Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Ethyl Acetate | HCID 8857 | — |
| Reactant | Maleic Acid | HCID 444266 | — |
| Reactant | Tivozanib | HCID 9911830 | — |
| Solvent | Methanol | HCID 887 | — |
| Solvent | Dimethylacetamide | HCID 31374 | — |
| Product | Maleate(2-) | HCID 5288227 | — |
| Product | HCID 69481966 | HCID 69481966 | 75.7% |
Reaction Steps
N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea (2.0 g) produced in Production Example was added to methanol (27 mL), a solution of maleic acid (1.5 g) in methanol (27 mL) was added dropwise thereto, and the mixture was stirred at room temperature for 4 hr. The resultant precipitate was collected by filtration, and the filtered product was then dried under the reduced pressure. The powder thus obtained was stirred in N,N-dimethylacetamide (10 mL) at 100° C. for complete dissolution. The solution was then cooled to room temperature. Ethyl acetate (20 mL) was added dropwise thereto, and the mixture was stirred at room temperature overnight. The resultant precipitate was filtered, and the filtered product was then dried under the reduced pressure to give a form IV crystal of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea maleate (1.9 g, yield 75.0%).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US07166722B2 |
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| Source dataset | uspto-grants-2007_01 |
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| ORD ID | ord-d853411fd9374d3dba2aa64e7b1d5c1b |
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| Source note | uspto-grants-2007_01 |
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