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

J Org Chem. 2006 May 12;71(10):4021-3. doi: 10.1021/jo0602571.

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.

MeSH terms

  • Molecular Structure
  • Niacin / analogs & derivatives*
  • Niacin / chemical synthesis*
  • Pyridines / chemical synthesis*
  • Pyrroles / chemical synthesis*

Substances

  • 2-((1H-pyrrolo(2,3-b)pyridine-4-yl)methylamino)-5- fluoronicotinic acid
  • Pyridines
  • Pyrroles
  • Niacin