반응 #324376

ord-bd028b5515d349159ca11131d2c0410d

반응 방정식

CCCCCC
n-hexane
CC(C)(C)[Si](C)(C)Oc1ccc(-c2cnc(N)c(-c3cccs3)n2)cc1
5-[4-(tert-butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine
CC(C)(C)[Si](C)(C)Oc1ccc(-c2cnc(N)c(-c3cccs3)n2)cc1
5-[4-(tert-Butyldimethylsilyloxy)phenyl]-3-(thiophen-2-yl)pyrazin-2-amine
CCOC(OCC)C(=O)Cc1ccc(O[Si](C)(C)C(C)(C)C)cc1
3-[4-(tert-butyldimethylsilyloxy)phenyl]-1,1-diethoxypropan-2-one
Cl
hydrochloric acid
O=c1c(Cc2ccc(O)cc2)nc2c(-c3cccs3)[nH]c(-c3ccc(O)cc3)cn1-2
Compound 3f
수율 22.8%
O=c1c(Cc2ccc(O)cc2)nc2c(-c3cccs3)[nH]c(-c3ccc(O)cc3)cn1-2
2-(4-Hydroxybenzyl)-6-(4-hydroxyphenyl)-8-(thiophen-2-yl)imidazo[1,2-a]pyrazin-3(7H)-one
수율 22.8%

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도the mixture was heated
  2. 2
    온도to reflux for 16 hours
  3. 3
    농축the mixture was concentrated under reduced pressure
  4. 4
    기타the 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
    기타To the suspension obtained during the concentration under reduced pressure
  6. 6
    여과The precipitates were collected by filtration
  7. 7
    기타dried in vacuo

실험 절차

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).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08642281B2uspto-grants-2014_02