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

HRID 902955Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 902955
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]

Komponenten

6

Edukt 2

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-bf0970a6a1e444df91a78a27ecc1f827
Quelldatensatz
uspto-grants-2008_04
Patentnummer
US07365091B2

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