Synthesis of deuterium labeled 2,4-dipyrrolidinylpyrimidine as a chemical probe for P450 mediated oxidation of tirilazad mesylate

Abstract

Selective deuterium labelled pyrrolidinylpyrimidine analogs were synthesized to provide a probe for the metabolite identification of Tirilazad. Synthesis of 2-[D8]-pyrrolidinyl-4-pyrrolidinylpyrimidine (1) and 4-[D8]-pyrrolidinyl-2-pyrrolidinylpyrimidine (2) was accomplished by reaction of pyrrolidine (3) with 2,4-dichloropyrimidine (4), separation of the two reaction products (5 and 6) and reaction of these products with [D8]pyrrolidine (7). [D16]- 2,4-dipyrrolidinylpyrimidine (8) was prepared by reaction of [D8]pyrrolidine (7) with 2,4-dichloropyrimidine (4). © 1998 John Wiley & Sons, Ltd.