Toluene → (2-Methyl-4-thiophen-2-yl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepin-10-yl)-methanone

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Reaction Steps

To a solution of (4-bromo-2-methyl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-methanone (0.5 g, 1.27 mmol) of Step A, thiophene-2-boronic acid (0.167 g, 1.30 mmol) and sodium carbonate (0.595 g, 5.6 mmol) in toluene (20 mL), ethanol (10 mL) and water (10 mL) under nitrogen was added tetrakis (triphenylphosphine) palladium(0) catalyst (0.066 g, 0.057 mmol). The mixture was heated at reflux for 19 hours. Additional boronic acid (0.170 g, 1.30 mmol) and catalyst (0.050 g, 0.043 mmol) were added and reflux resumed for 3 hours. After stirring overnight at room temperature, the mixture was filtered through Celite and the cake washed with ethyl acetate. The combined organic layers were washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was dissolved in dichloromethane, absorbed onto a silica Merck-60 flash column and eluted with an ethyl acetate- hexane gradient (from 30 to 50%) to provide the title compound (0.29 g) as a foam, which crystallized as a white solid by trituration with diethyl ether/ hexane, m.p. 118-120° C.

Provenance & Evidence