反应详情

Enantiomer B of tert-Butyl 4-((1-(5-cyclopropyl-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate. Enantiomer B of tert-Butyl 4-((1-(5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate(46 mg, 0.074 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 1.6 mL) and stirred at room temperature for 4 h. The reaction was concentrated and loaded onto a strong cation exchange cartridge in methanol. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated to give 30 mg of Enantiomer B of 5-cyclopropyl-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole (quant.). The crude amine (30 mg, 0.076 mmol) in dichloromethane (2 mL) was cooled to 0° C. and treated with di-tert-butyl dicarbonate (33.3 mg, 0.152 mmol). The reaction was stirred at 0° C. for 1 h and was quenched by addition of 2 M ammonia in methanol and concentrated. The residue was purified by column chromatography (25% EtOAc/Hex) to give 28 mg (74.4%) as oil. 1H-NMR (CDCl3, 300 MHz) δ 7.85 (s, 1H), 7.23 (m,2H), 7.03 (m, 3H), 6.76 (s, 1H), 4.46 (q, J=6 Hz, 1H), 3.57-3.75 (m, 2H), 3.32 (d, J=9 Hz, 1H), 3.22 (d, J=9 Hz, 1H), 2.9-3.1(m, 2H), 2.01-2.22 (m,2H), 1.65-1.8 (m, 2H), 1.37-1.41 (m, 12H), 0.91 (m, 2H), 0.64 (m, 2H); Mass spec.: 494.48 (MH)+.

1. concentrationThe reaction was concentrated
2. customThe cartridge was flushed with several volumes of methanol which
3. washThe product was eluted with 2 M ammonia in methanol
4. concentrationconcentrated