Synthesis of the lipophilic antifolate piritrexim via a palladium(0)-catalyzed cross-coupling reaction

被引：14

作者：

Chan, DCM

Rosowsky, A ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2005年 / 70卷 / 04期

关键词：

D O I：

10.1021/jo040268z

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A regiospecific and convergent route the lipophilic antifolate piritrexim (PTX) is described in which a key step is a Pd(0)-catalyzed cross-coupling reaction between 2-amino-3-cyano-4-methyl-5-bromopyridine and 2,5-dimethoxybenzylzinc chloride to form 2-amino-4-methyl-5-(2,5-dimethoxybenzyl)nicotinonitrile. To complete the synthesis, the amino group is replaced by a more reactive bromine atom via nonaqueous diazotization with tert-butyl nitrite, and the resultant bromo nitrile is cyclized with guanidine.

引用

页码：1364 / 1368

页数：5

共 45 条

[1]

ADAMSON PC, 1992, CANCER RES, V52, P521

[2]

ASSARAF YG, 1993, J BIOL CHEM, V268, P4556

[3] A PHASE-II STUDY OF ORAL PIRITREXIM IN RECURRENT HIGH-GRADE (III, IV) GLIOMA [J].