Methyl 4-aminobenzoate → Methyl 4-{[(5-chloro-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methyl]amino}benzoate

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Reaction Steps

To a mixture of (5-chloro-3-methylfuro[3,2-b]pyridin-2-yl)(cyclohexyl)methanone (1.00 g) synthesized above, methyl 4-aminobenzoate (599 mg), triethylamine (4.01 mL) and methylene chloride (10 mL) was added a 1.0M solution (4.32 mL) of titanium (IV) chloride in methylene chloride 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 (15 mL) of the obtained oil in tetrahydrofuran were added acetic acid (1.03 mL) and sodium cyanoborohydride (452 mg), and the mixture was stirred at room temperature for 2 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 (0-40% ethyl acetate/hexane) to give the title object compound (1.31 g, 81%) as an orange solid.

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