Hexane → HCID 9943500, compound

HRID 1835823Notes

Reaction equation

HRID 1835823 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[N:3]=1.C(N(CC)CC)C.[C:19]1([C:25]#[CH:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CCCCCC>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CN(C=O)C.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.C(OCC)(=O)C>[CH3:11][O:10][C:4]1[CH:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:26]#[C:25][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:3]=1

Participants

10

Reactant 4

HCID 8058HexaneHCID 8471TriethylamineHCID 10821Phenylacetylene2×HCID 51523232-Chloro-4,6-dimethoxypyrimidine

Product 1

HCID 9943500HCID 9943500, compoundYield 46%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Chloro-4,6-dimethoxypyrimidine (500 mg, 2.9 mmol), PdCl2(PPh3)2 (200 mg, 0.28 mmol), CuI (160 mg, 0.84 mmol), triethylamine (4.8 mL, 34 mmol), and n-Bu4NI (3.2 g, 8.7 mmol) were combined in DMF (24 mL). The mixture was cooled in an ice bath and then phenylacetylene (1.25 mL, 11.4 mmol) was added. The reaction mixture was allowed to warm to ambient temperature. After 2.5 h at ambient temperature the reaction mixture was heated to 45-50° C. After 2 h, additional phenylacetylene (1.0 mL, 9.1 mmol) was added. After an additional 17 h stirring at 45-50° C., the reaction mixture was filtered through a pad of Celite™, and the filter pad was washed thoroughly with ethyl acetate. The combined filtrates were washed with brine (4×20 mL), dried over MgSO4, filtered and concentrated in vacuo. The resulting black oil was purified by column chromatography eluting with hexane, 90:10, then 85:15 hexane:ethyl acetate to afford product contaminated with an impurity. Careful column chromatography of this impure material eluting with hexane then 90:10 hexane:ethyl acetate afforded 4,6-dimethoxy-2-(phenylethynyl)pyrimidine (320 mg, 46% yield) as a yellow solid. This material was carried on to the salt formation without further purification.

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. temperatureAfter 2.5 h at ambient temperature the reaction mixture was heated to 45-50° C
  3. filtrationthe reaction mixture was filtered through a pad of Celite™
  4. washthe filter pad was washed thoroughly with ethyl acetate
  5. washThe combined filtrates were washed with brine (4×20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting black oil was purified by column chromatography
  10. washeluting with hexane, 90:10
  11. custom85:15 hexane:ethyl acetate to afford product
  12. washCareful column chromatography of this impure material eluting with hexane

Sources & evidence

ORD record
ord-a25f31a66202444cb22504437824efc4
Source dataset
uspto-grants-2004_08
Patent number
US06774138B2

Reaction notes

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