Acetic Acid → 2-[3-(4-Chlorophenyl)ureido]-6-(cyclopropylmethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

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Reaction Steps

To a slurry of compound A4 (300 mg, 0.645 mmol) in methanol (4 mL) and tetrahydrofuran (2 mL) two drops of glacial acetic acid and cyclopropanecarbaldehyde (94.0 mg, 1.34 mmol) were added. After stirring at room temperature for 5 min, sodium cyanoborohydride (122 mg, 1.94 mmol) was added and the reaction mixture was stirred for an additional 3 h. After this time, the reaction was quenched with water (25 mL) and saturated aqueous sodium bicarbonate (50 mL). The resulting mixture was extracted with ethyl acetate (100 mL). The extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was triturated with methylene chloride to afford compound A5 as a white solid (245 mg, 94%): 1H NMR (500 MHz, DMSO-d6) δ 10.95 (s, 1H), 10.16 (s, 1H), 7.54-7.40 (m, 3H), 7.33 (d, J=9.0 Hz, 2H), 6.83 (bs, 1H), 3.54 (s, 2H), 2.84-2.78 (m, 2H), 2.78-2.69 (m, 2H), 2.36 (s, 2H), 0.95-0.87 (m, 1H), 0.53-0.45 (m, 2H), 0.17-0.09 (m, 2H). MS (M+H) 405.

Provenance & Evidence