Oxalyl chloride → N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]-5-methyl-1-phenyl-1H-pyrazole-3-carboxamide

HRID 2095883Notes

Reaction equation

HRID 2095883 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([C:13]([OH:15])=O)[CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[CH:44]=[CH:43][C:26]([O:27][C:28]2[CH:29]=[CH:30][C:31]3[N:32]([CH:34]=[C:35]([NH:37][C:38]([CH:40]4[CH2:42][CH2:41]4)=[O:39])[N:36]=3)[CH:33]=2)=[CH:25][CH:24]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.CN(C)C(=O)C>[CH:40]1([C:38]([NH:37][C:35]2[N:36]=[C:31]3[CH:30]=[CH:29][C:28]([O:27][C:26]4[CH:25]=[CH:24][C:23]([NH:22][C:13]([C:4]5[CH:3]=[C:2]([CH3:1])[N:6]([C:7]6[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=6)[N:5]=5)=[O:15])=[CH:44][CH:43]=4)=[CH:33][N:32]3[CH:34]=2)=[O:39])[CH2:41][CH2:42]1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 6983885-methyl-1-phenyl-1H-pyrazole-3-carboxylic acidHCID 58158625N-[6-(4-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158615N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]-5-methyl-1-phenyl-1H-pyrazole-3-carboxamideYield 58.5%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 5-methyl-1-phenyl-1H-pyrazole-3-carboxylic acid (197 mg, 973 μmol) in tetrahydrofuran (2 mL) were added oxalyl chloride (80 μL, 973 μmol) and N,N-dimethylformamide (2 drops) under ice-cooling, and the mixture was stirred at room temperature for 1 hr. A solution of N-[6-(4-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (200 mg, 649 μmol) in N,N-dimethylacetamide (2 mL) was added to the reaction solution, and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with 1N aqueous sodium hydroxide solution, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The obtained residue was recrystallized from ethanol/water to give the title compound (187 mg, 39%) as a white powder.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 2 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with 1N aqueous sodium hydroxide solution, water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe obtained residue was recrystallized from ethanol/water

Sources & evidence

ORD record
ord-12690475b7ae486f98bc9fc47434cab2
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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