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
PROCEDURE
实验过程
The title compound was prepared according to the procedure for Compound 97A diethyl[4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (30.0 mg, 0.0477 mmol) and [1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-pyrazol-3-yl]boronic acid (Compound 142A, 46.7 mg, 0.173 mmol). The afforded intermediate, diethyl (4-{[4-({7-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-pyrazol-3-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, was purified using an ISCO Combiflash system (eluting with 0-100% EtOAc:CH2Cl2). The product thus obtained was dissolved in CH2Cl2 (2 mL), treated with 4.0 M of HCl in dioxane (0.5 mL) and stirred at rt for 2 h. The solid was filtered off and rinsed with a mixture of CH2Cl2/heptane, giving the title material as an off-white solid, 24.6 mg (77%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.89 (s, 1H), 10.03 (br s, 1H), 8.89 (br s, 1H), 8.49 (s, 1H), 7.91 (d, J=8.6 Hz, 1H), 7.81 (d, J=2.3 Hz, 1H), 7.57 (br s, 2H), 7.30 (br d, J=6.6 Hz, 2H), 6.93 (br s, 1H), 4.72 (s, 2H), 4.21 (t, J=5.6 Hz, 2H), 3.97 (quin, J=7.4 Hz, 4H), 3.81 (t, J=5.7 Hz, 2H), 3.25 (d, J=21.5 Hz, 2H), 3.13 (s, 3H), 1.16 (t, J=7.1 Hz, 6H). MS (ES+): m/z 660.22 (100) [MH+]. HPLC: tR=2.72 min (ZQ3, nonpolar—5 min).
WORKUP
后处理
- customThe afforded intermediate, diethyl (4-{[4-({7-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-pyrazol-3-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate, was purified
- washan ISCO Combiflash system (eluting with 0-100% EtOAc:CH2Cl2)
- customThe product thus obtained
- filtrationThe solid was filtered off
- washrinsed with a mixture of CH2Cl2/heptane