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Cesium carbonate → (1,1-Dioxo-thiomorpholin-4-yl)-[1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

HRID 493987
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HRID 493987 반응식
[O:1]=[S:2]1(=[O:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.[CH:30](CS([O-])(=O)=O)([CH3:32])[CH3:31].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[O:29]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([CH:30]([CH3:32])[CH3:31])[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:27])[CH3:28])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1
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참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 16739577(1,1-Dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanoneHCID 22141912Isopropyl-methanesulfonate

생성물 1

HCID 16739606(1,1-Dioxo-thiomorpholin-4-yl)-[1-isopropyl-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone수율 47.3%

시약·촉매·용매 1

HCID 6228
Dimethylformamide
용매

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온도
95 °C

실험 절차

To a mixture of (1,1-dioxo-thiomorpholin-4-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (Example 2, 100 mg, 1.0 eq.) and isopropyl-methanesulfonate (67 mg, 2.0 eq.) in dimethylformamide (4 mL) was added cesium carbonate (156 mg, 2.0 eq.). The solution was stirred 22 h at 95° C. The reaction mixture was concentrated in vacuo and the residue partitioned between water and methyl-tert-butylether. The aqueous layer was extracted with methyl-tert-butylether. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo and then purified on silica, eluting with cyclohexane/ethyl acetate. One fraction was isolated and dried in vacuo, to yield 52 mg (47%) of the desired product as off-white solid. MS (m/e): 462.5 (MH+, 100%)

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between water and methyl-tert-butylether
  3. extractionThe aqueous layer was extracted with methyl-tert-butylether
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified on silica
  9. washeluting with cyclohexane/ethyl acetate
  10. customOne fraction was isolated
  11. customdried in vacuo

출처 및 근거

ORD 기록
ord-eda866f5f62647fe89f0a903dfa58cd2
출처 데이터셋
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07538101B2

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