Triethylamine → N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-3-methylpyridine-2-carboxamide

HRID 1663813Notes

Reaction equation

HRID 1663813 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.[CH3:24][C:25]1[C:26]([C:31](O)=[O:32])=[N:27][CH:28]=[CH:29][CH:30]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+]>CN(C)C=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:3]=[C:2]([NH:1][C:31]([C:26]5[C:25]([CH3:24])=[CH:30][CH:29]=[CH:28][N:27]=5)=[O:32])[CH:23]=[CH:22][CH:21]=4)=[N:11][N:10]3[CH:12]=2)=[O:17])[CH2:20][CH2:19]1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2687573-Methylpicolinic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505548N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-3-methylpyridine-2-carboxamideYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (100 mg, 0.323 mmol), 3-methylpyridine-2-carboxylic acid (66 mg, 0.485 mmol) and 1-hydroxybenzotriazole (71 mg, 0.522 mmol) in N,N-dimethylformamide (4.0 mL) were added triethylamine (0.08 mL, 0.549 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (99 mg, 0.517 mmol) under ice-cooling, and the mixture was stirred at room temperature for 20 hr. Under ice-cooling, aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=80/20→100/0) and recrystallized from ethyl acetate/methanol to give the title compound (98 mg, 71%) as colorless crystals.

Workup

  1. temperaturecooling
  2. temperatureUnder ice-cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=80/20→100/0)
  9. customrecrystallized from ethyl acetate/methanol

Sources & evidence

ORD record
ord-516c2421a3e5488aa18ae384a5cb8c8b
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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