2,4-Dichloro-5-fluoropyrimidine → HCID 59513809, compound

HRID 1160016Notes

Reaction equation

HRID 1160016 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]#[CH:18])[CH:12]=1>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>[Br:10][C:11]1[CH:12]=[C:13]([C:17]#[C:18][C:6]2[C:5]([F:9])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 114808181-Bromo-3-ethynylbenzene

Product 1

HCID 59513809HCID 59513809, compoundYield 80.2%

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-dichloro-5-fluoropyrimidine (1.66 g, 10 mmol), anhydrous, degassed THF (100 mL), dichlorobis(triphenyl-phosphine)palladium(II) (180 mg, 0.26 mmol), copper(I) iodide (29 mg, 0.15 mmol), and TEA (2.02 g, 20 mmol). After heating the reaction at 60° C. for 30 min, 1-bromo-3-ethynylbenzene (0.9 g, 5.0 mmol) was added dropwise as a solution in THF (25 mL) and the resulting mixture was allowed to heat overnight. The crude reaction mixture was adsorbed to silica gel and purified by column chromatography (2-10% EtOAc in hexanes) to afford the desired product (1.25 g, 78%) as an off white solid. ESIMS (M+H)+=311.

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 (2-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0c20b3abd8ba462d9fbd351d16590dc6
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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