反应详情

温度

100 °C

5,7-Dichloro-3-(2-chlorobenzyl)-1-(2-chloroethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.31 g, 0.75 mmol) and 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2(3H)-one (0.2 g, 0.75 mmol) were dissolved in anhydrous 1,4-dioxane (12 mL) while bubbling nitrogen into the solution. Lithium chloride (95 mg, 2.2 mmol) and [Tetrakis(triphenylphosphine)]palladium(0) (0.09 g, 0.074 mmol) were added followed by cesium hydroxide monohydrate (0.38 g, 2.2 mmol) and water (1 mL). The reaction mixture was stirred at 100° C. under a nitrogen atmosphere for 20 hours. The mixture was cooled, diluted with ethyl acetate, washed with water, then brine, dried with sodium sulfate, decanted and concentrated in vacuo. The product was purified by column chromatography eluting with a gradient of 80-100% ethyl acetate in hexanes, followed by 0-10% methanol in ethyl acetate. It was further purified by column chromatography eluting with a gradient of 0-12% methanol in dichloromethane to yield 7-chloro-3-(2-chlorobenzyl)-1-(2-hydroxyethyl)-5-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one. 1HNMR (DMSO-d6, 400 MHz) δ 11.09 (s, 1H), 7.81 (d, 1H), 7.68 (dd, 1H), 7.49 (d, 1H), 7.38 (d, 1H), 7.31-7.19 (m, 4H), 6.98 (m, 2H), 4.72 (t, 1H), 4.08 (m, 1H), 3.8 (m, 2H), 3.6-3.3 (m, 4H), 3.26 (s, 3M. HRMS [M+H]+ predicted: 509.1147. found: 509.1133.

1. customwhile bubbling nitrogen into the solution
2. temperatureThe mixture was cooled
3. washwashed with water
4. dry with materialbrine, dried with sodium sulfate
5. customdecanted
6. concentrationconcentrated in vacuo
7. customThe product was purified by column chromatography
8. washeluting with a gradient of 80-100% ethyl acetate in hexanes
9. customIt was further purified by column chromatography
10. washeluting with a gradient of 0-12% methanol in dichloromethane