HCID 90341045, Verbindung → HCID 77845567, Verbindung

HRID 595561Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 595561
[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:19]5[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])=[CH:21][C:22]6[O:26][C:25]([C:27]7[CH:32]=[CH:31][C:30](=[O:33])[NH:29][CH:28]=7)=[C:24]([C:34]([NH:36][CH3:37])=[O:35])[C:23]=6[CH:38]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1.Cl[C:46](C(O[Na])=O)([F:48])[F:47]>CC#N>[F:47][CH:46]([F:48])[O:33][C:30]1[N:29]=[CH:28][C:27]([C:25]2[O:26][C:22]3[CH:21]=[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])[C:19]([C:16]4[CH:17]=[CH:18][C:13]5[O:12][CH2:11][N:6]6[C:7]7[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[C:3]=7[CH:4]=[C:5]6[C:14]=5[N:15]=4)=[CH:38][C:23]=3[C:24]=2[C:34]([NH:36][CH3:37])=[O:35])=[CH:32][CH:31]=1.[F:47][CH:46]([F:48])[N:29]1[C:30](=[O:33])[CH:31]=[CH:32][C:27]([C:25]2[O:26][C:22]3[CH:21]=[C:20]([N:39]([CH3:44])[S:40]([CH3:43])(=[O:42])=[O:41])[C:19]([C:16]4[CH:17]=[CH:18][C:13]5[O:12][CH2:11][N:6]6[C:7]7[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[C:3]=7[CH:4]=[C:5]6[C:14]=5[N:15]=4)=[CH:38][C:23]=3[C:24]=2[C:34]([NH:36][CH3:37])=[O:35])=[CH:28]1

Komponenten

5

Edukt 2

HCID 90341045HCID 90341045, VerbindungHCID 178526069HCID 178526069, Verbindung

Produkt 2

HCID 77845567HCID 77845567, VerbindungHCID 90333930HCID 90333930, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a suspension of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-oxo-1,6-dihydropyridin-3-yl)benzofuran-3-carboxamide (40 mg, 0.06 mmol) in MeCN (5 mL) was added F2ClCCOONa (20 mg, 0.13 mol) under N2, and then the mixture was stirred at 100° C. for 12 hours. After concentrated in vacuo, the resulting residue was suspended in H2O and extracted with DCM. The combined organic layer was washed with H2O, brine, dried over Na2SO4, filtrated and concentrated in vacuo. The residue was purified by prep-HPLC to give the product of 2-(6-(difluoromethoxy)pyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide and 2-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide. 2-(6-(difluoromethoxy)pyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 47%). 1H-NMR (CDCl3, 400 MHz) δ 8.84 (d, J=2.0 Hz, 1H), 8.43˜8.47 (m, 1H), 7.96 (s, 1H), 7.73 (s, 0.25H), 7.69 (s, 1H), 7.55 (s, 0.5H), 7.50˜7.52 (m, 2H), 7.37 (s, 0.25H), 7.20˜7.24 (m, 2H), 7.13 (d, J=4.4 Hz, 1H), 7.04 (d, J=4.2 Hz, 1H), 6.84˜6.87 (m, 1H), 6.07 (s, 1H), 5.99 (s, 2H), 3.35 (s, 3H), 3.05 (d, J=4.8 Hz, 3H), 2.78 (s, 3H). MS (M+H)+: 664. 2-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (10 mg, yield: 23%). 1H-NMR (CDCl3, 400 MHz) δ 8.67 (d, J=2.0 Hz, 1H), 8.12˜8.15 (m, 1H), 7.92 (s, 1H), 7.76 (s, 0.25H), 7.69 (s, 0.5H), 7.61 (s, 0.25H), 7.51˜7.53 (m, 2H), 7.50 (s, 1H), 7.21˜7.24 (m, 2H), 7.14 (d, J=8.0 Hz, 1H), 6.84˜6.89 (m, 1H), 6.67 (d, J=8.0 Hz, 1H), 6.14 (s, 1H), 6.02 (s, 2H), 3.35 (s, 3H), 3.08 (d, J=4.8 Hz, 3H), 2.81 (s, 3H). MS (M+H)+: 664.

Aufarbeitung

  1. concentrationAfter concentrated in vacuo
  2. extractionextracted with DCM
  3. washThe combined organic layer was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltrated
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d5bb8ef252174fec8ba0bb7812acd462
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242998B2

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