Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Oxalyl chloride | HCID 65578 | — |
| Reactant | 1,3-dimethyl-1H-pyrazole-4-carboxylic acid | HCID 1273304 | — |
| Reactant | N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide | HCID 57505446 | — |
| Catalyst | Dimethylformamide | HCID 6228 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Solvent | Ethyl Acetate | HCID 8857 | — |
| Product | HCID 24767985 | HCID 24767985 | 39.2% |
Reaction Steps
To a solution of 1,3-dimethyl-1H-pyrazole-4-carboxylic acid (140 mg, 1.0 mmol) and N,N-dimethylformamide (2 drops) in tetrahydrofuran (10 mL) was added oxalyl chloride (0.171 mL, 2.0 mmol) with stirring under ice-cooling, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in N-methylpyrrolidone (5 mL) with stirring under ice-cooling, N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (164 mg, 0.50 mmol) was added, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was diluted with ethyl acetate (80 mL), and washed with 1N aqueous sodium hydroxide solution (10 mL) and water (10 mL×3). The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→70/30) and recrystallized from ethyl acetate to give the title compound (88 mg, yield 39%) as a white solid. melting point 205° C.
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-09dcba029e614dd68719c0d64a70b5f1 |
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| Source note | uspto-grants-2011_10 |
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