Facile regiospecific syntheses of N‐α,N‐1(τ)‐dialkyl‐l‐histidines

Abstract magnified image Two diverse methodologies describe the first synthesis of suitably protected N ‐α, N ‐1(τ)‐dialkyl‐Lhistidine derivatives. Synthesis of suitably protected N ‐α, N ‐1(τ)‐dialkyl‐L‐histidines 7‐9 containing different alkyl groups at the N ‐α and N ‐1(τ) positions was achieved in four steps starting from L‐histidine methyl ester. Whereas, in the one‐step alternate route N ‐α‐Boc‐L‐histidine methyl ester upon direct and simultaneous N ‐α and N ‐1(τ) alkylation with various alkyl halides in the presence of sodium hydride in DMF easily afforded N ‐α, N ‐1(τ)‐dialkyl‐L‐histidines 14 containing identical alkyl group at the N ‐α and N ‐1(τ) positions in high yields. Both procedures allowed facile entry to methyl and other higher alkyl groups at the N ‐α‐position of the histidine ring