| 主权项 |
1. A process for the preparation of a compound of Formula I-Acomprising 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 R4, R6 and R7 is independently selected from —CH3 and —CD3; each R5 is hydrogen or deuterium or a combination thereof; each Z2 is the same and is hydrogen or deuterium; each Z3 is the same and is hydrogen or deuterium; each Z4 is the same and is hydrogen or deuterium; each Z5 is the same and is hydrogen or deuterium; and 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 R7 is —CD3 or at least one of Z2, Z3, Z4 and Z5 is deuterium, and wherein the amount of deuterium incorporation at each deuterium in R7, Z2, Z3, Z4 and Z5 in the compound of Formula I-A is substantially equal to the amount of deuterium incorporation at corresponding deuterium atoms in R7, Z2, Z3, Z4 and Z5 in the compound of Formula II-A. |
