(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone → HCID 86716148, compound

HRID 627568Notes

Reaction equation

HRID 627568 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([O:18][CH3:19])[C:11]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)=[C:10]2[Cl:27].[CH3:28][N:29]1[C:33]([C:34]([C:36]2[CH:37]=[N:38][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:40][CH:41]=2)=[O:35])=[CH:32][N:31]=[CH:30]1>C1COCC1>[Cl:27][C:10]1[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]([C:34]([C:33]3[N:29]([CH3:28])[CH:30]=[N:31][CH:32]=3)([C:36]3[CH:37]=[N:38][C:39]([C:42]([F:44])([F:43])[F:45])=[CH:40][CH:41]=3)[OH:35])[CH:8]=2)[N:13]=[C:12]([O:18][CH3:19])[C:11]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1

Participants

5

Reactant 3

HCID 86715442(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone2×HCID 86716096HCID 86716096, compound2×HCID 178418339Butyllithium

Product 1

HCID 86716148HCID 86716148, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-BuLi (1.6 M in hexane, 2.19 mL, 3.50 mmol) was added over approximately 1 min to a solution of 6-bromo-4-chloro-3-(3-fluorophenyl)-2-methoxy-8-methylquinoline (1.40 g, 3.68 mmol, Intermediate 52) in THF (5 mL) under argon at −78° C. After 1 min, a solution of (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (939 mg, 3.68 mmol, Intermediate 15, step c) in 5 mL THF under argon was added via cannula. The resulting mixture was stirred at −78° C. for 10 min, then transferred to an ice water bath and stirred 30 min. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water and extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 45-60% CH3CN in [2% conc. aqueous NH4OH in DCM, aqueous phase removed]) to afford the title compound as a white foam.

Workup

  1. customtransferred to an ice water bath
  2. stirringstirred 30 min
  3. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  4. additiondiluted with water
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (silica gel, 45-60% CH3CN in [2% conc. aqueous NH4OH in DCM, aqueous phase removed])

Sources & evidence

ORD record
ord-3baa6ec835aa4f2da841fc1f81fc6698
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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