Method for the conversion of nitriles (cyano groups) to amidines

摘要

A process for the conversion of nitriles to amidines in the preparation of compounds which are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex. The process forms compounds of formula (I) by contacting a compound of formula (IV) with hydrogen under suitable pressure in the presence of a hydrogenation catalyst. Specific compounds that can be formed are shown in formula (III-i), (IV-i) and (V-i). In formula (I) R1 is H or NHR1a; R2 is H or C1-C10alkyl; R3 and R4 are independently selected from H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, and aryl substituted with 0-2 R3a; n is 0-4; and a is a single or double bond, with the proviso that if a is a double bond, it is not simultaneously substituted with R3 and R4. The compounds are potent thrombolytics and useful for the inhibition of platelet aggregation in the treatment of thromboembolic disorders.