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
- 120 °C
PROCEDURE
实验过程
A solution of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K3) (262 mg, 0.574 mmol), PdCl2(PPh3)2 (20 mg, 0.029 mmol,) t-Bu3PH.BF4 (8 mg, 0.03 mmol), CuI (5 mg, 0.03 mmol) and methyl 1-(2-ethynylphenyl)cyclopropanecarboxylate (K2) (138 mg, 0.689 mmol) in DMF (5.0 mL) was degassed with nitrogen for 10 minutes. Et3N (1.0 mL) was added and the resulting mixture heated under microwave irradiation for 20 minutes at 120° C. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.) to give the title compound A3 as a yellow solid (308 mg, 86%); 1H NMR (400 MHz, d6-DMSO) δ 10.37 (s, 1H), 8.79 (s, 1H), 7.67 (d, J=8.2 Hz, 2H), 7.60 (dd, J=7.6, 1.0 Hz, 1H), 7.54-7.38 (m, 3H), 7.21 (d, J=8.6 Hz, 2H), 4.07 (d, J=11.6 Hz, 2H), 3.52 (s, 3H), 2.80 (s, 2H), 2.65 (J m, 1H), 1.74 (d, J=12.4 Hz, 2H), 1.64 (q, J=4.0 Hz, 2H), 1.49 (td, J=12.6, 4.1 Hz, 2H), 1.42 (s, 9H), 1.29 (q, J=4.2 Hz, 2H). LCMS-A: rt 7.083 min; m/z 619 [M−H]−.
WORKUP
后处理
- custompurified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.)