Oxalyl chloride → N-{3-[(2-acetamidoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamide

HRID 1664023Notes

Reaction equation

HRID 1664023 reaction equation
[C:1]([C:3]1([C:6]2[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4]1)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:21][C:22]1[CH:23]=[C:24]([CH:39]=[CH:40][CH:41]=1)[O:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([CH:32]=[C:33]([NH:35][C:36](=[O:38])[CH3:37])[N:34]=2)[N:31]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.CN1CCCC1=O>[C:36]([NH:35][C:33]1[N:34]=[C:29]2[CH:28]=[CH:27][C:26]([O:25][C:24]3[CH:23]=[C:22]([NH:21][C:9](=[O:11])[C:8]4[CH:12]=[CH:13][CH:14]=[C:6]([C:3]5([C:1]#[N:2])[CH2:4][CH2:5]5)[CH:7]=4)[CH:41]=[CH:40][CH:39]=3)=[N:31][N:30]2[CH:32]=1)(=[O:38])[CH3:37]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 574410393-(1-Cyanocyclopropyl)benzoic acidHCID 57441053N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]acetamide

Product 1

HCID 57505748N-{3-[(2-acetamidoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamideYield 75%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 3-(1-cyanocyclopropyl)benzoic acid (1.50 g, 8.01 mmol) in tetrahydrofuran (30 mL) were added N,N-dimethylformamide (2 drops) and oxalyl chloride (1.16 mL, 13.3 mmol), and the mixture was stirred at room temperature for 1.5 hr. The solvent was evaporated under reduced pressure, and the residue and N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]acetamide (1.89 g, 6.67 mmol) were dissolved in N-methylpyrrolidone (30 mL), and the mixture was stirred at room temperature for 3 hr. Saturated 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, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0) to give the title compound (2.25 g, 75%) as a pale-brown powder.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 3 hr
  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 residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0)

Sources & evidence

ORD record
ord-09fcb50a28d943cd855dd864731edc8b
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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