Oxalyl chloride → N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]-3-(trifluoromethyl)pyridine-2-carboxamide

HRID 1874542Notes

Reaction equation

HRID 1874542 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[C:4]([C:9]([OH:11])=O)=[N:5][CH:6]=[CH:7][CH:8]=1.C(Cl)(=O)C(Cl)=O.[NH2:20][C:21]1[CH:22]=[C:23]([CH:40]=[CH:41][CH:42]=1)[O:24][C:25]1[CH:26]=[CH:27][C:28]2[N:29]([CH:31]=[C:32]([NH:34][C:35]([CH:37]3[CH2:39][CH2:38]3)=[O:36])[N:33]=2)[CH:30]=1>O1CCCC1.CN(C)C=O.C(=O)([O-])O.[Na+]>[CH:37]1([C:35]([NH:34][C:32]2[N:33]=[C:28]3[CH:27]=[CH:26][C:25]([O:24][C:23]4[CH:22]=[C:21]([NH:20][C:9]([C:4]5[C:3]([C:2]([F:1])([F:13])[F:12])=[CH:8][CH:7]=[CH:6][N:5]=5)=[O:11])[CH:42]=[CH:41][CH:40]=4)=[CH:30][N:29]3[CH:31]=2)=[O:36])[CH2:38][CH2:39]1

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 132338443-(Trifluoromethyl)pyridine-2-carboxylic acidHCID 57749361N-[6-(3-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57749271N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]-3-(trifluoromethyl)pyridine-2-carboxamideYield 70.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 3-(trifluoromethyl)pyridine-2-carboxylic acid (47.5 mg, 0.249 mmol) in tetrahydrofuran (5 mL) were added N,N-dimethylformamide (2 drops) and oxalyl chloride (43.2 μL, 0.498 mmol), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in N,N-dimethylacetamide (6 mL), and the solution was stirred at room temperature. N-[6-(3-Aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (66 mg, 0.214 mmol) was added thereto, and the mixture was stirred at room temperature for 3 days. The reaction mixture was diluted with aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (0%→100% ethyl acetate-hexane) to give the title compound (72.5 mg, 70%) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (6 mL)
  3. stirringthe solution was stirred at room temperature
  4. stirringthe mixture was stirred at room temperature for 3 days
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltrated
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (0%→100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-a4b2775e215c4071821a0a9ca31c4d40
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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