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AU700600B2 - (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine and its preparation - Google Patents

(S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine and its preparation Download PDF

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AU700600B2
AU700600B2 AU40994/97A AU4099497A AU700600B2 AU 700600 B2 AU700600 B2 AU 700600B2 AU 40994/97 A AU40994/97 A AU 40994/97A AU 4099497 A AU4099497 A AU 4099497A AU 700600 B2 AU700600 B2 AU 700600B2
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formula
preparation
difluoro
mixture
tetrahydronaphthalen
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AU4099497A (en
Inventor
Rekha P. Bansal
Owen W Gooding
Gregory R. Martinez
Alexander V. Muehldorf
Counde O'yang
David B. Repke
Philip J. Teitelbaum
Keith A.M. Walker
Roger L. Whiting
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Syntex USA LLC
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Priority claimed from US08/233,655 external-priority patent/US5438150A/en
Priority claimed from US08/403,209 external-priority patent/US5538988A/en
Priority claimed from AU22947/95A external-priority patent/AU687192B2/en
Application filed by Syntex USA LLC filed Critical Syntex USA LLC
Priority to AU40994/97A priority Critical patent/AU700600B2/en
Publication of AU4099497A publication Critical patent/AU4099497A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/32—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/32—One oxygen atom
    • C07D233/36—One oxygen atom with hydrocarbon radicals, substituted by nitrogen atoms, attached to ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/42—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/84—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

