Triethylamine → HCID 9855675, compound

HRID 902070Notes

Reaction equation

HRID 902070 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C(N(CC)CC)C.[C:14]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)#[CH:15]>CN(C=O)C.[Cu]I.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>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[C:15]#[C:14][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 764302-BromothiazoleHCID 1860033-Ethynylpyridine

Product 1

HCID 9855675HCID 9855675, compoundYield 53.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×

Procedure

2-Bromo-1,3-thiazole (0.15 mL, 1.6 mmol), CuI (98 mg, o.51 mmol), PdCl2(PPh3)2 (120 mg, 0.17 mmol) and triethylamine (2.8 mL, 20 mmol) were combined in DMF (6.8 mL) and cooled in an ice bath. 3-Ethynylpyridine (520 mg, 5.04 mmol) was then added to the mixture as a solution in DMF (3.0 ML). The ice bath was removed and the reaction was allowed to stir at ambient temperature for 16 h. The reaction mixture was filtered through a pad of Celite.™, and the pad was washed thoroughly with ethyl acetate. The filtrate was washed with brine (3.times.20 mL). A partial emulsion was observed. The mixture was concentrated in vacuo and the residue was taken up in CH2Cl2, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with 80:20 followed by 30:20 hexane:ethyl acetate to afford 3-(1,3-thiazol-2-ylethynyl)pyridine (160 mg) as a mixture with another product exhibiting a mass of 204 in the GC/MS, assigned as pyridylalkyne dimer. A portion of the mixture (100 mg) was further purified by preparative reverse phase HPLC eluting with a gradient of 80:20 to 0:100 water: acetonitrile over twenty minutes. The fractions containing the desired product were collected (detection by uv at 210 nm) to afford 3-(1,3-thiazol-2-ylethynyl)pyridine as a white waxy solid (15 mg). 1H NMR (CDCl3, 300 MHz) Δ9.3-8.5 (br s, 2H), 7.92-7.90 (m, 2H), 7.50-7.30 (m, 2H). MS (ESI) 187.0 (M++H).

Workup

  1. temperaturecooled in an ice bath
  2. customThe ice bath was removed
  3. filtrationThe reaction mixture was filtered through a pad of Celite
  4. wash™, and the pad was washed thoroughly with ethyl acetate
  5. washThe filtrate was washed with brine (3.times.20 mL)
  6. concentrationThe mixture was concentrated in vacuo
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography on silica gel eluting with 80:20

Sources & evidence

ORD record
ord-2fcecbd993054d9a887ebb64e43d0d65
Source dataset
uspto-grants-2008_04
Patent number
US07365074B2

Reaction notes

Loading…