Hydrochloric Acid → 3-(S)-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-3-(2-fluoro-phenyl)-propionic acid

Participants

Reaction Conditions

Reaction Steps

1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (50 mg, 0.156 mmol) was combined in an oven-dried flask with 3-(S)-amino-3-(2-fluoro-phenyl)-propionic acid (86 mg, 0.468 mmol) (commercially available from Combi-Blocks SS-1800) and N,N-dimethylacetamide (1.5 mL) was added with stirring. Solid sodium methoxide (25 mg, 0.468 mmol) was added and the reaction was heated to 150° C. in an oil bath for approximately five hours. The reaction was cooled and the solution diluted with five volumes of water. The solution was acidified to pH 3 with 1M hydrochloric acid to induce precipitation. Filtration of the solid followed by vacuum drying provided the desired product in 91% yield. LC-MS ESI+: 472 (M+1)+; ESI−: 470 (M−1)−.

Provenance & Evidence