Formaldehyde → HCID 25160456, compound

Participants

Reaction Steps

(±)-tert-Butyl 4-((1-(2-(2,2-difluoroethyl)-5-methyl-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (10 mg, 0.02 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 1 mL) and stirred at room temperature for 1 h. The reaction was concentrated, loaded onto a strong cation exchange cartridge in methanol, and flushed with several volumes of methanol which were discarded. The crude secondary amine was eluted in 2 M ammonia in methanol and concentrated. The resulting residue was dissolved in acetonitrile (1 mL), cooled to 0° C., and treated with sodium cyanoborohydride (5.9 mg, 0.01 mmol) and formalin (0.52 mL). After 5 min, the reaction was treated with a few drops of acetic acid. The ice bath was removed and stirring continued for 1 h. The reaction was concentrated and purified by column chromatography (10% methanolic ammonia/methylene chloride) to afford 4.5 mg (54%) as a clear oil. 1H-NMR (CDCl3, 500 MHz) δ 7.83 (s, 1H), 7.30-7.34 (m, 2H), 7.22 (m, 1H), 6.99-7.02 (m, 2H), 6.67 (m, 1H), 6.05-6.29 (m, 1H), 4.86 (q, J=6.4 Hz, 1H), 4.64-4.71 (m, 2H), 3.33-3.38 (m, 2H), 2.57 (m, 2H), 2.28 (s, 3H), 2.20 (s, 3H), 2.15-2.24 (m, 6H), 1.44 (d, J=6.4 Hz, 3H). Mass spec.: 446.63(MH)+.

Provenance & Evidence