Trimethylsilylacetylene → 2-Furan-2-yl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine

HRID 2242913Notes

Reaction equation

HRID 2242913 reaction equation
Br[C:2]1[N:3]=[C:4]([NH2:16])[C:5]2[N:6]([N:8]=[C:9]([C:11]3[O:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH:7]=1.[CH3:17][Si:18]([C:21]#[CH:22])([CH3:20])[CH3:19]>C1COCC1.[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>[O:12]1[CH:13]=[CH:14][CH:15]=[C:11]1[C:9]1[N:10]=[C:5]2[C:4]([NH2:16])=[N:3][C:2]([C:22]#[C:21][Si:18]([CH3:20])([CH3:19])[CH3:17])=[CH:7][N:6]2[N:8]=1

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 71401630[1,2,4]Triazolo[1,5-a]pyrazin-8-amine, 6-bromo-2-(2-furanyl)-

Product 1

HCID 685470552-Furan-2-yl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 6-bromo-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine (500 mg, 1.78 mmol, see Examples 1 and 2 above) and (trimethylsilyl)acetylene (1.5 mL, 10 mmol) in a mixture of THF (10 mL) and TEA (5 mL) was added copper(I) iodide (68 mg, 0.36 mmol, 20 mol %) and PdCl2(PPh3)2 (190 mg, 0.27 mmol, 15 mol %). The reaction vessel was degassed and heated at 50° C. for 18 hours. After cooling to room temperature, the reaction mixture was diluted with water and extracted with methylene chloride. The combined organic extracts were dried over magnesium sulfate, and concentrated in vacuo to yield a crude product, which was purified by flash chromatography (silica gel, elution with 20% to 40% EtOAc/Hexane in volume) to afford the resulting 2-furan-2-yl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine. The trimethylsilyl group was removed by treating a stirred solution of the crude material (2-furan-2-yl-6-trimethylsilanylethynyl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine) in wet MeOH (20 mL) with-Amberlyst A26 resin (2 g) for 1 hour. The suspension was filtered, and the resin was washed, sequentially with MeOH and THF. The filtrate was concentrated in vacuo to yield the desired 6-ethynyl-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrazin-8-ylamine (0.34 mg, 84% overall yield), which was used in the subsequent transformation without further purification.

Workup

  1. customThe reaction vessel was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture was diluted with water
  4. extractionextracted with methylene chloride
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto yield a crude product, which
  8. customwas purified by flash chromatography (silica gel, elution with 20% to 40% EtOAc/Hexane in volume)

Sources & evidence

ORD record
ord-065f593beefd4afa921f5cc4628c4b39
Source dataset
uspto-grants-2010_03
Patent number
US07674791B2

Reaction notes

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