Triethylamine → 2-[(2,6-difluoro-3,5-dimethoxyphenyl)ethynyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

HRID 1052310Notes

Reaction equation

HRID 1052310 reaction equation
[C:1]([C:3]1[C:4]([F:14])=[C:5]([O:12][CH3:13])[CH:6]=[C:7]([O:10][CH3:11])[C:8]=1[F:9])#[CH:2].Br[C:16]1[N:17]=[C:18]2[CH:24]=[CH:23][N:22]([S:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:19]2=[N:20][CH:21]=1.C(N(CC)CC)C>CN(C)C=O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:14][C:4]1[C:5]([O:12][CH3:13])=[CH:6][C:7]([O:10][CH3:11])=[C:8]([F:9])[C:3]=1[C:1]#[C:2][C:16]1[N:17]=[C:18]2[CH:24]=[CH:23][N:22]([S:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)(=[O:27])=[O:26])[C:19]2=[N:20][CH:21]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 867191713-Ethynyl-2,4-difluoro-1,5-dimethoxybenzeneHCID 899634192-Bromo-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 899632732-[(2,6-difluoro-3,5-dimethoxyphenyl)ethynyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazineYield 63%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-ethynyl-2,4-difluoro-1,5-dimethoxybenzene (340 mg, 1.72 mmol) and 2-bromo-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (696 mg, 2.06 mmol, from Example 1, Step 1) in N,N-dimethylformamide (4 mL), copper(I) iodide (26 mg, 0.14 mmol), bis(triphenylphosphine)palladium(II) chloride (60.0 mg, 0.0885 mmol) and triethylamine (0.36 mL, 2.6 mmol) were added sequentially at room temperature. After 14 hours, the reaction was quenched with saturated aq. NH4Cl, then extracted with methylene chloride. The combined organic layers were dried over MgSO4, then concentrated. The residue was purified on silica gel (eluting with 0 to 50% ethyl acetate (EtOAc) in hexanes) to give the desired product (490 mg, 63%). LCMS calculated for C22H15F2N3O4S (M+H)+: m/z=456.1. Found: 456.1.

Workup

  1. customthe reaction was quenched with saturated aq. NH4Cl
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel (eluting with 0 to 50% ethyl acetate (EtOAc) in hexanes)

Sources & evidence

ORD record
ord-4d5b6b41fe5840b8a178259f6eb9a1a3
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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