2,4-Dichloropyrimidine → N-[5-[(2-Chloro-4-pyrimidinyl)ethynyl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide

HRID 1157608Notes

Reaction equation

HRID 1157608 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([C:11]1[CH:12]=[CH:13][C:14]([O:24][CH3:25])=[C:15]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH:16]=1)#[CH:10]>C1COCC1.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.[Cu]I>[Cl:1][C:2]1[N:7]=[C:6]([C:10]#[C:9][C:11]2[CH:12]=[CH:13][C:14]([O:24][CH3:25])=[C:15]([NH:17][C:18](=[O:23])[C:19]([F:20])([F:21])[F:22])[CH:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 775312,4-DichloropyrimidineHCID 59511434N-[5-ethynyl-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide

Product 1

HCID 59511410N-[5-[(2-Chloro-4-pyrimidinyl)ethynyl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamideYield 83.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To an oven-dried flask under N2 was added 2,4-dichloropyrimidine (860 mg, 5.76 mmol), anhydrous degassed THF (100 mL), dichlorobis(triphenylphosphine)-palladium(II) (81 mg, 0.12 mmol), copper(I) iodide (13 mg, 0.07 mmol), and TEA (1.26 g, 0.013 mol). After heating the reaction at 60° C. for 30 min, N-[5-ethynyl-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide (560 mg, 2.30 mmol) was added dropwise as a solution in THF (10 mL) and the resulting mixture was allowed to heat overnight. The crude reaction mixture was adsorbed to silica gel and purified by column chromatography (0-10% EtOAc in hexanes) to afford the desired product (0.68 g, 42%) as an off white solid. ES-LC/MS m/z=356 [M+H]+.

Workup

  1. temperatureAfter heating
  2. customthe reaction at 60° C. for 30 min
  3. temperatureto heat overnight
  4. customThe crude reaction mixture
  5. custompurified by column chromatography (0-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-545fa9b335774add97a370f2255c05d0
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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