Ammonia → 4-[(4-Chlorophenyl)methoxy]-1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-2(1H)-pyridinone

HRID 2202836Notes

Reaction equation

HRID 2202836 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][NH:11][C:10](=[O:14])[CH:9]=2)=[CH:4][CH:3]=1.[CH:17]1([C:20]2[N:21]=[C:22]3[CH:27]=[CH:26][C:25](I)=[CH:24][N:23]3[C:29]=2[CH3:30])[CH2:19][CH2:18]1.CNCCNC.C(=O)([O-])[O-].[K+].[K+].N>[Cu](I)I.CS(C)=O>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:25]3[CH:26]=[CH:27][C:22]4[N:23]([C:29]([CH3:30])=[C:20]([CH:17]5[CH2:19][CH2:18]5)[N:21]=4)[CH:24]=3)[C:10](=[O:14])[CH:9]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 574978644-[(4-Chlorophenyl)methoxy]pyridin-2(1H)-one2×HCID 896903982-Cyclopropyl-6-iodo-3-methylimidazo[1,2-a]pyridine

Product 1

HCID 896914394-[(4-Chlorophenyl)methoxy]-1-(2-cyclopropyl-3-methylimidazo[1,2-a]pyridin-6-yl)-2(1H)-pyridinoneYield 55.2%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

Then a mixture of 4-((4-chlorobenzyl)oxy)pyridin-2(1H)-one (1.0 g), 2-cyclopropyl-6-iodo-3-methylimidazo[1,2-a]pyridine (1.27 g), N,N′-dimethylethylenediamine (0.48 ml), copper iodide (0.81 g), potassium carbonate (1.76 g) and DMSO (13 ml) was heated at 110° C. under microwave irradiation for 1 h. Other two batches using 200 mg and 1 g of 4-((4-chlorobenzyl)oxy)pyridin-2(1H)-one were conducted. Then these reaction mixtures were combined, and poured into 14% NH3 solution. The mixture was extracted with 1:1 mixture of EtOAc and THF. The extract was washed with brine, dried over MgSO4, concentrated, and purified by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH), followed by NH silica gel column chromatography (hexane/EtOAc) to give the title compound as a white solid (950 mg).

Workup

  1. customThen these reaction mixtures
  2. extractionThe mixture was extracted with 1:1 mixture of EtOAc and THF
  3. washThe extract was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. custompurified by silica gel column chromatography (hexane/EtOAc

Sources & evidence

ORD record
ord-3327f5269612405589794deea944617a
Source dataset
uspto-grants-2016_06
Patent number
US09365540B2

Reaction notes

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