Potassium Phosphate, Tribasic → 5-(6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 1776878Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776878
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18](C4C=CC=C(B5OC(C)(C)C(C)(C)O5)C=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.Cl[C:43]1[CH:44]=[CH:45][C:46]2[O:51][CH2:50][N:49]3[C:52]4[CH:58]=[CH:57][CH:56]=[CH:55][C:53]=4[N:54]=[C:48]3[C:47]=2[CH:59]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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>[CH:59]1[C:47]2[C:48]3[N:49]([C:52]4[CH:58]=[CH:57][CH:56]=[CH:55][C:53]=4[N:54]=3)[CH2:50][O:51][C:46]=2[CH:45]=[CH:44][C:43]=1[C:18]1[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][C:10]2[O:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=2[CH:17]=1

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 674032762-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamideHCID 712956192-chloro-6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazine

Produkt 1

HCID 715095445-(6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a degassed solution of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamide (117 mg, 0.23 mmol) and 2-chloro-6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazine (60 mg, 0.23 mmol) in dioxane:H2O (2 mL:0.5 mL) was added Pd2(dba)3 (21 mg, 0.02 mmol), X-Phos (22 mg, 0.05 mmol) and K3PO4 (184 mg, 0.69 mmol) under N2. The mixture was heated to 100° C. and stirred for about 15 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was washed with H2O, brine, dried over Na2SO4. After being concentrated in vacuo, the resulting resulting residue was purified using prep-HPLC to provide the product of Compound 133 (30 mg, yield: 22%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.59 (d, J=4.4 Hz, 1H), 8.14 (d, J=1.9 Hz, 1H), 8.08˜8.05 (m, 3H), 7.77˜7.72 (m, 2H), 7.69 (s, 1H), 7.63 (dd, J=8.7, 2.0 Hz, 1H), 7.46 (t, J=8.7 Hz, 2H), 7.37˜7.30 (m, 3H), 6.38 (s, 2H), 3.21 (s, 3H), 3.05 (s, 3H), 2.87 (d, J=4.4 Hz, 3H). MS (M+H)+: 597.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter being concentrated in vacuo
  6. customthe resulting resulting residue
  7. customwas purified

Quellen und Nachweise

ORD-Eintrag
ord-c842f1995b974bd9a952a87b7e53905f
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09265773B2

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