Triethylamine → 2-(4-Chloro-phenyl)-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylethynyl]-pyrazine

HRID 1916734Notes

Reaction equation

HRID 1916734 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][C:11](I)=[CH:10][N:9]=2)=[CH:4][CH:3]=1.[C:15]([C:17]1[CH:30]=[CH:29][C:20]([O:21][CH2:22][CH2:23][N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)=[CH:19][CH:18]=1)#[CH:16].C(N(CC)CC)C>C1COCC1.[Cu]I>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][C:11]([C:16]#[C:15][C:17]3[CH:18]=[CH:19][C:20]([O:21][CH2:22][CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[CH:29][CH:30]=3)=[CH:10][N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 859696362-(4-Chlorophenyl)-5-iodopyrazine2×HCID 859698151-[2-(4-Ethynyl-phenoxy)-ethyl]-pyrrolidine

Product 1

HCID 598358742-(4-Chloro-phenyl)-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylethynyl]-pyrazine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under an N2 atmosphere 19 mg (0.1 mmol) CuI, 82 mg (0.1 mmol) [1,1′-bis-(diphenylphosphine)-ferrocene]-palladium(II)-chloride are added to a solution of 316 mg (1.0 mmol) 2-(4-chloro-phenyl)-5-iodo-pyrazine and 215 mg (1.0 mmol) 1-[2-(4-ethynyl-phenoxy)-ethyl]-pyrrolidine in 50 mL THF and 0.4 mL (3 mmol) triethylamine and the reaction mixture is stirred overnight at RT. To complete the reaction another 100 mg (0.32 mmol) 2-(4-chloro-phenyl)-5-iodo-pyrazine are added and the mixture is again stirred overnight. It is evaporated down i. vac., the residue is combined with 10% Na2CO3 solution, extracted exhaustively with DCM, the combined organic phases are washed three times with water and dried over MgSO4. This is filtered through activated charcoal, evaporated down i.vac. and the residue is purified by chromatography (silica gel, gradient: EtOAc to EtOAc/MeOH/NH3 9:9:1).

Workup

  1. additionare added
  2. waitthe mixture is again stirred overnight
  3. customIt is evaporated down i
  4. extractionextracted exhaustively with DCM
  5. washthe combined organic phases are washed three times with water
  6. dry with materialdried over MgSO4
  7. filtrationThis is filtered through activated charcoal
  8. customevaporated down i.vac
  9. customand the residue is purified by chromatography (silica gel, gradient: EtOAc to EtOAc/MeOH/NH3 9:9:1)

Sources & evidence

ORD record
ord-8e322d987deb46ec83bd736682e2ef57
Source dataset
uspto-grants-2013_12
Patent number
US08618132B2

Reaction notes

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