Acetic Acid → HCID 178467571, compound

Participants

Reaction Steps

(±)-tert-Butyl 4-((1-(3,5-dichloro-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (120 mg, 0.23 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 2 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 (2 mL), cooled to 0° C., and treated with sodium cyanoborohydride (72 mg, 1.15 mmol) and formalin (0.84 mL). After 5 min, the reaction was treated with a drop of acetic acid. The ice bath was removed and stirring continued for 1 h. The reaction was concentrated and purified by preparative HPLC to afford 30 mg (30%) as a clear oil. 1H-NMR (CD3OD, 500 MHz) δ 7.53 (d, J=1.8 Hz, 1H), 7.33-7.45 (m, 2H), 6.99-7.14 (m, 3H), 4.66 (q, J=6.7 Hz, 1H), 3.41-3.52 (m, 2H), 3.38 (qAB, JAB=9.2 Hz, 2H), 2.81-2.90 (m, 2H), 2.77(s, 3H), 2.61-2.69(m, 2H), 2.07-2.18 (m, 2H), 1.48 (m, 3H). Mass spec.: 442.44 (MH)+.

Provenance & Evidence