反应详情

(±)-tert-Butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (810 mg, 1.31 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 4 mL). The reaction was stirred at room temperature for 3 h and concentrated. The crude trifluoroacetic acid salt was loaded onto a strong cation exchange cartridge in methanol and washed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated. The crude amine was dissolved in dichloromethane (5 mL) and treated with di-tert-butyl dicarbonate (572 mg, 2.62 mmol) and triethylamine (0.27 mL, 2.0 mmol). The reaction was stirred at room temperature for 1 h. The reaction was quenched by addition of 2 M ammonia in methanol and concentrated. The residue was purified by column chromatography (30% ethyl acetate/hexanes) to give 400 mg (63%) as a viscous oil. 1H-NMR (CDCl3, 500 MHz) δ 9.90 (s, 1H), 7.89 (s, 1H), 7.55 (d, J=1.8 Hz, 1H), 7.22-7.25 (m, 2H), 7.02-7.06 (m, 2H), 6.96 (d, J=1.8 Hz, 1H, 1H), 4.49 (q, J=6.7 Hz, 1H), 3.62-3.72 (m, 2H), 3.23-3.36 (m, 2H), 2.94-3.06 (m, 2H), 2.05-2.24 (m, 2H), 1.70-1.86 (m, 2H), 1.44 (m, 3H), 1.41 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 171.1, 161.7 (d, J=246.6 Hz), 155.0 135.7, 133.8, 128.7, 127.5, 126.2, 124.8, 124.2, 119.0, 115.7, 79.6, 78.6, 78.2, 60.4, 41.2, 28.5, 22.2, 14.3. Mass spec.: 488.39 (MH)+.

1. concentrationconcentrated
2. washwashed with several volumes of methanol which
3. washThe product was eluted with 2 M ammonia in methanol
4. concentrationconcentrated
5. dissolutionThe crude amine was dissolved in dichloromethane (5 mL)
6. stirringThe reaction was stirred at room temperature for 1 h
7. customThe reaction was quenched by addition of 2 M ammonia in methanol
8. concentrationconcentrated
9. customThe residue was purified by column chromatography (30% ethyl acetate/hexanes)
10. customto give 400 mg (63%) as a viscous oil