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

HRID 526371노트

반응식

HRID 526371 반응식
C(O[C:9]1[CH:10]=[C:11]([C@@H:15]([NH:21][C:22]([C@@H:24]2[CH2:29][CH2:28][CH2:27][N:26]([C:30](=[O:46])[CH2:31][CH2:32][CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[CH2:25]2)=[O:23])[CH2:16][C:17]([O:19][CH3:20])=[O:18])[CH:12]=[N:13][CH:14]=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC(S([O:62][CH2:63][CH2:64][O:65][S:66]([C:69]2[CH:74]=[CH:73][C:72]([CH3:75])=[CH:71][CH:70]=2)(=[O:68])=[O:67])(=O)=O)=CC=1>CN(C)C=O>[CH3:20][O:19][C:17](=[O:18])[CH2:16][C@H:15]([NH:21][C:22]([C@@H:24]1[CH2:29][CH2:28][CH2:27][N:26]([C:30](=[O:46])[CH2:31][CH2:32][CH:33]2[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:43])([CH3:45])[CH3:44])=[O:40])[CH2:37][CH2:38]2)[CH2:25]1)=[O:23])[C:11]1[CH:12]=[N:13][CH:14]=[C:9]([O:62][CH2:63][CH2:64][O:65][S:66]([C:69]2[CH:70]=[CH:71][C:72]([CH3:75])=[CH:73][CH:74]=2)(=[O:67])=[O:68])[CH:10]=1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 228289Ethylene glycol ditosylateHCID 71259024Tert-butyl 4-{3-[(3R)-3-({(1S)-1-[5-(benzyloxy)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

생성물 1

HCID 71609635tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat수율 39.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Tert-butyl 4-{3-[(3R)-3-({(1S)-1-[5-(benzyloxy)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 5e, 200 mg, 0.37 mmol) was dissolved in N,N-dimethylformamide (25.3 mL). Cesium carbonate (298 mg, 0.92 mmol) and ethylene glycol bis-p-toluenesulfonate (203 mg, 0.55 mmol) were added. The mixture was stirred at room temperature for 2 hours and stored at 5° C. for 17 hours. The mixture was quenched by addition of saturated aqueous ammonium chloride solution and extracted with 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 preparative thin layer chromatography on silica gel (ethyl acetate 100%) to yield 109 mg of tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat.

후처리

  1. waitstored at 5° C. for 17 hours
  2. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationThe solution was concentrated under reduced pressure
  7. customthe residue was purified by preparative thin layer chromatography on silica gel (ethyl acetate 100%)

출처 및 근거

ORD 기록
ord-20a6e253964b488281338652614098da
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345793B2

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