Potential mechanism-based tyrosine kinase inhibitors. Part 1. Phosphorylation chemistry of pyridine N-oxides

Abstract

Phosphorylated derivatives of 4-picoline N-oxide have been observed on treatment with both phos-phorylating and phosphitylating agents. These intermediates were trapped by external nucleophiles. Propane-1-thiol reacted preferentially at carbon to yield a propylsulfanylpyridine whereas propylamine reacted preferentially at phosphorus. This chemistry carries implications for the design of mechanism-based tyrosine kinase inhibitors.