Lithium Chloride → 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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence