反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 20 °C
PROCEDURE
实验过程
A mixture of tert-butyl 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazol-6-yl-carbamate (Example 64) (313 mg, 0.61 mmol), 1-methyl-1H-pyrazol-4-ylboronic acid (155 mg, 1.22 mmol), and aq. 2 M K2CO3 (4.1 mL) in 1,4-dioxane (20 mL) was degassed with N2 for 30 min and then Pd(dppf)Cl2 (30 mg) was added, and the mixture was degassed for a further 10 min. The reaction mixture was heated under reflux for 1 hr, cooled to 20° C., diluted with water, and extracted with CH2Cl2 (20 mL×3). The combined CH2Cl2 extracts were dried (Na2SO4) and the solvents were removed to gave a crude product which was purified by chromatography on silica, eluting with CH2Cl2/EtOAc (4:1) to give tert-butyl 2-(difluoromethyl)-4-methoxy-1-[4-(1-methyl-1H-pyrazol-3-yl)-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-6-ylcarbamate (233 mg, 69% yield): mp (CH2Cl2/hexanes) 224-227° C.; 1H NMR (DMSO-d6) δ 9.60 (s, 1H), 8.75 (s, 1H), 8.64 (s, 1H), 8.28 (m, 1H), 7.82 (t, JHF=53.1 Hz, 1H), 6.92 (d, J=1.7 Hz, 1H), 3.99-3.96 (m, 4H), 3.96 (s, 3H), 3.92 (s, 3H), 3.76 (m, 4H), 1.53 (s, 9H); Anal. Calcd. for C25H29F2N9O4.0.25H2O: C, 53.4; H, 5.3; N, 22.4. Found: C, 53.3; H, 5.3; N, 22.3%.
WORKUP
后处理
- customwas degassed with N2 for 30 min
- additionPd(dppf)Cl2 (30 mg) was added
- customthe mixture was degassed for a further 10 min
- temperatureThe reaction mixture was heated
- temperatureunder reflux for 1 hr
- additiondiluted with water
- extractionextracted with CH2Cl2 (20 mL×3)
- dry with materialThe combined CH2Cl2 extracts were dried (Na2SO4)
- customthe solvents were removed
- customto gave a crude product which
- customwas purified by chromatography on silica
- washeluting with CH2Cl2/EtOAc (4:1)