反应详情

温度

35 °C

Method Q—Step a To a mixture of 1-[4-chloro-3-(5-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperidine-4-carboxylic acid hydrochloride (obtained as described in general method 3,4, step e) (0.01 g, 0.25 mmol) in dcm (2 mL), HATU (0.10 g, 0.26 mmol), TEA (0.07 mL, 0.53 mmol) and methyl-(1-methyl-pyrrolidin-3-yl)-amine (0.03 g, 0.31 mmol) were added. The reaction mixture was heated at 35° C. overnight, cooled to room temperature, washed with ammonium chloride solution (2 mL), filtered through a phase separator and organic phase was filtered by SCX column (eluent: first dcm:MeOH/1:1 then NH3 in MeOH (2N)). This work up was done using the Zinsser Speedy (version 6.1.3). The crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1) to obtain 0.04 g of the title compound (37%). 1H-NMR (400 MHz, CD3OD): δ 1.76-1.93 (5H, m), 2.08-2.23 (2H, m), 2.36-2.48 (6H, m), 2.51-3.09 (9H, m), 3.83-3.86 (2H, m), 5.13-5.20 (1H, m), 7.09-7.13 (2H, m), 7.38-7.40 (3H, m), 7.51 (1H, bs); m/z 466 (M+H)+, retention time (method b)=2.30 (10 min run)

1. additionwere added
2. temperaturecooled to room temperature
3. washwashed with ammonium chloride solution (2 mL)
4. filtrationfiltered through a phase separator and organic phase
5. filtrationwas filtered by SCX column (eluent
6. customThe crude was then purified by flash chromatography (eluent: gradient from EtOAc to EtOAc:NH3 in MeOH (2N)/10:1)