Sodium hydride → 4-Bromo-2-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)benzonitrile

HRID 1431265Notes

Reaction equation

HRID 1431265 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:19])=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[Br:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25](F)[CH:24]=1>CN(C=O)C.CCOC(C)=O.[Li+].[Cl-]>[Br:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([O:19][C:6]2[C:5]3[C:10](=[CH:11][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:7]=2[CH3:18])[CH:24]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 7360294-Bromo-2-fluorobenzonitrileHCID 178421969HCID 178421969, compound

Product 1

HCID 596310624-Bromo-2-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)benzonitrile

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 433294Lithium ChlorideSolvent

Procedure

To a stirred solution of 7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ol (130 mg, 0.51 mmol) in DMF (2.5 mL) was added sodium hydride (18.4 mg, 0.77 mmol). The reaction was stirred at rt for 20 min and then treated with 4-bromo-2-fluorobenzonitrile (102 mg, 0.51 mmol). The reaction was stirred at rt for 20 min and then at 110° C. for 12 h. After this time the reaction was cooled to rt and diluted with EtOAc (100 mL) and LiCl (1M aq. solution, 40 mL). The separated organic layer was dried over magnesium sulfate, filtered and evaporated in vacuo and the residue was purified by flash chromatography (hexanes:EtOAc, 1:0 to 2:1) to give 4-bromo-2-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)oxy)benzonitrile. 1H NMR (400 MHz, chloroform-d) δ ppm 8.75 (1H, d, J=5.1 Hz), 7.90-7.98 (2H, m), 7.77-7.89 (2H, m), 7.62 (1H, d, J=8.2 Hz), 7.29-7.45 (3H, m), 6.64 (1H, d, J=2.0 Hz), 2.41 (3H, s). Mass Spectrum (ESI) m/e=434.0 [(M+1) (79Br)] and 435.8 [(M+1) (81Br)].

Workup

  1. stirringThe reaction was stirred at rt for 20 min
  2. waitat 110° C. for 12 h
  3. temperatureAfter this time the reaction was cooled to rt
  4. dry with materialThe separated organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customthe residue was purified by flash chromatography (hexanes:EtOAc, 1:0 to 2:1)

Sources & evidence

ORD record
ord-140b305b76c444beb2c49a88dda24d52
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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