Ethanol → Lenvatinib

HRID 1433132노트

반응식

HRID 1433132 반응식
[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.C(O)C>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

참가 물질

6

반응물 4

HCID 702EthanolHCID 962WaterHCID 69828CyclopropylamineHCID 22936529(4-((6-(Aminocarbonyl)-7-methoxy-4-quinolinyl)oxy)-2-chlorophenyl)carbamic acid phenyl ester

생성물 1

HCID 9823820Lenvatinib

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Phenyl N-(4-(6-carbamoyl-7-methoxy-4-quinolyl)oxy-2-chlorophenyl)carbamate (17.5 g, 37.7 mmol) disclosed in WO 02/32872 was dissolved in N,N-dimethylformamide (350 mL), and then cyclopropylamine (6.53 mL, 94.25 mmol) was added to the reaction mixture under a nitrogen atmosphere, followed by stirring overnight at room temperature. To the mixture was added water (1.75 L), and the mixture was stirred. Precipitated crude crystals were filtered off, washed with water, and dried at 70° C. for 50 min. To the obtained crude crystals was added ethanol (300 mL), and then the mixture was heated under reflux for 30 min to dissolve, followed by stirring overnight to cool slowly down to room temperature. Precipitated crystals was filtered off and dried under vacuum, and then further dried at 70° C. for 8 hours to give the titled crystals (12.91 g; 80.2%).

후처리

  1. stirringthe mixture was stirred
  2. customPrecipitated crude crystals
  3. filtrationwere filtered off
  4. washwashed with water
  5. customdried at 70° C. for 50 min
  6. customTo the obtained crude crystals
  7. temperaturethe mixture was heated
  8. temperatureunder reflux for 30 min
  9. dissolutionto dissolve
  10. stirringby stirring overnight
  11. temperatureto cool slowly down to room temperature
  12. customPrecipitated crystals
  13. filtrationwas filtered off
  14. customdried under vacuum
  15. customfurther dried at 70° C. for 8 hours
  16. customto give the titled crystals (12.91 g; 80.2%)

출처 및 근거

ORD 기록
ord-b60d29f2f73a4e2ba2e5c3f7312651aa
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612208B2

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