Pyridine → 2,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl 4-(chloromethyl)benzoate

HRID 1078142Notes

Reaction equation

HRID 1078142 reaction equation
[C:1]([NH:11][C@H:12]([C:16]([NH:18][CH:19]([CH:27]([OH:54])[CH:28]([NH:36][C:37](=[O:53])[C@H:38]([CH:50]([CH3:52])[CH3:51])[NH:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:17])[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[Cl:55][CH2:56][C:57]1[CH:65]=[CH:64][C:60]([C:61](Cl)=[O:62])=[CH:59][CH:58]=1.N1C=CC=CC=1>C(Cl)(Cl)Cl.C(Cl)Cl.CO>[Cl:55][CH2:56][C:57]1[CH:65]=[CH:64][C:60]([C:61]([O:54][CH:27]([CH:19]([NH:18][C:16](=[O:17])[C@H:12]([CH:13]([CH3:14])[CH3:15])[NH:11][C:1]([O:3][CH2:4][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2])[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:28]([NH:36][C:37](=[O:53])[C@H:38]([CH:50]([CH3:52])[CH3:51])[NH:39][C:40]([O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[O:41])[CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:62])=[CH:59][CH:58]=1

Participants

7

Reactant 3

HCID 1049PyridineHCID 701364-(Chloromethyl)benzoyl 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 228455672,4-Bis-(N-(Cbz-valinyl)amino)-1,5-diphenyl-3-pentyl 4-(chloromethyl)benzoateYield 46.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent4×

Procedure

The resultant compound of Example 70 (1.3 g, 1.76 mmol) was combined with 4-(chloromethyl)benzoyl chloride (1.0 g, 5.3 mmol) and pyridine (418 mg, 5.3 mmol) in 10 mL of freshly distilled methylene chloride. The reaction mixture was heated at reflux under nitrogen for approximately 10 h and then diluted with 150 mL of chloroform. The chloroform solution was washed with 75 mL of water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue (2.1 g) was taken up in ~10 mL of chloroform and applied to a 1.8×45 cm column of 40 mesh silica gel. The column was eluted @~5 p.s.i. sequentially with 200 mL of methylene chloride, 250 mL of 0.5% methanol in methylene chloride and 600 mL of 1% methanol in methylene chloride to give 721 mg (46% yield) of the title compound; FAB MS M/Z: 889 (M+H)+. The 300 MHz 1H NMR spectrum was consistent with the assigned structure.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux under nitrogen for approximately 10 h
  3. washThe chloroform solution was washed with 75 mL of water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. washThe column was eluted @~5 p.s.i

Sources & evidence

ORD record
ord-268fc2c9bf2e4a298b1672e14f090ace
Source dataset
uspto-grants-1996_08
Patent number
US05545750

Reaction notes

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