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

HRID 2214284ノート

反応式

HRID 2214284 の反応式
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]

参加物

6

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-93129b9716ac4756972b4e23bb90530d
出典データセット
uspto-grants-2006_09
特許番号
US07105539B2

反応ノート

読み込み中…