3-Pyridinyl[4-(trifluoromethyl)phenyl]methanone → HCID 74220681, compound

HRID 928835Notes

Reaction equation

HRID 928835 reaction equation
[Li]CCCC.[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22](Br)=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([C:40]2[CH:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][CH:41]=2)=[O:39])[CH:33]=1>C1COCC1>[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22]([C:38]([C:34]3[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=3)([C:40]3[CH:41]=[CH:42][C:43]([C:46]([F:47])([F:48])[F:49])=[CH:44][CH:45]=3)[OH:39])=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

Participants

5

Reactant 3

HCID 129300623-Pyridinyl[4-(trifluoromethyl)phenyl]methanone2×HCID 867155963-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline2×HCID 178418339Butyllithium

Product 1

HCID 74220681HCID 74220681, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-BuLi (2.5 M in hexanes, 0.07 mL, 0.175 mmol) was added dropwise by syringe to a solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (75.9 mg, 0.177 mmol, Intermediate 16) in dry THF (3 mL) in a dry ice-acetone bath. After 1.5 minutes, a solution of pyridin-3-yl(4-(trifluoromethyl)phenyl)methanone (48.0 mg, 0.191 mmol, Intermediate 26: step b) in dry THF (0.2 mL) was added dropwise. The reaction mixture was stirred for 5 minutes in a dry ice-acetone bath, then the reaction flask was placed into an ice-water bath. After 10 minutes, the mixture was warmed to room temperature and the reaction was quenched with methanol and water. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 10-50% EtOAc-Hexanes) to provide the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.51 (d, J=2.2 Hz, 1H), 8.48 (dd, J=4.8, 1.4 Hz, 1H), 8.02 (d, J=2.1 Hz, 1H), 7.83 (d, J=2.4 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.66 (d, J=1.6 Hz, 1H), 7.66-7.63 (m, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.49 (dd, J=8.8, 2.2 Hz, 1H), 7.46 (d, J=8.3 Hz, 2H), 7.34 (d, J=8.5 Hz, 2H), 7.26-7.23 (m, 1H), 6.42 (t, J=2.1 Hz, 1H), 4.29 (s, 2H), 4.08 (s, 3H); MS m/e 602.1 [M+H]+.

Workup

  1. customthe reaction flask was placed into an ice-water bath
  2. waitAfter 10 minutes
  3. customthe reaction was quenched with methanol and water
  4. customThe mixture was partitioned between water and ethyl acetate
  5. extractionThe separated aqueous phase was further extracted with ethyl acetate
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash column chromatography (silica gel, 10-50% EtOAc-Hexanes)

Sources & evidence

ORD record
ord-e0034694d3a7472f80086b1b03f415b7
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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