Nitric Acid → HCID 69355199, compound

HRID 1375161Notes

Reaction equation

HRID 1375161 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].[N+:33]([O-:36])([OH:35])=[O:34]>CO>[N+:33]([O-:36])([OH:35])=[O:34].[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

4

Reactant 2

HCID 944Nitric AcidHCID 9911830Tivozanib

Product 1

HCID 69355199HCID 69355199, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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 (40 mL), 70% nitric acid (1.2 g) was added dropwise thereto, and the mixture was stirred at room temperature for 2 hr. The resultant precipitate was collected by filtration, and the filtered product was then dried under the reduced pressure. The resultant powder was stirred in N,N-dimethylformamide (10 mL) at 100° C. for complete dissolution of the powder. The solution was then cooled to room temperature, ethyl acetate (20 mL) was added dropwise thereto, 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 II crystal of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea nitrate (2.0 g, yield 91.0%).

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. stirringThe resultant powder was stirred in N,N-dimethylformamide (10 mL) at 100° C. for complete dissolution of the powder
  5. temperatureThe solution was then cooled to room temperature
  6. additionethyl acetate (20 mL) was added dropwise
  7. stirringthe mixture was 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-96ac533af0ac414499dda7d503e96e24
Source dataset
uspto-grants-2007_01
Patent number
US07166722B2

Reaction notes

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