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 3-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate (K4) (260 mg, 0.606 mmol), PdCl2(PPh3)2 (21 mg, 0.030 mmol), PPh3 (16 mg, 0.061 mmol), CuI (12 mg, 0.061 mmol) and methyl 1-(2-ethynylphenyl)cyclopropanecarboxylate (K2) (146 mg, 0.728 mmol) in DMF (3.0 mL) was degassed with nitrogen for 10 minutes. Et3N (1.0 mL) was added and the resulting mixture heated under microwave irradiation at 120° C. for 20 minutes. The resulting mixture was adsorbed onto silica and purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60° C.) to give the title compound A7 as an orange oil (359 mg, >95%); 1H NMR (400 MHz, d6-DMSO) δ 10.45 (s, 1H), 8.82 (s, 1H), 7.75 (d, J=8.4 Hz, 2H), 7.61 (dd, J=7.5, 1.0 Hz, 1H), 7.55-7.38 (m, 3H), 7.32 (d, J=8.6 Hz, 2H), 4.32-4.17 (m, 2H), 3.89-3.74 (m, 3H), 3.52 (s, 3H), 1.64 (q, J=4.0 Hz, 2H), 1.40 (s, 9H), 1.29 (q, J=4.2 Hz, 2H). LCMS-A: rt 6.550 min; m/z 593 [M+H]+.
WORKUP
后处理
- custompurified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-25% EtOAc in petroleum benzine 40-60° C.)