Methanol → HCID 86603570, compound

HRID 1375167Notes

Reaction equation

HRID 1375167 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].CO.[CH3:35][S:36]([OH:39])(=[O:38])=[O:37].C(OCC)(=O)C>CN(C)C=O>[CH3:35][S:36]([OH:39])(=[O: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

6

Reactant 4

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 8857Ethyl AcetateHCID 9911830Tivozanib

Product 1

HCID 86603570HCID 86603570, compoundYield 82.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 (50 mL), methanesulfonic acid (1.3 g) 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-dimethylformamide (5 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 V crystal of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea methanesulfonate (2.0 g, yield 82.0%).

Workup

  1. additionwas added dropwise
  2. filtrationThe resultant precipitate was collected by filtration
  3. customthe filtered product was then dried under the reduced pressure
  4. customThe powder thus obtained
  5. temperatureThe solution was then cooled to room temperature
  6. stirringthe mixture was stirred at room temperature overnight
  7. filtrationThe resultant precipitate was filtered
  8. customthe filtered product was then dried under the reduced pressure

Sources & evidence

ORD record
ord-d62204c3130648ffbc1bc03e23ac70ee
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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