Cesium carbonate → 2-(4-Chloro-phenyl)-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylethynyl]-pyridine

HRID 1916736Notes

Reaction equation

HRID 1916736 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Br[C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[N:12][CH:13]=1.[C:21]([C:23]1[CH:36]=[CH:35][C:26]([O:27][CH2:28][CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[CH:25][CH:24]=1)#[CH:22]>C1COCC1.[Cu]I>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C:11]2[CH:10]=[CH:9][C:8]([C:22]#[C:21][C:23]3[CH:24]=[CH:25][C:26]([O:27][CH2:28][CH2:29][N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)=[CH:35][CH:36]=3)=[CH:13][N:12]=2)=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 131283835-Bromo-2-(4-chlorophenyl)pyridineHCID 859698151-[2-(4-Ethynyl-phenoxy)-ethyl]-pyrrolidine

Product 1

HCID 598359092-(4-Chloro-phenyl)-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylethynyl]-pyridine

Reagents, catalysts & solvents 2

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

Procedure

Under an N2 atmosphere 773 mg (2.25 mmol) Cs2CO3, 14 mg (0.08 mmol) CuI and 87 mg (0.08 mmol) tetrakis-triphenylphosphane-palladium are added to a solution of 403 mg (1.5 mmol) 5-bromo-2-(4-chloro-phenyl)-pyridine and 322 mg (1.5 mmol) 1-[2-(4-ethynyl-phenoxy)-ethyl]-pyrrolidine in 10 mL THF and the reaction mixture is stirred for 4 h at RT. Then it is heated to 60° C. for 16 h. The mixture is evaporated down i. vac., the residue is combined with 30 mL water, 5 mL 3% NH3 solution and 60 mL EtOAc, the organic phase is separated off and dried over Na2SO4. After the desiccant and solvent have been eliminated the residue is purified first by chromatography (silica gel, EtOAc/MeOH/NH3 19:1:0.1) and then by HPLC.

Workup

  1. temperatureThen it is heated to 60° C. for 16 h
  2. customThe mixture is evaporated down i
  3. customthe organic phase is separated off
  4. dry with materialdried over Na2SO4
  5. customis purified first by chromatography (silica gel, EtOAc/MeOH/NH3 19:1:0.1)

Sources & evidence

ORD record
ord-100bb86f70fd4f1aa6232c5bb4706a84
Source dataset
uspto-grants-2013_12
Patent number
US08618132B2

Reaction notes

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