2,4-Dichloropyrimidine → N-[3-(2-Chloro-pyrimidin-4-ylethenyl)-phenyl]-2,2,2-trifluoro-acetamide

HRID 1157531Notes

Reaction equation

HRID 1157531 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]=[C:13]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH:14]=[CH:15][CH:16]=1)#[CH:10]>C1COCC1.C(Cl)Cl.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]([CH:10]=[CH:9][C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:23])[C:19]([F:20])([F:21])[F:22])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 2

HCID 775312,4-DichloropyrimidineHCID 59513885N-(3-ethynylphenyl)-2,2,2-trifluoroacetamide

Product 1

HCID 86631082N-[3-(2-Chloro-pyrimidin-4-ylethenyl)-phenyl]-2,2,2-trifluoro-acetamide

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a mixture of 2,4-dichloropyrimidine (14.5 g, 97.5 mmol), dichlorobis(triphenyl-phosphine)palladium(II) (1.3 g, 2.6 mmol), and copper(I) iodide (25 mg, 0.13 mmol) in degassed THF was added TEA (34 mL, 263 mmol), and the mixture was heated to 50° C. A solution of N-(3-ethynyl-phenyl)-2,2,2-trifluoro-acetamide (14 g, 65 mmol) in THF was added to the mixture over 45 minutes. After several h, the reaction was cooled to rt and diluted with DCM. The organic mixture was washed with water and brine, dried over MgSO4 and concentrated. The crude material was purified through silica to give the title compound as an off-white solid. 1H NMR (400 MHz, d6-DMSO): δ 11.43 (s, 1H), 8.83 (d, J=4.8 Hz, 1H), 8.00 (s, 1H), 7.80 (d, J=4.8 Hz, 1H), 7.76 (m, 1H), 7.54-7.52 (m, 2H).

Workup

  1. temperatureAfter several h, the reaction was cooled to rt
  2. washThe organic mixture was washed with water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude material was purified through silica

Sources & evidence

ORD record
ord-855fcf463e8d4c93b76abe084064f3d4
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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