Diisopropylethylamine → 7-amino-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 7-aminothieno[2,3-b]pyrazine-6-carboxylic acid (8) (1.6 g, 8.20 mmol), HATU (3.43 g, 9.02 mmol) and DIPEA (4.06 mL, 24.59 mmol) in DMF (20 mL) was stirred at rt for 20 min. N-(3-amino-4-methylphenyl)-3-(2-cyanopropan-2-yl)benzamide hydrochloride 6 (2.70 g, 8.20 mmol) was added and stirred overnight at 80° C. Quenched in cold citric acid solution and the resulting precipitate was collected and dried to give crude compound 9 (3.55 g). Triturating with acetonitrile, stirred in water at 90° C. for 30 min, filtrated and dried to yield the title compound 7-amino-N-(5-(3-(2-cyanopropan-2-yl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 9 (2.12 g, 55.0%). 1H-NMR (400 MHz, DMSO-d6) 1.77 (s, 6H), 2.23 (s, 3H), 7.06 (br s, 2H), 7.27 (d, J=8.6 Hz, 1H), 7.60 (t, J=7.8 Hz, 2H), 7.75 (m, 1H), 7.82 (br s, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.05 (m, 1H), 8.78 (q, J=2.7 and 2.3 Hz, 2H), 9.47 (br s, 1H), 10.32 (br s, 1H). (m/z)=471 (M+H)+.

Provenance & Evidence