反应详情

温度

80 °C

A mixture of 5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile (1.5 g, 5.4 mmol) and K2CO3 (2.24 g, 16.3 mmol) in 50 mL of DMF at 80° C. was stirred under N2 for 45 min before tert-butyl 3-bromo-4-oxopiperidine-1-carboxylate (4.5 g, 16.3 mmol) was added in one portion. Then the mixture was stirred at 80° C. for 1 hr. After cooling down to RT, 150 mL of water and 150 mL of EA was added. Aqueous phase was further extracted with EA (100 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to get crude product which was chromatographed on 15 g of silica gel using DCM/MeOH (400/1 to 200/1) as eluant to afford 850 mg (35%) of tert-butyl 3-cyano-2-(4-phenoxyphenyl)-5,6-dihydro-4H-pyrazolo[5′,1′:2,3]imidazo[4,5-c]pyridine-7(8H)-carboxylate as an off-white solid. MS (ESI) m/e [M+1]+ 455.9.

1. additionwas added in one portion
2. temperatureAfter cooling down to RT
3. extractionAqueous phase was further extracted with EA (100 mL×3)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customto get crude product which
8. customwas chromatographed on 15 g of silica gel