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

HRID 1078143Notes

Reaction equation

HRID 1078143 reaction equation
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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21912085Dimethylsulfoxide-dichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0e2b16a8485847129400b96cd5f5335e
Source dataset
uspto-grants-1996_08
Patent number
US05545750

Reaction notes

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