Bromotrimethylsilane → N-[1-Carboxy-2-(1H-indol-3-yl)-ethyl]-3-(4-phenyl-2-phosphono-butyrylamino]-succinamic acid

HRID 2214284Notes

Reaction equation

HRID 2214284 reaction equation
C([O:8][C:9](=[O:56])[CH2:10][CH:11]([NH:36][C:37](=[O:55])[CH:38]([P:47]([O:52]CC)([O:49]CC)=[O:48])[CH2:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:12]([NH:14][CH:15]([C:26]([O:28]CC1C=CC=CC=1)=[O:27])[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][CH:18]=1)=[O:13])C1C=CC=CC=1.C[Si](Br)(C)C>C(Cl)Cl.CO.[Pd]>[C:26]([CH:15]([NH:14][C:12](=[O:13])[CH:11]([NH:36][C:37](=[O:55])[CH:38]([P:47]([OH:52])([OH:49])=[O:48])[CH2:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:10][C:9]([OH:56])=[O:8])[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][CH:18]=1)([OH:28])=[O:27]

Participants

6

Reactant 2

HCID 76113BromotrimethylsilaneHCID 87735201N-[1-benzyloxycarbonyl-2-(1H-indol-3-yl)-ethyl]-3-[2-(diethoxy-phosphoryl)4-phenyl-butyrylamino]-succinamic acid benzyl ester

Product 1

HCID 21957074N-[1-Carboxy-2-(1H-indol-3-yl)-ethyl]-3-(4-phenyl-2-phosphono-butyrylamino]-succinamic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

The more polar peptide phosphonate of Example 159 (54 mg, 69 μmol) was dissolved in dry CH2Cl2 (2 mL) followed by the addition of TMSBr (73 μL, 552 μmol). The resulting pale yellow solution was stirred for 40 h. The volatile materials were evaporated in vacuum at room temperature and the obtained residue was suspended in a water/methanol mixture (20:1) and vigorously stirred for 2 h after which it was lyophilized to give the crude phosphonic acid intermediate. This crude product was taken up in methanol (5 mL) and treated with Pd/C powder (10%, 25 mg). The mixture was stirred under an H2 atmosphere (45 PSI) for 12 h and then the catalyst was removed by filtration through a celite pad. The resulting mixture was concentrated to give the crude title compound which was purified by HPLC.

Workup

  1. customThe volatile materials were evaporated in vacuum at room temperature
  2. stirringvigorously stirred for 2 h after which it
  3. customto give the crude phosphonic acid intermediate
  4. stirringThe mixture was stirred under an H2 atmosphere (45 PSI) for 12 h
  5. customthe catalyst was removed by filtration through a celite pad
  6. concentrationThe resulting mixture was concentrated

Sources & evidence

ORD record
ord-93129b9716ac4756972b4e23bb90530d
Source dataset
uspto-grants-2006_09
Patent number
US07105539B2

Reaction notes

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