Triethylamine → N-{5-[(2-Chloro-4-pyrimidinyl)ethynyl]-2-fluorophenyl}-2,2,2-trifluoroacetamide

HRID 1159960Notes

Reaction equation

HRID 1159960 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[C:16]([C:18]1[CH:19]=[CH:20][C:21]([F:31])=[C:22]([NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[CH:23]=1)#[CH:17]>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:17]#[C:16][C:18]2[CH:19]=[CH:20][C:21]([F:31])=[C:22]([NH:24][C:25](=[O:30])[C:26]([F:27])([F:28])[F:29])[CH:23]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 775312,4-DichloropyrimidineHCID 59511405N-(5-ethynyl-2-fluorophenyl)-2,2,2-trifluoroacetamide

Product 1

HCID 59511388N-{5-[(2-Chloro-4-pyrimidinyl)ethynyl]-2-fluorophenyl}-2,2,2-trifluoroacetamideYield 49.3%

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 (520 mg, 3.49 mmol), anhydrous degassed THF (100 mL), dichlorobis(triphenylphosphine)-palladium(II) (62 mg, 0.09 mmol), copper(I) iodide (10 mg, 0.05 mmol), and triethylamine (718 mg, 7.10 mmol). After heating the reaction at 60° C. for 30 min, N-(5-ethynyl-2-fluorophenyl)-2,2,2-trifluoroacetamide (410 mg, 1.77 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 (5-50% EtOAc in hexanes) to afford the desired product (300 mg, 49%) as an off white solid. ESIMS (M+H)+=344.

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 (5-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8303f2ce6e104c5a91d695a0eee4ba71
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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