Reaction of Pteridine and Its 8-0xide with Grignard Reagents, Regioselective 7-Alkylation of Pteridine

Abstract

Reaction of 2-amino-4-butoxypteridine (1) with alkyl- or phenylmagnesium bromide followed by protonative and oxidative work-up with a solution of iodine in acetic acid gives 7 -alkyl- or 7 -phenylpteridines (2 ). Regioselective oxidation of 1 to 2-amino-4-butoxypteridine 8-oxide (3) by hydrogen peroxide proceeds in trifluoroacetic acid, and reaction of 3 with Grignard reagent or an organolithium compound affords 2 together with its 8-oxide 4. The products (2 and 4) are easily derived to 7-substituted 2-amino-4- hydroxypteridines. The mechanism of the regioselectivity can be explained based on electron density and molecular orbitals (MO) which are obtained by calculation on the methoxy analogs of 1 and 3.