2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamide

HRID 1776920Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776920
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Br[C:36]1[C:37]([N:56]2[CH2:60][CH2:59][O:58][C:57]2=[O:61])=[CH:38][C:39]2[O:43][C:42]([C:44]3[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=3)=[C:41]([C:51]([NH:53][CH3:54])=[O:52])[C:40]=2[CH:55]=1.[F:62][C:63]1[C:64]2[CH:65]=[C:66]3[C:75]4[N:76]=[C:77]([Sn](C)(C)C)[CH:78]=[CH:79][C:74]=4[O:73][CH2:72][N:67]3[C:68]=2[CH:69]=[CH:70][CH:71]=1>O1CCOCC1.O.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:62][C:63]1[C:64]2[CH:65]=[C:66]3[C:75]4[N:76]=[C:77]([C:36]5[C:37]([N:56]6[CH2:60][CH2:59][O:58][C:57]6=[O:61])=[CH:38][C:39]6[O:43][C:42]([C:44]7[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=7)=[C:41]([C:51]([NH:53][CH3:54])=[O:52])[C:40]=6[CH:55]=5)[CH:78]=[CH:79][C:74]=4[O:73][CH2:72][N:67]3[C:68]=2[CH:69]=[CH:70][CH:71]=1

Komponenten

6

Edukt 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 673939695-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamideHCID 8672829411-fluoro-2-(trimethylstannyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

Produkt 1

HCID 867282965-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamideAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Pd2(dba)3 (10 mg, 0.01 mmol) and X-Phos (11 mg, 0.02 mmol) was added to the mixture of 5-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamide (100 mg, 0.23 mmol), 11-fluoro-2-(trimethylstannyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (140 mg, 0.35 mmol) in dioxane/H2O (4 mL/0.2 mL) under N2. Then the reaction mixture was heated to 100° C. for 1 hour and filtered. The resulting residue was extracted with EtOAc. The combined organic phase was dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (petroleum ether:EtOAc=1:2) to provide 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamide (32 mg, yield: 24%). 1H-NMR (CDCl3, 400 MHz) δ 8.01 (s, 1H), 7.94˜7.98 (m, 2H), 7.58 (s, 1H), 7.51 (m, 2H), 7.19˜7.23 (m, 4H), 7.11˜7.13 (d, J=8.0 Hz, 1H), 6.83˜6.88 (m, 1H), 6.12 (s, 1H), 6.00 (s, 2H), 4.37˜7.41 (m, 2H), 4.12˜4.14 (m, 2H), 3.00 (d, J=4.8 Hz, 3H). MS (M+H)+: 593.

Aufarbeitung

  1. filtrationfiltered
  2. extractionThe resulting residue was extracted with EtOAc
  3. dry with materialThe combined organic phase was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified

Quellen und Nachweise

ORD-Eintrag
ord-b8323624b5ee422c954190297eff4b1d
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09265773B2

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