Back to results
US 6,646,130 B2Granted
Process to chiral integrin antagonist beta-amino acid intermediate
AssigneeMerck & Co., Inc.
InventorsNelo R. Rivera, Christopher J. Welch, Yi Xiao, Nobuyoshi Yasuda
Life of this patent
Estimating the term…
Abstract
The invention discloses a novel process for the preparation of enantiomerically enriched mixtures of compounds of structural formula I which are useful intermediates in the synthesis of αvβ3 integrin receptor antagonists
Claims8
A process for the preparation of an enantiomerically enriched mixture of a major and minor diatereoisomer compounds of structural formula I:
- wherein
- R1 is C1-4 alkyl;
- which comprises forming a salt of a compound of formula I with an (R)- or (S)-amino acid of structural formula II:
- wherein R2 is selected from the group consisting of phenyl, benzyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-imidazolylmethyl, and 4-hydroxybenzyl;
- and and R3 is tert-butyl, benzyl or 9-fluorenylmethyl.
2 more elements
A process for the preparation of an enantiomerically enriched mixture of a major and minor diastereoisomer compounds of structural formula I:
- wherein
- R1 is C1-4 alkyl;
- comprising the steps of:
- (a) mixing a compound of structural formula I with an (R)- or (S)-amino acid of structural formula II:
- wherein R2 is selected from the group consisting of phenyl, benzyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-imidazolylmethyl, and 4-hydroxybenzyl;
- and and R3 is tert-butyl, benzyl or 9-fluorenylmethyl;
- in an alcohol solvent system to form a mixture;
- (b) heating the mixture from about 10° C. to about 100° C.;
- (c) allowing the mixture to cool so that a crystalline (R)- or (S)-amino acid salt of said compound of formula I is formed;
- (d) filtering the mixture to separate the crystalline salt from the supernatant;
- and
- (e) liberating said compound of formula I from the crystalline salt by treating the salt with a base.
9 more elements
Dependencies are inferred from the claim text.