Water → HCID 90041235, compound

HRID 523015Notes

Reaction equation

HRID 523015 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].O.Br[C:9]1[C:10]([NH2:17])=[N:11][C:12]([CH3:16])=[C:13]([Br:15])[N:14]=1.C(N(CC)CC)C>O1CCCC1.[Cu]I>[Br:15][C:13]1[N:14]=[C:9]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])[C:10]([NH2:17])=[N:11][C:12]=1[CH3:16]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 217851463,5-Dibromo-6-methylpyrazin-2-amine

Product 1

HCID 90041235HCID 90041235, compoundYield 77.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of trimethylsilylacetylene (1.03 g, 29.4 mmol) in tetrahydrofuran (2 mL) was added dropwise to a cooled (water bath at ca. 15° C.) mixture of 3,5-dibromo-6-methyl-pyrazin-2-ylamine (7.48 g, 28 mmol), copper (I) iodide (1.07 g, 5.6 mmol), bis-triphenylphosphine palladium dichloride (1.97 g, 2.3 mmol), triethylamine (3.542 g, 35 mmol) and tetrahydrofuran (75 mL). The mixture was stirred under an atmosphere of argon, for 16 hours, during which time the reaction was allowed to warm to ambient temperature. The reaction mixture was poured onto water and extracted with hexanes-ethyl acetate (2:1). The organic layer was washed successively with saturated ammonium chloride solution, water, and then again with saturated ammonium chloride solution, water, then dried over anhydrous magnesium sulfate, treated with activated charcoal, filtered through celite and concentrated under reduced pressure. Purification by chromatography (silica, 20% ethyl acetate in hexanes) gave (6.19 g, 77%) of 5-bromo-6-methyl-3-trimethylsilanylethynyl-pyrazin-2-ylamine as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.26 (s, 9H), 2.39 (s, 3H), 6.71 (br s, 2H, —NH2).

Workup

  1. temperaturea cooled
  2. additionThe reaction mixture was poured onto water
  3. extractionextracted with hexanes-ethyl acetate (2:1)
  4. washThe organic layer was washed successively with saturated ammonium chloride solution, water
  5. dry with materialagain with saturated ammonium chloride solution, water, then dried over anhydrous magnesium sulfate
  6. additiontreated with activated charcoal
  7. filtrationfiltered through celite and
  8. concentrationconcentrated under reduced pressure
  9. customPurification by chromatography (silica, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-49a1f1f6830241a28e6b9e0755c90df8
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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