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Cesium carbonate → tert-butyl 4-(3-{(3R)-3-[(1-{5-[4-(2-fluoroethoxy)phenyl]pyridin-3-yl}-3-methoxy-3-oxopropyl)carbamoyl]piperidin-1-yl}-3-oxopropyl)piperidine-1-carboxylate

HRID 526339
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HRID 526339 반응식
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH:14]([NH:20][C:21]([C@@H:23]3[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]4[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]4)[CH2:24]3)=[O:22])[CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH:11]=[N:12][CH:13]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:53][CH2:54][F:55]>O1CCCC1.O>[F:55][CH2:54][CH2:53][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([CH:14]([NH:20][C:21]([C@@H:23]3[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]4[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[CH2:36][CH2:37]4)[CH2:24]3)=[O:22])[CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH:11]=[N:12][CH:13]=2)=[CH:6][CH:7]=1
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참가 물질

6

반응물 3

HCID 10796Cesium carbonate2회HCID 69804Ethane, 1-fluoro-2-iodo-6회HCID 71259050tert-butyl 4-{3-[(3R)-3-({1-[5-(4-hydroxyphenyl)pyridin-3-yl]-3-m ethoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

생성물 1

HCID 71609305tert-butyl 4-(3-{(3R)-3-[(1-{5-[4-(2-fluoroethoxy)phenyl]pyridin-3-yl}-3-methoxy-3-oxopropyl)carbamoyl]piperidin-1-yl}-3-oxopropyl)piperidine-1-carboxylate
수율 66.1%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

120 mg (0.19 mmol) tert-butyl 4-{3-[(3R)-3-({1-[5-(4-hydroxyphenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate were dissolved in 2.11 ml tetrahydrofurane. 126 mg (0.39 mmol) cesium carbonate and 64 mg (0.37 mmol) 1-iodo-2-fluoroethane were added. The mixture was stirred at room temperature for 70 hours. 64 mg (0.37 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 48 hours. 64 mg (0.37 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 70 hours. 64 mg (0.37 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 24 hours. 64 mg (0.37 mmol) 1-iodo-2-fluoroethane, 2 ml tetrahydrofurane and 126 mg (0.39 mmol) cesium carbonate were added and the mixture stirred at room temperature for 24 hours. 64 mg (0.37 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 24 hours, diluted with water and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated in vacuum. Chromatography over 10 g silica gel (dichloromethane/ethanol 100/0-90/10) gave 84 mg (62%) tert-butyl 4-(3-{(3R)-3-[(1-{5-[4-(2-fluoroethoxy)phenyl]pyridin-3-yl}-3-methoxy-3-oxopropyl)carbamoyl]piperidin-1-yl}-3-oxopropyl)piperidine-1-carboxylate.

후처리

  1. stirringthe mixture stirred at room temperature for 48 hours
  2. stirringthe mixture stirred at room temperature for 70 hours
  3. stirringthe mixture stirred at room temperature for 24 hours
  4. stirringthe mixture stirred at room temperature for 24 hours
  5. stirringthe mixture stirred at room temperature for 24 hours
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. concentrationconcentrated in vacuum

출처 및 근거

ORD 기록
ord-dd737fd63ea544e1bfc7fb57682ca20a
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09345793B2

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