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
PROCEDURE
实验过程
To a mixture of 7-bromo-2,4,4-trimethyl-1,2,3,4-tetrahydro-isoquinoline (140 mg, 0.55 mmol), 4,4,5,5,4′,4′,5′,5′-octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl] (140 mg, 0.55 mmol), DPPF (9 mg, 0.017 mmol), and KOAc (162 mg, 1.65 mmol) in DMSO, add PdCl2(DPPF)-DCM complex (13 mg, 0.0165 mmol). Purge the reaction mixture for 10 minutes with dry N2. Heat the stirring reaction mixture overnight at 80° C. Cool to room temperature. Add 4-chloro-2-(2-methyl-pyrrolidin-1-yl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidine (141 mg, 0.33 mmol), Pd(PPh3)4 (19 mg, 0.017 mmol), and Cs2CO3 (162 mg, 0.50 mmol). Heat the stirring reaction mixture overnight at 80° C., cool to room temperature, and partition between water and EtOAc. Dry the solution (Na2SO4), concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with DCM:MeOH (9:1) to afford 2,4,4-trimethyl-7-{2-(2-methyl-pyrrolidin-1-yl)-6-[4-(3-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyrimidin-4-yl}-1,2,3,4-tetrahydro-isoquinoline. 1H NMR (400 MHz, CDCl3): δ 1.30 (m, 9H, 3×CH3); 1.68 (m, 1H, CH2CH2); 1.91 (m, 1H, CH2CH2); 2.05 (m, 2H, CH2CH2); 2.40 (s, 2H); 2.43 (s, 3H, NCH3); 3.39 (m, 4H); 3.61 (s, 2H); 3.67 (m, 2H); 3.79 (m, 4H); 4.34 (m, 1H); 6.27 (s, 1H, Ar—H); 7.01 (m, 1H); 7.35 (m, 1H); 7.63 (s, 1H); 7.88 (m, 1H); 7.88 (m, 1H); 8.44 (m, 1H).
WORKUP
后处理
- additionadd PdCl2(DPPF)-DCM complex (13 mg, 0.0165 mmol)
- customPurge the reaction mixture for 10 minutes with dry N2
- temperatureHeat
- customthe stirring reaction mixture overnight at 80° C
- temperatureHeat
- customthe stirring reaction mixture overnight at 80° C.
- temperaturecool to room temperature
- custompartition between water and EtOAc
- dry with materialDry the solution (Na2SO4)
- concentrationconcentrate under reduced pressure
- customPurify the residue by flash column chromatography
- washeluting with DCM:MeOH (9:1)