Sodium hydride → 1-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-((2,4-difluorobenzyl)oxy)pyridin-2(1H)-one

HRID 2202863Notes

Reaction equation

HRID 2202863 reaction equation
[H-].[Na+].[CH:3]1([C:6]2[N:7]=[C:8]3[CH:13]=[CH:12][C:11]([N:14]4[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]4=[O:21])=[CH:10][N:9]3[C:22]=2[CH3:23])[CH2:5][CH2:4]1.[F:24][C:25]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:26]=1[CH2:27]Br>C1COCC1>[CH:3]1([C:6]2[N:7]=[C:8]3[CH:13]=[CH:12][C:11]([N:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:27][C:26]5[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:25]=5[F:24])=[CH:16][C:15]4=[O:21])=[CH:10][N:9]3[C:22]=2[CH3:23])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 896902811-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 896905191-(2-Cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-((2,4-difluorobenzyl)oxy)pyridin-2(1H)-oneYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred suspension of NaH (40% oil dispersion, 19 mg) in THF (6 ml) was added a solution of 1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-4-hydroxypyridin-2 (1H)-one (75 mg) in THF (1 ml) at 0° C., and then the mixture was stirred at room temperature for 30 min. 2,4-Difluorobenzyl bromide (67 mg) in THF (0.5 ml) was added, and the resulting mixture was stirred at room temperature for further 3 h followed by heating at reflux for 6 h. The reaction mixture was then cooled to room temperature and quenched with ice-water. The mixture was extracted with DCM, and the extract was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel column chromatography (MeOH/DCM) to give the title compound (38 mg) as an off-white solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for further 3 h
  2. temperatureby heating
  3. temperatureat reflux for 6 h
  4. temperatureThe reaction mixture was then cooled to room temperature
  5. customquenched with ice-water
  6. extractionThe mixture was extracted with DCM
  7. washthe extract was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel column chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-694a898808c64a83a6b48e3d70002227
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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