A scaleable synthesis of fiduxosin

被引：54

作者：

Haight, AR ^{[1
]}

Bailey, AE ^{[1
]}

Baker, WS ^{[1
]}

Cain, MH ^{[1
]}

Copp, RR ^{[1
]}

DeMattei, JA ^{[1
]}

Ford, KL ^{[1
]}

Henry, RF ^{[1
]}

Hsu, MC ^{[1
]}

Keyes, RF ^{[1
]}

King, SA ^{[1
]}

McLaughlin, MA ^{[1
]}

Melcher, LM ^{[1
]}

Nadler, WR ^{[1
]}

Oliver, PA ^{[1
]}

Parekh, SI ^{[1
]}

Patel, HH ^{[1
]}

Seif, LS ^{[1
]}

Staeger, MA ^{[1
]}

Wayne, GS ^{[1
]}

Wittenberger, SJ ^{[1
]}

Zhang, WJ ^{[1
]}

机构：

[1] Abbott Labs, GPRD Proc Res & Dev, N Chicago, IL 60064 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2004年 / 8卷 / 06期

关键词：

D O I：

10.1021/op049889k

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Fiduxosin (1) has been under development at Abbott Laboratories for the treatment of benign prostatic hyperplasia. A convergent strategy required methodologies for preparation of an enantiomerically pure 3,4-cis-disubstituted pyrrolidine and a 2,3,5-trisubstituted thienopyrazine in a regiospecific manner. A [3+2] cycloaddition of an enantiopure azomethine ylide followed by a diastereoselective crystallization was employed to prepare the benzopyranopyrrolidine in high diastereomeric and enantiomeric purity. Conditions for reduction of an O-aryl lactone susceptible to epimerization were developed, and cyclization of the alcohol/phenol to the ether was accomplished in high yield. The thienopyrazine was prepared by condensation of methyl thioglycolate and a regiospecifically prepared 2-bromo-3-cyano-5-phenylpyrazine. Conditions for effective halogen substitutive deamination to prepare regiospecific trisubstituted pyrazines will be described.

引用

页码：897 / 902

页数：6

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