Dichloromethane → 5,5-dimethyl-6-oxo-6-[2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-hexanenitrile

HRID 1677522Notes

Reaction equation

HRID 1677522 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:20])[C:12]([CH3:19])([CH3:18])[CH2:13][CH2:14][CH2:15][C:16]#[N:17])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30].C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>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]>[CH3:18][C:12]([CH3:19])([C:11](=[O:20])[C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:25]3[CH:26]=[C:27]([O:31][CH3:32])[C:28]([O:29][CH3:30])=[C:23]([O:22][CH3:21])[CH:24]=3)[N:3]=2)[NH:8][CH:9]=1)[CH2:13][CH2:14][CH2:15][C:16]#[N:17]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 595407676-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5,5-dimethyl-6-oxo-hexanenitrile

Product 1

HCID 595407395,5-dimethyl-6-oxo-6-[2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-hexanenitrileYield 4%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 6-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5,5-dimethyl-6-oxo-hexanenitrile (0.079 g, 0.236 mmol), 3,4,5-trimethoxyphenylboronic acid (0.055 g, 0.26 mmol), potassium carbonate (0.098 g, 0.71 mmol) and Pd(dppf)Cl2.CH2Cl2 (0.019 g, 0.024 mmol) in 2.4 mL of 1,4-dioxane and 0.4 mL of water was stirred at 120° C. in a microwave for 1 h, then at 130° C. in a microwave for 1 h. The resulting mixture was partitioned between 50 mL of ethyl acetate and 25 mL of water. The organic layer was dried over MgSO4, filtered, and concentrated to a residue. Column chromatography (0→100% EtOAc/hexanes) afforded 0.004 g (4%) of 5,5-dimethyl-6-oxo-6-[2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-hexanenitrile as a white solid.

Workup

  1. customThe resulting mixture was partitioned between 50 mL of ethyl acetate and 25 mL of water
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-096b93453aab47e6a0cf25c7f77b20a2
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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