2,4-Dichloro-5-fluoropyrimidine → HCID 59513761, compound

HRID 1157612Notes

Reaction equation

HRID 1157612 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[C:10]([C:12]1[CH:13]=[C:14]([NH:18][C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH:15]=[CH:16][CH:17]=1)#[CH:11]>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:11]#[C:10][C:12]2[CH:13]=[C:14]([NH:18][C:19](=[O:24])[C:20]([F:21])([F:22])[F:23])[CH:15]=[CH:16][CH:17]=2)[C:5]([F:9])=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 59513885N-(3-ethynylphenyl)-2,2,2-trifluoroacetamide

Product 1

HCID 59513761HCID 59513761, compoundYield 78%

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 (1.56 g, 9.4 mmol), anhydrous, degassed THF (100 mL), dichlorobis(triphenyl-phosphine)palladium(II) (62 mg, 0.09 mmol), copper(I) iodide (10 mg, 0.05 mmol), and TEA (0.164 g, 0.23 mmol). After heating the reaction at 60° C. for 30 min. N-(3-ethynylphenyl)-2,2,2-trifluoroacetamide (1.0, 4.69 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 onto 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. ES-LC/MS m/z=344 [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 (2-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b584fa3b3e224879934cbcd6c59eac5b
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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