反应详情

温度

100 °C

A mixture of (R)-2-chloro-6-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine (65 mg, 0.24 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (80 mg, 0.36 mmol), Pd(OAc)2 (1 mg, 10 mol %), (S)-phos (4.1, 20 mol %) and potassium phosphate tribasic (106 mg, 0.50 mmol) in n-butanol (2.25 mL) and water (0.25 mL) was degassed and then heated at 100° C. for 18 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 purified by column chromatography (SiO2, gradient 0-5% methanol in DCM) affording 102 (23 mg, 29%). LCMS: RT=3.09 min, [M+H]+=331. 1H NMR (400 MHz, DMSO): δ 9.15 (2H, s), 5.73 (2H, s), 4.44 (1H, dd, J=11.44, 2.17 Hz), 4.31-4.24 (1H, m), 4.08 (1H, dd, J=11.45, 8.21 Hz), 3.89-3.73 (8H, m), 1.42 (3H, d, J=6.38 Hz).

1. customwas degassed
2. additionThe reaction mixture was diluted with water
3. extractionextracted with ethyl acetate
4. dry with materialThe combined organic extracts were dried (Na2SO4)
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by column chromatography (SiO2, gradient 0-5% methanol in DCM)