反应 #73404

反应方程式

Potassium carbonate

acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester

NH4Cl

water

→

4-fluoro-5-(2-hydroxymethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

溶剂

MeOH

反应条件

后处理

1. 1
   萃取the mixture is extracted with EtOAc (3×50 mL)
2. 2
   洗涤washed with brine (30 mL)
3. 3
   干燥dried (Na2SO4)
4. 4
   浓缩concentrated
5. 5
   其他The residue is purified by silica gel chromatography (10-100% EtOAc/heptane)

实验过程

Potassium carbonate (289 mg, 2.09 mmol) is added to a solution of acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester (1.05 g, 2.09 mmol) in MeOH (40 mL) at 23° C. The resulting mixture is stirred at 23° C. for 1 h. Saturated aqueous NH4Cl (50 mL) and water (20 mL) are added and the mixture is extracted with EtOAc (3×50 mL). The organic layers are combined, washed with brine (30 mL), dried (Na2SO4), and concentrated. The residue is purified by silica gel chromatography (10-100% EtOAc/heptane) to provide 4-fluoro-5-(2-hydroxymethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 461.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.02 (s, 1 H)8.69 (d, J=5.56 Hz, 1 H)8.12 (s, 1 H)7.91 (s, 1 H)7.66 (t, J=7.96 Hz, 1 H)7.52 (t, J=8.34 Hz, 2 H)7.17 (dd, J=8.84, 7.83 Hz, 1 H)7.05 (d, J=5.56 Hz, 1 H)6.63 (s, 1 H)5.14 (t, J=6.19 Hz, 1 H)4.38 (d, J=6.32 Hz, 2 H)2.59 (s, 3 H).

来源