Synthesis of Alkaloid Sinomenine Derivatives Containing a Pyrimidine Substituent in Ring A

Chemistry of Heterocyclic Compounds
2021.0

Abstract

The alkaloid 4-O-methylsinomenine was modified by introducing pyrimidine substituents at the C-1 position of the backbone. Two methods were used to synthesize these hybrid molecules. The first method involves the preparation of 1-ethynyl-4-O-methylsinomenine and a sequence of cross-coupling reactions with benzoic acid chlorides and cyclocondensation with amidines. The second method is based on palladium-catalyzed carbonylation-cross coupling of 1-iodo-4-O-methylsinomenine with phenylacetylene in the presence of Mo(CO)(6) as a source of CO in MeCN and subsequent cyclocondensation of alkynyl ketone with amidines. The carbonylation-crosscoupling reaction proceeded selectively in the presence of the PdCl2/(1-Ad)2PBn catalytic system.

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