Diisopropylethylamine → N2-(9-fluorenylmethoxycarbonyl)-N5-(4-(2,2-bis(diallylphosphoryl)ethyl)phenyl)-L-glutamine

HRID 39273

Reaktionsgleichung

Reaktionsgleichung von HRID 39273
[NH:1]([C:15]([O:17][CH2:18][CH:19]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[C@H:2]([C:8]([O:10]C(C)(C)C)=[O:9])[CH2:3][CH2:4][C:5](=[O:7])O.CCN([CH:38]([CH3:40])[CH3:39])C(C)C.CN(C(ON1N=NC2C=C[CH:54]=[CH:55][C:50]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:65][C:66]1[CH:81]=[CH:80][C:69]([CH2:70][CH:71]([P:76](=[O:79])([O-])[O-])[P:72](=[O:75])([O-])[O-])=[CH:68][CH:67]=1>CN(C=O)C.C(Cl)Cl>[CH:30]1[C:31]2[CH:19]([CH2:18][O:17][C:15]([NH:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH:65][C:66]3[CH:67]=[CH:68][C:69]([CH2:70][CH:71]([P:72]([CH2:40][CH:38]=[CH2:39])([CH2:50][CH:55]=[CH2:54])=[O:75])[P:76]([CH2:20][CH:19]=[CH2:18])([CH2:8][CH:2]=[CH2:3])=[O:79])=[CH:80][CH:81]=3)=[O:16])[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:26]=2[CH:27]=[CH:28][CH:29]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7017912(4S)-5-(tert-Butoxy)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-oxopentanoic acidHCID 200590851-(4-Aminobenzyl)methylenebisphosphonate

Produkt 1

HCID 86762032N2-(9-fluorenylmethoxycarbonyl)-N5-(4-(2,2-bis(diallylphosphoryl)ethyl)phenyl)-L-glutamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of Fmoc-Glu-Ot-Bu (253 mg, 0.59 mmol) in DMF (3 mL) at 0° C. was added DIEA (207 μL, 1.19 mmol) and HBTU (225 mg, 0.59 mmol). After stirring for 10 min at 0° C., aminobenzyl bisphosphonate 104 (262 mg, 0.59 mmol) in DMF (2 mL) was added and stirring was pursued for 2 h at 0° C. The reaction mixture was diluted with CH2Cl2, washed with H2O, 0.5N HCl solution, saturated NaHCO3 solution and saturated NaCl solution. The organic layer was dried over MgSO4, filtered and concentrated to dryness. The crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system using 1-10% methanol in CH2Cl2. Compound 105 was obtained as a yellow gum (431 mg, 86%). 1H NMR (400 MHz, CDCl3) δ 1.46 (s, 9H), 1.86-1.92 (m, 1H), 2.26-2.38 (m, 3H), 2.70 (tt, J=24.0, 6.3 Hz, 1H), 3.24 (dt, J=16.8, 6.3 Hz, 2H), 4.19-4.29 (m, 2H), 4.40-4.60 (m, 10H), 5.19-5.22 (m, 4H), 5.28-5.34 (m, 4H), 5.58 (d, J=8.0 Hz, 1H), 5.83-5.93 (m, 4H), 7.21 (d, J=8.3, 2H), 7.27-7.34 (m, 2H), 7.38-7.43 (m, 2H), 7.50 (d, J=8.2 Hz, 2H), 7.60 (d, J=7.4 Hz, 2H), 7.77 (d, J=7.5 Hz, 2H), 8.28 (s, 1H).

Aufarbeitung

  1. stirringstirring
  2. waitwas pursued for 2 h at 0° C
  3. washwashed with H2O, 0.5N HCl solution, saturated NaHCO3 solution and saturated NaCl solution
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system

Quellen und Nachweise

ORD-Eintrag
ord-b88715a941f946c08de545f661a27637
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524691B2

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