(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ノート

反応式

HRID 928856 の反応式
[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

参加物

5

反応物 4

HCID 11521405(4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone2 回HCID 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

生成物 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

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-92131e0fec67420195d776e6d166bfbb
出典データセット
uspto-grants-2016_03
特許番号
US09290476B2

反応ノート

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