TY - JOUR
T1 - A highly convergent synthesis of a fibrinogen receptor antagonist
AU - Hartner, Frederick W.
AU - Cvetovich, Raymond J.
AU - Tsay, Fuh Rong
AU - Amato, Joseph S.
AU - Pipik, Brenda
AU - Grabowski, Edward J.J.
AU - Reider, Paul J.
PY - 1999/10/15
Y1 - 1999/10/15
N2 - 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- α][1,4]diazepin-2-yl]carbonyl]amino]propionic acid pentahydrate (1), an oral fibrinogen receptor antagonist, is described. The nine-step convergent process, which afforded 1 in 37% overall yield, included pyrazole 5a and N- tosylaminoalanine 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-Tosylaminoalanine 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 reduction completed the synthesis.
AB - 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- α][1,4]diazepin-2-yl]carbonyl]amino]propionic acid pentahydrate (1), an oral fibrinogen receptor antagonist, is described. The nine-step convergent process, which afforded 1 in 37% overall yield, included pyrazole 5a and N- tosylaminoalanine 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-Tosylaminoalanine 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 reduction completed the synthesis.
UR - http://www.scopus.com/inward/record.url?scp=0032724026&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032724026&partnerID=8YFLogxK
U2 - 10.1021/jo990644t
DO - 10.1021/jo990644t
M3 - Article
AN - SCOPUS:0032724026
SN - 0022-3263
VL - 64
SP - 7751
EP - 7755
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 21
ER -