Dimethyl Sulfoxide → Sorafenib

HRID 2094789ノート

反応式

HRID 2094789 の反応式
[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]

参加物

6

反応物 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

生成物 1

HCID 216239Sorafenib収率 59.9%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
115 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-238572794da14ee3894610ce64b4a0bc
出典データセット
uspto-grants-2013_05
特許番号
US08445687B2

反応ノート

読み込み中…