Pyridine → HCID 57505563, compound

HRID 2391324Notes

Reaction equation

HRID 2391324 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-e44b4b39bbaa4d5fa7a3a8d51d617502
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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