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

HRID 1663854Notes

Reaction equation

HRID 1663854 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[F: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.[CH3:25][N:26]1[C:30]([CH3:31])=[CH:29][C:28]([C:32](O)=[O:33])=[N:27]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.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]=[CH:22][C:23]([F:24])=[C:2]([NH:1][C:32]([C:28]5[CH:29]=[C:30]([CH3:31])[N:26]([CH3:25])[N:27]=5)=[O:33])[CH:3]=4)=[N:11][N:10]3[CH:12]=2)=[O:17])[CH2:20][CH2:19]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 5877571,5-dimethyl-1H-pyrazole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57505446N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505592N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-fluorophenyl]-1,5-dimethyl-1H-pyrazole-3-carboxamideYield 26.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.61 mmol) in N,N-dimethylformamide (4.0 mL) were added 1,5-dimethyl-1H-pyrazole-3-carboxylic acid (171 mg, 1.22 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (351 mg, 1.83 mmol), 1-hydroxybenzotriazole (248 mg, 1.83 mmol) and triethylamine (256 μL, 1.83 mmol), and the mixture was stirred at 60° C. for 36 hr. 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 obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=3/1→ethyl acetate alone) to give the title compound (72 mg, 26%) 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 purified by silica gel column chromatography (ethyl acetate/hexane=3/1→ethyl acetate alone)

Sources & evidence

ORD record
ord-c7f7d196a67a475a86002d7ccf36e51c
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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