Dichloromethane → methyl 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylate

HRID 1402491Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1402491
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][C:25]=2[F:26])[C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=2[F:22])=[O:13])[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:35]2[NH:39][CH:38]=[C:37]([C:40]([O:42][CH3:43])=[O:41])[CH:36]=2)O1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O.O1CCOCC1>[F:26][C:25]1[CH:24]=[CH:23][C:11]([C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=2[F:22])=[O:13])=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:35]2[NH:39][CH:38]=[C:37]([C:40]([O:42][CH3:43])=[O:41])[CH:36]=2)[CH:7]=1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 53405106Methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrrole-3-carboxylateHCID 866515583-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide

Produkt 1

HCID 51001539methyl 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 3-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide (1.217 g, 3.25 mmol), methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate (1.63 g, 6.50 mmol) and potassium carbonate (0.67 g, 4.87 mmol) in water (2.5 mL) and dioxane (15 mL) was purged with nitrogen for several minutes. To the mixture was added tetrakis-triphenylphosphine palladium(0) (0.18 g, (0.16 mmol). The reaction was sealed under nitrogen and heated at 100° C. for 15 h. The cooled reaction was mixed with dichloromethane and filtered through Celite. The red solution was evaporated. The resulting oil was dissolved in dichloromethane, put on a column of silica gel (80 g) and eluted with hexane/EtOAc (1:1) to afford methyl 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylate as white solid. Yield: 1.162 g, 77%.

Aufarbeitung

  1. customwas purged with nitrogen for several minutes
  2. additionTo the mixture was added tetrakis-triphenylphosphine palladium(0) (0.18 g, (0.16 mmol)
  3. customThe reaction was sealed under nitrogen
  4. customThe cooled reaction
  5. filtrationfiltered through Celite
  6. customThe red solution was evaporated
  7. dissolutionThe resulting oil was dissolved in dichloromethane
  8. washeluted with hexane/EtOAc (1:1)

Quellen und Nachweise

ORD-Eintrag
ord-783b09c0ae3a4bfab4d38483d333f5c1
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906944B2

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