Hydrochloric Acid → N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)-5-fluorophenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 1874435

Reaction equation

HRID 1874435 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([N+:24]([O-])=O)[CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([N:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[CH:11]=1.Cl.C(O)C.[CH3:31][N:32]1[C:36]([C:37](Cl)=[O:38])=[CH:35][C:34]([CH3:40])=[N:33]1>C(=O)([O-])O.[Na+].O>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:21]=[C:22]([NH:24][C:37]([C:36]5[N:32]([CH3:31])[N:33]=[C:34]([CH3:40])[CH:35]=5)=[O:38])[CH:23]=[C:2]([F:1])[CH:3]=4)=[CH:11][N:10]3[N:12]=2)=[O:17])[CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 27362992,5-Dimethyl-2H-pyrazole-3-carbonyl chlorideHCID 57749369N-[6-(3-fluoro-5-nitrophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57749191N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)-5-fluorophenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of N-[6-(3-fluoro-5-nitrophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide (130 mg, 0.364 mmol), reduced iron (150 mg), concentrated hydrochloric acid (300 μL), ethanol (3 mL) and water (3 mL) was stirred under refluxing conditions for 1 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in N,N-dimethylacetamide (3 mL). 1,3-Dimethyl-1H-pyrazole-5-carbonyl chloride (69.3 mg, 0.437 mmol) was added thereto with stirring under ice-cooling, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution 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 (45.0 mg, 28%) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-5913721a6e12429ca753542011bd4828
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Linked notes

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