Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Pyridine | HCID 1049 | — |
| Reactant | Phenyl chloroformate | HCID 15891 | — |
| Reactant | 3-Amino-5-methylisoxazole | HCID 66172 | — |
| Reactant | Sodium Bicarbonate | HCID 516892 | — |
| Reactant | N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide | HCID 57505446 | — |
| Solvent | Dimethylformamide | HCID 6228 | — |
| Product | HCID 57505563 | HCID 57505563 | 22.4% |
Reaction Steps
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.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US08044049B2 |
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| Source dataset | uspto-grants-2011_10 |
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| ORD ID | ord-c2f5aebe4ec045aa89b29de9e026945c |
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| Source note | uspto-grants-2011_10 |
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