Process development of 5-fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-1H-indole dihydrochloride

被引：22

作者：

Anderson, NG

Ary, TD

Berg, JL

Bernot, PJ

Chan, YY

Chen, CK

Davies, ML

DiMarco, JD

Dennis, RD

Deshpande, RP

Do, HD

Droghini, R

Early, WA

Gougoutas, JZ

Grosso, JA

Harris, JC

Haas, OW

Jass, PA

Kim, DH

Kodersha, GA

Kotnis, AS

LaJeunesse, J

Lust, DA

Madding, GD

Modi, SP

Moniot, JL

Nguyen, A

Palaniswamy, V

Phillipson, DW

Simpson, JH

Thoraval, D

Thurston, DA

Tse, K

Polomski, RE

Wedding, DL

Winter, WJ

机构：

[1] Bristol Myers Squibb, Pharmaceut Res Inst, Dept Chem Proc Dev, New Brunswick, NJ 08903 USA

[2] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Solid State Chem, Princeton, NJ 08543 USA

[3] Bristol Myers Squibb Co, Chem Proc Res, Quebec City, PQ J5R 1J1, Canada

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 1997年 / 1卷 / 04期

关键词：

D O I：

10.1021/op970213h

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

5-fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]-propyl]-1H-indole dihydrochloride (1) facilitates 5-HT neurotransmission and was an antidepressant drug candidate. The development of a safe, rugged process for the large-scale, chromatography-free preparation of this compound is described, The main areas of optimization included a Fischer indole synthesis, preparation and chlorination of a monohydroxypyrimidine, and coupling of the resultant fragments to prepare the drug substance.

引用

页码：300 / 310

页数：11

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[1] A VERSATILE ROUTE TO POTENTIAL DIHYDROFOLATE-REDUCTASE INHIBITORS VIA THE HITHERTO UNKNOWN 6-BENZYL-2-(O-METHYL)URACILS - SYNTHESIS OF ISOTRIMETHOPRIM [J].