Formaldehyde → HCID 57546068, compound

Participants

Reaction Conditions

Reaction Steps

(±)-7-(1-((4-Phenylpiperidin-4-yl)methoxy)ethyl)-5-(trifluoromethyl)-1H-indazole-3-carbonitrile (24 mg, 0.06 mmol) and formaldehyde (37 wt. % solution in water, 77 μL) were combined in acetonitrile (2 mL) and cooled to 0° C. The reaction was treated with sodium cyanoborohydride (18 g, 0.28 mmol) and a few drops of acetic acid. The reaction was stirred at 0° C. for 30 min and at room temperature for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. The solvents were evaporated and the compound purified by flash chromatography on silica gel (1% aq. methanolic ammonia/8% methanol/methylene chloride) to afford 15 mg (59%). 1H-NMR (CDCl3, 500 MHz) δ 8.05 (s, 1H), 7.37-7.40 (m, 2H), 7.31-7.34 (m, 2H), 7.22-7.23 (m, 2H), 4.66 (q, J=6.7 Hz, 1H), 3.36-3.43 (m, 2H), 3.34 (q, J=9.2 Hz, 1H), 3.17 (d, J=9.2 Hz, 1H), 2.73-2.84 (m, 2H), 2.59 (s, 3H), 2.53-2.58 (m, 2H), 2.13-2.29 (m, 2H), 1.59 (m, 3H). Mass spec.: 442.48 (MH)+.

Provenance & Evidence