Patent ID: 9074233
Filing Date: 2015-07-07
Classification: C07B,C07D,C12P

Abstract:
1. A process for the preparation of a compound of Formula I-A comprising the step of reacting a compound of Formula II-A: or a salt thereof, with a hydride source or a deuteride source in the presence of a ketoreductase or carbonyl reductase to form a compound of Formula I-A with an enantiomeric excess of at least 80%, wherein: the ketoreductase or carbonyl reductase is selected from CRED A131, CRED A801, CRED A901, CRED A251, CRED A271, KRED-119, KRED-137, KRED-148, KRED-169, KRED-174, KRED-NAD 101, KRED-NAD 102, KRED-NAD112, KRED-NAD 126, ES-KRED-121, ES-KRED-128, ES-KRED-130, ES-KRED-142, ES-KRED-175, ES-KRED-169, and ES-KRED-171; each of R each R each Z each Z each Z each Z Y is H when a compound of Formula II-A is reacted with a hydride source; or Y is D when a compound of Formula II-A is reacted with a deuteride source, wherein either R 7 is —CD 3 or at least one of Z 2 , Z 3 , Z 4 and Z 5 is deuterium, and wherein the amount of deuterium incorporation at each deuterium in R 7 , Z 2 , Z 3 , Z 4 and Z 5 in the compound of Formula I-A is substantially equal to the amount of deuterium incorporation at corresponding deuterium atoms in R 7 , Z 2 , Z 3 , Z 4 and Z 5 in the compound of Formula II-A.