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

HRID 2201835Notes

Reaction equation

HRID 2201835 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.[N:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[N:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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]>[Cl:25][C:23]1[CH:24]=[C:2]([C:31]2[CH:32]=[N:27][CH:28]=[N:29][CH:30]=2)[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 3

HCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 71062890N-[3-(4-bromo-2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide

Product 1

HCID 71618483N-{3-[2,6-dichloro-4-(pyrimidin-5-yl)benzoyl]-1H-pyrrolo[2,3-c]pyridin-7yl}cyclopropane carboxamideYield 14.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-[3-(4-bromo-2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]cyclopropanecarboxamide (108 mg, 0.23 mmol), pyrimidin-5-yl-boronic acid (42 mg, 0.34 mmol), potassium carbonate (95.22 mg, 0.69 mmol), water (0.5 mL) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (34.8 mg, 0.047 mmol) in 1,4 dioxane (3 mL) was heated overnight at 100° C. in a sealed vial. The reaction mixture was cooled to room temperature, diluted with water (10 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layer was dried over anhydrous sodium sulphate and concentrated under vacuum. The resulting crude mass was purified by preparative thin layer chloromatography using 10% methanol in dichloromethane to afford N-{3-[2,6-dichloro-4-(pyrimidin-5-yl)benzoyl]-1H-pyrrolo[2,3-c]pyridin-7yl}cyclopropane carboxamide (15 mg, 14.01%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulphate
  4. concentrationconcentrated under vacuum
  5. customThe resulting crude mass was purified by preparative thin layer chloromatography

Sources & evidence

ORD record
ord-cf663ea9ad9c42dbb1b9bea365175e42
Source dataset
uspto-grants-2016_06
Patent number
US09364466B2

Reaction notes

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