Ammonia → 1-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-(phenylmethoxy)-2(1H)-pyridinone

HRID 2202847Notes

Reaction equation

HRID 2202847 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:17]1[CH:18]=[CH:19][C:20]2[N:24]=[C:23]([CH:25]3[CH2:27][CH2:26]3)[N:22]([CH3:28])[C:21]=2[CH:29]=1.C(=O)([O-])[O-].[K+].[K+].CNCCNC.N>[Cu](I)I.CS(C)=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:17]2[CH:18]=[CH:19][C:20]3[N:24]=[C:23]([CH:25]4[CH2:26][CH2:27]4)[N:22]([CH3:28])[C:21]=3[CH:29]=2)[C:11](=[O:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 838254226-Bromo-2-cyclopropyl-1-methyl-1H-benzoimidazole

Product 1

HCID 896910321-(2-Cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-(phenylmethoxy)-2(1H)-pyridinoneYield 54.2%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 4-(benzyloxy)pyridin-2(1H)-one (1.60 g), 6-bromo-2-cyclopropyl-1-methyl-1H-benzimidazole (2 g), potassium carbonate (3.30 g), N,N′-dimethylethylenediamine (0.855 ml), copper iodide (1.52 g) and DMSO (40 ml) was stirred at 150° C. under Ar atmosphere for 1 h. The mixture was poured into 28% NH3 solution. The precipitate was collected by filtration and washed with water and EtOAc. The solid was dissolved in THF, put on through silica gel pad and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/MeOH). The resulting solid was dissolved in MeOH, and stirred with activated charcoal at room temperature for 10 min. The insoluble material was removed by filtration, and the filtrate was concentrated in vacuo to give the title compound (1.60 g) as an off-white solid.

Workup

  1. filtrationThe precipitate was collected by filtration
  2. washwashed with water and EtOAc
  3. dissolutionThe solid was dissolved in THF
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (EtOAc/MeOH)
  6. dissolutionThe resulting solid was dissolved in MeOH
  7. stirringstirred with activated charcoal at room temperature for 10 min
  8. customThe insoluble material was removed by filtration
  9. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-f671287c57ed4c5cab1748e60f8df828
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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