Methanol → HCID 69353823, compound

HRID 1375162Notes

Reaction equation

HRID 1375162 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.[S:35](=[O:39])(=[O:38])([OH:37])[OH:36].O>C(#N)C>[S:35]([OH:39])([OH:38])(=[O:37])=[O:36].[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 962WaterHCID 1118Sulfuric AcidHCID 9911830Tivozanib

Product 1

HCID 69353823HCID 69353823, compoundYield 78.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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 (53 mL), concentrated sulfuric acid (concentration 98%) (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 acetonitrile (200 mL) and water (40 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 I crystal of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea sulfate (1.9 g, yield 78.0%).

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. 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-8de5a08d72664d4098bd02d955dcf483
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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