Dimethylformamide → (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide

HRID 2192942노트

반응식

HRID 2192942 반응식
[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][C@H:21]3[CH2:25][CH2:24][C:23](=[O:26])[CH2:22]3)[C:17]([OH:19])=O)[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.C[N:34](C=O)C.[CH3:38][O:39][C:40]1[CH:61]=[CH:60][C:43]([CH2:44][O:45][C:46]([CH3:59])([CH3:58])[CH2:47][O:48][C:49]2[N:50]=[CH:51][C:52](C(N)=O)=[N:53][CH:54]=2)=[CH:42][CH:41]=1>ClCCl.O.N1C=CC=CC=1>[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][C@H:21]3[CH2:25][CH2:24][C:23](=[O:26])[CH2:22]3)[C:17]([NH:34][C:52]3[CH:51]=[N:50][C:49]([O:48][CH2:47][C:46]([O:45][CH2:44][C:43]4[CH:60]=[CH:61][C:40]([O:39][CH3:38])=[CH:41][CH:42]=4)([CH3:59])[CH3:58])=[CH:54][N:53]=3)=[O:19])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:14][CH2:15]2)(=[O:11])=[O:12])[CH2:2][CH2:3]1

참가 물질

8

반응물 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 59570882(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoic acidHCID 686713995-{2-[(4-Methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-amide

생성물 1

HCID 68671583(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide

시약·촉매·용매 3

HCID 962Water용매HCID 1049Pyridine용매HCID 6344Dichloromethane용매

실험 절차

To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoic acid (99 mg) in dichloromethane (2.0 mL) were added oxalyl chloride (27 μL) and DMF (3 μL) under ice-cooling, followed by stirring for 10 minutes. Thereafter, pyridine (28 μL) and 5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-amide (53 mg) were added thereto under ice-cooling, followed by stirring for 20 minutes. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1) to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide (82 mg) as a white amorphous substance. A mixture of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-{2-[(4-methoxybenzyl)oxy]-2-methylpropoxy}pyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide (82 mg), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (56 mg), dichloromethane (7.5 mL), and water (0.38 mL) was stirred at room temperature for 10 minutes. To the reaction mixture was added water, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=80:20). The obtained residue was sonicated with diethyl ether and the resulting precipitate was collected by filtration to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(2-hydroxy-2-methylpropoxy)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide (52 mg) as a white solid.

후처리

  1. temperaturecooling
  2. temperatureunder ice-cooling
  3. stirringby stirring for 20 minutes
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1-1:1)

출처 및 근거

ORD 기록
ord-f599982603074e10991738abfbddd55a
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329707B2

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