Trimethylsilylacetylene → 5-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine

HRID 2204462Notes

Reaction equation

HRID 2204462 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Br:8])[N:7]=1.[CH3:10][Si:11]([C:14]#[CH:15])([CH3:13])[CH3:12]>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>[Br:8][C:6]1[N:7]=[C:2]([C:15]#[C:14][Si:11]([CH3:13])([CH3:12])[CH3:10])[C:3]([NH2:9])=[N:4][CH:5]=1

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 6200042-Amino-3,5-dibromopyrazine

Product 1

HCID 533931895-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amineYield 85.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3,5-dibromopyrazin-2-amine (40.0 g, 158 mmol), TEA (66.1 mL, 475 mmol), and copper(I) iodide (0.301 g, 1.58 mmol) in THF (1172 ml) was added PdCl2(PPh3)2(1.11 g, 1.58 mmol). The reaction mixture was cooled at about 0° C. and a solution of (trimethylsilyl)acetylene (20.8 mL, 150 mmol) in THF (146 mL) was added drop-wise. The reaction mixture was stirred at about 0-10° C. for about 7 h and then concentrated under reduced pressure. The dark brown residue was dissolved in DCM (600 mL) and filtered through a Celite® pad (3 cm in height×9 cm in diameter) while eluting with DCM (300 mL). The filtrate was washed with water (2×500 mL) and brine (500 mL), dried over anhydrous MgSO4, filtered through a Florisil® pad (1 cm in height by 9 cm in diameter) while washing with DCM/MeOH (9:1, 200 mL), and concentrated under reduced pressure to give a brown solid. The solid was triturated and sonicated with warm petroleum ether (b.p. 30-60° C., 250 mL), cooled and collected, washing with petroleum ether (b.p. 30-60° C.; 2×100 mL), and dried in a vacuum oven at about 70° C. to give 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (34.6 g 70%): LC/MS (Table 2, Method d) Rt=1.59 min; MS m/z: 272 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe dark brown residue was dissolved in DCM (600 mL)
  3. filtrationfiltered through a Celite® pad (3 cm in height×9 cm in diameter)
  4. washwhile eluting with DCM (300 mL)
  5. washThe filtrate was washed with water (2×500 mL) and brine (500 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered through a Florisil® pad (1 cm in height by 9 cm in diameter)
  8. washwhile washing with DCM/MeOH (9:1, 200 mL)
  9. concentrationconcentrated under reduced pressure
  10. customto give a brown solid
  11. customThe solid was triturated
  12. customsonicated with warm petroleum ether (b.p. 30-60° C., 250 mL)
  13. temperaturecooled
  14. customcollected
  15. washwashing with petroleum ether (b.p. 30-60° C.; 2×100 mL)
  16. customdried in a vacuum oven at about 70° C.

Sources & evidence

ORD record
ord-948f42f388c6413a8567af4a44f0955a
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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