Sodium hydride → tert-Butyl-2-(6-((2-(acetylamino)-1,3-benzothiazol-4-yl)oxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate

HRID 859036노트

반응식

HRID 859036 반응식
[OH:1][C:2]1[C:7]2[N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:17]([O:21][C:22](=[O:41])[NH:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38](Cl)[N:37]=[CH:36][N:35]=1)([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C>[C:17]([O:21][C:22](=[O:41])[NH:23][C:24]1[CH:29]=[C:28]([C:30]([F:32])([F:31])[F:33])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38]([O:1][C:2]2[C:7]3[N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[S:10][C:6]=3[CH:5]=[CH:4][CH:3]=2)[N:37]=[CH:36][N:35]=1)([CH3:20])([CH3:18])[CH3:19]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 540449Acetamide, N-(4-hydroxy-2-benzothiazolyl)-HCID 23577237Tert-butyl 2-(6-chloropyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate

생성물 1

HCID 11957782tert-Butyl-2-(6-((2-(acetylamino)-1,3-benzothiazol-4-yl)oxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of N-(4-hydroxybenzo-thiazol-2-yl)-acetamide, (Example 144(c)), (96 g, 27 mmol) in DMF (200 mL) was added NaH (0.68 g, 28 mmol, 60% dispersion in oil, Aldrich) and the mixture was stirred at 0° C. for 15 min. [2-(6-Chloro-pyrimidin-4-yl)-5-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester, (Example 148(b)), (10 g, 26 mmol) was then added and the reaction mixture was allowed to warm to room temperature, and stirred for 4.5 h. The reaction mixture was quenched with H2O (200 mL) and poured into a solution containing 30% ethyl acetate/hexanes (500 mL) and 1 N NaOH (800 mL). A white precipitate which formed was filtered and the filtercake was washed with H2O (100 mL) and 10% EtOAc/hexanes (100 mL). The filtercake was dried in vacuum, redissolved in an acetone/methanol mixture and adsorbed on silica gel. Purification by silica gel chromatography (2:1 EtOAc/hexanes) afforded the product as a white crystalline solid. Mp: 194–195° C. MS (ESI, pos. ion) m/z: 546 (M+1).

후처리

  1. additionwas then added
  2. customThe reaction mixture was quenched with H2O (200 mL)
  3. additionpoured into a solution
  4. additioncontaining 30% ethyl acetate/hexanes (500 mL) and 1 N NaOH (800 mL)
  5. customA white precipitate which formed
  6. filtrationwas filtered
  7. washthe filtercake was washed with H2O (100 mL) and 10% EtOAc/hexanes (100 mL)
  8. customThe filtercake was dried in vacuum
  9. dissolutionredissolved in an acetone/methanol mixture
  10. customPurification by silica gel chromatography (2:1 EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-1f1736aee1714473afdf2e368c85c034
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07148221B2

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