5-Bromo-6-methyl-2-pyridinecarbonitrile

Under an inert atmosphere, 3-bromo-6-iodo-2-methylpyridine 12 (4.19 mmol, 1.25 g) in acetonitrile (15 mL) was combined with copper cyanide (0.5 eq., 2.0 mmol, 185 mg) and sodium cyanide (0.8 eq., 3.35 mmol, 165 mg). The reaction mixture was stirred for 30 min and heated at 80 °C with stirring under nitrogen for 16 h. The slurry was cooled to RT, diluted with a 0.5M aqueous solution of ammonia and stirred for 15 min, filtered over Celite ® and the filter cake was washed with ethyl acetate. Organic layer was then separated. The organic layer was washed sequentially with 0.5M aqueous solution of ammonia and brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to afford the desired product which was purified by flash chromatography over silica gel using an elution of 7percent ethyl acetate in hexane to give 650 mg (Yield: 79percent) of the title compound 13 as an oil. 1H NMR (400 MHz, CDCl3): δ 7.95 (1H, d, J = 8.4 Hz), 7.40 (1H, d, J = 8.4 Hz), 2.17 (3H, s); ESI-MS: m/z 197 [M + H]+Under an inert atmosphere, 3- bromo-6-iodo-2-methylpyridine (intermediate compound 32) (1 .25 g, 4.19 mmol) and acetonitrile (15 ml_) were combined and stirred for 30 min with copper cyanide (0.5 eq., 2.0 mmol, 185 mg), sodium cyanide (0.8 eq., 3.35 mmol, 165 mg). The reaction mixture was heated at 80Under an inert atmosphere, 3- bromo-6-iodo-2-methylpyridine intermediate compound 54 (1 .40g, 4.7 mmol) and acetonitrile (15 mL) were combined and stirred for 30 min with copper cyanide (0.8 eq., 3.76 mmol, 184 mg), sodium cyanide (0.8 eq., 3.35 mmol, 165 mg). The reaction mixture was heated at 80NaCN (4 g, 82 mmol) was added to a solution of 3-bromo-6-fluoro-2-methyl-pyridine (4 g, 21 mmol) in DMSO (100 mL) The mixture was stirred for 2 h at 100° C., poured into HNaCN (4 g, 82 mmol) was added to a solution of 3-bromo-6-fluoro-2-methyl-pyridine (4 g, 21 mmol) in DMSO (100 mL) The mixture was stirred for 2 h at 100°C, poured into Ha) 5-Bromo-6-methyl-pyridine-2-carbonitrile NaCN (4 g, 82 mmol) was added to a solution of 3-bromo-6-fluoro-2-methyl-pyridine (4 g, 21 mmol) in DMSO (100 mL) The mixture was stirred for 2 h at 100 °C, poured into H3, 6-Dibromo-2-methylpyridine(4.9 g, 19.53 mmol), copper(I)cyanide (1.75 g, 19.53 mmol) and N, N-dimethylformamide (20 mL) were combined in a sealable vessel with a stirbar. The resulting mixture was sealed, stirred vigorously and heated at 110 Example 35-Bromo-2-cyano-6-methylpyridine synthesisIn a 2-l. four-necked round bottom flask equipped with agitation, a dropping funnel, and a gas inlet adapter, was placed a solution of sodium cyanide (147 grams, 3.0 moles) dissolved in water (400 ml). While agitating, the apparatus was flushed with nitrogen for 1 hr. The solution in the flask was then cooled below 0° C. with an ice bath, and a solution of 3-bromo-1-methoxy-2-methylpyridinium methyl sulfate (314 grams, 1.0 mole) dissolved in water (300 ml) was added drop-wise at a rate that the temperature was maintained between 0-5° C. The dropping funnel and the thermometer-adapter were then quickly removed and replaced by stoppers, and the flask was allowed to stand in a refrigerator overnight (16 hrs.). The flask, containing the crude nitrile, was removed from the refrigerator and the contents were stirred at room temperature for 4 hours. After filtration, the obtained brown crude was washed with water to pH 7 then recrystallized with ethyl acetate and activated carbon. Off-white solid (124 grams, 63percent) was obtained. The purity of the product was >98percent.

Molecular Weight:197.03
XLogP3:2
Hydrogen Bond Acceptor Count:2
Exact Mass:195.96361
Monoisotopic Mass:195.96361
Topological Polar Surface Area:36.7
Heavy Atom Count:10
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes