Trimethylsilylacetylene → 4-Chloro-5-nitro-3-((trimethylsilyl)ethynyl)pyridin-2-amine

Temperature

60 °C

To a solution of 4-chloro-3-iodo-5-nitropyridin-2-amine (5.30 g, 17.7 mmol) in THF (90 mL) was added TEA (15.0 mL, 108 mmol). The reaction mixture was degassed and purged with nitrogen 3 times. Bis(triphenylphosphine)-palladium(II) dichloride (0.62 g, 0.88 mmol, Strem), copper(I) iodide (0.17 g, 0.89 mmol), and trimethylsilylacetylene (5.4 mL, 39 mmol) were added to the reaction mixture, degassed, and purged 3 times with nitrogen. The reaction was heated at about 60° C. for about 16 h. The reaction mixture was cooled to ambient temperature. The reaction mixture was filtered and washed with THF (200 mL). The filtrate was concd under reduced pressure. DCM (100 mL) was added to the residue and the precipitate that formed was filtered and collected to give 4-chloro-5-nitro-3-((trimethylsilyl)ethynyl)pyridin-2-amine (0.77 g). The remaining filtrate was concd under reduced pressure and the crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-100% EtOAc in DCM. The purified material was combined with the 0.77 g of precipitate to afford 4-chloro-5-nitro-3-((trimethylsilyl)ethynyl)pyridin-2-amine (2.22 g, 47%) as a yellow solid: LC/MS (Table 1, Method c) Rt=1.62 min; MS m/z 268 (M−H)−.

1. customThe reaction mixture was degassed
2. custompurged with nitrogen 3 times
3. customdegassed
4. custompurged 3 times with nitrogen
5. temperatureThe reaction mixture was cooled to ambient temperature
6. filtrationThe reaction mixture was filtered
7. washwashed with THF (200 mL)
8. additionDCM (100 mL) was added to the residue
9. customthe precipitate that formed
10. filtrationwas filtered
11. customcollected

ORD record

ord-49c4769411c44ee796cd9100cecb92cd

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2