Dimethylformamide → HCID 21904921, compound

Participants

Reaction Steps

To a stirred solution of (RS)-2-(3-amino-2,6-difluoro-phenyl)-N-(4-cyano-benzyl)-2-methoxy-acetamide (example 307.5) 81 mg) at rt in THF (5 ml) under an argon atmosphere were added N-ethyldiisopropylamine (0.017 ml) and 2-iodopropane (0.01 ml). The mixture was heated to reflux and stirring was continued for 17 h. More 2-iodopropane (0.1 ml) and N-ethyldiisopropylamine (0.17 ml) were added and stirring at reflux was continued for 7 h. DMF (5 ml) was added and the mixture was stirred at 120° C. for 21 h. The mixture had turned to light brown. More DMF (5 ml), N-ethyldiisopropylamine (0.35 ml,) and 2-iodopropane (0.2 ml) were added and stirring at 90° C. was continued for 17 h. The mixture was cooled to rt, diluted with 20 ml water and extracted with EtOAc. The combined organics were washed with water and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (cyclohexane=>cyclohexane/EtOAc 1:1) to give N-(4-cyano-benzyl)-2-(2,6-difluoro-3-isopropylamino-phenyl)-2-methoxy-acetamide (28 mg) as light brown gum.

Provenance & Evidence