Journal of Organic Chemistry 2006-05-12

A practical synthesis of 2-((1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic acid.

Xin Wang, Ben Zhi, Jean Baum, Ying Chen, Richard Crockett, Liang Huang, Shawn Eisenberg, John Ng, Robert Larsen, Mike Martinelli, Paul Reider

Index: J. Org. Chem. 71 , 4021-4023, (2006)

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Abstract

A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.