Methanol → HCID 86603570, compound

HRID 1375166Notes

Reaction equation

HRID 1375166 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]>CN(C)C=O>[CH3:9][C:18]1[CH:13]=[CH:14][C:15]([S:36]([OH:39])(=[O:38])=[O:37])=[CH:16][CH:17]=1.[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 3

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 9911830Tivozanib

Product 2

HCID 6101p-Toluenesulfonic acidHCID 86603570HCID 86603570, compoundYield 123.8%

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 5° C. and the mixture 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 III crystal of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea methanesulfonate (1.5 g, yield 61.0%).

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 5° C.
  6. stirringthe mixture was 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-a9da70410f3d4cd2817a6a03babd17ed
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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