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

HRID 526336노트

반응식

HRID 526336 반응식
[OH:1][C:2]1[CH:3]=[C:4]([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:5]=[CH:6][CH:7]=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]=[C:4]([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:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonate2회HCID 69804Ethane, 1-fluoro-2-iodo-8회HCID 71258986tert-butyl 4-{3-[(3R)-3-({1-[5-(3-hydroxyphenyl)pyridin-3-yl]-3-m ethoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

생성물 1

HCID 71609303tert-butyl 4-{3-[(3R)-3-{[1-{5-[3-(2-fluoroethoxy)phenyl]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate수율 71.2%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

128 mg (0.21 mmol) tert-butyl 4-{3-[(3R)-3-({1-[5-(3-hydroxyphenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate were dissolved in 2.25 ml tetrahydrofurane. 134 mg (0.41 mmol) cesium carbonate and 68 mg (0.39 mmol) 1-iodo-2-fluoroethane were added. The mixture was stirred at room temperature for 70 hours. 68 mg (0.39 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 48 hours. 68 mg (0.39 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 70 hours. 68 mg (0.39 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 24 hours. 68 mg (0.39 mmol) 1-iodo-2-fluoroethane, 2 ml tetrahydrofurane and 134 mg (0.41 mmol) cesium carbonate were added and the mixture stirred at room temperature for 24 hours. 68 mg (0.39 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 24 hours. 68 mg (0.39 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 24 hours. 68 mg (0.39 mmol) 1-iodo-2-fluoroethane were added and the mixture stirred at room temperature for 70 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 100 mg (65%) tert-butyl 4-{3-[(3R)-3-{[1-{5-[3-(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. stirringthe mixture stirred at room temperature for 24 hours
  7. stirringthe mixture stirred at room temperature for 70 hours
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic phase was dried over sodium sulfate
  10. concentrationconcentrated in vacuum

출처 및 근거

ORD 기록
ord-77a3d4e1f8e24d0d9538cdef982ba982
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345793B2

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