Sodium Carbonate → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-(4-fluorophenoxyl)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595566Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 595566
[F:1][C:2]1[CH:42]=[CH:41][C:5]([O:6][C:7]2[N:12]=[CH:11][C:10]([C:13]3[O:14][C:15]4[CH:25]=[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:29])=[O:28])[C:23](B5OC(C)(C)C(C)(C)O5)=[CH:22][C:16]=4[C:17]=3[C:18]([NH:20][CH3:21])=[O:19])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Cl[C:44]1[CH:45]=[CH:46][C:47]2[O:60][CH2:59][N:50]3[C:51]4[CH:52]=[CH:53][CH:54]=[C:55]([F:58])[C:56]=4[CH:57]=[C:49]3[C:48]=2[N:61]=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]>[F:58][C:55]1[C:56]2[CH:57]=[C:49]3[C:48]4[N:61]=[C:44]([C:23]5[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:28])=[O:29])=[CH:25][C:15]6[O:14][C:13]([C:10]7[CH:11]=[N:12][C:7]([O:6][C:5]8[CH:41]=[CH:42][C:2]([F:1])=[CH:3][CH:4]=8)=[CH:8][CH:9]=7)=[C:17]([C:18]([NH:20][CH3:21])=[O:19])[C:16]=6[CH:22]=5)[CH:45]=[CH:46][C:47]=4[O:60][CH2:59][N:50]3[C:51]=2[CH:52]=[CH:53][CH:54]=1

Komponenten

7

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 903338672-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

Produkt 1

HCID 778456625-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-(4-fluorophenoxyl)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideAusbeute 31,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a stirring mixture of 2-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (50 mg, 0.09 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (28 mg, 0.10 mmol) and Na2CO3 (18 mg, 0.17 mmol) in dioxane (0.8 mL) was added X-Phos (5 mg) and Pd2(dba)3 (5 mg) under N2 protection. The mixture was stirred at a pre-heated oil-bath 100° C. for 3 h. The mixture was concentrated and the residue was extracted with EA. The residue was washed with H2O, brine and dried over Na2SO4. After concentrated, the crude product was purified by prep-HPLC to give the product of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 30%). 1H-NMR (CDCl3, 400 MHz) δ 8.70 (d, J=2.0 Hz, 1H), 8.31˜8.34 (m, 1H), 7.91 (s, 1H), 7.62 (s, 1H), 7.44 (s, 2H), 7.15 (s, 2H), 7.04˜7.10 (m, 5H), 6.98 (d, J=8.8 Hz, 1H), 6.76˜6.81 (m, 1H), 5.94 (s, 2H), 5.90 (d, J=8.8 Hz, 1H), 3.30 (s, 3H), 2.96 (d, J=4.8 Hz, 3H), 2.70 (s, 3H). MS (M+H)+: 708.

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. extractionthe residue was extracted with EA
  3. washThe residue was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrated
  6. customthe crude product was purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-26203b2ac18c458dbb8490064ad3aa33
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242998B2

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