反应详情

(±)-tert-Butyl 4-((1-(5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate(70.5 mg, 0. 113 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 1 mL) and stirred at room temperature overnight. 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 40.5 mg of (±)-5-cyclopropyl-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-2H-indazole (91%). The crude amine (40.5 mg, 0. 103 mmol) in dichloromethane (2 mL) was cooled to 0° C. and treated with di-tert-butyl dicarbonate (44.9 mg, 0.206 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 (1%→30% EtOAc/Hex) to give 30 mg (59%) as oil. LC/MS (HPLC method 3): tR=3.15 min, 494.12(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