Potassium Carbonate → (4R)-1-(5-chloro-3-(2-methoxyphenyl)-1-{[2-methoxy-4-(trifluoromethoxy)phenyl]sulfonyl}-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-L-prolinamide

HRID 1662590노트

반응식

HRID 1662590 반응식
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([N:20]1[CH2:29][C@H:28]([OH:30])[CH2:27][C@H:21]1[C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19].[H-].[Na+].[CH3:33][O:34][C:35]1[CH:40]=[C:39]([O:41][C:42]([F:45])([F:44])[F:43])[CH:38]=[CH:37][C:36]=1[S:46](Cl)(=[O:48])=[O:47].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:46]([C:36]1[CH:37]=[CH:38][C:39]([O:41][C:42]([F:43])([F:44])[F:45])=[CH:40][C:35]=1[O:34][CH3:33])(=[O:47])=[O:48])[C:6](=[O:11])[C:5]2([N:20]1[CH2:29][C@H:28]([OH:30])[CH2:27][C@H:21]1[C:22]([N:24]([CH3:25])[CH3:26])=[O:23])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19]

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 67044068(2S,4R)-1-(5-Chloro-3-(2-methoxyphenyl)-2-oxoindolin-3-YL)-4-hydroxy-N,N-dimethylpyrrolidine-2-carboxamideHCID 717442152-Methoxy-4-(trifluoromethoxy)benzene-1-sulfonyl chloride

생성물 1

HCID 59867939(4R)-1-(5-chloro-3-(2-methoxyphenyl)-1-{[2-methoxy-4-(trifluoromethoxy)phenyl]sulfonyl}-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-L-prolinamide수율 68.9%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 512 mg of (4R)-1-[5-chloro-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimet hyl-L-prolinamide (levorotatory isomer), which is the compound described in Preparation 3.2 (Isomer B) of Brochure No. WO01/55130 in DMF (5 ml) was added 57.1 mg of NaH under ice cooling, and the solution was stirred for 30 minutes at the same temperature. A solution of 415 mg of 2-methoxy-4-(trifluoromethoxy)benzene sulfonyl chloride in DMF (3 ml) was added, then, the solution was stirred for 30 minutes at the same temperature. To the reaction solution was added an aqueous solution of 10% K2CO3, and the resulting mixture was stirred at room temperature for 1 hour. Water and EtOAc were added, liquid separation was performed, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed with water and saturated brine, then, was dried over MgSO4. The drying agent was separated by filtration, solvent was evaporated under reduced pressure. The obtained residue was purified by column chromatography (silicagel 60; mobile phase: n-hexane/EtOAc=1/2 to 1/2.5; v/v), to obtain 561 mg of the title compound (colorless amorphous).

후처리

  1. customdescribed in Preparation 3.2 (Isomer B) of Brochure No
  2. stirringthe solution was stirred for 30 minutes at the same temperature
  3. stirringthe resulting mixture was stirred at room temperature for 1 hour
  4. customliquid separation
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic layer was washed with water and saturated brine
  7. dry with materialwas dried over MgSO4
  8. customThe drying agent was separated by filtration, solvent
  9. customwas evaporated under reduced pressure
  10. customThe obtained residue was purified by column chromatography (silicagel 60; mobile phase: n-hexane/EtOAc=1/2 to 1/2.5; v/v)

출처 및 근거

ORD 기록
ord-31fdc89fc61f466396f0a6984635b420
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030499B2

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