Hydantoin intermediates for the synthesis of omapatrilat and methods for producing and using the same
AssigneeDixie Chemical Company
InventorsJoseph C. Rongione, Robert E. Brown, Dwight E. Raff
Life of this patent
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Abstract
Omapatrilat (I) is a potent inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo and is currently undergoing large scale clinical trials as an anti-hypertensive. Omapatrilat may be synthesized using the S-stereoisomer of compound (V). Compound (V) may be prepared from a novel hydantoin (III). The hydantoin may be prepared from a monoacetal (XI) or via a dinitrile (V).
Claims38
A compound of the formula:
- wherein R1 is —H, a C1-C5 alkyl group or benzyl, and R2 is represented by the formula:
- wherein R3, R4, R5, and R6 are independently selected from the group consisting of —H or a C1-C5 alkyl group and R7 and R8 are independently selected from the group consisting of a C1-C5 alkyl group.
A process of preparing a compound of the formula:
- wherein R1 is —H, a C1-C5 alkyl group, or benzyl and R2 is represented by the formula:
- wherein R3, R4, R5, and R6 are independently selected from the group consisting of —H or a C1-C5 alkyl group and R7 and R8 are independently selected from the group consisting of a C1-C5 alkyl group, said process comprising mixing monoacetal having the formula:
- with ammonium carbonate and either an alkali cyanide or a cyanohydrin for a time and at a temperature sufficient to render a compound of formula (III).
A process of preparing a hydantoin of the formula:
- wherein R1 is —H, a C1-C5 alkyl group, or benzyl and R2 is represented by the formula:
- wherein R3, R4, R5, and R6 are independently selected from the group consisting of —H or a C1-C5 alkyl group and R7 and R8 are independently selected from the group consisting of a C1-C5 alkyl group, said process comprising mixing a dinitrile having the formula:
- with carbon dioxide or a carbon dioxide generating compound in an aqueous medium for a time and at a temperature sufficient to generate the compound of formula (III).
A process of preparing a compound of the formula:
- wherein R2 is either
- wherein R3, R4, R5, and R6 are independently selected from the group consisting of —H or a C1-C5 alkyl group and R7 and R8 are independently selected from the group consisting of a C1-C5 alkyl group, said process comprising mixing a hydantoin having the formula:
- wherein R1 is —H, a C1-C5 alkyl group or benzyl under alkaline conditions for a time and at a temperature sufficient to generate the compound of formula (V).
Dependencies are inferred from the claim text.