Citric Acid → N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2,4-difluorophenyl)thieno[2,3-b]pyrazine-6-carboxamide

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Reaction Steps

A mixture of thieno[2,3-b]pyrazine-6-carboxylic acid (57.1 mg, 0.317 mmol), HATU (145 mg, 0.381 mmol) and DIPEA (0.105 mL, 0.634 mmol) in DMF (3 mL) was stirred for 15 min. N-(5-amino-2,4-difluorophenyl)-3-(2-cyanopropan-2-yl)benzamide 73 (100 mg, 0.317 mmol) was added and stirred for 2 h at 80° C. Citric acid solution (3%) was added and the resulting precipitate was collected. Purification by HPLC gave the title compound N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2,4-difluorophenyl)thieno[2,3-b]pyrazine-6-carboxamide 74 (31 mg, 20%). NMR (400 MHz, DMSO-d6) 1.76 (s, 6H), 7.61 (m, 2H), 7.79 (m, 1H), 7.85 (t, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.10 (t, J=2.0 Hz, 1H), 8.56 (s, 1H), 8.77 (d, J=2.3 Hz, 1H), 8.89 (d, J=2.3 Hz, 1H), 10.35 (s, 1H), 10.80 (br s, 1H). (m/z)=478 (M+H)+.

Provenance & Evidence