Efficient synthesis of a trisubstituted 1, 6-naphthyridone from acetonedicarboxylate and regioselective suzuki arylation

…, JC McWilliams, RA Reamer, PG Dormer…

Index: Chung, John Y. L.; Cai, Chaoxian; McWilliams, J. Christopher; Reamer, Robert A.; Dormer, Peter G.; Cvetovich, Raymond J. Journal of Organic Chemistry, 2005 , vol. 70, # 25 p. 10342 - 10347

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Citation Number: 9

Abstract

An efficient five-step synthesis of 1, 6-naphthyridone 3b, a p38 mitogen-activated protein (MAP) kinase inhibitor intermediate, in 32% overall yield starting from acetonedicarboxylate (ADC) is described. The synthesis began with a selective monoamidation of ADC dimethyl ester enolate 9. A novel concomitant enamine formation and an imide cyclization afforded the nitrogen differentially protected enamide imide 12. Treatment of 12 with KO t Bu and 3- ...