Sodium Carbonate → 2-(4-(difluoromethyl)phenyl)-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

HRID 595568Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 595568
[F:1][CH:2]([F:37])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19](B4OC(C)(C)C(C)(C)O4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:5][CH:4]=1.Cl[C:39]1[CH:40]=[CH:41][C:42]2[O:55][CH2:54][N:45]3[C:46]4[CH:47]=[CH:48][CH:49]=[C:50]([F:53])[C:51]=4[CH:52]=[C:44]3[C:43]=2[N:56]=1.C([O-])([O-])=O.[Na+].[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:1][CH:2]([F:37])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19]([C:39]4[CH:40]=[CH:41][C:42]5[O:55][CH2:54][N:45]6[C:46]7[CH:47]=[CH:48][CH:49]=[C:50]([F:53])[C:51]=7[CH:52]=[C:44]6[C:43]=5[N:56]=4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:5][CH:4]=1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 903335872-(4-(difluoromethyl)phenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

Produkt 1

HCID 903339412-(4-(difluoromethyl)phenyl)-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-carboxamideAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a degassed solution of 2-(4-(difluoromethyl)phenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.18 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (50 mg, 0.20 mmol), Na2CO3 (39 mg, 0.37 mmol), in 1,4-dioxane (3 mL) and H2O (0.1 mL) were added Pd2(dba)3 (5 mg) and X-Phos (5 mg) under N2. Then the mixture was stirred at 100° C. for 2 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 2-(4-(difluoromethyl)phenyl)-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 (50 mg, yield: 41%). 1H-NMR (CDCl3, 400 MHz) δ 8.08 (d, J=7.6 Hz, 2H), 8.05 (s, 1H), 7.73 (s, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.53 (s, 2H), 7.30 (s, 1H), 7.25 (d, J=2.8 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.88˜6.93 (m, 1H), 6.75 (s, 1H), 6.09 (d, J=4.4 Hz, 1H), 6.04 (s, 2H), 3.41 (s, 3H), 3.04 (d, J=4.8 Hz, 3H), 2.79 (s, 3H). MS (M+H)+: 647.

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-1e727269b23f466c912bc3585d3f90b9
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242998B2

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