Water → N-[5-({2-[(cyclopropylsulfonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide

HRID 1663878Notes

Reaction equation

HRID 1663878 reaction equation
Cl.[NH2:2][C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][C:8]([O:11][C:12]3[CH:13]=[CH:14][C:15](F)=[C:16]([NH:18][C:19]([C:21]4[N:25]([CH3:26])[N:24]=[C:23]([CH3:27])[CH:22]=4)=[O:20])[CH:17]=3)=[N:7][N:6]2[CH:29]=1.[CH2:30](N(CC)CC)C.[CH:37]1([S:40](Cl)(=[O:42])=[O:41])[CH2:39][CH2:38]1.O>CN1CCCC1=O>[CH:37]1([S:40]([NH:2][C:3]2[N:4]=[C:5]3[CH:10]=[CH:9][C:8]([O:11][C:12]4[CH:13]=[CH:14][C:15]([CH3:30])=[C:16]([NH:18][C:19]([C:21]5[N:25]([CH3:26])[N:24]=[C:23]([CH3:27])[CH:22]=5)=[O:20])[CH:17]=4)=[N:7][N:6]3[CH:29]=2)(=[O:42])=[O:41])[CH2:39][CH2:38]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 2760919Cyclopropanesulfonyl chlorideHCID 57505567N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-fluorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide hydrochloride

Product 1

HCID 57505614N-[5-({2-[(cyclopropylsulfonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamideYield 16%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of N-{5-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]-2-fluorophenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide.hydrochloride (400 mg, 0.97 mmol) in 1-methyl-2-pyrrolidone (4.0 mL) were added triethylamine (404 μL, 2.90 mmol) and cyclopropanesulfonyl chloride (204 mg, 1.45 mmol), and the mixture was stirred at 70° C. for 16 hr. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate/tetrahydrofuran, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate alone) and recrystallized from hexane/ethyl acetate to give the title compound (74 mg, 16%) as a white powder.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate alone) and
  8. customrecrystallized from hexane/ethyl acetate

Sources & evidence

ORD record
ord-2da6753bd9d4458e947ccc0f4187b094
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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