1,2-Dichloroethane → HCID 178445682, Verbindung

HRID 1992803Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1992803
[C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12]([C:14]2[N:18]([CH2:19][C:20]3[CH:28]=[CH:27][C:23](C(O)=O)=[CH:22][N:21]=3)[N:17]=[C:16]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=3)[CH:15]=2)=[O:13])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C1C=NC2N(O)N=NC=2C=1.C([O:51][C:52](=[O:56])[CH2:53][CH2:54][NH2:55])(C)(C)C.CCN(C(C)C)C(C)C.C(Cl)CCl.[C:70](O)(C(F)(F)F)=[O:71]>CN(C=O)C.C(OCC)(=O)C.C(Cl)Cl>[C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12]([C:14]2[N:18]([CH2:19][C:20]3[N:21]=[CH:22][C:23]([C:70]([NH:55][CH2:54][CH2:53][C:52]([OH:51])=[O:56])=[O:71])=[CH:27][CH:28]=3)[N:17]=[C:16]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[C:31]([Cl:36])[CH:30]=3)[CH:15]=2)=[O:13])[CH2:7][CH2:6]1)([CH3:2])([CH3:4])[CH3:3]

Komponenten

10

Edukt 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 4192171tert-Butyl 3-aminopropanoateHCID 178445683HCID 178445683, Verbindung

Produkt 1

HCID 178445682HCID 178445682, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of the intermediate from step H (65 mg, 0.122 mmol) in DMF (2 mL) was added HOAt (25 mg, 0.184 mmol), β-alanine-tert-butyl ester (34 mg, 0.184 mmol), DIEA (64 μL, 0.37 mmol) and EDC (36 mg, 0.184 mmol). After stirring the reaction at room temperature for 18 hours, the reaction was diluted with ethyl acetate and washed with 1N HCl , saturated NaHCO3 and saturated NaCl solution. The organic layer was dried over anhydrous Na2SO4 filtered and concentrated in vacuo. The residue was purified by flash chromatography using 30% ethyl acetate-hexanes. Colorless oil was obtained. This material was dissolved in DCM (2 mL) and TFA was added (2 mL). After 1 hour the reaction mixture was concentrated in vacuo and azeotroped with toluene (3×) to give the title compound as a solid. 1H NMR (DMSO, 500 MHz): 8.88 (d, J=1.4 Hz, 1H), 8.72 (t, J=5.4 Hz, 1H), 8.2 (d, J=8.7 Hz, 1H), 8.14 (dd, J=2.3, 8.2 Hz, 1H), 8.02 (d, J=1.8 Hz, 1H), 7.81 (dd, J=2.0, 8.5 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.48 (s, 1H), 7.15 (d, J=8.0 Hz, 1H), 5.85 (s, 2H), 3.48 (q, J=6.9 Hz, 2H), 1.83 (bd, J=12.6 Hz, 2H), 1.45 (m, 4H), 1.25 (m, 2H), 0.98 (m, 1H), 0.83 (s, 9H). LC-MS=3.99 min, (M+H)=600.2.

Aufarbeitung

  1. customthe reaction at room temperature for 18 hours
  2. washwashed with 1N HCl , saturated NaHCO3 and saturated NaCl solution
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography
  7. customColorless oil was obtained
  8. concentrationAfter 1 hour the reaction mixture was concentrated in vacuo
  9. customazeotroped with toluene (3×)

Quellen und Nachweise

ORD-Eintrag
ord-1d453662620e4b2ab59a86d589522244
Quelldatensatz
uspto-grants-2010_01
Patentnummer
US07649009B2

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