Viorpu5 Nev 162: 43-8.

Sottype 193(1): 268-76. 20. Naddet", S., eyi a). (1993). Vio! Rzuspiainu Z4(10): 4. Konep, N., eyi ai. (1996). ) Meigospet 66(1): 47- 702-12 56. 21. Gee, M.A., Yei ai. (1994). In Siip Rzuspiayu 55 5. Maga, V.R., Yei ai. (1996). In Sotr Meshgo! 370(3): zirri V : 82-7. 405-14. 22. Rygdop, 5.E., et al. (2000). Agsy Sep Rzuspianu b. Maga, V.R., et al. (1995). Meshygozsiepse 64(4): 57(3): 249-58. 1105-11. 23. Ragada, M.A., et al. (1997). U Rpaptaso!i Ehr 7. Segaga, S., et al. (1997). Vgaip Vez 746 (1-2): 207- Tneg 281(1): 582-8. 19. 24. Vodeg5, O.S., yei ai. (1999). Vg In Riagatsoi! 8. Segaga, S, yei a. ( 1996). Zuparze 23(3): 164-73. 127(rev.): 22R. 9. Sieppop, V. A., et al. (2000). U Mei Snpet 43(5): 25. YuOamwop, G .A., ei ai. (2000). Vg U RPaptasoi! 1011-8. 130(1): 23-6. 10. Vo, V.I.., ei ai. (1994). U Rnaptasoi Ehr Teg 26 . OtsakKip, K.M., et al. (1996). Meshygozsi Venpam 268(3): 1403-10. RPuzioi! 26(6): 545-51. 11. Bieidny, A.U., et al. ( 1998). Vg u РНаптасой! 27. Koespiip, E., ей аи. (1999). Mashge 399(6732): 124(3): 556-62 . 148-51.

Computer layout 0. Gaponenko Signature Circulation 26 approx.

Ministry of Education and Science of Ukraine

State Department of Intellectual Property, str. Urytskogo, 45, Kyiv, MSP, 03680, Ukraine

SE "Ukrainian Institute of Industrial Property", str. Glazunova, 1, Kyiv - 42, 01601