Chloroacetaldehyde → 6-(2-Chloroethyl)-2-[3-(4-chlorophenyl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

Participants

Reaction Steps

To a slurry of compound A4 (200 mg, 0.431 mmol) and magnesium sulfate (2 g) in methanol (4 mL) and tetrahydrofuran (2 mL) was added two drops of glacial acetic acid and 2-chloroacetaldehyde (45% in water, 0.340 mL, 1.95 mmol). After stirring at room temperature for 5 min, sodium cyanoborohydride (271 mg, 4.31 mmol) was added and the reaction mixture was stirred for an additional 16 h at room temperature. After this time, the reaction was diluted with saturated aqueous sodium bicarbonate (100 mL), sonicated, and filtered. The filter cake was washed with water (50 mL) and triturated with methylene chloride to afford compound B1 as a white solid (176 mg, 99%): 1H NMR (300 MHz, DMSO-d6) δ 10.94 (s, 1H), 10.19 (s, 1H), 7.57-7.29 (m, 5H), 6.87 (bs, 1H), 3.76 (t, J=6.6 Hz, 2H), 3.57 (s, 2H), 2.87-2.71 (m, 6H). MS (M+H) 413.

Provenance & Evidence