Dimethyl Sulfoxide → 2,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentanone

HRID 847648노트

반응식

HRID 847648 반응식
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([NH:21][C@H:22]([C:26]([NH:28][CH:29]([CH:37]([OH:64])[CH:38]([NH:46][C:47](=[O:63])[C@H:48]([CH:60]([CH3:62])[CH3:61])[NH:49][C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:27])[CH:23]([CH3:25])[CH3:24])([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].C(N(CC)CC)C>C(Cl)Cl.CS(C)=O.C(Cl)Cl>[C:50]([NH:49][C@H:48]([C:47]([NH:46][CH:38]([C:37](=[O:64])[CH:29]([NH:28][C:26](=[O:27])[C@H:22]([CH:23]([CH3:25])[CH3:24])[NH:21][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:63])[CH:60]([CH3:61])[CH3:62])([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51]

참가 물질

7

반응물 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 3011026benzyl N-[(1S)-1-[[1-benzyl-3-[[(2S)-2-(benzyloxycarbonylamino)-3-methyl-butanoyl]amino]-2-hydroxy-4-phenyl-butyl]carbamoyl]-2-methyl-propyl]carbamate

생성물 1

HCID 228455602,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentanone수율 84%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 21912085Dimethylsulfoxide-dichloromethane용매

실험 절차

To a cold (-78° C.) solution of oxalyl chloride (93 mg, 0.73 mmol) in 11 mL of freshly distilled methylene chloride was added, with stirring, 103 μL (1.46 mmol) of DMSO. To this soltuion at -78° C. after stirring for 5 minutes was added a solution of the resultant compound of Example 70 (450 mg, 0.61 mmol) in 5.5 mL of methylene chloride/DMSO (10:1). The reaction mixture was stirred at -78° C. for ~50 min, triethylamine (426 μL, 3.0 mmol) was added and stirring was continued for 5 min at -78° C. The cold bath was removed and the reaction mixture was allowed to warm to ambient temperature. The reaction mixture was diluted with 150 mL of chloroform. The chloroform solution was washed with 100 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was taken up in -3 mL of chloroform and applied to a 1.0×45 cm column of silica gel. The column was eluted with 100 mL of chloroform and 100 mL of 0.5% methanol in chloroform to give 376 mg (84% yield) of the title compound; DCI/NH3 MS M/Z: 501 (M+ NH4)+. The 300 MHz 1H NMR spectrum was consistent with the assigned structure.

후처리

  1. stirringTo this soltuion at -78° C. after stirring for 5 minutes
  2. stirringThe reaction mixture was stirred at -78° C. for ~50 min
  3. stirringstirring
  4. customThe cold bath was removed
  5. additionThe reaction mixture was diluted with 150 mL of chloroform
  6. washThe chloroform solution was washed with 100 mL of brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. washThe column was eluted with 100 mL of chloroform and 100 mL of 0.5% methanol in chloroform

출처 및 근거

ORD 기록
ord-5b418dc67d044223bfb9f34d56c96a9c
출처 데이터셋
uspto-grants-1992_08
특허 번호
US05142056

반응 노트

불러오는 중…