Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1997-04-17
1999-11-02
Shah, Mukund J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
C07D22316
Patent
active
059773553
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel processes for the preparation of benzo[b]azepine-2-one CCK antagonists of formula VII, described below, and to novel intermediates used in the processes.
PCT Patent Publication WO 93/15059, published Aug. 5, 1993, refers to the CCK receptor antagonists of formula VII and processes for their preparation.
PCT Patent Publication WO 94/07483, published Apr. 14, 1994, refers to benzo-fused lactam derivatives that are stated to be growth hormone release agents and are prepared in a process analogous to that described in PCT Patent Publication WO 93/15059.
PCT Patent Publication WO 94/07483, published Apr. 14, 1994, generically refers to benzo[b]azepine-2-ones, but does not refer to any specific stereoisomers of these intermediates.
SUMMARY OF THE INVENTION
The present invention relates to the intermediate (+)-cis-(3R)-amino-8-methyl-(5R)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one.
The present invention also relates to a process for preparing the diasteriomeric salt (+)-cis-(3R)-amino-8-methyl-(5R)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one.cndot.(D)-(+)-dibenzoyltartarate or (-)-cis-(3S)-amino-8-methyl-(5S)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one.cndot.(L)-(-)-dibenzoyltartarate, comprising reacting (D)-(+)-dibenzoyltartaric acid with either racemic or optically enriched cis-3-amino-8-methyl-5-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine-2-one, or reacting (L)-(-)-dibenzoyltartaric acid with either racemic or enantiomerically enriched cis-3-amino-8-methyl-5-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine-2-one in an organic solvent, preferably acetone or ethyl acetate.
Preferably, the diastereomeric salt (+)-cis-(3R)-amino-8-methyl-(5R)-phenyl-1,3,4,5-tetrahydro-benzo [b]azepine-2-one.cndot.(D)-(+)-dibenzoyltartarate or (-)-cis-(3S)-amino-8-methyl-(5S)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one.cndot.(L)-(-)-dibenzoyltartarate is neutralized to form, respectively, (+)-cis-(3R)-amino-8-methyl-(5R)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one or (-)-cis-(3S)-amino-8-methyl-(5S)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one.
Preferably, the diastereomeric salt (+)-cis-(3R)-amino-8-methyl-(5R)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one.cndot.(D)-(+)-dibenzoyltartarate or (-)-cis-(3S)-amino-8-methyl-(5S)-phenyl-1,3,4,5-tetrahydro-benzo[b]azepine -2-one.cndot.(L)-(-)-dibenzoyltartarate is neutralized with a base, preferably sodium hydroxide.
The present invention also relates to a process for the preparation of racemic compounds of formula ##STR2## wherein X and NH.sub.2 are in the cis configuration in at least 90% of the molecules of formula Ia; (C.sub.1 -C.sub.6)alkyl optionally substituted with from one to three fluorine atoms and (C.sub.1 -C.sub.6)alkoxy optionally substituted with from one to three fluorine atoms; and -C.sub.8)straight or branched alkyl and (C.sub.5 -C.sub.8)cycloalkyl, wherein said phenyl may optionally be substituted with one or two substituents independently selected from the group consisting of halo, (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6)alkoxy, nitro, amino and trifluoromethyl, and wherein said (C.sub.5 -C.sub.8)cycloalkyl may optionally be substituted with one or two substituents independently selected from (C.sub.1 -C.sub.6)alkyl; comprising reducing a compound of the formula ##STR3## wherein Y.sup.1, Y.sup.2 and X are defined as above, with Raney-nickel and a hydrogen source.
The present invention also relates to a process for the preparation of a compound of the formula ##STR4## wherein X, Y.sup.1 and Y.sup.2 are defined as above, comprising a) reacting a compound of the formula ##STR5## wherein X, Y.sup.1 and Y.sup.2 are defined as above, with a compound of formula ##STR6## wherein L is hydroxy, chloro, --O.sub.2 COR, and R is (C.sub.1 -C.sub.6)alkyl, or L is a group of the formula ##STR7## to form a compound of the formula ##STR8## wherein X, Y.sup.1 and Y.sup.2 are defined as above, in an organic solvent, preferably dichloromethane; agent, preferably dicyclohexylcarbodiimide, 1-(3dimethylaminopropyl)-3-ethy
REFERENCES:
patent: 5696111 (1997-12-01), Baldwin et al.
Schoen et al. (J. Med. Chem. 1994, 37, 897-906.
Methoden Der Organischen Chemie, 1955, pp. 513-519.
Dryer Mark
Ginsburg Paul H.
Kifle Bruck
Pfizer Inc.
Richardson Peter C.
LandOfFree
Processes and intermediates for preparing 3-amino-benzo(b)azepin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Processes and intermediates for preparing 3-amino-benzo(b)azepin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Processes and intermediates for preparing 3-amino-benzo(b)azepin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2137266