Sodium hydride → 3-[3-tert-Butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

HRID 1036834노트

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HRID 1036834 반응식
[CH2:1]([O:3][C:4](=[O:31])[C:5]([CH3:30])([CH3:29])[CH2:6][C:7]1[NH:8][C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)=[CH:11][CH:10]=2)[CH3:2].[H-].[Na+].[CH3:34][O:35][C:36]1[N:41]=[CH:40][C:39]([C:42]2[CH:53]=[CH:52][C:45]([CH2:46]OS(C)(=O)=O)=[CH:44][CH:43]=2)=[CH:38][CH:37]=1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:31])[C:5]([CH3:30])([CH3:29])[CH2:6][C:7]1[N:8]([CH2:46][C:45]2[CH:44]=[CH:43][C:42]([C:39]3[CH:40]=[N:41][C:36]([O:35][CH3:34])=[CH:37][CH:38]=3)=[CH:53][CH:52]=2)[C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)=[CH:11][CH:10]=2)[CH3:2]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 444749063-[3-tert-Butylsulfanyl-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl esterHCID 59556522Methanesulfonic acid 4-(6-methoxy-pyridin-3-yl)-benzyl ester

생성물 1

HCID 162262693-[3-tert-Butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
-10 °C

실험 절차

3-[3-tert-Butylsulfanyl-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester (A-4; 20.0 g, 45.4 mmol) was dissolved in DMF (150 mL) and cooled to −10° C. under N2. Sodium hydride (60% dispersion in mineral oil; 2.0 g, 50.0 mmol) was added portionwise, and the reaction was stirred at −10° C. for 45 minutes until the foam had disappeared. To this dark brown-reddish solution was added methanesulfonic acid 4-(6-methoxy-pyridin-3-yl)-benzyl ester (Int-72; 16.0 g, 54.5 mmol) in DMF dropwise. The reaction was then stirred at −10° C. for 1 hour and allowed to warm to room temperature slowly. After 16 hours, LCMS confirmed the formation of the product. The reaction was quenched with saturated NH4Cl and diluted with methyl tert-butyl ether (MTBE) and water. The aqueous phase was extracted twice with MTBE. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the crude product was purified by column chromatography to give the desired product (A-5).

후처리

  1. stirringThe reaction was then stirred at −10° C. for 1 hour
  2. temperatureto warm to room temperature slowly
  3. waitAfter 16 hours
  4. customThe reaction was quenched with saturated NH4Cl
  5. additiondiluted with methyl tert-butyl ether (MTBE) and water
  6. extractionThe aqueous phase was extracted twice with MTBE
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customthe crude product was purified by column chromatography

출처 및 근거

ORD 기록
ord-e9064f7d17ad4defb067fb8936ed5406
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546431B2

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