Water → HCID 86721457, compound

HRID 869603Notes

Reaction equation

HRID 869603 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([CH2:14][C:15]3[CH:34]=[CH:33][C:18]4/[C:19](=[C:29](/[CH3:32])\[C:30]#[N:31])/[C:20]5[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:21]=5[O:22][CH2:23][C:17]=4[CH:16]=3)=[C:9]([CH:11]3[CH2:13][CH2:12]3)[N:10]=[C:4]2[CH:3]=1.O.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:65](=O)([O-:67])[O-:66].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:30](/[C:29](=[C:19]1/[C:20]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:21]=2[O:22][CH2:23][C:17]2[CH:16]=[C:15]([CH2:14][C:8]3[N:5]4[CH:6]=[CH:7][C:2]([C:65]([OH:67])=[O:66])=[CH:3][C:4]4=[N:10][C:9]=3[CH:11]3[CH2:13][CH2:12]3)[CH:34]=[CH:33][C:18]/1=2)/[CH3:32])#[N:31]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 86721458HCID 86721458, compound

Product 1

HCID 86721457HCID 86721457, compoundYield 104.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

[step 5] (E)-2-{8-[(7-bromo-2-cyclopropylimidazo[1,2-a]pyridin-3-yl)methyl]-3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene}propanenitrile (2.5 g, 4.8 mmol) obtained in step 4 was dissolved in DMF (26 mL), water (6.8 mL), 1,3-bis(diphenylphosphino)propane (0.60 g, 1.5 mmol), potassium carbonate (0.80 g, 5.8 mmol) and palladium acetate (0.33 g, 1.5 mmol) were added. After purging 3 times with carbon monoxide under reduced pressure, the mixture was stirred with heating at 80° C. for 7 hr. The reaction mixture was filtered through celite, activated carbon (0.75 g) was added to the obtained filtrate, and the mixture was stirred with heating at 60° C. for 1.5 hr. The mixture was filtered again through celite, 2 mol/L hydrochloric acid was added to the filtrate, and the mixture was extracted 3 times with a mixed solvent of chloroform-methanol. The combined organic layers were washed 3 times with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue were added isopropylalcohol (25 mL) and ethanol (20 mL), and the mixture was stirred at 80° C. for 1 hr and further at room temperature for 1 hr. The precipitated crystals were collected by suction filtration to give (E)-3-{[11(6H)-(1-cyanoethylidene)-3-fluorodibenzo[b,e]oxepin-8-yl]methyl}-2-cyclopropylimidazo[1,2-a]pyridine-7-carboxylic acid (2.4 g, quantitative).

Workup

  1. customAfter purging 3 times with carbon monoxide under reduced pressure
  2. filtrationThe reaction mixture was filtered through celite, activated carbon (0.75 g)
  3. additionwas added to the obtained filtrate
  4. stirringthe mixture was stirred
  5. temperaturewith heating at 60° C. for 1.5 hr
  6. filtrationThe mixture was filtered again through celite, 2 mol/L hydrochloric acid
  7. additionwas added to the filtrate
  8. extractionthe mixture was extracted 3 times with a mixed solvent of chloroform-methanol
  9. washThe combined organic layers were washed 3 times with water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. additionTo the obtained residue were added isopropylalcohol (25 mL) and ethanol (20 mL)
  13. stirringthe mixture was stirred at 80° C. for 1 hr and further at room temperature for 1 hr
  14. filtrationThe precipitated crystals were collected by suction filtration

Sources & evidence

ORD record
ord-75c222d6596e43a38935298705cffd78
Source dataset
uspto-grants-2015_03
Patent number
US08969345B2

Reaction notes

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