反应详情

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).

1. temperaturethe mixture was heated
2. temperatureto reflux for 16 hours
3. concentrationthe mixture was concentrated under reduced pressure
4. customthe 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. customTo the suspension obtained during the concentration under reduced pressure
6. filtrationThe precipitates were collected by filtration
7. customdried in vacuo