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

HRID 1025166Notes

Reaction equation

HRID 1025166 reaction equation
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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-128e083657f54f868aa01c05fcfa758e
Source dataset
uspto-grants-2014_05
Patent number
US08722688B2

Reaction notes

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