The Journal of organic chemistry

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

DCM Chan, A Rosowsky

Index: Chan, David C. M.; Rosowsky, Andre Journal of Organic Chemistry, 2005 , vol. 70, # 4 p. 1364 - 1368

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Citation Number: 9

Abstract

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 ...