反应详情

tert-butyl 4-((1-(5-chloro-1H-indazol-7-yl)-2-methoxy-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (20 mg) was dissolved in trifluoroacetic acid (20% in dichloromethane, 1.5 mL) and stirred for 20 min at room temperature. The reaction was concentrated and the resulting residues loaded onto a strong cation exchange cartridge. The cartridge was flushed with several volumes of methanol which were discarded. The amine was eluted with 2M ammonia in methanol and concentrated. The unprotected piperidine was dissolved in acetonitrile (1 mL) and treated with formalin (50 μL) and sodium cyanoborohydride (2.4 mg) and one drop of acetic acid. The reaction was stirred at room temperature for 1 h. The reaction was concentrated. The resulting residue was dissolved in trifluoroacetic acid (25% in dichloromethane, 2 mL), stirred for 5 min, and concentrated. The resulting residue was purified by preparative HPLC to afford the title compound. 1H-NMR (CD3OD, 500 MHz) δ 8.05 (m, 1H), 7.78 (m, 1H), 7.44 (m, 2H), 7.22 (m, 0.75H), 7.13 (m, 1.8H), 7.03 (m, 0.6H), 5.34 (s, 0.3H), 5.27 (s, 0.7H), 3.69 (m, 4H), 3.47 (m, 4H), 2.55-3.00 (m, 7H), 2.00-2.55 (m, 2.5H). Mass spec.: 446.24 (MH)+.

1. concentrationThe reaction was concentrated
2. customThe cartridge was flushed with several volumes of methanol which
3. washThe amine was eluted with 2M ammonia in methanol
4. concentrationconcentrated
5. dissolutionThe unprotected piperidine was dissolved in acetonitrile (1 mL)
6. additiontreated with formalin (50 μL) and sodium cyanoborohydride (2.4 mg) and one drop of acetic acid
7. stirringThe reaction was stirred at room temperature for 1 h
8. concentrationThe reaction was concentrated
9. dissolutionThe resulting residue was dissolved in trifluoroacetic acid (25% in dichloromethane, 2 mL)
10. stirringstirred for 5 min
11. concentrationconcentrated
12. customThe resulting residue was purified by preparative HPLC