(S)-5,7-DIFLUORO-1 ,2,3,4-TETRAHYDRONAPHTHALEN- 2-YLAMINE AND ITS PREPARATION This invention relates to a novel compound of the formula namely, (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine and processes for its preparation.
'The compound is useful for the preparation of benzocycloalkylazolethione dopamine 3-hydroxylase inhibitors.
DETAILED DESCRIPTION OF THE INVENTION Definitions: As used therein: "Alkyl" means a straight or branched saturated hydrocarbon radical having from one to the number of carbon atoms designated (C 1 -4)alkyl includes the radicals methyl, ethyl, prop-l-yl, prop-2-yl, but-l-yl, but-2-yl, 2-methylpropyl and 1,1-dimethylethyl).
"Alcyloxy" means the radical -OR wherein R is alkyl having from one to the number of carbon atoms designated (C 1 -4)alkyloxy includes the radicals methoxy, ethoxy, prop-l-yloxy, prop-2-yloxy, but-l-yloxy, but-2-yloxy, 2methylprop- 1 -yloxy and 2-methylprop-2-yloxy).
"Halo" means fluoro, chloro or bromo.
The compound of Formula may be prepared following Reaction Scheme I.
Scheme I (R t^ (2) and preferably at approximately 50'C, and requires 12 to 18 hours. Reduction of the
(I)
alwherein R is independently halo, hydroxy, or (ec.
4 alkyloxy, and t is 0, 1, 2 or 3.
The compound of Formula can be prepared by reacting a compound of f Formula in which L is a leaving group with an appropriate azide salt sodium For:': azide, lithium azide, etc.) in a suitable solvent dimethyl sulfoxide (DMSO), N,Ndimethylformamide (DMF), etc.) to give an azide of Formula and then reducing.
S The reaction with the azide salt is carried out at 50 to 90C, typically at 50 to and preferably at approximately 50°C, and requires 12 to 18 hours. Reduction of the compound of Formula can be effected by catalytic hydrogenation H 2 palladium on carbon; or H2, platinum on carbon, etc.) i a suitable solvent ethyl acetate, ethanol, etc.). Further details of the reaction steps set forth in this paragraph are provided in Example 3.
The compound of Formula is prepared by treating a compound of Formula with an appropriate agent to create leaving group L. For example, the compound of Formula in which L is mesyloxy can be prepared by reacting a compound of Formula with mesyloxy chloride in a suitable solvent diethyl ether, tetrahydrofuran (THF), methylene chloride, any appropriate mixture of suitable solvents, etc.). The reaction is carried out in the presence oftriethylamine at -20 to typically at -15 to -5 0 C and preferably at approximately -10 0 C, and requires 3 to hours (for further details see Example 2).
The compound of the present invention is useful for the preparation of benzocycloalkylazolethione dopamine P-hydroxylase inhibitors. For example, it can be used for preparing 1-(5,7-difluoro- 1,2,3,4-tetrahydronaphthalen-2-yl)- 1,3dihydroimidazole-2-thione as shown in the following Reaction Scheme II.
Scheme II F C R 2 CHCHO FR2
(I)
F
F
S(4)
F
F
in which R 2 is alkyl, preferably methyl or ethyl.
1-(5,7-Difluoro-1,2,3,4-tetrhydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione can be prepared by reacting a compound of Formula with thiocyanic acid in a suitable solvent, typically an alcohol methanol, ethanol, any appropriate mixture of suitable alcohols, etc.) and preferably methanol. The reaction is carried out with potassium thiocyanate in the presence of aqueous acid dilute hydrochloric acid, phosphoric acid or sulfuric acid, etc.) at 50 to 100 0 C, typically at 70 to 90 0 C and preferably at approximately 80 0 C, and requires 1 to 5 hours.
The compound of Formula can be prepared by reductive amination of a dialkyloxyacetaldehyde, preferably dimethoxyacetaldehyde or diethoxyacetaldehyde, with a compound of Formula The reductive amination is carried out in the presence of a chemical reducing agent sodium cyanoborohydride, sodium borohydride, etc.) or catalytic hydrogenation H 2 palladium on carbon, H 2 Raney® nickel, etc.) in a suitable solvent methanol, ethanol, ethyl acetate, any appropriate mixture of suitable solvents, etc.). Optionally water is removed from the reaction mixture by standard methods with drying agents such as molecular sieves or by azeotroping). Further details of the reaction steps set forth in this and the preceding paragraph are provided in Example 4.
Other compounds which maybe prepared from the compound of the invention are disclosed in PCT/US95/04783 (WO 95/29165). The present application is a division of Australian Patent Application No. 22947/95 which is derived from PCT/US95/04783.
Example 1 (R)-5,7-Difluoro-1,2,3,4-tetrahydro-2-hydroxynaphthalene The following is the preparation of the compound of Formula A mixture 3,5-difluorophenylacetic acid (100 g, 0.58 mmol) and thionyl chloride (13.7 M, 100 mL, 1.37 mol) was stirred for 15 hours at room temperature.
Evaporation gave 3,5-difluorophenylacetyl chloride as an oily residue. A stirred suspension of aluminum chloride (154 g, 1.16 mmol) in 1 L of methylene chloride was cooled to -65 0 C and the acid chloride in 200 mL of methylene chloride was added dropwise such that the reaction temperature did not exceed -60 0 C. Ethylene gas was bubbled through the suspension at a rapid rate for 10 minutes at -65 0 C. The reaction mixture was allowed to warm to 0°C over 2 hours, then cooled to -10 0 C and treated with 500 mL of water. The organic layer was separated, washed with 100 mL of aqueous sodium chloride, and then dried over magnesium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure. Distillation of the residue in vacuo (bp 90-110 0 C [1.0 to 0.7 mm]) gave a clear distillate. Redistillation (bp 100-105°C [0.3 mm]) gave 5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-one (73.56 g, 0.342 mol) as a white solid, m.p. 46 0
C.
A solution of(1R,2S)-N-methylephedrine (81.3 g, 0.454 mol) in 1.2 L of anhydrous diethyl ether was added to lithium aluminum hydride (1.0 M in diethyl ether, 416 mL, 0.416 mol) over 45 minutes. The mixture was heated under reflux for 1 hour and then allowed to cool to room temperature. A solution of 2-ethylaminopyridine (110.7 g, 0.907 mol) in 100 mL of anhydrous diethyl ether was added over 45 minutes. The mixture was heated under reflux for 1 hour and then cooled to -65 0 C. A solution of 5,7-difluoro-1,2,3,4-tetrahydro-naphthalen-2-one (23.0 g, 0.107 mol) in 100 mL of diethyl ether was added dropwise such that the reaction temperature did not exceed -60 0 C. The mixture was stirred at -65 0 C to -68 0 C for 3 hours and then 100 mL of methanol was added such that the reaction temperature did not exceed -60 0 C. The mixture was stirred at -65 0 C to -68 0 C for 10 minutes, then S. allowed to warm to -20 0 C, and 3.0 L of 3N hydrochloric acid was added such that the reaction temperature did not exceed 35 0 C. The diethyl ether layer was separated, washed with 200 mL of saturated sodium chloride, and dried over magnesium sulfate.
The mixture was filtered and the filtrate concentrated under reduced pressure.
Crystallization from 20 mL of diethyl ether and 200 mL of hexane and drying in vacuo Sgave (R)-5,7-difluoro-1,2,3,4-tetrahydro-2-hydroxynaphthalene (10.87 g, 0.05 mol), m.p. 85 0 C. [a]D 25 +36.030 (c 1.59, CHC13).
Example 2 (R)-5,7-Difluoro-1,2,3,4-tetrahydronaphthalen-2-yl methanesulfonate The following is the preparation of the compound of Formula in which L is mesyloxy.
A mixture of (R)-5,7-difluoro-1,2,3,4-tetrahydro-2-hydroxynaphthalene (59.0 g, 0.32 mol), prepared as in Example 1, and triethylamine (13.8 M, 74.2 mL, 0.53 mol) in 1.78 L of diethyl ether was cooled using a methanol/ice bath. Methanesulfonyl chloride (12.9 M, 37.2 mL, 0.48 mol) was added under argon over 5-10 minutes and the mixture was stirred at room temperature for 18 hours. The mixture was partitioned between water and ether and the ether layer was separated and the aqueous layer was extracted with ether. The combined ether layers were washed once with each of IN hydrochloric acid, saturated sodium bicarbonate solution and brine and then dried over magnesium sulfate. Evaporation gave crude (R)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl methanesulfonate as an off-white solid (87.12 m.p. 79-80 0
C.
[a]D 25 16.770 (c 2.0, CHC1 3 Example 3 (S)-5,7-Difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride The following is the preparation of the compound of Formula r" A mixture of (R)-5,7-difluoro-l,2,3,4-tetrahydronaphthalen-2-yl methanesulfonate (54.0 prepared as in Example 2, and lithium azide (15.8 g, 0.322 mol) in 400 mL of DMF was stirred under argon at 50 0 C for 16 hours. The reaction S was quenched with 200 mL of water and the mixture extracted with 1 L of pentane.
The extract was washed with 50 mL of water and dried over magnesium sulfate.
Evaporation under reduced pressure at 35 0 C gave crude (S)-2-azido-5,7-difluoro- 1,2,3,4-tetrahydronaphthalene as a yellow oil residue (59.8 g).
The azide residue was dissolved in 1.2 L of ethyl acetate and hydrogenated over palladium on carbon (6 g) for 6 hours, recharging with hydrogen every hour to remove evolved nitrogen gas. The mixture was then filtered through Celite and stirred with ethereal hydrogen chloride (1N, 250 mL) giving a crystalline material. The material was isolated by filtering over 4 hours and the filter residue was washed with ethyl acetate. Removing the remaining solvents in vacuo gave (S)-5,7-difluoro- 1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride (48.2 g, 0.22 mol) as a white solid, m.p. 280 0 C. [a]D 25 -60.15 (c 2.7, Example 4 5,7-Difluoro-1-(1,2,3,4-tetrahydronaphthalen-2-yl)- 1,3-dihydroimidazole-2-thione A mixture of (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine (2.05 g, 11.2 mmol), prepared as in Example 3, and dimethoxyacetaldehyde (1.73 g, 13.1 mmol) in 50 mL of ethanol was hydrogenated over 10% palladium on carbon (500 mg) for 18 hours. The mixture was filtered and concentrated by evaporation. The residue was combined with potassium thiocyanate (1.57 g, 16.2 mmol) in 30 mL of 1 N hydrochloric acid and 20 mL of ethanol and the mixture was heated at 70-80 0 C for 18 hours. The mixture was cooled in an ice bath giving a crystalline material which was isolated by filtration. Recrystallization from ethyl acetate/hexane gave 1-(5,7difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione (1.27 g, 4.76 mmol), m.p. 250-251 0
C.
*.i THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: 1. A compound of the formula: namely (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine.
2. A process for the preparation of a S-enantiomer of Formula
(I)
in which: t is O, 1,2 or 3; and
R
1 is independently halo, hydroxy or (C 1 alkyloxy; which process comprises: stereoselectively reducing, in the presence of 2S-dimethylamino-1Rphenylpropanol and 2-ethylaminopyridine, a compound of the following formula: o to give an (R)-enantiomer of Formula (1) treating the (R)-enantiomer of Formula with mesyl chloride and then o reacting the resulting compound with an azide salt to give a (S)-enantiomer of Formula (3) and 8 PVr o,

