Potassium Carbonate → N-{3-[2,6-dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)benzoyl]-1H-pyrrolo[2,3-c]pyridin-7-yl}cyclopropanecarboxamide

HRID 2201834Notes

Reaction equation

HRID 2201834 reaction equation
Br[C:2]1[CH:24]=[C:23]([Cl:25])[C:5]([C:6]([C:8]2[C:16]3[C:11](=[C:12]([NH:17][C:18]([CH:20]4[CH2:22][CH2:21]4)=[O:19])[N:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)=[O:7])=[C:4]([Cl:26])[CH:3]=1.[CH3:27][C:28]1[C:32](B(O)O)=[C:31]([CH3:36])[O:30][N:29]=1.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:25][C:23]1[CH:24]=[C:2]([C:32]2[C:28]([CH3:27])=[N:29][O:30][C:31]=2[CH3:36])[CH:3]=[C:4]([Cl:26])[C:5]=1[C:6]([C:8]1[C:16]2[C:11](=[C:12]([NH:17][C:18]([CH:20]3[CH2:22][CH2:21]3)=[O:19])[N:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)=[O:7]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 71062890N-[3-(4-bromo-2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide

Product 1

HCID 86720646N-{3-[2,6-dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)benzoyl]-1H-pyrrolo[2,3-c]pyridin-7-yl}cyclopropanecarboxamideYield 16%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×

Conditions

Temperature
90 °C

Procedure

A mixture of N-[3-(4-bromo-2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide (0.1 g, 0.2 mmol) and (3,5-dimethyl-1,2-oxazol-4-yl)boronic acid (0.037 g, 0.26 mmol) was taken in a vial. To the reaction mixture, 1,4 dioxane (3 mL), potassium carbonate (0.091 g, 0.6 mmol) and water (0.5 mL) were added. The whole reaction mixture was stirred with argon gas for about five minutes. Finally dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (0.018 g, 0.02 mmol) was added to the reaction mixture, the vial was sealed properly and heated at 90° C. for about 4 hours. The reaction mixture was cooled to room temperature, followed by addition of water (25 mL), extracted with ethyl acetate (2×50 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under vacuum to get the crude. The crude was purified by preparative thin layer chloromatography using methanol (6%) in dicloromethane to obtain N-{3-[2,6-dichloro-4-(3,5-dimethyl-1,2-oxazol-4-yl)benzoyl]-1H-pyrrolo[2,3-c]pyridin-7-yl}cyclopropanecarboxamide (0.015 g, 15%).

Workup

  1. customThe whole reaction mixture
  2. customthe vial was sealed properly
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  6. concentrationconcentrated under vacuum
  7. customto get the crude
  8. customThe crude was purified by preparative thin layer chloromatography

Sources & evidence

ORD record
ord-51e809406e0f4dc58c7d5f5ee32634a8
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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