Auristatin E → HCID 59998486, compound

HRID 30417Notes

Reaction equation

HRID 30417 reaction equation
[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[CH3:12][CH2:13][C@@H:14]([C@H:16]([N:46]([C:48]([C@@H:50]([NH:54][C:55]([C@@H:57]([N:61]([CH3:63])[CH3:62])[CH:58]([CH3:60])[CH3:59])=[O:56])[CH:51]([CH3:53])[CH3:52])=[O:49])[CH3:47])[C@H:17]([O:44][CH3:45])[CH2:18][C:19]([N:21]1[C@H:25]([C@H:26]([O:42][CH3:43])[C@H:27]([C:29]([NH:31][C@@H:32]([C@@H:34]([OH:41])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH3:33])=[O:30])[CH3:28])[CH2:24][CH2:23][CH2:22]1)=[O:20])[CH3:15]>C(Cl)Cl.N1C=CC=CC=1>[CH3:63][N:61]([CH3:62])[C@H:57]([C:55]([NH:54][C@H:50]([C:48]([N:46]([C@@H:16]([C@@H:14]([CH3:15])[CH2:13][CH3:12])[C@H:17]([O:44][CH3:45])[CH2:18][C:19]([N:21]1[CH2:22][CH2:23][CH2:24][C@H:25]1[C@H:26]([O:42][CH3:43])[C@@H:27]([CH3:28])[C:29]([NH:31][C@H:32]([CH3:33])[C:34](=[O:41])[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:30])=[O:20])[CH3:47])=[O:49])[CH:51]([CH3:53])[CH3:52])=[O:56])[CH:58]([CH3:60])[CH3:59]

Participants

5

Reactant 2

HCID 11498622Auristatin EHCID 178418287HCID 178418287, compound

Product 1

HCID 59998486HCID 59998486, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Pyridinium chlorochromate (PCC) (13.6 mg, 0.06 mmol, 4.5 eq.) was added to a solution of Auristatin E (29a) (10 mg, 0.014 mmol, 1 eq.) in CH2Cl2 (2 mL) and pyridine (50 μL). The reaction mixture was stirred at room temperature for 3 h. HPLC analysis of the reaction mixture showed complete conversion of the 10.2 min peak into a new 11.3 min peak with different UV spectrum (max 245 nm, shoulder 280 nm). The product was purified by flash chromatography on a silica gel column (120×12 mm) in a step gradient of MeOH in CH2Cl2 from 0 to 10%. After concentration in vacuum, the residue was triturated with hexane to give white solid. Yield 35: 6.4 mg (64%); Rf 0.3 (CH2Cl2/MeOH, 10/1); UV λmax 215, 245 nm. HRMS m/z: found 730.5119 [M+H]+. C40H68N5O7 requires 730.5108.

Workup

  1. customconversion of the 10.2 min peak
  2. custominto a new 11.3 min
  3. customThe product was purified by flash chromatography on a silica gel column (120×12 mm) in a step gradient of MeOH in CH2Cl2 from 0 to 10%
  4. concentrationAfter concentration in vacuum
  5. customthe residue was triturated with hexane
  6. customto give white solid

Sources & evidence

ORD record
ord-a021a21bcf7e4a0cace8560ed0ca5c5e
Source dataset
uspto-grants-2008_09
Patent number
US07423116B2

Reaction notes

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