Oxalyl chloride → HCID 25128179, compound

HRID 1874481Notes

Reaction equation

HRID 1874481 reaction equation
[CH2:1]([N:3]1[C:7]([C:8]([OH:10])=O)=[CH:6][C:5]([CH3:11])=[N:4]1)[CH3:2].C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[CH:20]=[C:21]([CH:38]=[CH:39][C:40]=1[F:41])[O:22][C:23]1[CH:24]=[CH:25][C:26]2[N:27]([N:29]=[C:30]([NH:32][C:33]([CH:35]3[CH2:37][CH2:36]3)=[O:34])[N:31]=2)[CH:28]=1>O1CCCC1.CN(C)C=O.O>[CH:35]1([C:33]([NH:32][C:30]2[N:31]=[C:26]3[CH:25]=[CH:24][C:23]([O:22][C:21]4[CH:38]=[CH:39][C:40]([F:41])=[C:19]([NH:18][C:8]([C:7]5[N:3]([CH2:1][CH3:2])[N:4]=[C:5]([CH3:11])[CH:6]=5)=[O:10])[CH:20]=4)=[CH:28][N:27]3[N:29]=2)=[O:34])[CH2:36][CH2:37]1

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 27437941-Ethyl-3-methyl-1H-pyrazole-5-carboxylic acidHCID 57749270N-[6-(3-amino-4-fluorophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 25128179HCID 25128179, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-ethyl-3-methyl-1H-pyrazole-5-carboxylic acid (188 mg, 1.22 mmol) in tetrahydrofuran (7 mL) were added oxalyl chloride (160 μL, 1.83 mmol) and N,N-dimethylformamide (1 drop), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (3 mL). N-[6-(3-Amino-4-fluorophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide (200 mg, 0.611 mmol) was added with stirring under ice-cooling, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (NH silica gel, ethyl acetate) and recrystallized from ethyl acetate to give the title compound (254 mg, 90%) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (3 mL)
  3. stirringwith stirring under ice-
  4. temperaturecooling
  5. stirringthe mixture was stirred at room temperature for 15 hr
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltrated
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by column chromatography (NH silica gel, ethyl acetate)
  12. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-2309f470562c4ac280d31ded0652dc3b
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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