Water → Lenvatinib

HRID 1670405Notes

Reaction equation

HRID 1670405 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[CH:9][CH:8]=[C:7]2[O:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24](=O)[O:25]C2C=CC=CC=2)=[C:19]([Cl:33])[CH:18]=1)(=[O:3])[NH2:2].[CH:34]1([NH2:37])[CH2:36][CH2:35]1.O>CN(C)C=O>[Cl:33][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][C:20]=1[NH:23][C:24]([NH:37][CH:34]1[CH2:36][CH2:35]1)=[O:25])[O:16][C:7]1[C:6]2[C:11](=[CH:12][C:13]([O:14][CH3:15])=[C:4]([C:1]([NH2:2])=[O:3])[CH:5]=2)[N:10]=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 962WaterHCID 69828CyclopropylamineHCID 22936529(4-((6-(Aminocarbonyl)-7-methoxy-4-quinolinyl)oxy)-2-chlorophenyl)carbamic acid phenyl ester

Product 1

HCID 9823820LenvatinibYield 80.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of phenyl N-(4-(6-carbamoyl-7-methoxy-4-quinolyl)oxy-2-chlorophenyl)carbamate (described in WO02/32872; 17.5 g, 37.7 mmol) dissolved in N,N-dimethylformamide (350 mL), was added cyclopropylamine (6.53 mL, 94.25 mmol) under nitrogen atmosphere, and the mixture were stirred at room temperature overnight. The mixture was poured into water (1.75 L), and stirred. Precipitated crude crystals were filtered off, washed with water, and dried at 70° C. for 50 minutes. Ethanol (300 mL) was added to the crude crystals, the mixture was heated to reflux for about 30 minutes to dissolve the crystals, and gradually cooled to room temperature overnight while stirring. Precipitated crystals were filtered off, dried in vacuo, and dried at 70° C. for 8 hours to give crystals of the title compound (12.91 g, yield 80.2 %).

Workup

  1. stirringstirred
  2. customPrecipitated crude crystals
  3. filtrationwere filtered off
  4. washwashed with water
  5. customdried at 70° C. for 50 minutes
  6. additionEthanol (300 mL) was added to the crude crystals
  7. temperaturethe mixture was heated
  8. temperatureto reflux for about 30 minutes
  9. dissolutionto dissolve the crystals
  10. temperaturegradually cooled to room temperature overnight
  11. stirringwhile stirring
  12. customPrecipitated crystals
  13. filtrationwere filtered off
  14. customdried in vacuo
  15. customdried at 70° C. for 8 hours

Sources & evidence

ORD record
ord-6d69b1fb098449688de18acd3bf45d71
Source dataset
uspto-grants-2011_08
Patent number
US07994159B2

Reaction notes

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