Triethylamine → HCID 57505557, compound

HRID 2391319Notes

Reaction equation

HRID 2391319 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.Cl.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH2:32][C:33](O)=[O:34].C(N(CC)CC)C.P(C#N)(OCC)(OCC)=O.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:24][C:23]1[CH:22]=[CH:21][C:4]([O:5][C:6]2[CH:7]=[CH:8][C:9]3[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]4[CH2:20][CH2:19]4)=[O:17])[N:14]=3)[N:11]=2)=[CH:3][C:2]=1[NH:1][C:33](=[O:34])[CH2:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 853172-Pyridineacetic acid, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 57505476N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505557HCID 57505557, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (120 mg, 0.371 mmol) and pyridin-2-ylacetic acid hydrochloride (129 mg, 0.742 mmol) in N,N-dimethylformamide (4.0 mL) were added dropwise triethylamine (0.21 mL, 1.484 mmol) and diethyl cyanophosphate (0.12 mL, 0.816 mmol) under ice-cooling, and the mixture was stirred at room temperature for 3 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/methanol=100/0→95/5) and recrystallized from ethyl acetate to give the title compound (67 mg, 41%) as pale-yellow 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/methanol=100/0→95/5)
  9. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-deda3ce2e5c94c14bcf828ef3e25c116
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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