Triethylamine → N-[3-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 1874514

Reaction equation

HRID 1874514 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([O:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]([C:21]3[N:25]([CH3:26])[N:24]=[C:23]([CH3:27])[CH:22]=3)=[O:20])[CH:15]=[CH:16][CH:17]=1)[N:5]=2.C(N(CC)CC)C.[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1>O1CCCC1.O>[CH:35]1([C:38]([NH:1][C:2]2[S:3][C:4]3[C:9]([N:10]=2)=[CH:8][CH:7]=[C:6]([O:11][C:12]2[CH:13]=[C:14]([NH:18][C:19]([C:21]4[N:25]([CH3:26])[N:24]=[C:23]([CH3:27])[CH:22]=4)=[O:20])[CH:15]=[CH:16][CH:17]=2)[N:5]=3)=[O:39])[CH2:37][CH2:36]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 77637Cyclopropanecarbonyl chloride2×HCID 57749158N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide

Product 1

HCID 25128180N-[3-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (1.03 g, 2.71 mmol) and triethylamine (563 μL, 4.07 mmol) in tetrahydrofuran (15 mL) was added with stirring under ice-cooling cyclopropanecarbonyl chloride (295 μL, 3.25 mmol), and the mixture was stirred at room temperature for 2 hr. Cyclopropanecarbonyl chloride (500 μL, 5.51 mmol) was further added thereto, and the mixture was stirred for 2 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, sodium carbonate (750 mg), methanol (15 mL) and water (100 μL) were added to the residue, and the mixture was stirred at 70° C. for 2 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 (silica gel, hexane/ethyl acetate=60/40→0/100) and recrystallized from ethanol-ethyl acetate-hexane to give the title compound (675 mg, 56%) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hr
  2. stirringthe mixture was stirred for 2 hr
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. concentrationThe filtrate was concentrated under reduced pressure, sodium carbonate (750 mg), methanol (15 mL) and water (100 μL)
  8. additionwere added to the residue
  9. stirringthe mixture was stirred at 70° C. for 2 hr
  10. additionThe reaction mixture was diluted with water
  11. extractionextracted with ethyl acetate
  12. washThe organic layer was washed with water and saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltrated
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. customthe residue was purified by column chromatography (silica gel, hexane/ethyl acetate=60/40→0/100)
  17. customrecrystallized from ethanol-ethyl acetate-hexane

Sources & evidence

ORD record
ord-d9bb58bd62e941d484a407026a426832
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Linked notes

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