2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. II. C-alkylation of pyrimidines with Mannich bases and application to the synthesis of trimethoprim and analogues

Article abstract of DOI:10.1021/jm00178a007

A new route to 5-(p-hydroxybenzyl)pyrimidines has been developed which utilizes phenolic Mannich bases plus pyrimidines containing at least two activating groups. The products can be alkylated on the phenolic oxygen or on the pyrimidine N-1 atom, depending on conditions. This method has been used to prepare trimethoprim, a broad-spectrum antibacterial agent, starting from 2,4-diaminopyrimidine and 2,6-dimethoxyphenol.