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

HRID 2382123Notes

Reaction equation

HRID 2382123 reaction equation
[F:1][C:2]1[CH:3]=[C:4](I)[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:10][Si:11]([C:14]#[CH:15])([CH3:13])[CH3:12].C(N(CC)CC)C>C1COCC1.[Cu]I>[F:1][C:2]1[CH:3]=[C:4]([C:15]#[C:14][Si:11]([CH3:13])([CH3:12])[CH3:10])[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

6

Reactant 3

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

Product 1

HCID 597068495-Fluoro-3-((trimethylsilyl)ethynyl)pyridin-2-amineYield 94.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-fluoro-3-iodo-pyridin-2-ylamine (4 g, 16.8 mmol) in THF (50 mL) and trimethylsilylacetylene (4.7 mL, 33.6 mmol) is treated with PdCl2(PPh3)4 (353 mg, 0.5 mmol), CuI (96 mg, 0.5 mmol) and triethylamine (7 mL, 50.4 mmol) and stirred at rt for 2 h. The mixture is filtered through Celite and concentrated. The residue is purified by silica gel chromatography eluting with 10%-35% EtOAc in heptane to afford 5-fluoro-3-trimethylsilanylethynyl-pyridin-2-ylamine (3.3 g, 94%). MS: 209 (M+H); 1H NMR (300 MHz, CDCl3): δ 7.90 (d, 1H), 7.30 (m, 1H), 4.89 (s, NH2, 2H), 0.25 (s, 9H).

Workup

  1. filtrationThe mixture is filtered through Celite
  2. concentrationconcentrated
  3. customThe residue is purified by silica gel chromatography
  4. washeluting with 10%-35% EtOAc in heptane

Sources & evidence

ORD record
ord-fe1467693b864b58baf6f1d2b82451fa
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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