Cesium carbonate → tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat

HRID 526377노트

반응식

HRID 526377 반응식
[C:1]([O:5][C:6](=[O:38])[CH2:7][C@H:8]([NH:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:37])[CH2:26][CH2:27][CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O-:36])=[O:35])[CH2:30][CH2:29]2)[CH2:20]1)=[O:18])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([OH:15])[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[C:45]1([CH3:68])[CH:50]=[CH:49][C:48]([S:51]([O:54][CH2:55][CH2:56]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:53])=[O:52])=[CH:47][CH:46]=1>CN(C)C=O>[C:1]([O:5][C:6](=[O:38])[CH2:7][C@H:8]([NH:16][C:17]([C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](=[O:37])[CH2:26][CH2:27][CH:28]2[CH2:29][CH2:30][N:31]([C:34]([O:36][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:35])[CH2:32][CH2:33]2)[CH2:20]1)=[O:18])[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([O:15][CH2:56][CH2:55][O:54][S:51]([C:48]2[CH:49]=[CH:50][C:45]([CH3:68])=[CH:46][CH:47]=2)(=[O:53])=[O:52])[CH:14]=1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 10796Cesium carbonate2회HCID 228289Ethylene glycol ditosylate2회HCID 1317355954-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

생성물 1

HCID 71609636tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat수율 154.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-(5-hydroxypyridin-3-yl)-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (200 mg, 0.34 mmol) were dissolved in N,N-dimethylformamide (39 mL). Cesium carbonate (277 mg, 0.85 mmol) and ethylene glycol bis-p-toluenesulfonate (188 mg, 0.51 mmol) were added. The mixture was stirred at room temperature for 4 hours, the addition of cesium carbonate (277 mg, 0.85 mmol) and ethylene glycol bis-p-toluenesulfonate (188 mg, 0.51 mmol) was repeated and stirring at 5° C. was continued for 17 hours. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and extracted with diethyl ether and ethyl acetate. The combined extracts were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 60%) to yield 207 mg of tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat.

후처리

  1. stirringstirring at 5° C.
  2. waitwas continued for 17 hours
  3. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
  4. extractionextracted with diethyl ether and ethyl acetate
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe solution was concentrated under reduced pressure
  8. customthe residue was purified by chromatography on silica gel (ethyl acetate in hexane 20% to 100% followed by dioxane in ethyl acetate 0 to 60%)

출처 및 근거

ORD 기록
ord-e82a4768d3d6418cb7996574f111be72
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345793B2

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