Triethylamine → 5-Fluoro-3-((trimethylsilyl)ethynyl)pyridin-2-amine

HRID 490503Notes

Reaction equation

HRID 490503 reaction equation
[C:1]([Si:3]([CH3:6])([CH3:5])[CH3:4])#[CH:2].[Cl-].[Li+].C(N(CC)CC)C.[F:16][C:17]1[CH:18]=[C:19](I)[C:20]([NH2:23])=[N:21][CH:22]=1>CN(C)C=O.[Cu](I)I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:16][C:17]1[CH:18]=[C:19]([C:2]#[C:1][Si:3]([CH3:6])([CH3:5])[CH3:4])[C:20]([NH2:23])=[N:21][CH:22]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 433294Lithium ChlorideHCID 184559742-Amino-5-fluoro-3-iodopyridine

Product 1

HCID 597068495-Fluoro-3-((trimethylsilyl)ethynyl)pyridin-2-amine

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

12.47 cm3 of ethynyltrimethylsilane, 2.24 g of copper iodide, 2.74 g of lithium chloride, 41.33 cm3 of triethylamine and 2.15 g of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride are added to a solution of 14 g of 5-fluoro-3-iodo-pyrid-2-ylamine in 440 cm3 of dimethylformamide, degassed with argon. The solution obtained is maintained at a temperature in the region of 55° C. for about 5 hours. After cooling to a temperature in the region of 20° C., the mixture is concentrated under reduced pressure (13 kPa); the residue is taken up in 300 cm3 of water and extracted with three times 100 cm3 of ethyl acetate. The combined organic phases are washed with three times 100 cm3 of water, dried over magnesium sulfate, filtered and concentrated under reduced pressure (13 kPa). 7.91 g of 5-fluoro-3-trimethylsilanylethynylpyrid-2-ylamine are thus obtained, after flash chromatography on a column of silica (eluent; dichloromethane), in the form of a solid, the characteristics of which are as follows:

Workup

  1. customdegassed with argon
  2. customThe solution obtained
  3. temperatureAfter cooling to a temperature in the region of 20° C.
  4. concentrationthe mixture is concentrated under reduced pressure (13 kPa)
  5. extractionextracted with three times 100 cm3 of ethyl acetate
  6. washThe combined organic phases are washed with three times 100 cm3 of water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure (13 kPa)

Sources & evidence

ORD record
ord-92987fe74a664443a5753eac8406e32c
Source dataset
uspto-grants-2009_05
Patent number
US07528147B2

Reaction notes

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