Potassium Phosphate, Tribasic → 5-(11-fluoro-5,6-dihydropyridazino[4',3':3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595712Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 595712
Cl[C:2]1[N:19]=[N:18][C:5]2[CH2:6][CH2:7][N:8]3[C:16]4[CH:15]=[CH:14][CH:13]=[C:12]([F:17])[C:11]=4[CH:10]=[C:9]3[C:4]=2[CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B(O)O)=[CH:36][C:30]=3[C:31]=2[C:32](=[O:35])[NH:33][CH3:34])=[CH:23][CH:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[F:17][C:12]1[C:11]2[CH:10]=[C:9]3[C:4]4[CH:3]=[C:2]([C:37]5[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]6[O:28][C:27]([C:24]7[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=7)=[C:31]([C:32]([NH:33][CH3:34])=[O:35])[C:30]=6[CH:36]=5)[N:19]=[N:18][C:5]=4[CH2:6][CH2:7][N:8]3[C:16]=2[CH:15]=[CH:14][CH:13]=1

Komponenten

5

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 90332474(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acidHCID 903335802-Chloro-11-fluoro-5,6-dihydropyridazino[4',3':3,4]pyrido[1,2-a]indole

Produkt 1

HCID 903410165-(11-fluoro-5,6-dihydropyridazino[4',3':3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideAusbeute 13,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a degassed solution of 2-chloro-11-fluoro-5,6-dihydropyridazino[4′,3′:3,4]pyrido[1,2-a]indole (100 mg, 0.37 mmol), (2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acid (169 mg, 0.4 mmol) and K3PO4 (155 mg, 0.73 mmol) in DMF (3 mL) was added Pd(dtbpf)Cl2 (5 mg) under N2. Then the mixture was stirred at 100° C. for 3 hours. The reaction mixture was cooled to RT and filtered. The filtrate was washed with H2O and dried over Na2SO4. After being concentrated, the residue was purified by prep-HPLC to give the product of 5-(11-fluoro-5,6-dihydropyridazino[4′,3′:3,4]pyrido[1,2-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (30 mg, yield: 13%). 1H-NMR (CDCl3, 400 MHz) δ 8.11 (d, J=9.0 Hz, 2H), 8.00 (dd, J=5.6, 8.8 Hz, 2H), 7.66 (s, 1H), 7.25 (s, 1H), 7.15˜7.23 (m, 4H), 6.81 (dd, J=7.6, 9.6 Hz, 1H), 6.17 (d, J=4.0 Hz, 1H), 4.47 (t, J=6.4 Hz, 2H), 3.67 (t, J=6.4 Hz, 2H), 3.21 (s, 3H), 3.00 (d, J=4.8 Hz, 3H), 2.97 (s, 3H). MS (M+H)+: 614.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O
  4. dry with materialdried over Na2SO4
  5. concentrationAfter being concentrated
  6. customthe residue was purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-9c882cbd7e7849cdbe15e902909de49e
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09243002B2

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