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

HRID 2202909Notes

Reaction equation

HRID 2202909 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]=[CH:28][C:27]=1[F:32]>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]=[CH:28][C:27]=5[F:32])=[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 67968alpha-Bromo-o-fluorotolueneHCID 896910841-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one

Product 1

HCID 896911301-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-((2-fluorobenzyl)oxy)pyridin-2(1H)-oneYield 27%

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-2-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 (19:1, 2 ml) to give the title compound (56 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 (19:1, 2 ml)

Sources & evidence

ORD record
ord-3e049a89529c4a96bcf6bcd12652cdda
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

Loading…