Potassium Phosphate, Tribasic → 5-[(6R)-6-methyl-4-morpholino-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidin-2-yl]pyrimidin-2-amine

온도

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)

ORD 기록

ord-b86958cb67c640c29cc1c3d0ed0c13ca

출처 데이터셋

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09346817B2