Facile Synthesis of 2-Amino-4-alkoxypyrimidines via Consecutive Nucleophilic Aromatic Substitution (SNAr) Reactions

A transition-metal-free and regioselective synthesis of a series of 2-amino-4-alkoxypyrimidines is described. The SNAr alkoxylation of 2,4-dichloropyrimidines regioselectively provided 2-chloro-4-alkoxypyrimidines, which were subsequently subject to the second SNAr amination with cyclic amines in the presence of triethylamine at high temperature to afford 2-amino-4-alkoxypyrimidines in good overall yield.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1677) and the research fund of Hanyang University (HY-2015-N)