1-Hydroxybenzotriazole → HCID 57505678, compound

HRID 1668131Notes

Reaction equation

HRID 1668131 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[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.[Cl:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][C:26]=1[C:34]([F:37])([F:36])[F:35].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O>[Cl:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([NH:1][C:2]2[CH:23]=[CH:22][CH:21]=[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:3]=2)=[O:30])=[CH:27][C:26]=1[C:34]([F:35])([F:36])[F:37]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27738574-Chloro-3-(trifluoromethyl)benzoic acidHCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505678HCID 57505678, compoundYield 78.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (100 mg, 0.32 mmol) in N,N-dimethylformamide (6.0 mL) were added 4-chloro-3-(trifluoromethyl)benzoic acid (73 mg, 0.32 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (65 mg, 0.34 mmol) and 1-hydroxybenzotriazole (46 mg, 0.34 mmol), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was 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/hexane=30/70→80/20) and precipitated from ethyl acetate/diisopropyl ether to give the title compound (130 mg, 77%) as a white powder.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=30/70→80/20)
  7. customprecipitated from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-1f827c65ecac4fa293c24e01b0092310
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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