反应详情

温度

140 °C

A mixture of (R)-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (320 mg, 0.557 mmol), 5-chloro-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde (217 mg, 1.114 mmol) and cesium fluoride (169 mg, 1.114 mmol) in DMA (2.2 mL) was heated at 140° C. for 1.5 h. The reaction mixture was then partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2×). The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by FCC (EtOAc-heptane 10-100%) to provide (R)-3-(difluoromethyl)-5-(2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-methyl-1H-pyrazole-4-carbaldehyde. MS (ESI+) m/z 733.4 (M+H)+.

1. customThe reaction mixture was then partitioned between EtOAc and water
2. extractionThe aqueous layer was extracted with EtOAc (2×)
3. washThe combined organics were washed with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by FCC (EtOAc-heptane 10-100%)