HCID 59540985, compound → HCID 59540523, compound

HRID 1677370Notes

Reaction equation

HRID 1677370 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[N:12]=[C:13]3[C:19](I)=[CH:18][N:17]([S:21]([C:24]4[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=4)(=[O:23])=[O:22])[C:14]3=[N:15][CH:16]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[C:31]([Cu])#[N:32]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[N:12]=[C:13]3[C:19]([C:31]#[N:32])=[CH:18][N:17]([S:21]([C:24]4[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=4)(=[O:23])=[O:22])[C:14]3=[N:15][CH:16]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

7

Reactant 2

HCID 59540985HCID 59540985, compoundHCID 178418546HCID 178418546, compound2×

Product 1

HCID 59540523HCID 59540523, compoundYield 20%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(3,4-dimethoxy-phenyl)-7-iodo-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine (380 mg, 0.71 mmol), CuCN (256, 2.8 mmol), bis(dibenzylideneacetone)palladium(0) [Pd2(dba)3] (26 mg, 0.03 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (63 mg, 0.11 mmol) in dioxane (7 mL) was stirred at 90° C. overnight. Additional CuCN (50, 0.56 mmol), Pd2(dba)3 (6 mg, 0.01 mmol), and 1,1′-bis(diphenylphosphino)ferrocene (15 mg, 0.03 mmol) was added to the reaction mixture which was then stirred at 90° C. for 4 h and partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc and the combined organic phases were concentrated. The residue was purified by flash chromatography using 40 g of silica gel and 0-70% EtOAc in hexanes as eluant to afford 60 mg (20%) of 2-(3,4-dimethoxy-phenyl)-5-(toluene-4-sulfonyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonitrile as a white solid and 50 mg (16%) as a yellow solid. MP 233-234° C., M+H 435.

Workup

  1. stirringwas then stirred at 90° C. for 4 h
  2. custompartitioned between water and EtOAc
  3. extractionThe aqueous layer was extracted with EtOAc
  4. concentrationthe combined organic phases were concentrated
  5. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-672e94be1898423a891554ba045f5a05
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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