Claims (3)

  1. 3. The process of claim 2 in which the reducing agent used in Step is lithium aluminum hydride.
  2. 4. The process of claim 2 in which t is 2 and R' is fluoro at the 5- and 7- position. A process for the preparation of a S-enantiomer of Formula in which: (I) t is 0, 1, 2 or 3; and R 1 is independently halo, hydroxy or (C 1 4 alkyloxy; which process comprises: reacting the (S)-enantiomer of Formula (3) (3) with a reducing agent.
  3. 6. The process of claim 5 wherein the reducing agent is palladium on carbon. DATED this 9th day of November, 1998. SYNTEX (USA) INC. WATERMARK PATENT TRADEMARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA DOC 23 AU4099497.WPC IAS/KMH/ML 9 p 1 H 9 ~6-v i- rv a": q 0 1 ABSTRACT A process for the preparation of a S-enantiomer of Formula (I) in which: t is 0, 1, 2 or 3; and R1 is independently halo, hydroxy or (i-4)alkyloxy. The compounds of this process are useful for the preparation of di benzocycloalkylaxolethione dopamine 13-hydroxylase inhibitors.
AU40994/97A 1994-04-26 1997-10-14 (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine and its preparation Ceased AU700600B2 (en)

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AU40994/97A AU700600B2 (en) 1994-04-26 1997-10-14 (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine and its preparation

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US23383594A 1994-04-26 1994-04-26
US233835 1994-04-26
US08/233,655 US5438150A (en) 1994-04-26 1994-04-26 Process for making 1-benzocycloalkyl-1,3-dihydroimidazole-2-thione derivatives
US233655 1994-04-26
US08/403,209 US5538988A (en) 1994-04-26 1995-03-17 Benzocycloalkylazolethione derivatives
US403209 1995-03-17
AU22947/95A AU687192B2 (en) 1994-04-26 1995-04-25 Benzocycloalkylazolethione derivatives
AU40994/97A AU700600B2 (en) 1994-04-26 1997-10-14 (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine and its preparation

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2290790A (en) * 1994-06-30 1996-01-10 Merck & Co Inc Asymmetric synthesis of 6-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2290790A (en) * 1994-06-30 1996-01-10 Merck & Co Inc Asymmetric synthesis of 6-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes

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