Hydrochloric Acid → 4'-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}-N,N-dimethylbiphenyl-3-carboxamide

Participants

Reaction Steps

A solution of the compound (232 mg, 0.5 mmol) obtained in Example 1-2), 3-(N,N-dimethylaminocarbonyl)phenylboronic acid (97 mg, 0.5 mmol), tris(dibenzylideneacetone)dipalladium(0) (23 mg, 0.05 mmol), tricyclohexylphosphine (17 mg, 0.12 mmol), and tripotassium phosphate (186 mg, 0.85 mmol) in dioxane (2 mL) and water (1 mL) was stirred at 140° C. for 2 h under microwave irradiation. The reaction mixture was partially purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 20:80, gradient). A solution of the obtained partially purified product (238 mg, 0.7 mmol) and 4 M hydrochloric acid (1,4-dioxane solution, 0.26 mL) in methanol (2 mL) was stirred at room temperature for 21 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (149 mg, 46%) as a colorless solid.

Provenance & Evidence