4-Fluorobenzylamine → 3-Amino-5-chloro-6-[(4-fluoro-benzylcarbamoyl)-methoxy]-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

Participants

Reaction Steps

To a solution of (3-amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid (0.300 g, 0.843 mmol) in a 1:1 mixture of THF:DMF (2.0 ml each) are added 1-hydroxybenzotriazole hydrate (0.148 g, 1.096 mmol), N,N-diisopropylethylamine (0.163 g, 1.265 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.242 g, 1.265 mmol), and 4-fluorobenzylamine (0.317 g, 2.529 mmol). The resulting solution is stirred at room temperature for 16 hours. The reaction is quenched by the addition of water (25 ml). A yellow precipitate is formed. The mixture is cooled to 0° C. and stirred for 10 minutes, then filtered. The collected solid is slurried in 10:1 hexane:EtOAc and stirred for 10 minutes. The solid is collected by filtration and dried in the vacuum oven at 50° C. for 1 hour. This affords the title compound as a pale yellow solid (0.143 g, 37%). Mass (m/z): 463.1 (M++1), 461.1 (M+−1).

Provenance & Evidence