反应 #1755490

反应方程式

H2O2

6-(4-chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphen-yl)thieno[3,2-d]pyrimidin-4(3H)-one

dibenzyl diisopropylphosphoramidite

1H-1,2,4-triazole

→

dibenzyl 1-((4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutyl phosphate

收率 85.0%

溶剂

CH2Cl2

1,2-dichloroethane

反应条件

后处理

1. 1
   温度was heated
2. 2
   温度at reflux temperature
3. 3
   洗涤washed sequentially with water, 5% aq. sodium thiosulfate and water
4. 4
   干燥The organic layer was dried over MgSO4
5. 5
   浓缩concentrated

实验过程

A mixture of 6-(4-chlorophenyl)-3-(4-((3,3-difluoro-1-hydroxycyclobutyl)methoxy)-3-methoxyphen-yl)thieno[3,2-d]pyrimidin-4(3H)-one (1.01 g, 2.000 mmol) described in Example 2, dibenzyl diisopropylphosphoramidite (2.073 g, 6.00 mmol) and 1H-1,2,4-triazole (0.414 g, 6.00 mmol) in 1,2-dichloroethane (30 mL) was heated at reflux temperature. After 1 h, the mixture was cooled to RT; whereupon, 2 mL 50% H2O2 was added. After stirring for 15 minutes at RT, the mixture was diluted with CH2Cl2, washed sequentially with water, 5% aq. sodium thiosulfate and water. The organic layer was dried over MgSO4, concentrated and the crude product was subjected to flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient) to afford dibenzyl 1-((4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutyl phosphate (1.3 g, 1.699 mmol, 85% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 8.10 (1 H, s), 7.66 (2 H, d, J=8.56 Hz), 7.54 (1 H, s), 7.45 (2H, d, J=8.56 Hz), 7.28-7.40 (10 H, m), 6.95 (1 H, d, J=8.56 Hz), 6.92 (1 H, d, J=2.27 Hz), 6.87 (1 H, dd, J=8.31, 2.27 Hz), 5.08 (4 H, dd, J=7.81, 1.26 Hz), 4.32 (2 H, s), 3.76 (3 H, s), 2.89-3.30 (4 H, m).

来源