2-METHOXY-4,6-DIMETHYLNICOTINONITRILE

Add a solution of NaOCH3 in MeOH (30 mass percent, 175 mL, 940 mmol) drop wise to a solution of 2-chloro-4, 6-dimethyl-pyridine-3 -carbonitrile (75 g, 441.1 mmol) inMeOH (450 mL) in a water bath followed by another drop wise addition of NaOCH3 in MeOH (25 mass percent, 250 mL, 1090 mmol). Stir the resulting mixture for 1 hr, pour in ice cold water, stir for 30 mm, and filter the resulting solid. Wash filter cake with hexane and dry in a vacuum oven overnight. Extract the aqueous filtrate with DCM, dry the organic phase over Mg504, filter and concentrate in vacuo. Combine the filtered solid and theevaporated residue to afford title compound as a solid (71.8 g, quantitative yield). ES/MS (mlz): 163 (M+H).2-chloro-4, 6-dimethyl-nicotinonitrile (2.5 g, 15.01 mmol) was dissolved in anhydrous methanol (70mL), added with sodium methoxide (4. 27 g, 75.03 mmol) at 0 °C and stirred for about 10 hours at nitrogen atmosphere. The above mixture was concentrated under reduced pressure and then neutrailized with a saturated solution of ammonium chloride and then extracted twice with 150 mL of methylenechloride. The resulting organic layer was dried using anhydrous sodium sulfate, filtered and concentrated. A silica gel column chromatography (20percent EtOAc/Hexanes) was performed on the resulting residue and 2.41g (99percent) of 2- methoxy-4, 6-dimethyl-nicotinonitrile was obtained in white solid. 'H NMR (300 MHz, CDC13) 8 2.44 (s, 3H), 2.45 (s, 3H), 4.01 (s, 3H), 6.68 (s, 1H).Step 2: 3-Cyano-4, 6-dimethyl-2-methoxypyridine: A solution of 2-chloro-3-cyano-4, 6- dimethylpyridine (4.60 g, 27.7 mmol) in methanol (30 mL) is added to a stirred solution of sodium methoxide (2.09 g, 38.78 mmol) in methanol (20 mL) and the reaction mixture is heated at 60°C for 4 hr. After cooling, the reaction is diluted with water (150 mL) and the solids are collected by filtration, washed with water and dried to yield 3-cyano-4, 6-dimethyl-2- methoxypyridine (2.90 g, 65percent) as an off-white solid containing the same impurity as the starting material. LC/MS: MS m/e = 163 (M + H) ; RT 3.29 min; Sodium (23 g, 0.99 mol) was added to dry MeOH (800 mL) portion-wise.

Molecular Weight:162.19
XLogP3:1.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:162.079312947
Monoisotopic Mass:162.079312947
Topological Polar Surface Area:45.9
Heavy Atom Count:12
Complexity:196
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes