Ethylenediamine → HCID 86761829, compound

Participants

Reaction Steps

To a mixture of cyclohexyl(3-methylthieno[3,2-c]pyridin-2-yl)methanone (864 mg) synthesized above, methyl 4-aminobenzoate (553 mg), triethylamine (3.71 mL) and methylene chloride (20 mL) was added titanium (IV) chloride (439 μL) at 0° C., and the mixture was stirred under argon atmosphere overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a dark brown oil. To a solution (20 mL) of the obtained oil in tetrahydrofuran were added acetic acid (268 μL) and sodium cyanoborohydride (419 mg), and the mixture was stirred at room temperature stirred for 1.5 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30-70% ethyl acetate/hexane) to give a pale-brown solid. To a mixture of the obtained solid, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (5.00 mL), and the mixture was stirred overnight with heating under reflux. Tetrahydrofuran (5 mL), ethanol (5 mL) and 1N aqueous sodium hydroxide solution (5.00 mL) were additionally added, and the mixture was stirred with heating under reflux for 2.5 hr, and ethylenediamine (1.00 mL) was added. The mixture was stirred with heating under reflux for 4 hr, and concentrated under reduced pressure. The residue was acidified with 1N hydrochloric acid to pH=4, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50-100% ethyl acetate/hexane) to give the title object compound (432 mg, 34%) as a pale-yellow solid.

Provenance & Evidence