Sitagliptin synthesis

摘要

The present invention relates to novel processes for the preparation of enantiomerically enriched β-amino acid derivatives such as β-amino esters useful for the synthesis of enantiomerically enriched biologically active molecules such as sitagliptin. The key step involves the resolution of the racemate with mandelic acid.;

主权项

1. A process for the preparation of enantiomerically enriched sitagliptin, or a pharmaceutically acceptable salt thereof, comprising the steps:
(i) resolving a racemic β-amino acid, or a derivative thereof, with an acid resolving agent to form an enantiomerically enriched β-amino acid or a derivative thereof; (ii) reacting the enantiomerically enriched β-amino acid or derivative thereof with 3-trifluoromethyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine or a salt thereof; and (iii) isolating enantiomerically enriched sitagliptin; wherein the derivative is an alkyl, alkenyl, alkynyl, aryl or arylalkyl ester.