p-Toluenesulfonic acid monohydrate → HCID 21079510, compound

HRID 1375170Notes

Reaction equation

HRID 1375170 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].O.[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40]([OH:43])(=[O:42])=[O:41])=[CH:36][CH:35]=1>C(#N)C.CO>[C:34]1([CH3:44])[CH:35]=[CH:36][C:37]([S:40]([OH:43])(=[O:41])=[O:42])=[CH:38][CH:39]=1.[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 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 9911830Tivozanib

Product 1

HCID 21079510HCID 21079510, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

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 acetonitrile (27 mL), a solution of p-toluenesulfonic acid monohydrate (2.5 g) in acetonitrile (27 mL) was added dropwise thereto, and the mixture was stirred at room temperature for 3 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 methanol (160 mL) under reflux for complete dissolution. The solution was then cooled to room temperature 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 p-toluenesulfonate (2.0 g, yield 74.0%).

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. temperatureunder reflux for complete dissolution
  5. temperatureThe solution was then cooled to room temperature
  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-ff466516e10b433d85a842075dce5aa6
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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