Diisopropylcarbodiimide → (3Ez,5s)-1-(biphenyl-4-ylcarbonyl)-5-[(3-methyl-1,2,4oxadiazol-5-yl)methyl]pyrrolidin-3-one o-methyloxime

HRID 225971

반응식

HRID 225971 반응식
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:14][O:15][CH3:16])[CH2:11][C@H:10]2[CH2:17][C:18](O)=[O:19])=[O:8])=[CH:3][CH:2]=1.O[N:28]=[C:29]([NH2:31])[CH3:30].CC(C)N=C=NC(C)C>ClCCl>[CH3:16][O:15][N:14]=[C:12]1[CH2:11][C@@H:10]([CH2:17][C:18]2[O:19][N:31]=[C:29]([CH3:30])[N:28]=2)[N:9]([C:7]([C:4]2[CH:3]=[CH:2][C:1]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[CH:6][CH:5]=2)=[O:8])[CH2:13]1

참가 물질

5

반응물 3

HCID 12734DiisopropylcarbodiimideHCID 30926N-HydroxyacetamidineHCID 131727525[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl] acetic acid2회

생성물 1

HCID 131727534(3Ez,5s)-1-(biphenyl-4-ylcarbonyl)-5-[(3-methyl-1,2,4oxadiazol-5-yl)methyl]pyrrolidin-3-one o-methyloxime수율 102.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of [(2S,4EZ)-1-biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl]acetic acid (Intermediate 7, 50 mg, 0.14 mmol) in dichloromethane (3 ml) was added N′-hydroxyethanimidamide (12 mg, 0.16 mmol) followed by DIC (36 mg, 0.28 mmol). The reaction mixture was stirred 1 h30. The precipitate was filtered and the solution was concentrated in vacuo. Pyridine (1 ml) was added and the reaction mixture was stirred at reflux overnight The solvent was removed and dichloromethane was added. The organic phase was washed with HCl 1N then NaHCO3. The organic phase was dried (MgSO4), concentrated and purified on silica gel column chromatography (Ethyl acetate/cyclohexane, 40:60) to afford (3EZ,5S)-1-(biphenyl-4-ylcarbonyl)-5-[(3-methyl-1,2,4oxadiazol-5-yl)methyl]pyrrolidin-3-one O-methyloxime (56 mg). Yield: 91%. HPLC purity: 90%

후처리

  1. filtrationThe precipitate was filtered
  2. concentrationthe solution was concentrated in vacuo
  3. additionPyridine (1 ml) was added
  4. stirringthe reaction mixture was stirred
  5. temperatureat reflux overnight The solvent
  6. customwas removed
  7. additiondichloromethane was added
  8. washThe organic phase was washed with HCl 1N
  9. dry with materialThe organic phase was dried (MgSO4)
  10. concentrationconcentrated
  11. custompurified on silica gel column chromatography (Ethyl acetate/cyclohexane, 40:60)

출처 및 근거

ORD 기록
ord-0ac680e44b2a4b5faab3f1a675f39c0c
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557136B2

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