Triethylamine → 3,5-Bis-trimethylsilanylethynyl-pyrazin-2-ylamine

HRID 547467Notes

Reaction equation

HRID 547467 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].NC1C(Br)=[N:12][CH:11]=[C:10](Br)[N:9]=1.[CH2:16]([N:18](CC)CC)[CH3:17]>O1CCCC1.C(OCC)(=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>[CH3:1][Si:2]([CH3:4])([CH3:3])[C:5]1[C:6]([NH:18][C:16]#[CH:17])=[N:12][CH:11]=[C:10]([Si:2]([CH3:4])([CH3:3])[CH3:1])[N:9]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111Trimethylsilylacetylene2×HCID 510516652-Amino-3,6-dibromopyrazine

Product 1

HCID 866336003,5-Bis-trimethylsilanylethynyl-pyrazin-2-ylamineYield 82.7%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trimethylsilylacetylene (11.1 mL, 80 mmol) was added to a solution of 2-amino-3,6-dibromopyrazine (5.06 g, 20 mmol), Pd(PPh3)2Cl2 (0.140 g, 0.20 mmol), triethylamine (11.4 mL, 80 mmol) and copper(I) iodide (0.114 g, 0.60 mmol) in 50 mL of tetrahydrofuran at 0-5° C. The reaction mixture was allowed to warm to RT and stirred for 64 h. Additional trimethylsilylacetylene (5.6 mL, 40 mmol), Pd(PPh3)2Cl2 (0.140 g, 0.20 mmol) and copper(I) iodide (0.114 g, 0.60 mmol) were added, and the mixture was stirred at 50° C. for 22 h then allowed to cool to RT. The mixture was diluted with 200 mL of ethyl acetate and 200 mL of hexanes, then sequentially washed with three 200 mL portions of water and 200 mL of a sat. aq. NaHCO3 solution, dried over MgSO4, filtered and concentrated to a residue. Silica gel chromatography (0->25% EtOAc/hexanes) afforded 4.36 g (76%) of 3,5-bis-trimethylsilanylethynyl-pyrazin-2-ylamine as a brown oil.

Workup

  1. stirringthe mixture was stirred at 50° C. for 22 h
  2. temperatureto cool to RT
  3. washsequentially washed with three 200 mL portions of water and 200 mL of a sat. aq. NaHCO3 solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-0a4e2282fefb46cba0c97779cead2bd4
Source dataset
uspto-grants-2011_05
Patent number
US07939531B2

Reaction notes

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