(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone → HCID 74221463, compound

HRID 926448

Reaction equation

HRID 926448 reaction equation
[N:1]1([C:6]2[CH:25]=[CH:24][C:9]([CH2:10][C:11]3[C:12]([Cl:23])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17](Br)=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[CH3:26][N:27]1[C:31]([C:32]([C:34]2[CH:35]=[N:36][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:38][CH:39]=2)=[O:33])=[CH:30][N:29]=[CH:28]1.[Li]CCCC>C(=O)=O.CC(C)=O>[N:1]1([C:6]2[CH:25]=[CH:24][C:9]([CH2:10][C:11]3[C:12]([Cl:23])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:32]([C:31]3[N:27]([CH3:26])[CH:28]=[N:29][CH:30]=3)([C:34]3[CH:35]=[N:36][C:37]([C:40]([F:42])([F:41])[F:43])=[CH:38][CH:39]=3)[OH:33])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 86715442(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone2×HCID 867155943-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloroquinoline2×HCID 178418339Butyllithium

Product 1

HCID 74221463HCID 74221463, compound

Reagents, catalysts & solvents 1

HCID 18522661Acetone cardiceSolvent

Procedure

A round bottom flask was charged with 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloroquinoline (827 mg, 1.91 mmol, Intermediate 3: step c) and (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (536 mg, 2.10 mmol, Intermediate 2: step c). The flask was evacuated and back-filled with argon, then THF (27 mL) was added. The resulting yellow suspension was heated until nearly all solid dissolved, and the slightly cloudy yellow suspension was allowed to cool to room temperature, and then was cooled in a dry ice acetone bath for 7 minutes before addition of n-BuLi (1.6 M in hexane, 1.55 mL, 2.48 mmol) dropwise. The mixture was stirred for 5 minutes in dry ice/acetone bath, then was moved to an ice/water bath and stirred for 1 hour. The reaction was quenched by the addition of saturated aqueous NH4Cl, and was diluted with water. The aqueous was then extracted with EtOAc (3×). The organic layers were combined and washed once with water. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The residue was purified by flash column chromatography (silica gel, 0-2% MeOH-DCM) affording impure title compound which was used without further purification in the next step.

Workup

  1. customThe flask was evacuated
  2. additionback-filled with argon
  3. additionTHF (27 mL) was added
  4. temperatureThe resulting yellow suspension was heated until nearly all solid
  5. dissolutiondissolved
  6. customwas moved to an ice/water bath
  7. customThe reaction was quenched by the addition of saturated aqueous NH4Cl
  8. additionwas diluted with water
  9. extractionThe aqueous was then extracted with EtOAc (3×)
  10. washwashed once with water
  11. dry with materialThe organic phase was dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. customThe residue was purified by flash column chromatography (silica gel, 0-2% MeOH-DCM)

Sources & evidence

ORD record
ord-04c7ee5b60f944e995d037238d973309
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Linked notes

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