反应详情

温度

100 °C

A mixture of 2-chloro-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (114 mg, 0.44 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (196 mg, 0.88 mmol), PdCl2dppf.DCM (36 mg, 0.04 mmol) and cesium carbonate (430 mg, 1.32 mmol) in dioxane (5 mL) and water (0.5 mL) was degassed and then heated at 100° C. for 2 hours. Further 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (100 mg, 0.44 mmol), PdCl2dppf.DCM (36 mg, 0.04 mmol) were added and the mixture heated at 100° C. for a further 2 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with methanol and the product eluted with 2M ammonia in methanol. The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0-10% methanol in DCM) then triturated with diethyl ether affording 101 (37 mg, 27%). LCMS: RT=2.75 min, [M+H]+=317. 1H NMR (400 MHz, DMSO): δ 8.90 (2H, s), 7.01 (2H, s), 4.42-4.36 (2H, m), 4.25-4.18 (2H, m), 3.70 (8H, s).

1. temperaturethe mixture heated at 100° C. for a further 2 hours
2. extractionextracted with ethyl acetate
3. dry with materialThe combined organic extracts were dried (Na2SO4)
4. concentrationconcentrated in vacuo
5. washwas washed with methanol
6. washthe product eluted with 2M ammonia in methanol
7. concentrationconcentrated in vacuo
8. customThe resulting residue was purified by column chromatography (SiO2, gradient 0-10% methanol in DCM)
9. customthen triturated with diethyl ether affording 101 (37 mg, 27%)