Maleic Acid → HCID 69481966, compound

HRID 1375172Notes

Reaction equation

HRID 1375172 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:23][C:24]([NH:26][C:27]1[CH:31]=[C:30]([CH3:32])[O:29][N:28]=1)=[O:25].[C:33]([OH:40])(=[O:39])/[CH:34]=[CH:35]\[C:36]([OH:38])=[O:37]>CO.C(O)C>[C:33]([OH:40])(=[O:39])/[CH:34]=[CH:35]\[C:36]([OH:38])=[O:37].[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:23][C:24]([NH:26][C:27]1[CH:31]=[C:30]([CH3:32])[O:29][N:28]=1)=[O:25]

Participants

5

Reactant 2

HCID 444266Maleic AcidHCID 9911830Tivozanib

Product 1

HCID 69481966HCID 69481966, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent2×

Procedure

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 ethanol (300 mL) under reflux for complete dissolution. The solution was then cooled to 5° C. and was stirred at that temperature overnight. The resultant precipitate was filtered, and the filtered product was then dried under the reduced pressure to give a form II crystal of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea maleate (1.9 g, yield 76.0%).

Workup

  1. filtrationThe resultant precipitate was collected by filtration
  2. customthe filtered product was then dried under the reduced pressure
  3. customThe powder thus obtained
  4. temperatureunder reflux for complete dissolution
  5. temperatureThe solution was then cooled to 5° C.
  6. stirringwas stirred at that temperature overnight
  7. filtrationThe resultant precipitate was filtered
  8. customthe filtered product was then dried under the reduced pressure

Sources & evidence

ORD record
ord-37ca22bcb51e4ad5bb6b9fe64231f16e
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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