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Indoline → 1-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-2,3-dihydro-1H-indole

HRID 1667617
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HRID 1667617 반응식
Br[C:2]1[CH:7]=[C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C@@H:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[CH:5]=[CH:4][N:3]=1.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:25][CH2:24]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.O>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([C@H:13]([N:9]2[CH2:10][CH2:11][CH2:12][C@H:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([N:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24]3)[CH:7]=2)[CH3:14])=[CH:16][CH:17]=1
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참가 물질

9

반응물 4

HCID 10328IndolineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23665647Potassium tert-butoxideHCID 581118522-Bromo-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine

생성물 1

HCID 581119481-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-2,3-dihydro-1H-indole수율 85.5%

시약·촉매·용매

4
HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
85 °C

실험 절차

To a solution of 2-Bromo-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (0.15 g, 0.41 mmol) in toluene (30 mL) are added indoline (0.10 g, 0.83 mmol), 2-(dicyclohexylphosphino)-biphenyl (14 mg, 0.04 mmol), Pd2(dba)3 (19 mg, 0.02 mmol) and potassium tert-butoxide (0.11 g, 1.04 mmol). The reaction mixture is stirred at 85° C. for 3 h and cooled to room temperature. Water and EtOAc are added to the mixture. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜25%) to give (1-(4-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-2,3-dihydro-1H-indole (140 mg, 84%) as an oil. M/Z=400.2 [M+1]

후처리

  1. temperaturecooled to room temperature
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with EtOAc
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated down
  8. customThe crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜25%)

출처 및 근거

ORD 기록
ord-68c2fcf38305444eb4251c21e1cec851
출처 데이터셋
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08044209B2

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