Carbon Dioxide → (3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol

HRID 928855

반응식

HRID 928855 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.[CH3:54][N:55]1[C:59]([C:60]([C:62]2[CH:63]=[N:64][C:65]([C:68]([F:71])([F:70])[F:69])=[CH:66][CH:67]=2)=[O:61])=[CH:58][N:57]=[CH:56]1.[Li]CCCC.C(=O)=O>>[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:60]([C:59]3[N:55]([CH3:54])[CH:56]=[N:57][CH:58]=3)([C:62]3[CH:63]=[N:64][C:65]([C:68]([F:70])([F:69])[F:71])=[CH:66][CH:67]=3)[OH:61])=[CH:16][C:15]=4[CH3:23])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

참가 물질

6

반응물 5

HCID 280Carbon DioxideHCID 86715442(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-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 86715672(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-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 (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (224 mg, 0.880 mmol, Intermediate 36: step c) in dry degassed THF (16 mL, THF was degassed with nitrogen for 1 h) 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 bath was replaced with an ice water bath. Stirring was continued for 1 hour after which 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) 623.2.

후처리

  1. customdegassed THF (16 mL, THF was degassed with nitrogen for 1 h)
  2. stirringStirring
  3. waitwas continued for 1 hour
  4. customafter which the 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-8c02b199d11844e6a12625e885169c24
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290476B2

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