Sodium Bicarbonate → 1-tert-butyl-N-[5-((2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-3-methyl-1H-pyrazole-5-carboxamide

HRID 2391386Notes

Reaction equation

HRID 2391386 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[CH3:24])[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[N:11]=1.[C:25]([N:29]1[C:33]([C:34](Cl)=[O:35])=[CH:32][C:31]([CH3:37])=[N:30]1)([CH3:28])([CH3:27])[CH3:26].C(OCC)(=O)C.O1CCCC1.C(=O)([O-])O.[Na+]>CN(C)C(=O)C>[C:25]([N:29]1[C:33]([C:34]([NH:1][C:2]2[CH:3]=[C:4]([O:5][C:6]3[CH:7]=[CH:8][C:9]4[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]5[CH2:20][CH2:19]5)=[O:17])[N:14]=4)[N:11]=3)[CH:21]=[CH:22][C:23]=2[CH3:24])=[O:35])=[CH:32][C:31]([CH3:37])=[N:30]1)([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 27993401-tert-Butyl-3-methyl-1H-pyrazole-5-carbonyl chlorideHCID 21939870Tetrahydrofuran ethyl acetateHCID 57505476N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 575056241-tert-butyl-N-[5-((2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-3-methyl-1H-pyrazole-5-carboxamideYield 4.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (210 mg, 0.65 mmol) in N,N-dimethylacetamide (5 mL) was added a solution of 1-tert-butyl-3-methyl-1H-pyrazole-5-carbonylchloride (160 mg, 0.78 mmol) in N,N-dimethylacetamide (1 mL), and the mixture was stirred at room temperature for 30 min. Ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution were added to the mixture, the aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4). Combined organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→90/10) to give the title compound (14 mg, 4%) as a white solid.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4)
  2. washCombined organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→90/10)

Sources & evidence

ORD record
ord-9e1cb8699068433aa1cff00d2b1b1374
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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