反应详情

温度

70 °C

150.0 mg (0.28 mMol) 6-(6-Chloro-pyrimidin-4-yloxy)-isoquinoline-1-carboxylic acid [5-tert-butyl-2-(4-methoxy-phenyl)-2H-pyrazol-3-yl]-amide is dissolved in 5 ml dioxane. After addition of 131 mg Cs2CO3 (>99%, Fluka 20959; 0.40 mMol), 25 mg (0.43 mMol) acetamide, 20 mg Xantphos (Aldrich 52, 646-0; 0.034 mMol) and 10.5 mg Pd2(dba)3 (Aldrich 32, 877-4; 0.011 mMol) the reaction mixture is heated to 70° C. for 20 h. It is cooled to rt again and worked up by addition of H2O and EtOAc. The phases are separated and the aq. layer is repeatedly extracted with EtOAc. Combined organic extracts are washed with brine, dried and concentrated. The residual crude product is purified by flash chromatography (combi-flash: 40 g column, hexanes/EtOAc; gradient 0-50% EtOAc) to give the title compound as a yellow solid: MS: [M+1]+=553; 1H MNR (CDCl3): δ ppm 10.70 (s, 1H), 9.43 (d, 1H), 8.44 (s, 1H), 8.38 (d, 1H), 8.15 (bs, HN), 7.84 (s, 1H), 7.74 (d, 1H), 7.63 (s, 1H), 7.52-7.48 (m, 3H), 7.05 (d, 2H), 6.87 (s, 1H), 5.29 (s, 1H), 3.88 (s, 3H), 2.25 (s, 3H), 1.41 (s, 9H).

1. temperatureIt is cooled to rt again
2. customThe phases are separated
3. extractionthe aq. layer is repeatedly extracted with EtOAc
4. washCombined organic extracts are washed with brine
5. customdried
6. concentrationconcentrated
7. customThe residual crude product is purified by flash chromatography (combi-flash: 40 g column, hexanes/EtOAc; gradient 0-50% EtOAc)