Pyridine → HCID 57505563, compound

HRID 1668014Notes

Reaction equation

HRID 1668014 reaction equation
N1C=CC=CC=1.[NH2:7][C:8]1[CH:12]=[C:11]([CH3:13])[O:10][N:9]=1.[C:14](Cl)(=O)[O:15]C1C=CC=CC=1.[NH2:24][C:25]1[CH:26]=[C:27]([CH:44]=[CH:45][C:46]=1[F:47])[O:28][C:29]1[CH:30]=[CH:31][C:32]2[N:33]([CH:35]=[C:36]([NH:38][C:39]([CH:41]3[CH2:43][CH2:42]3)=[O:40])[N:37]=2)[N:34]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[F:47][C:46]1[CH:45]=[CH:44][C:27]([O:28][C:29]2[CH:30]=[CH:31][C:32]3[N:33]([CH:35]=[C:36]([NH:38][C:39]([CH:41]4[CH2:43][CH2:42]4)=[O:40])[N:37]=3)[N:34]=2)=[CH:26][C:25]=1[NH:24][C:14]([NH:7][C:8]1[CH:12]=[C:11]([CH3:13])[O:10][N:9]=1)=[O:15]

Participants

7

Reactant 5

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 661723-Amino-5-methylisoxazoleHCID 516892Sodium BicarbonateHCID 57505446N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505563HCID 57505563, compoundYield 22.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of pyridine (475 mg, 6 mmol) and 3-amino-5-methylisoxazole (147 mg, 1.5 mmol) in N,N-dimethylformamide (2.0 mL) was added dropwise a solution of phenyl chlorocarbonate (235 mg, 1.5 mmol) in N,N-dimethylformamide (2.0 mL) under ice-cooling. After the mixture was stirred at room temperature for 2 hr, N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (327 mg, 1.0 mmol) was added to the mixture, and the mixture was stirred at 80° C. for 15 hr and at 100° C. for 2 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 basic silica gel column chromatography (ethyl acetate/hexane=80/20→100/0) and recrystallized from tetrahydrofuran/ethanol to give the title compound (101 mg, 22%) as colorless crystals.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at 80° C. for 15 hr and at 100° C. for 2 hr
  3. temperatureUnder ice-cooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=80/20→100/0)
  10. customrecrystallized from tetrahydrofuran/ethanol

Sources & evidence

ORD record
ord-c2f5aebe4ec045aa89b29de9e026945c
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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