Cesium carbonate → 2-(4-Fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

HRID 555136Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 555136
Br[C:2]1[C:3]([CH3:22])=[CH:4][C:5]([O:20][CH3:21])=[C:6]([CH:19]=1)[C:7]([NH:9][C:10]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:12][CH2:11]1)=[O:8].O1CCOCC1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[O:37][C:38]3[CH:48]=[CH:47][C:46](B4OC(C)(C)C(C)(C)O4)=[CH:45][C:39]=3[C:40]=2[C:41]([NH:43][CH3:44])=[O:42])=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[O:37][C:38]3[CH:48]=[CH:47][C:46]([C:2]4[CH:19]=[C:6]([C:7](=[O:8])[NH:9][C:10]5([C:13]6[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=6)[CH2:12][CH2:11]5)[C:5]([O:20][CH3:21])=[CH:4][C:3]=4[CH3:22])=[CH:45][C:39]=3[C:40]=2[C:41]([NH:43][CH3:44])=[O:42])=[CH:32][CH:31]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 592754752-(4-fluorophenyl)-N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 672118695-bromo-2-methoxy-4-methyl-N-(1-(pyridin-2-yl)cyclopropyl)benzamide

Produkt 1

HCID 592757562-(4-Fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamideAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

Alternative synthesis. To a sealed tube was added 5-bromo-2-methoxy-4-methyl-N-(1-(pyridin-2-yl)cyclopropyl)benzamide (1.9024 g, 5.27 mmol), dioxane (70 mL), 2-(4-fluorophenyl)-N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (2.529 g, 6.40 mmol), cesium carbonate (2.57 g, 7.90 mmol), water (14.00 mL) and finally tetrakis(triphenylphosphine)palladium(0) (0.304 g, 0.263 mmol). The vessel was sealed and heated for 16 hours at 85° C. in an oil bath. The mixture was cooled to room temperature, diluted with 20 ml of DCM and pushed through a plug of CELITE®. The resulting dark solution was concentrated to a grey oil. To this residue was added 20 ml of 0.5N HCl, followed by 20 ml of water. The flask was cooled in an ice bath for 30 minutes and the resulting solids were collected by filtration and washed with 10 ml of water and dried under vacuum. The crude product was taken up in 1:1 ethyl acetate/hexane and pushed through a plug of silica gel. Solvent was removed giving 1.65 grams of the product as a light tan solid.

Aufarbeitung

  1. customAlternative synthesis
  2. customThe vessel was sealed
  3. temperatureThe mixture was cooled to room temperature
  4. concentrationThe resulting dark solution was concentrated to a grey oil
  5. additionTo this residue was added 20 ml of 0.5N HCl
  6. temperatureThe flask was cooled in an ice bath for 30 minutes
  7. filtrationthe resulting solids were collected by filtration
  8. washwashed with 10 ml of water
  9. customdried under vacuum
  10. customSolvent was removed

Quellen und Nachweise

ORD-Eintrag
ord-508a120c6648462b85bc03d9d2919f16
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08048887B2

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