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

HRID 2095847Notes

Reaction equation

HRID 2095847 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[CH3:27].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]([CH3:27])[CH:20]=1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 68001Benzene, 1-fluoro-2-methyl-4-nitro-HCID 58158532N-(6-Hydroxyimidazo[1,2-A]pyridin-2-YL)cyclopropanecarboxamide

Product 1

HCID 58158593N-[6-(4-amino-2-methylphenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamideYield 43%

Reagents, catalysts & solvents 5

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of N-(6-hydroxyimidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide (300 mg, 1.38 mmol) and 4-fluoro-3-methyl-1-nitrobenzene (279 mg, 1.80 mmol) in dimethyl sulfoxide (3 mL) was added cesium carbonate (67.4 mg, 2.07 mmol), and the mixture was stirred at room temperature for 24 hr. Ethyl acetate, tetrahydrofuran and water 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. The obtained residue was washed with ethyl acetate and collected by filtration. A mixed solution of the obtained solid, reduced iron (406 mg, 6.9 mmol) and ammonium chloride (738 mg, 13.8 mmol) in ethanol (5 mL)/tetrahydrofuran (3 mL)/water (2 mL) was stirred at 80° C. for 6 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 (190 mg, 43%) 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. washThe obtained residue was washed with ethyl acetate
  5. filtrationcollected by filtration
  6. filtrationfiltered through celite
  7. additionWater was added to the filtrate
  8. extractionthe mixture was extracted twice with ethyl acetate
  9. washThe organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customThe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1→ethyl acetate alone)

Sources & evidence

ORD record
ord-ba71b38e27e24015a7ef6d4cce0a1bf2
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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