反应 #324376

反应方程式

n-hexane

5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine

5-[4-(tert-Butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine

3-[4-(tert-butyldimethylsilyloxy)phenyl]-1,1-diethoxypropan-2-one

hydrochloric acid

→

Compound 3f

收率 22.8%

2-(4-Hydroxybenzyl)-6-(4-hydroxyphenyl)-8-(thiophen-2-yl)imidazo[1,2-a]pyrazin-3(7H)-one

收率 22.8%

溶剂

1,4-dioxane

反应条件

后处理

1. 1
   温度the mixture was heated
2. 2
   温度to reflux for 16 hours
3. 3
   浓缩the mixture was concentrated under reduced pressure
4. 4
   其他the residue was purified by column chromatography in an argon flow (acidic silica gel 20 g, n-hexane/ethyl acetate=1/2→ethyl acetate→ethyl acetate/methanol=20/1)
5. 5
   其他To the suspension obtained during the concentration under reduced pressure
6. 6
   过滤The precipitates were collected by filtration
7. 7
   其他dried in vacuo

实验过程

Under an argon atmosphere, to a mixture of 5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine (7f) (276 mg, 720 μmol) and 3-[4-(tert-butyldimethylsilyloxy)phenyl]-1,1-diethoxypropan-2-one (8) (381 mg, 1.08 mmol) dissolved in 1,4-dioxane (2 mL) was added 4 M hydrochloric acid (780 μL) at 0° C. and the mixture was heated to reflux for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure and the residue was purified by column chromatography in an argon flow (acidic silica gel 20 g, n-hexane/ethyl acetate=1/2→ethyl acetate→ethyl acetate/methanol=20/1). To the suspension obtained during the concentration under reduced pressure was added n-hexane. The precipitates were collected by filtration and dried in vacuo to give Compound 3f (TMD-278) (68.2 mg, 164 μmol, 22.8%) as a brown solid. Rf=0.67 (ethyl acetate/methanol=20/1); HPLC retention time 9.5 min; 1H NMR (400 MHz, CD3OD) δ 4.22 (s, 2H), 6.72-6.78 (AA′BB′, 2H), 6.90-6.97 (AA′BB′, 2H), 7.11-7.18 (AA′BB′, 2H), 7.32 (dd, 1H, J=3.8, 5.2 Hz), 7.87 (dd, 1H, J=1.1, 5.2 Hz), 7.91-7.97 (AA′BB′, 2H), 8.12 (dd, 1H, J=1.1, 3.8 Hz), 8.48 (s, 1H); IR (KBr, cm−1) 521, 581, 629, 721, 777, 841, 881, 966, 1109, 1172, 1261, 1341, 1429, 1508, 1533, 1609, 1653, 2822, 3107; HRMS (ESI+) m/z 416.1075 ([M+H]+, C23H18N3O3S+ requires 416.1063).

来源