1-Hydroxybenzotriazole → N-(5-{[2-(acetylamino)imidazo[1,2-b]pyridazin-6-yl]oxy}-2-methylphenyl)-1-methyl-1H-imidazole-2-carboxamide

HRID 2391342Notes

Reaction equation

HRID 2391342 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16](=[O:18])[CH3:17])[N:14]=2)[N:11]=1.[CH3:23][N:24]1[CH:28]=[CH:27][N:26]=[C:25]1[C:29](O)=[O:30].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O>[C:16]([NH:15][C:13]1[N:14]=[C:9]2[CH:8]=[CH:7][C:6]([O:5][C:4]3[CH:19]=[CH:20][C:21]([CH3:22])=[C:2]([NH:1][C:29]([C:25]4[N:24]([CH3:23])[CH:28]=[CH:27][N:26]=4)=[O:30])[CH:3]=3)=[N:11][N:10]2[CH:12]=1)(=[O:18])[CH3:17]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 5576781-methyl-1H-imidazole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57505579N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]acetamide

Product 1

HCID 57505583N-(5-{[2-(acetylamino)imidazo[1,2-b]pyridazin-6-yl]oxy}-2-methylphenyl)-1-methyl-1H-imidazole-2-carboxamideYield 56.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]acetamide (150 mg, 0.50 mmol) in N,N-dimethylformamide (3.0 mL) were added 1-methyl-1H-imidazole-2-carboxylic acid (127 mg, 1.01 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (290 mg, 1.51 mmol) and 1-hydroxybenzotriazole (205 mg, 1.51 mmol), and the mixture was stirred at room temperature for 16 hr. Saturated aqueous sodium hydrogencarbonate solution 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 obtained residue was recrystallized from ethyl acetate/ethanol to give the title compound (115 mg, 56%) as a white powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. customThe solvent was evaporated under reduced pressure
  6. customthe obtained residue was recrystallized from ethyl acetate/ethanol

Sources & evidence

ORD record
ord-971efa61efb249b5b9f3cf42091c53a5
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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