(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone → (3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 928856

반응식

HRID 928856 반응식
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([Cl:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17](Br)=[CH:16][C:15]=4[CH3:23])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.N1(C2C=CC(CC3C(OC)=NC4C(C=3Cl)=CC(Br)=CC=4C)=CC=2)C=CC=N1.[Cl:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]([C:63]2[N:67]([CH3:68])[CH:66]=[N:65][CH:64]=2)=[O:62])=[CH:57][CH:56]=1.[Li]CCCC>>[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([Cl:24])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:61]([C:58]3[CH:59]=[CH:60][C:55]([Cl:54])=[CH:56][CH:57]=3)([C:63]3[N:67]([CH3:68])[CH:66]=[N:65][CH:64]=3)[OH:62])=[CH:16][C:15]=4[CH3:23])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

참가 물질

5

반응물 4

HCID 11521405(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone2회HCID 867155983-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloro-8-methylquinolineHCID 867155993-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxy-8-methylquinolineHCID 178418339Butyllithium

생성물 1

HCID 74221529(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

반응 조건

온도
-78 °C

실험 절차

A mixture of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloro-8-methylquinoline (393 mg, 0.880 mmol, Intermediate 19: step a) and (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (194 mg, 0.880 mmol, Intermediate 1: step b) in dry degassed THF (16 mL) was cooled to −78° C. and n-BuLi (1.6 M in hexane, 0.5 mL, 0.8 mmol) was added over 1.5 minutes. Stirring was continued at −78° C. for 10 minutes and the dry ice acetone bath was replaced with an ice water bath. Stirring was continued for 1 hour and the reaction mixture was quenched with saturated aqueous NH4Cl solution. EtOAc was added and the layers were separated and the aqueous mixture again extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification using flash column chromatography (5% MeOH in dichloromethane) yielded the substantially pure title compound. MS (ESI) 588.2.

후처리

  1. customdegassed THF (16 mL)
  2. stirringStirring
  3. waitwas continued for 1 hour
  4. customthe reaction mixture was quenched with saturated aqueous NH4Cl solution
  5. additionEtOAc was added
  6. customthe layers were separated
  7. extractionthe aqueous mixture again extracted with EtOAc
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. filtrationfiltered
  10. customthe solvents were removed under reduced pressure
  11. customPurification

출처 및 근거

ORD 기록
ord-92131e0fec67420195d776e6d166bfbb
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290476B2

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