Triethylamine → HCID 57546017, compound

Participants

Reaction Conditions

Reaction Steps

(±)-tert-Butyl 4-((1-(3-cyano-5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-phenylpiperidine-1-carboxylate (95 mg, 0.14 mmol) was treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 2 mL) for 3 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 solvent was concentrated to afford a crude product which was dissolved in dichloromethane (3 mL), cooled to 0° C., and treated with di-tert-butyl carbonate (63 mg, 0.29 mmol) and triethylamine (30 μL, 0.22 mmol). After 1 h, the reaction was treated with a few drops of 2 M ammonia in methanol and concentrated. The residue was dissolved in ethyl acetate, washed with water (2×), brine (2×), dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel (15% ethyl acetate/hexanes) afforded 40 mg (53%). 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H), 7.38-7.46 (m, 3H), 7.31-7.33 (m, 3H), 4.70 (q, J=6.7 Hz, 1H), 4.46 (m, 2H), 3.78-3.79 (m, 2H), 3.55 (d, J=8.9 Hz, 1H), 3.35 (d, J=8.9 Hz, 1H), 2.98-3.12 (m, 2H), 2.08-2.40 (m, 2H), 1.68-1.87 (m, 2H), 1.46 (m, 3H), 1.43 (s, 9H). Mass spec.: 529.19 (MH)+.

Provenance & Evidence