Ethyl Acetate → HCID 69481966, compound

HRID 1375173Notes

Reaction equation

HRID 1375173 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].C(OCC)(=O)C>CO.CN(C)C(=O)C>[C:33]([O-:40])(=[O:39])/[CH:34]=[CH:35]\[C:36]([O-:38])=[O:37].[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

7

Reactant 3

HCID 8857Ethyl AcetateHCID 444266Maleic AcidHCID 9911830Tivozanib

Product 2

HCID 5288227Maleate(2-)HCID 69481966HCID 69481966, compoundYield 75.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 31374DimethylacetamideSolvent

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 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%).

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. temperatureThe solution was then cooled to room temperature
  5. stirringthe mixture was stirred at room temperature overnight
  6. filtrationThe resultant precipitate was filtered
  7. customthe filtered product was then dried under the reduced pressure

Sources & evidence

ORD record
ord-d853411fd9374d3dba2aa64e7b1d5c1b
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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