Cesium carbonate → N-[6-(4-amino-2-chlorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

HRID 2095844Notes

Reaction equation

HRID 2095844 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[CH:7]=1.F[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][C:19]=1[Cl:27].C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[NH4+]>CS(C)=O.C(O)C.C(OCC)(=O)C.O1CCCC1.O>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:1][C:2]2[CH:3]=[CH:4][C:5]3[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]4[CH2:15][CH2:16]4)=[O:13])[N:10]=3)[CH:7]=2)=[C:19]([Cl:27])[CH:20]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium Chloride2×HCID 676882-Chloro-1-fluoro-4-nitrobenzeneHCID 58158532N-(6-Hydroxyimidazo[1,2-A]pyridin-2-YL)cyclopropanecarboxamide

Product 1

HCID 58158542N-[6-(4-amino-2-chlorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamideYield 56.2%

Reagents, catalysts & solvents 5

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of N-(6-hydroxyimidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide (200 mg, 0.921 mmol) and 4-fluoro-3-chloro-1-nitrobenzene (193 mg, 1.11 mmol) in dimethyl sulfoxide (2 mL) was added cesium carbonate (450 mg, 1.38 mmol), and the mixture was stirred at room temperature for 6 hr. Ethyl acetate and saturated aqueous ammonium chloride solution were added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. A mixed solution of the obtained residue, reduced iron (271 mg, 4.61 mmol) and ammonium chloride (493 mg, 9.21 mmol) in ethanol (2 mL)/tetrahydrofuran (2 mL)/water (1 mL) was stirred at 80° C. for 7 hr. The reaction mixture was diluted with ethyl acetate and tetrahydrofuran, and filtered through celite. Water was added to the filtrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1→ethyl acetate alone) to give the title compound (177.5 mg, 56%) as a white solid.

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. customthe solvent was evaporated under reduced pressure
  4. filtrationfiltered through celite
  5. additionWater was added to the filtrate
  6. extractionthe mixture was extracted twice with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customThe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1→ethyl acetate alone)

Sources & evidence

ORD record
ord-d74e9ac6236e4ae0b70089f080c7a6e8
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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