Sodium hydride → 1-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((3-fluorobenzyl)oxy)pyridin-2(1H)-one

HRID 2202910Notes

Reaction equation

HRID 2202910 reaction equation
[H-].[Na+].[CH:3]1([C:6]2[N:10]([CH3:11])[C:9]3[CH:12]=[C:13]([N:16]4[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]4=[O:23])[CH:14]=[CH:15][C:8]=3[N:7]=2)[CH2:5][CH2:4]1.Br[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1>C1COCC1>[CH:3]1([C:6]2[N:10]([CH3:11])[C:9]3[CH:12]=[C:13]([N:16]4[CH:21]=[CH:20][C:19]([O:22][CH2:25][C:26]5[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=5)=[CH:18][C:17]4=[O:23])[CH:14]=[CH:15][C:8]=3[N:7]=2)[CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680073-Fluorobenzyl bromideHCID 896910841-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 896910671-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((3-fluorobenzyl)oxy)pyridin-2(1H)-oneYield 23.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred suspension of NaH (40% oil dispersion, 50 mg) in THF (9 ml) was added a solution of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (150 mg) in THF (1 ml) at 0° C., and then the mixture was stirred at room temperature for 30 min. 1-Bromomethyl-3-fluorobenzene (150 mg) in THF (0.5 ml) was added, and the resulting mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with ice-water and extracted with DCM. 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) followed by crystallization with DCM/hexane to give the title compound (49 mg) as a white solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 12 h
  2. customThe reaction mixture was quenched with ice-water
  3. extractionextracted with DCM
  4. washThe extract was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel column chromatography (MeOH/DCM)
  8. customfollowed by crystallization with DCM/hexane

Sources & evidence

ORD record
ord-67a092307b004018902435b3e6c99048
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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