Glycine → 2-(1H-imidazol-2-ylamino)acetic acid

Participants

Reaction Steps

Different N-substituted amino acid derivatives can be used to synthesize other compounds of Formula III wherein Y′ is NHR3 and R3 is not hydrogen. For example, 2-chloro-1H-imidazole or 4-bromo-1H-imidazole can be treated with glycine in water (for example, according to the procedure set forth in European Journal of Medicinal Chemistry (1989), 24(6), 623-5) to form 2-(1H-imidazol-2-ylamino)acetic acid or 2-(1H-imidazol-4-ylamino)acetic acid, respectively, which can then be used to synthesize (2S,4R)-1-(2-(1H-imidazol-2-ylamino)acetyl)-4-benzamidopyrrolidine-2-carboxylic acid or (2S,4R)-1-(2-(1H-imidazol-4-ylamino)acetyl)-4-benzamidopyrrolidine-2-carboxylic acid in a manner similar to Scheme 1. Compounds such as (2S,4R)-4-benzamido-1-(2-(pyridin-2-ylamino)acetyl)pyrrolidine-2-carboxylic acid, (2S,4R)-4-benzamido-1-(2-(pyrimidin-4-ylamino)acetyl)pyrrolidine-2-carboxylic acid, and (2S,4R)-4-benzamido-1-(2-(pyrimidin-2-ylamino)acetyl)pyrrolidine-2-carboxylic acid can be similarly synthesized from 2-(pyridin-2-ylamino)acetic acid, 2-(pyrimidin-4-ylamino)acetic acid, and 2-(pyrimidin-2-ylamino)acetic acid, respectively.

Provenance & Evidence