A highly convergent synthesis of a fibrinogen receptor antagonist

A practical multikilogram synthesis of 2(S)-[(p-toluenesulfonyl)amino]-3-[[ [5,6,7,8-tetrahydro-4-oxo-5-[2-(piperidin-4-yl)ethyl]-4H-pyrazolo[1,5-a][1, 4]diazepin-2-yl]carbonyl]amino]propionic acid pentahydrate (1), an oral fib rinogen receptor antagonist, is described. The nine-step convergent process , which afforded 1 in 37% overall yield, included pyrazole 5a and N-tosylam inoalanine 16 as key fragments. Pyrazole 5a was obtained from pyrazole-3,5- dicarboxylic acid by esterification with MeOH, alkylation/cyclization with 3-bromopropylamine, and Michael addition with 4-vinylpyridine. N-Tosylamino alanine 16 was prepared by tosylation of asparagine, Hofmann reaction, and benzyl esterification. Saponification of pyrazole 5a, coupling of the acid with N-tosylaminoalanine 16, and Pd-catalyzed hydrogenolysis and pyridine r eduction completed the synthesis.