5-Methyl-2-pyridinecarbonitrile

Light yellow Cryst

Commercially available 2-cyano-5-methylpyridine (1.90 g, 16.1 mmol) was dissolved in chloroform (100 mL), and the mixture was stirred at 60C for 6 hours after adding N-bromosuccinimide (4.29 g, 24.1 mmol) and alpha, alpha-azobisisobutyronitrile (0.792 g, 4.82 mmol). After ice-cooling the reaction mixture, the precipitate was separated by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 5-bromomethyl-2-cyanopyridine (1.69 g, 53%). 1H NMR (CDCl3) delta(ppm) 4.80 (s, 2H), 8.03 (dd, J = 0.92, 8.07 Hz, 1H), 8.12 (dd, J = 2.20, 8.07 Hz, 1H), 8.81 (bd, J = 1.83 Hz, 1H). (1 g, 8.46 mmol), N-bromosuccinimide (1.66 g, 9.31 mmol) and benzoyl peroxide (206 mg, 0.85 mmol) were dissolved in 50 mL of carbon tetrachloride and refluxed for 5 hours.After drying, the solvent was evaporated, and the crude product was purified by petroleum ether: ethyl acetate=5/1 column chromatography.Compound 37A was obtained as a yellow solid (800 mg, 48.2percent yield).Preparation 16; 2-Aminomethyl-5-o-propylthiomethyl-pyridine; 5-Bromomethyl-pyridine-2-carbonitrile; Add AIBN (0.25 g, 1.5 mmol) to a slurry of 5- methyl-pyridine-2-carbonitrile (2.5 g, 21.1 mmol) and NBS (3.7 g, 21.1 mmol) in carbon tetrachloride (150 mL) at reflux under a nitrogen atmosphere. Add AIBN (3x0.25 g, 3x1.5 mmol) to the reaction in 0.25 g portions every hour for 3 h. Stir the resulting mixture for one additional hour at reflux. Cool the mixture to room temperature and wash with saturated aqueous NaHCO3 (30 mL). Collect the organic phase, concentrate in EPO A solution of compound C2 (7.5 g, 63.6 mmol), benzoylperoxide (0.54 g, 2.24 mmol), and Lambda/-bromosuccinimide (12.5 g, 70.2 mmol) in 100 mL of CCI4 was refluxed for 2 h. The resulting suspension was filtered and the filtrate diluted with 400 mL of DCM, washed with a saturated sodium bicarbonate solution, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: PE/EtOAc = 10/1) to give 3.3 g Qf crude compound C3 as a yellow solid used in the following reaction without further purification.Synthesis of compound C3: [Show Image] A solution of compound C2 (7.5 g, 63.6 mmol), benzoylperoxide (0.54 g, 2.24 mmol), and N-bromosuccinimide (12.5 g, 70.2 mmol) in 100 mL of CCl4 was refluxed for 2 h. The resulting suspension was filtered and the filtrate diluted with 400 mL of DCM, washed with a saturated sodium bicarbonate solution, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: PE/EtOAc = 10/1) to give 3.3 g of crude compound C3 as a yellow solid used in the following reaction without further purification.2-bromo-5-methylpyridine (5 g, 29.06 mmol), benzoyl peroxide (410 mg, 1.692 mmol), and N-bromosuccinimide (3 g, 16.92 mmol) were dissolved in CCl4 (50 ml), and reflux-stirred for 12 hours. After the reaction was completed, the organic layer was separated by H2O and EA, and dried and filtered with MgSO4. The resultant mixture was purified by column chromatography (EA/n-Hex = 1:4) so as to provide 5-(bromomethyl)picolinonitrile (500 mg) mixture.36 g (209 mmol) 2-bromo-5-methylpyridine and 37.5 g (418 mmol) copper cyanide are refluxed for two hours in [500 ML DIMETHYLFORMAMIDE.] After cooling down to [50°C, ] 10percent aqueous ammonia solution (500 ml) is added with stirring. The product is extracted with dichloromethane, the organic phase is dried over magnesium sulfate, and the solvent is removed in vacuo. The product is purified by column chromato- graphy (silica, eluent cyclohexane/ethyl acetate 9: [1) :] Yield: [18 G] (73percent [OF TH.)] [1H-NMR] (300 MHz, [CDC13)] : [8] = 2.4 (s, [3H), ] 7.6 (m, 2H), 8.6 (s, 1H) ppm.5-Methyl-2-pyridinecarbonitrile 36 g (209 mmol) 2-bromo-5-methylpyridine and 37.5 g (418 mmol) copper cyanide are refluxed for two hours in 500 ml dimethylformamide. After cooling down to 50°C, 10percent aqueous ammonia solution (500 ml) is added with stirring. The product is extracted with dichloromethane, the organic phase is dried over magnesium sulfate, and the solvent is removed in vacuo_ The product is purified by column chromatography (silica, eluent: cyclohexane/ethyl acetate 9: 1). Yield: 18 g (73percent of th.) 'H-NMR (300 MHz, CDC13) : 8 = 2.4 (s, 3H), 7.6 (m, 2H), 8.6 (s, 1H) ppm.

Molecular Weight:118.14
XLogP3:1.4
Hydrogen Bond Acceptor Count:2
Exact Mass:118.053098200
Monoisotopic Mass:118.053098200
Topological Polar Surface Area:36.7
Heavy Atom Count:9
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes