Triethylamine → 5-(2-(Trimethylsilyl)ethynyl)pyridin-2-amine

HRID 1293751Notes

Reaction equation

HRID 1293751 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH3:9][Si:10]([C:13]#[CH:14])([CH3:12])[CH3:11].CCN(CC)CC>CN(C=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.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][Si:10]([C:13]#[C:14][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=1)([CH3:12])[CH3:11]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 706222-Amino-5-bromopyridine

Product 1

HCID 224828585-(2-(Trimethylsilyl)ethynyl)pyridin-2-amineYield 76%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of commercially available 2-amino-5-bromopyridine (50.0 g, 289 mmol), trimethylsilylacetylene (112 mL, 809 mmol), Et3N (120 mL, 867 mmol), PdCl2(PPh3)2 (4.06 g, 2 mol %) and PPh3 (1.52 g, 2 mol %) in DMF (290 mL) was purged for 10 min with argon. Then CuI (340 mg, 1 mol %) was added and the reaction mixture was heated up to 90° C., stirring was continued at 90° C. for 4.5 h. Cooled to 23° C., the reaction mixture was concentrated in vacuum to remove all volatiles, poured the residue onto water (300 mL) and extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with water (300 mL) and brine (2×250 mL), dried over MgSO4. Removal of the solvent in vacuum left a dark brown residue which was purified by flash chromatography with n-heptane and acetone to give the title compound as a brown solid (41.65 g, 76%). MS (ISP) 191 [(M+H)+].

Workup

  1. customwas purged for 10 min with argon
  2. additionThen CuI (340 mg, 1 mol %) was added
  3. temperatureCooled to 23° C.
  4. concentrationthe reaction mixture was concentrated in vacuum
  5. customto remove all volatiles
  6. additionpoured the residue onto water (300 mL)
  7. extractionextracted with ethyl acetate (3×500 mL)
  8. washThe combined organic layers were washed with water (300 mL) and brine (2×250 mL)
  9. dry with materialdried over MgSO4
  10. customRemoval of the solvent in vacuum
  11. waitleft a dark brown residue which
  12. customwas purified by flash chromatography with n-heptane and acetone

Sources & evidence

ORD record
ord-180d53c52905452883abdf6905b93a02
Source dataset
uspto-grants-2007_07
Patent number
US07238808B2

Reaction notes

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