Diisopropylethylamine → (S)-4-bromo-7-(2-oxo-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidin-1-yl)ethyl)-6,7-dihydro-3H-oxepino[3,4-e]indazol-8(10H)-one

HRID 2378708Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2378708
[Br:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][O:12][C:13](=[O:20])[C@H:14]([CH2:16][C:17]([OH:19])=O)[CH2:15][C:4]=2[CH:3]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[NH:53]1[CH2:58][CH2:57][CH:56]([C:59]2[C:60](=[O:69])[NH:61][C:62]3[C:67]([CH:68]=2)=[CH:66][CH:65]=[CH:64][CH:63]=3)[CH2:55][CH2:54]1>CN(C)C=O>[Br:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][O:12][C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:19])[N:53]3[CH2:54][CH2:55][CH:56]([C:59]4[C:60](=[O:69])[NH:61][C:62]5[C:67]([CH:68]=4)=[CH:66][CH:65]=[CH:64][CH:63]=5)[CH2:57][CH2:58]3)[CH2:15][C:4]=2[CH:3]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59732081(S)-2-(4-bromo-8-oxo-6,7,8,10-tetrahydro-3H-oxepino[3,4-e]indazol-7-yl)acetic acidHCID 673176623-piperidin-4-yl-1H-quinolin-2-one;hydrochloride

Produkt 1

HCID 24783157(S)-4-bromo-7-(2-oxo-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidin-1-yl)ethyl)-6,7-dihydro-3H-oxepino[3,4-e]indazol-8(10H)-oneAusbeute 19 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(S)-2-(4-Bromo-8-oxo-6,7,8,10-tetrahydro-3H-oxepino[3,4-e]indazol-7-yl)acetic acid (90 mg, 0.265 mmol) was dissolved in N,N-dimethylformamide (2.5 mL). N,N-Diisopropylethylamine (150 μl, 0.861 mmol) was added to the mixture followed by TBTU (94.5 mg, 0.294 mmol). 3-(Piperidin-4-yl)quinolin-2(1H)-one hydrochloride (90.3 mg, 0.341 mmol) was added to the reaction mixture. Reaction stirred at room temperature for 3 hours. Reaction was quenched with water. Material was extracted twice with ethyl acetate. Organic phase was filtered. Filtrate was concentrated by roto-vap. Residue was purified by prep HPLC (acetonitrile-water-trifluoroacetic acid). Acetonitrile was removed from the fractions by roto-vap. Remaining aqueous was made basic with aqueous sodium bicarbonate. Material was extracted twice with ethyl acetate. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as white solid in 19% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.98 (s, 1H) 12.21 (s, 1H) 8.86 (s, 1H) 8.13 (d, J=3.36 Hz, 1H) 8.05 (t, J=6.87 Hz, 1H) 7.81-7.93 (m, 2H) 7.70 (d, J=8.24 Hz, 1H) 7.57 (t, J=7.63 Hz, 1H) 6.38 (d, J=14.65 Hz, 1H) 6.00 (d, J=14.95 Hz, 1H) 4.98 (d, J=13.12 Hz, 1H) 4.48-4.56 (m, 2H) 3.67-3.74 (m, 1H) 3.54-3.67 (m, 1H) 3.30-3.53 (m, 3H) 3.04-3.16 (m, 1H) 2.95-3.04 (m, 1H) 2.36 (t, J=11.14 Hz, 1H) 2.28 (t, J=9.46 Hz, 1H) 1.91-2.04 (m, 1H) 1.77-1.90 (m, 1H). High resolution M/E (M+H)+=549.1132.

Aufarbeitung

  1. customReaction
  2. customReaction
  3. customwas quenched with water
  4. extractionMaterial was extracted twice with ethyl acetate
  5. filtrationOrganic phase was filtered
  6. concentrationFiltrate was concentrated by roto-vap
  7. customResidue was purified by prep HPLC (acetonitrile-water-trifluoroacetic acid)
  8. customAcetonitrile was removed from the fractions by roto-vap
  9. extractionMaterial was extracted twice with ethyl acetate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-5277aabf6d2f4382a8280d959009a978
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07470679B2

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