Toluene → ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]-3-(N,N-dimethylamino)acrylate

HRID 246959ノート

反応式

HRID 246959 の反応式
C1(C)C=CC=CC=1.[CH3:8][N:9]([CH3:12])[CH:10]=O.S(OC)(OC)(=O)=O.C[O-].[Na+].[C:23]([NH:26][CH:27]1[CH2:31][CH2:30][N:29]([C:32]2[C:45]([F:46])=[CH:44][C:35]([C:36]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:37])=[C:34]([NH:47][C:48]3[CH:53]=[CH:52][C:51]([F:54])=[CH:50][C:49]=3[F:55])[N:33]=2)[CH2:28]1)(=[O:25])[CH3:24]>O.C(Cl)(Cl)Cl>[C:23]([NH:26][CH:27]1[CH2:31][CH2:30][N:29]([C:32]2[C:45]([F:46])=[CH:44][C:35]([C:36]([C:38](=[CH:8][N:9]([CH3:12])[CH3:10])[C:39]([O:41][CH2:42][CH3:43])=[O:40])=[O:37])=[C:34]([NH:47][C:48]3[CH:53]=[CH:52][C:51]([F:54])=[CH:50][C:49]=3[F:55])[N:33]=2)[CH2:28]1)(=[O:25])[CH3:24]

参加物

7

反応物 4

HCID 1140TolueneHCID 10942334Sodium MethoxideHCID 11127270DMF dimethylsulfateHCID 13849322Ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate

生成物 1

HCID 70391376ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]-3-(N,N-dimethylamino)acrylate収率 84.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6212Chloroform溶媒

実験手順

To 4 ml of toluene was added 245 mg of (N,N-dimethylformamide-dimethyl sulfate) complex compound, and 66 mg of sodium methoxide was added thereto with ice-cooling after which the resulting mixture was subjected to reaction at room temperature for 30 minutes. Subsequently, 200 mg of ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate was added thereto, and the resulting mixture was subjected to reaction under reflux for 5 hours. To the reaction mixture were added 20 ml of chloroform and 20 ml of water, and the organic layer was separated, washed with 20 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the residue thus obtained was purified by a column chromatography [Wako Silica Gel C-200, eluant: chloroform-ethanol (50:1 by volume)] to obtain 190 mg (yield 84.9%) of ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]-3 -(N,N-dimethylamino)acrylate having a melting point of 184°-186° C.

後処理

  1. additionwas added
  2. temperaturewith ice-cooling after which the resulting mixture
  3. customwas subjected to reaction at room temperature for 30 minutes
  4. customthe resulting mixture was subjected to reaction
  5. temperatureunder reflux for 5 hours
  6. customthe organic layer was separated
  7. washwashed with 20 ml of saturated aqueous sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was removed by distillation under reduced pressure
  10. customthe residue thus obtained
  11. customwas purified by a column chromatography [Wako Silica Gel C-200, eluant: chloroform-ethanol (50:1 by volume)]

出典と根拠

ORDレコード
ord-d5d3234db92b43dca8e17a67d2ebdbe6
出典データセット
uspto-grants-1987_11
特許番号
US04704459

反応ノート

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