ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate → HCID 86612090, Verbindung

HRID 500413

Reaktionsgleichung

Reaktionsgleichung von HRID 500413
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:38][N:39](C1CC1)[CH2:40][CH2:41][CH2:42][CH:43]=[CH2:44])[C:10]([N:12]1[CH2:16][C@H:15]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:14][C@H:13]1[C:25]([NH:27][C@:28]1([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:30][C@H:29]1C=C)=[O:26])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:10](=[O:11])[N:12]2[C@@H:13]([CH2:14][C@@H:15]([O:17][Si:18]([C:21]([CH3:23])([CH3:22])[CH3:24])([CH3:19])[CH3:20])[CH2:16]2)[C:25](=[O:26])[NH:27][C@@:28]2([C:33]([O:35][CH2:36][CH3:37])=[O:34])[C@@H:30]([CH2:29]2)[CH:44]=[CH:43][CH2:42][CH2:41][CH2:40][NH:39][CH2:38]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Komponenten

4

Edukt 1

HCID 67331048ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate

Produkt 1

HCID 86612090HCID 86612090, VerbindungAusbeute 64,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11147261(1,3-Dimesitylimidazolidin-2-ylidene)(tricyclohexylphosphine)benzylidene ruthenium dichlorideKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate (1.45 g, 2.14 mmoL) in 1 L of methylene chloride was added 181 mg (0.21 mmoL) of Grubb's 2nd generation catalyst [(1,3-Bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium]. The mixture was heated at reflux for 1 h. A second fraction of the catalyst (50 mg, 0.058 mmol) was added, and the mixture was stirred at rt overnight. The residue was concentrated in vacuo, and then purified by flash chromatography eluting with 50% ether/hexane to give 0.84 g (62%) of (1S,4R,6S,14S,18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid, ethyl ester as a white solid: LC-MS (Phenomenex 10 μm C18HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 2 min. Hold time: 1 min. Flow rate: 5 mL/min. Detector Wavelength: 220 nM. Solvent A: 10% MeOH/90% H2O/0.1% TFA. Solvent B: 10% H2O/90% MeOH/0.1% TFA.) (Retention time: 2.43 min), MS m/z 649 (M++1).

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 h
  3. concentrationThe residue was concentrated in vacuo
  4. custompurified by flash chromatography
  5. washeluting with 50% ether/hexane

Quellen und Nachweise

ORD-Eintrag
ord-cdd241aa466a4cabb90bd727abae591c
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772183B2

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