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 83914

反応式

HRID 83914 の反応式
[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]

参加物

7

反応物 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

生成物 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)propanoate収率 77%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
65 °C

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-eb474dea4a9c4a919fa7f8608b4b1e68
出典データセット
uspto-grants-2014_09
特許番号
US08846739B2

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