Acetic Acid → ethyl (E)-6-(3,4-dichlorostyryl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate

HRID 48353

反応式

HRID 48353 の反応式
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH:7]=[CH:8][C:9]1=[N:10][CH2:11][C:12](=O)[NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]1=2.P(Cl)(OCC)(OCC)=O.C([N-]C(C)C)(C)C.[Li+].[N+:42]([CH2:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])#[C-:43].C(O)(=O)C>CN(C)C=O.O1CCCC1.C(OCC)(=O)C.O>[Cl:3][C:4]1[CH:5]=[C:6]([CH:21]=[CH:22][C:23]=1[Cl:24])[CH:7]=[CH:8][C:9]1=[N:10][CH2:11][C:12]2[N:13]([CH:43]=[N:42][C:44]=2[C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]1=2

参加物

11

反応物 6

HCID 176Acetic AcidHCID 13139Diethyl chlorophosphateHCID 24758Sodium hydrideHCID 533707Ethyl isocyanoacetateHCID 2724682Lithium diisopropylamideHCID 69892950(E)-5-(3,4-dichlorostyryl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

生成物 1

HCID 85326063ethyl (E)-6-(3,4-dichlorostyryl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate収率 12.4%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-20 °C

実験手順

100 mg (2.5 mmol) of 60% sodium hydride disperion in mineral oil were added to a solution of 728 mg (2.2 mmol) of (E)-5-(3,4-dichlorostyryl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 5 ml of anhydrous dimethylformamide at room temperature under a nitrogen atmosphere and stirred for 30 minutes. The mixture was cooled to −20° C., 431 mg (2.5 mmol) of diethyl chlorophosphate were added and stirring was continued for a further 30 minutes at −10° C. before being added to a solution prepared by addition of 1.65 ml (3.3 mmol) of 2M lithium diisopropylamide to a solution of 375 mg (3.32 mmol) of ethyl isocyanoacetate in 5 ml of anhydrous tetrahydrofuran at −78° C. under a nitrogen atmosphere. The resulting mixture was stirred at −78° C. for 2 hours then warmed to −30° C. and 180 mg (3 mmol) of acetic acid were added followed by water and ethyl acetate. The organic phase was washed twice with water, dried over magnesium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel using ethyl acetate/methanol (49:1) for the elution. The product was dissolved in 1 ml of ethyl acetate and 10 ml of diethyl ether and left to crystallize. There was obtained 116 mg of ethyl (E)-6-(3,4-dichlorostyryl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate as a light-brown solid. MS: m/e 425.9 [M+H]+.

後処理

  1. stirringstirring
  2. waitwas continued for a further 30 minutes at −10° C.
  3. additionbefore being added to a solution
  4. stirringThe resulting mixture was stirred at −78° C. for 2 hours
  5. temperaturethen warmed to −30° C.
  6. washThe organic phase was washed twice with water
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe residue was chromatographed on silica gel
  11. washfor the elution
  12. dissolutionThe product was dissolved in 1 ml of ethyl acetate
  13. wait10 ml of diethyl ether and left
  14. customto crystallize

出典と根拠

ORDレコード
ord-943b2b930a5e4df58d4e009d6b0befad
出典データセット
uspto-grants-2004_03
特許番号
US06703387B2

関連ノート

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