反应详情

(±)-tert-Butyl 4-((1-(5-dimethylamino-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (206 mg, 0.329 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 3.5 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 124 mg of (±)-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-N,N-dimethyl-2H-indazol-5-amine (95%). The crude amine (124 mg, 0.313 mmol) in dichloromethane (2.7 mL) was cooled to 0° C. and treated with di-tert-butyl dicarbonate (137 mg, 0.625 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 (18%→45% EtOAc/Hex) to give 138 mg (89%) as clear oil. LC/MS (HPLC method 3): tR=2.816 min, 497.50(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