Oxalyl chloride → HCID 58158588, compound

HRID 2095950Notes

Reaction equation

HRID 2095950 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[C:11]([C:14]([OH:16])=O)=[C:10]([CH3:17])[N:9]2[CH3:18])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[CH:47]=[CH:46][C:29]([O:30][C:31]2[CH:32]=[CH:33][C:34]3[N:35]([CH:37]=[C:38]([NH:40][C:41]([CH:43]4[CH2:45][CH2:44]4)=[O:42])[N:39]=3)[CH:36]=2)=[C:28]([F:48])[CH:27]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.CN(C)C(=O)C.C(OCC)(=O)C.O1CCCC1>[CH:43]1([C:41]([NH:40][C:38]2[N:39]=[C:34]3[CH:33]=[CH:32][C:31]([O:30][C:29]4[CH:46]=[CH:47][C:26]([NH:25][C:14]([C:11]5[C:12](=[O:13])[N:8]([C:5]6[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=6)[N:9]([CH3:18])[C:10]=5[CH3:17])=[O:16])=[CH:27][C:28]=4[F:48])=[CH:36][N:35]3[CH:37]=2)=[O:42])[CH2:44][CH2:45]1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamideHCID 58368347HCID 58368347, compound

Product 1

HCID 58158588HCID 58158588, compoundYield 77.3%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

To a solution of 2-(4-fluorophenyl)-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylic acid (1130 mg, 4.5 mmol) in tetrahydrofuran (75 mL) were added N,N-dimethylformamide (6 drops) and oxalyl dichloride (780 μL, 9.1 mmol), and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and the obtained residue was dissolved in N,N-dimethylacetamide (10 mL). The solution was added to a solution of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (1230 mg, 3.8 mmol) in N,N-dimethylacetamide (30 mL), and the mixture was stirred at room temperature for 4 hr. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution were added to the mixture, and the aqueous layer was extracted 4 times with ethyl acetate/tetrahydrofuran. The combined organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was washed with ethyl acetate and collected by filtration to give the title compound (1640 mg, 67%) as a white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe obtained residue was dissolved in N,N-dimethylacetamide (10 mL)
  3. stirringthe mixture was stirred at room temperature for 4 hr
  4. extractionthe aqueous layer was extracted 4 times with ethyl acetate/tetrahydrofuran
  5. washThe combined organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe solvent was evaporated under reduced pressure
  9. washthe residue was washed with ethyl acetate
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-8aead18996584922b589649fb5df6c6d
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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