2,6-DIMETHYL-4-CYANOPYRIDINE

Scheme 4, step A: Zinc cyanide (3.82g, 31.9 mmol) is added to a mixture of 4- bromo-2, 6-dimethylpyridine (5.09 g, 26.5 mmol) and DMF (40 mL) stirring under nitrogen at RT. Nitrogen is bubbled through the stirred suspension for 15 min, and tetrakis(triphenylphoshpine) palladium(O) (1.54 g, 1.33 mmol) is added. After heating the reaction mixture at 120 °C for 5.5 hr, the mixture is cooled to RT and diluted with EtOAc (150 mL). The solids are removed via paper filtration and the filter cake is washed with EtOAc (50 mL). The combined organic filtrate and wash is washed sequentially with 15percent aqueous NHZinc cyanide (3.82g, 31.9 mmol) is added to a mixture of 4- bromo-2, 6-dimethylpyndine (5.09 g, 26.5 mmol) and DMF (40 mL) stirring under nitrogen at RT. Nitrogen is bubbled through the stirred suspension for 15 min, and tetrakis(triphenylphosphine) palladium(O) (1 , 54 g, 1.33 mmol) is added. After heating th reaction mixture at 120 °C for 5.5 hr, the mixture is cooled to RT and diluted with EtOAc (150 mL). The solids are removed via paper filtration and the filter cake is washed with EtOAc (50 mL). The combined organic filtrate and wash is washed sequentially with 15percent aqueous NH2, 6-DimethylisonicotinonitrileTo a stirred quantity of 2, 6-lutidine-l -oxide (12.3 g, lOOmmol) was slowly added dimethyl sulphate (12.6 g, lOOmmol) at such a rate that the temperature of the reaction mixture was maintained at 8O Synthesis of4-cyano-2, 6-dimethylpyddine; [0103] 2, 6-Lutidine-N-oxide (25 g, 0.2 moles) and dimethylsulfate (25.3 g, . 2 moles) were combined and let sit until a solid precipitated, <1 hr. The salt was dissolved in water (100 ml) and potassium cyanide in water (150 ml) was added in one portion. After two days, in which the nitrile precipitated, the solution was filtered, washed with water and dried. 4-cyano-2, 6-dimethylpyridine was isolated as a tan solid in 13.7 percent yield.'H NMR (DMSO-d6) 2.48 (6 H, s), 7.51 (2H, s).A mixture of 1 g (7.56 mmol) of (1) and 5 ml of concentrated sulfuric acid is heated at 100 C. for 5 hours. The resulting solution is then cooled on an ice bath, brought to pH 3.5 with 10 N sodium hydroxide and then concentrated to dryness. Extraction with ether for 48 hours (soxhlet) of a portion of the residue obtained gives 50 mg of 2, 6-dimethylisonicotinic acid (2) for analysis. The remaining crude reaction product, not treated with ether, is used in its present form in the esterification reaction without further purification. [0133] NMR: 1H (D20); internal reference tBuOH 1.29 ppm. [0134] 2.82 (s, 6H, CH3); 8.05 (s, 2H, Py). [0135] MS (EI): 151 (M+, 100); 134 (M+-OH, 7.2); 106 (M+-CO2H, 16.4) [0136] MA: C8H9NO2+0.1 NaHSO4 (163.16) [0137] calculated: C 58.89H 5.62 N 8.58 O 23.53 [0138] found: C 58.73H 5.90 N 8.37 O 23.72, 6-??????????(2)1g(7.56mmol)?(1)???5ml????????5??100?????????????????????????10N????????pH3.5??????????????????????????48????????(??????)??????????50mg'2, 6-??????????(2)?????????????(????????????)?????????????????????????????????

Molecular Weight:132.16
XLogP3:1.4
Hydrogen Bond Acceptor Count:2
Exact Mass:132.068748264
Monoisotopic Mass:132.068748264
Topological Polar Surface Area:36.7
Heavy Atom Count:10
Complexity:146
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes