methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate → methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate

HRID 715953노트

반응식

HRID 715953 반응식
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:21]=[CH:20][C:19]2[N:18]3[CH2:22][CH2:23][CH2:24][C:17]3=[CH:16][C:15]=2[C:14]=1[C:25]([O:27][CH3:28])=[O:26])(=[O:11])=[O:10].[CH2:29]([N:31]([CH2:48][CH3:49])[CH2:32]/[CH:33]=[CH:34]\[Sn](CCCC)(CCCC)CCCC)[CH3:30]>O1CCOCC1.CS(C)=O>[CH2:29]([N:31]([CH2:48][CH3:49])[CH2:32]/[CH:33]=[CH:34]\[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:21]=[CH:20][C:19]2[N:18]3[CH2:22][CH2:23][CH2:24][C:17]3=[CH:16][C:15]=2[C:14]=1[C:25]([O:27][CH3:28])=[O:26])(=[O:11])=[O:10])[CH3:30]

참가 물질

5

반응물 2

HCID 70984190methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate2회HCID 86684726N,N-diethyl-N-((Z)-1-tributylstannanylprop-1-en-3-yl)amine2회

생성물 1

HCID 86712101methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate수율 90.7%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 312751,4-Dioxane용매

반응 조건

온도
95 °C

실험 절차

A mixture of methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 17, 0.100 g) and N,N-diethyl-N—((Z)- 1-tributylstannanylprop-1-en-3-yl)-amine (Intermediate 3, 0.172 g) in dioxane (2 mL) and DMSO (0.2 mL) was de-gassed and purged with nitrogen. Tris-(dibenzylideneacetone)-dipalladium (0.009 g) and tri-tert-butylphosphonium tetrafluoroborate (0.006 g) were added and the reaction mixture was heated at 95° C., under an atmosphere of nitrogen for 45 minutes. After cooling, the mixture was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-7.5% to give methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3-dihydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (0.097 g) as a yellow oil.

후처리

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. additionTris-(dibenzylideneacetone)-dipalladium (0.009 g) and tri-tert-butylphosphonium tetrafluoroborate (0.006 g) were added
  4. temperatureAfter cooling
  5. customthe mixture was partitioned between ethyl acetate and water
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated in vacuo
  11. customThe residue was purified by chromatography on silica
  12. washeluting with a mixture of methanol and DCM with a gradient of 0-7.5%

출처 및 근거

ORD 기록
ord-367d0332ee7f46a7a29008324d16f3e5
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187494B2

반응 노트

불러오는 중…