5-ACETYL-2-METHOXYPYRIDINE, 97%

Step 2: The amide (10.4 g, 53 mmol) was taken up in THF (100 ml_) and cooled to 0 oC. Methylmagnesium bromide (26.5 ml_ of a 3 M solution in EtStep-2: Preparation of l-(6-methoxypyridin-3-yl)ethanone [0169] To a solution of N, 4-dimethoxy-N-methylbenzamide (1.4 g, 7.14 mmol) in a mixture of tetrahydrofuran (5 mL):diethyl ether (100 mL), 3M methyl magnesium bromide in diethyl ether (4.75 mL, 4.27 mmol) was added at 0 °C and the reaction mixture was stirred at room temperature for 16 h under nitrogen atmosphere. The solution was quenched with saturated ammonium chloride solution (20 mL) and extracted with ethyl acetate (100 mL x 2). The combined organic layer was dried over anhydrous sodium sulfate and evaporated under vacuum to get crude which was purified by silica gel flash column chromatography using 12percent ethyl acetate in hexane to afford the title compound l-(6-methoxypyridin-3- yl)ethanone (0.825 g, 77.1percent) as off-white solid. Calculated (M+H): 152.16; Found (M+l): 152.1.Under nitrogen, a solution of N, 6-dimethoxy-N-methylpyridine-3-carboxamide 28 (3.66g, 18.67mmol) in THF (64mL) was stirred at 0°C for 15m. Methyl magnesium bromide (3M solution in THF, 6.42mL, 19.26mmol) was added dropwise over 5min and the solution was stirred at 0°C for 1h. The solution was allowed to warm to room temperature and stirred for 1d before the solution was concentrated under reduced pressure and HCl (2M, 10mL) was added. Following extraction with diethyl ether (3×30mL), the organic extracts were washed with brine, dried (MgSO[0559] To a solution of III-1 (30 g, 0.162 mol, 1 eq.) in 300 mL of anhydrous THF was added dropwise a solution of n-BuLi (2.5M in hexane, 77.5 mL, 0.19 mol, 1.2 eq.) at −70° C. After completion of addition, the mixture was stirred at −70° C. for 20 min, followed by addition of a solution of N-methoxy-N-methylacetamide (33 g, 0.322 mol, 2 eq.) in 100 mL of anhydrous THF by drop wise, the solution was allowed to warm to rt and stirred for 2 hrs. The reaction was quenched with saturated aq. NHTo a solution of Ill-i (30 g, 0.162 mol, 1 eq.) in 300 mL of anhydrous THF was added dropwise a solution of n-BuLi (2.5M in hexane, 77.5 mL, 0.19 mol, 1.2 eq.) at -70°C. After completion of addition, the mixture was stuffed at -70°C for 20 mm, followed by addition of a solution of N-methoxy-N-methylacetamide (33 g, 0.322 mol, 2 eq.) in 100 mL of anhydrous THF by drop wise, the solution was allowed to warm to rt and stirred for 2 hrs. The reaction was quenched with saturated aq. NH4C1 (100 mL), extracted with EtOAc (300 mLx3), the organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with petroleum ether/EtOAc (100:1) to yield 111-2 (14.8 g, 62percent yield) as a white solid. ‘H NMR (DMSO-d6, 400 MHz) (58.81 (d, J= 2.0 Hz, 1H), 8.16 (dd, J= 2.4, 8.4 Hz, 1H), 6.90 (d, J = 8.8 Hz, 1H), 3.93 (s, 3H), 2.55 (s, 3H). MS (ES) m/z [M+H] 15 1.6.Methyllithium (0.98M diethyl ether solution, 135 mL) was added dropwise at -78°C to the obtained 6-methoxynicotinic acid N-methoxy-N-methylamide (19.21 g) in tetrahydrofuran (400 mL) over 30 minutes, followed by stirring for 30 minutes. A mixture of 15 mL of methanol, 500 mg (2.89 mmol) of 1-(6-chloropyrid-3-yl)ethanone and 1.17 g (21.69 mmol) of sodium methoxide is heated in a microwave reactor at 160°C for 4 hours. The reaction medium is evaporated to dryness. After purification by chromatography on silica gel (eluent A B: heptane/EtOAc, gradient A/B: t 0 min 0percent B, t 5 min 20percent B, t 30 min 40percent B), 230 mg of 1-(6-methoxypyrid-3-yl)ethanone were obtained, corresponding to the following characteristics: LC/MS (method G): ESI+ [M+H]+: m/z 152. tr (min) = 1.33. A mixture of 15 mL of methanol, 500 mg (2.89 mmol) of 1-(6-chloropyrid-3-yl)ethanone and 1.17 g (21.69 mmol) of sodium methoxide is heated in a microwave reactor at 160° C. for 4 hours. To a solution of

Molecular Weight:151.16
XLogP3:0.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:151.063328530
Monoisotopic Mass:151.063328530
Topological Polar Surface Area:39.2
Heavy Atom Count:11
Complexity:147
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes