Dimethylformamide → (R)-Methyl 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate

HRID 83914노트

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HRID 83914 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][C:28]([S:32]([OH:35])(=[O:34])=O)=[CH:27][C:26]=3[F:36])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:37][CH3:38].S(Cl)(Cl)=O.CN(C=O)C.[CH3:48][O:49][C:50](=[O:54])[C@@H:51]([CH3:53])[NH2:52]>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([S:23][CH2:24][C:25]3[C:30]([F:31])=[CH:29][C:28]([S:32]([NH:52][C@H:51]([CH3:53])[C:50]([O:49][CH3:48])=[O:54])(=[O:35])=[O:34])=[CH:27][C:26]=3[F:36])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:37][CH3:38]

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 89020methyl D-alaninateHCID 866622244-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzenesulfonic acid

생성물 1

HCID 68070481(R)-Methyl 2-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propanoate수율 77%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 10340Sodium Carbonate용매

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온도
65 °C

실험 절차

To a solution of 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorbenzenesulfonic acid (3.0 g, 5.1 mmol) in DCM (15 mL) was added thionyl chloride (7.5 mL) and DMF (0.1 mL). The mixture was heated at 65° C. for 1 h then concentrated in vacuo and azeotroped with toluene (10 mL) and DCM (10 mL). The pale yellow foam was dissolved in DCM (15 mL) and was added dropwise to a solution of D-alanine methyl ester (2.9 g, 20.6 mmol) in 2M Na2CO3 (30 mL) with vigorous stirring. Upon complete addition the layers were separated and the organics were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with 0-70% ethyl acetate/hexane to afford a white foam (2.4 g, 77%). MS (EI) m/z 601.3 (M+).

후처리

  1. concentrationthen concentrated in vacuo
  2. customazeotroped with toluene (10 mL) and DCM (10 mL)
  3. dissolutionThe pale yellow foam was dissolved in DCM (15 mL)
  4. additionUpon complete addition the layers
  5. customwere separated
  6. dry with materialthe organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography
  10. washeluting with 0-70% ethyl acetate/hexane

출처 및 근거

ORD 기록
ord-eb474dea4a9c4a919fa7f8608b4b1e68
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846739B2

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