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

HRID 716027Notes

Reaction equation

HRID 716027 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Br:8])[N:7]=1.C(N(CC)CC)C.[CH3:17][Si:18]([C:21]#[CH:22])([CH3:20])[CH3:19].C(OCC)(=O)C>C(#N)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:8][C:6]1[N:7]=[C:2]([C:22]#[C:21][Si:18]([CH3:20])([CH3:19])[CH3:17])[C:3]([NH2:9])=[N:4][CH:5]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 66111TrimethylsilylacetyleneHCID 6200042-Amino-3,5-dibromopyrazine

Product 1

HCID 533931895-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amineYield 74.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a 500 ml three necked round bottom flask, 3,5-dibromopyrazine-2-amine (25.0 g, 0.0988 mole) was taken in acetonitrile (250 ml). The reaction mixture was cooled to 0° C. and triethylamine (50.0 g, 0.4941 mole), copper (1) iodide (2.26 g, 0.0119 mole), and Pd(PPh3)4 (5.7 g, 0.0049 mole) were added under nitrogen atmosphere. The reaction mixture was stirred for 10 min at 0° C. followed by slow addition of trimethylsilylacetylene (10.7 g, 0.1089 mole) over 15 min at the same temperature. After completion of the addition, the reaction mixture was warmed up to RT and stirred for 90 min. The completion of the reaction was monitored on TLC using hexanes:ethyl acetate (5:5) as a mobile phase. After completion of the reaction, the reaction mixture was diluted by ethyl acetate and filtered through high flow. Filtrate was collected and washed with water. Layers were separated and aq. layer was re-extracted by ethyl acetate. Combined organic layer was dried over Na2SO4, filtered and concentrated to afford crude product which was subjected for the column purification. The crude compound was purified using column purification by eluting the compound with 7-10% ethyl acetate in hexanes to yield 20.0 g of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazine-2-amine.

Workup

  1. additionAfter completion of the addition
  2. temperaturethe reaction mixture was warmed up to RT
  3. stirringstirred for 90 min
  4. customAfter completion of the reaction
  5. filtrationfiltered through high flow
  6. customFiltrate was collected
  7. washwashed with water
  8. customLayers were separated
  9. extractionaq. layer was re-extracted by ethyl acetate
  10. dry with materialCombined organic layer was dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto afford crude product which
  14. customwas subjected for the column purification
  15. customThe crude compound was purified
  16. customcolumn purification
  17. washby eluting the compound with 7-10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-af3da2c9ae3f4ab4b0d1cdf0b3da6624
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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