Methanol → HCID 86603570, compound

HRID 1375165Notes

Reaction equation

HRID 1375165 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(O)C>[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

5

Reactant 3

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 9911830Tivozanib

Product 1

HCID 86603570HCID 86603570, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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 ethanol (120 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 methanesulfonate (1.9 g, yield 80.0%).

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. temperatureunder reflux for complete dissolution
  6. temperatureThe solution was then cooled to 5° C.
  7. stirringwas stirred at that temperature overnight
  8. filtrationThe resultant precipitate was filtered
  9. customthe filtered product was then dried under the reduced pressure

Sources & evidence

ORD record
ord-656c9ca3f35445f7af0910420e18135e
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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