反应详情

温度

80 °C

To 3-(4-(7-chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-3-cyclopropyl-propanenitrile (Preparation M; 50 mg, 0.16 mmol) in dioxane (5 mL) was added K2CO3 (66 mg, 0.48 mmol), diacetoxypalladium (1.8 mg, 0.0080 mmol), 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-ylboronic acid (89 mg, 0.32 mmol) and sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (8.2 mg, 0.016 mmol). The reaction mixture was degassed with argon, sealed and heated to 80° C. for 5 hours. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM/MeOH 10:1) to give the intermediate product, to which was added DCM/TFA (1 mL/1 mL). The reaction mixture was stirred for 30 minutes and concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10:1:0.1) to give the final product (20 mg, 31% yield). MS (apci) m/z=410.3 (M+H).

1. customThe reaction mixture was degassed with argon
2. customsealed
3. temperatureThe reaction was cooled to ambient temperature
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by silica gel chromatography (DCM/MeOH 10:1)
6. customto give the intermediate product
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10:1:0.1)