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
- 100 °C
PROCEDURE
实验过程
A mixture of ethyl 3-[4-(tributylstannanyl)-1H-1,2,3-triazol-1-yl]propyl (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 64A, 0.331 mmol assumed) and Pd(PPh3)2Cl2 (11.6 mg, 0.0166 mmol) in 1,4-dioxane (8 mL) was evacuated and refilled with nitrogen (3×), then heated at 100° C. for 5 h. The mixture was concentrated under reduced pressure, the residue was purified by silica gel chromatography (ISCO system: MeOH/DCM-EtOAc (1:1)=0-15%) to give the desired product as a white solid, (51 mg, 24% yield over 2 steps). 1H NMR (CDCl3, 400 MHz): δ 10.86 (s, 1H), 8.53 (s, 1H), 8.48 (m, 1H), 8.36 (s, 1H), 8.15 (d, J=8.6 Hz, 1H), 7.80 (d, J=8.6 Hz, 1H), 7.79 (br s, 1H), 7.56 (d, J=7.8 Hz, 1H), 6.66 (s, 1H), 6.25 (d, J=8.4 Hz, 1H), 4.66-4.77 (m, 2H), 4.05-4.11 (m, 2H), 3.89-3.97 (m, 2H), 3.84 (s, 3H), 3.09 (dd, J=21.2, 2.2 Hz, 2H), 3.04 (d, J=5.0 Hz, 3H), 2.36-2.49 (m, 2H), 1.28 (t, J=7.1 Hz, 3H). MS (ESI): m/z 648.69 [M+H]+. UPLC: tR=1.08 min (UPLC-SQD: analytical—2 min).
WORKUP
后处理
- customwas evacuated
- additionrefilled with nitrogen (3×)
- concentrationThe mixture was concentrated under reduced pressure
- customthe residue was purified by silica gel chromatography (ISCO system: MeOH/DCM-EtOAc (1:1)=0-15%)