Diisopropylethylamine → N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

Participants

Reaction Steps

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 15 (249 mg, 1.27 mmol), 16 (500 mg, 1.16 mmol), N,N-diisopropylethylamine (600 mg, 4.64 mmol) and anhydrous DMF (5 mL). Benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP, 616 mg, 1.39 mmol) was added, and the reaction was stirred for 4 h. After this time, the reaction was diluted with water (10 mL), and the resulting suspension was filtered. The filter cake was dissolved in methylene chloride (20 mL), and the solution was washed with 10% aqueous citric acid (10 mL), saturated aqueous sodium bicarbonate (10 mL), and water (10 mL), and dried over sodium sulfate. The drying agent was removed by filtration, and the solvent was evaporated under reduced pressure. The resulting residue was purified by flash chromatography to afford a 52% yield of 17 (370 mg) as a white solid: mp 154-155° C.; 1H NMR (500 MHz, CD2Cl2) δ 8.31 (s, 1H), 7.81 (dd, 1H, J=7.5, 1.5 Hz), 7.76-7.72 (m, 3H), 7.50 (s, 1H), 7.28-7.23 (m, 4H), 6.73 (s, 1H), 3.64 (td, 1H, J=11.5, 4.5 Hz), 3.57 (s, 1H), 3.55 (s, 3H), 3.14 (dt, 1H, J=11.5, 3.5 Hz), 2.93 (m, 1H), 2.88-2.86 (m, 5H), 2.62-2.57 (m, 3H), 2.36 (s, 3H), 2.17 (m, 2H), 2.09 (s, 3H); MS (ESI+) m/z 611.2 (M+H).

Provenance & Evidence