反应详情

温度

120 °C

A mixture of 8-amino-4-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one and 2-(2,5-dichloropyrimidin-4-ylamino)-N-methylbenzamide (22 mg, 0.08 mmol), and camphorsulfonic acid (17.4 mg, 0.08 mmol) were heated in IPA (3 mL) at 120° C. for 16 hours. The mixture was heated for another 2.5 hours at 120° C. after the addition of 10 drops of 4 N HCl/dioxane. Concentration and chromatography on preparative TLC with methylene chloride and methanol (100:8) followed by semi-preparative HPLC gave 5 mg of 2-[5-chloro-2-(4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-8-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide (16% yield): 1H NMR (300 MHz, CD3OD) δ 8.7 (d, 1H), 8.13 (s, 1H), 7.96 (s, 1H), 7.67 (m, 3H), 7.4 (m, 1H), 7.2 (m, 1H), 3.95 (s, 1H), 3.7 (s, 1H), 3.6 (s, 2H), 2.95 (s, 3H), 2.53 (s, 3H); MS (m/e): 452.2 (M+1).

1. concentrationConcentration and chromatography on preparative TLC with methylene chloride and methanol (100:8)