1-(2-Methyl-4-pyridinyl)ethanone

4-Acetyl-2-methylpyridine is an aromatic ketone.

To a stirred solution of N-methoxy-N, 2-dimethylisonicotinamide (266c) (26 g, 144.28Immol) in THF (520 rnL) was added MeLi (6.342 g, 288.562 mmoi, 1 M solution inTHF) under nitrogen atmosphere at -78°C. The reaction mixture was warmed to room temperature over a period of 1 h, quenched with saturated NH4CI solution at 0°C. The resulting reaction mixture was extracted with ethyl acetate and the organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Theresidue obtained was purified by column chromatography to afford I -(2-methylpyridin-4-yl)ethanone (266d) (11 g, 56.4percent yield) as a reddish thick liquid; ‘H NMR (CDCI3) 3 8.6 1-8.59 (d, 1H), 7.51-7.45 (d, IH), 7.45-7.44 (m, lH), 2.56(s, 3H), 2.53 (s, 3H); MS (ES+)136. l(M+I).Step-3 : Preparation of l-(2-methylpyridin-4-yl)ethanone (46d) To a stirred solution of N-methoxy-N, 2-dimethylisonicotinamide (46c) (26 g, 144.28 lmmol) in THF (520 mL) was added MeLi (6.342 g, 288.562 mmol, 1 M solution in THF) under nitrogen atmosphere at -78°C. The reaction mixture was warmed to room temperature over a period of 1 h, quenched with saturated HMethyl lithium (3M, 1.7 mL, 3.48mmol) was added to a solution of N-methoxy-N2- dimethylisonicotinamide (314 mg, 1.74mmol) in dry THF (4 mL) at -78 °C under nitrogen protection. The mixture was stirred at -78 °C and slowly warm up to rt for 1.5h. After completion, 10 mL of NH(b) I -(2-methyipyridin-4-yl)ethanone: Methyl lithium (3M, 1.7 mL, 3.48inniol) was added to a solution of W-methoxy-X, 2-dimethyiisonieotinamide (314 ing, I .74mmol) in dry THE (4 mL) at -78 °C under nitrogen protection. The mixture was stirred at -78 °C and slowly warm up to it for l.5h. After completion, 10 niL of NI-LCI solution (saturated) was added to the mixture, and it was extracted with EtOAc (10 mLx3). The combined organic layers were washed with brine (20mL), dried over Na2SO4, and filtered. The filtrate was eoneeitmated, and the residue was purified by silica gel column chromatography (CH2C12/MeOH=50/i) to obtain title compound (120mg, yield: 51percent). LCMS-A0i0: 136.1 [M+H] R = 0.585 mm[0352] l-(2-Methyl-4-pyridinyl)ethanone (143). A solution of MeMgBr (3 M in hexanes, 6.0 mL, 17.9 mmol) was added slowly to a stirred solution of nitrile 142 (1.76 g, 14.9 mmol) in dry THF (100 mL) at 0 To a solution of 4-bromo-2-methylpyridine (10.0 g, 58 mmol) in toluene (100 mL) was added tributyl(l-ethoxyvinyl)stannane (39.7 g, 110 mmol) and Pd(PPhTo a stirred solution of N-methoxy-N, 2-dimethylisonicotinamide (266c) (26 g, 144.28Immol) in THF (520 rnL) was added MeLi (6.342 g, 288.562 mmoi, 1 M solution inTHF) under nitrogen atmosphere at -78°C. The reaction mixture was warmed to room temperature over a period of 1 h, quenched with saturated NH4CI solution at 0°C. The resulting reaction mixture was extracted with ethyl acetate and the organic layer was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Theresidue obtained was purified by column chromatography to afford I -(2-methylpyridin-4-yl)ethanone (266d) (11 g, 56.4percent yield) as a reddish thick liquid; ‘H NMR (CDCI3) 3 8.6 1-8.59 (d, 1H), 7.51-7.45 (d, IH), 7.45-7.44 (m, lH), 2.56(s, 3H), 2.53 (s, 3H); MS (ES+)136. l(M+I).Step-3 : Preparation of l-(2-methylpyridin-4-yl)ethanone (46d) To a stirred solution of N-methoxy-N, 2-dimethylisonicotinamide (46c) (26 g, 144.28 lmmol) in THF (520 mL) was added MeLi (6.342 g, 288.562 mmol, 1 M solution in THF) under nitrogen atmosphere at -78°C. The reaction mixture was warmed to room temperature over a period of 1 h, quenched with saturated HMethyl lithium (3M, 1.7 mL, 3.48mmol) was added to a solution of N-methoxy-N2- dimethylisonicotinamide (314 mg, 1.74mmol) in dry THF (4 mL) at -78 °C under nitrogen protection. The mixture was stirred at -78 °C and slowly warm up to rt for 1.5h. After completion, 10 mL of NH(b) I -(2-methyipyridin-4-yl)ethanone: Methyl lithium (3M, 1.7 mL, 3.48inniol) was added to a solution of W-methoxy-X, 2-dimethyiisonieotinamide (314 ing, I .74mmol) in dry THE (4 mL) at -78 °C under nitrogen protection. The mixture was stirred at -78 °C and slowly warm up to it for l.5h. After completion, 10 niL of NI-LCI solution (saturated) was added to the mixture, and it was extracted with EtOAc (10 mLx3). The combined organic layers were washed with brine (20mL), dried over Na2SO4, and filtered. The filtrate was eoneeitmated, and the residue was purified by silica gel column chromatography (CH2C12/MeOH=50/i) to obtain title compound (120mg, yield: 51percent). LCMS-A0i0: 136.1 [M+H] R = 0.585 mm[0352] l-(2-Methyl-4-pyridinyl)ethanone (143). A solution of MeMgBr (3 M in hexanes, 6.0 mL, 17.9 mmol) was added slowly to a stirred solution of nitrile 142 (1.76 g, 14.9 mmol) in dry THF (100 mL) at 0 To a solution of 4-bromo-2-methylpyridine (10.0 g, 58 mmol) in toluene (100 mL) was added tributyl(l-ethoxyvinyl)stannane (39.7 g, 110 mmol) and Pd(PPhGeneral procedure: To a stirred solution of amide 12 (1.0 eq) in dry THF (0.3 M)A solution of MeMgBr (1 M, 1.5 eq) in THF was added slowly at 0 C. and the mixture was stirred at 0 C.The reaction mixture was quenched with saturated NH4Cl and extracted with ethyl acetate.The combined organic layers were washed with water, washed with saturated saline, dried over Na2SO4 and the solvent was evaporated.The residue was purified by column chromatography to obtain ketone 16.To a stirred solution of ketone 16 (1.0 eq.) In 5.1 M HBr / HOAc (2.8 eq.), Br2 (1.1 eq.) Was added dropwise at room temperature.The reaction mixture was quenched with saturated aqueous Na2CO3 and extracted three times with CH2Cl2.Dry the combined organic layers over Na2SO4, TFA was added, filtered and concentrated under reduced pressure to give compound 19 as a TFA salt.A suspension of 4-(1-ethoxyvinyl)-2-methylpyridine (2.6g, 15.9mmol) in 6N HCI (10ml_) was stirred at rt for 3h. The TLC showed the reaction to be complete. The reaction mixture was diluted with water (20mL), basified to pH 1 1 with 5N NaOH and extracted with EtOAC (3x20mL). The organic layer was dried (Na2S04), filtered and concentrated under reduced pressure to afford

Molecular Weight:135.16
XLogP3:0.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:135.068413911
Monoisotopic Mass:135.068413911
Topological Polar Surface Area:30
Heavy Atom Count:10
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes