Dimethyl Sulfoxide → Sorafenib

HRID 2094789노트

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HRID 2094789 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH2:11])=[O:10])=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].N12CCCN=C1CCCCC2.N[C:28]1[CH:44]=[CH:43][C:31]([O:32][C:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39]([NH:41][CH3:42])=[O:40])[CH:34]=2)=[CH:30][CH:29]=1.CS(C)=O>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:10])[NH:11][C:28]2[CH:44]=[CH:43][C:31]([O:32][C:33]3[CH:38]=[CH:37][N:36]=[C:35]([C:39]([NH:41][CH3:42])=[O:40])[CH:34]=3)=[CH:30][CH:29]=2)=[CH:4][C:3]=1[C:12]([F:13])([F:14])[F:15]

참가 물질

6

반응물 4

HCID 679Dimethyl SulfoxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 166551294-(4-Aminophenoxy)-N-methylpicolinamideHCID 179250491-(4-Chloro-3-(trifluoromethyl)phenyl)urea

생성물 1

HCID 216239Sorafenib수율 59.9%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

반응 조건

온도
115 °C

실험 절차

1-(4-chloro-3-(trifluoromethyl)phenyl)urea (15 g, 0.0628 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (11.75 ml, 0.078 mol) and 4-(4-aminophenoxy)-N-methylpicolinamide (15.27 g, 0.0628 mol) were mixed with dimethyl sulfoxide (45 ml) and the reaction mass was then heated to 110-120° C. for 12-18 hours. The reaction mass was cooled to room temperature and quenched in water (250 ml). The quenched mass was extracted repeatedly with ethyl acetate and the combined ethyl acetate layer was then back washed with water. It was dried over sodium sulfate and evaporated under vacuum to obtain solid. The obtained solid was slurried in acetonitrile (150 ml) at ambient temperature and filtered to give 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido) phenoxy)-N-methylpicolinamide (sorafenib base) (17.5 g).

후처리

  1. temperatureThe reaction mass was cooled to room temperature
  2. customquenched in water (250 ml)
  3. extractionThe quenched mass was extracted repeatedly with ethyl acetate
  4. washthe combined ethyl acetate layer was then back washed with water
  5. dry with materialIt was dried over sodium sulfate
  6. customevaporated under vacuum
  7. customto obtain solid
  8. filtrationfiltered

출처 및 근거

ORD 기록
ord-238572794da14ee3894610ce64b4a0bc
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445687B2

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