Process for converting heterocyclic ketones to amido-substituted heterocycles that are used as intermediates in the synthesis of cannabinoid (CB-1) antagonists

摘要

Disclosed is a safe and convenient process for preparing amido-substituted heterocyclic compounds of formula (I) from the corresponding heterocyclic ketone, wherein the process comprises the steps of: (1) reacting a compound having a formula R4d-NH-R4d' and a cyanide source with a compound of formula (la) to form an intermediate of formula (lb); (2) hydrolyzing the nitrile group of the compound of formula (Ib) with alkaline hydrogen peroxide in the presence of dimethylsulfoxide to form a compound of formula (Ic); (3) removing the amino-protecting group to form the compound of formula(I) ; and (4) optionally forming a pharmaceutically acceptable salt of said compound of formula(I), wherein the variables are as defined in the specification.