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

HRID 48353

반응식

HRID 48353 반응식
[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

참가 물질

11

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
-20 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-943b2b930a5e4df58d4e009d6b0befad
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06703387B2

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