Ethanone, 1-(3-methoxy-2-pyridinyl)- (9CI)

3-Methoxy-2-cyanopyridine (0.88 g, 6.5 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) in a 3-neck flask under a nitrogen atmosphere.The reaction was cooled to 0 °C, and a solution of methylmagnesium iodide in tetrahydrofuran (3M, 4.3 ml, 12.8mmol) was added. The reaction was stirred at 0 °C for 2 hours and then quenched with 50 mL of water at 0 °C. The pH was adjusted to 7 with 2N HCl, and the resulting solution was extracted with ethyl acetate (3 x 50 mL)), the combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to provide the crude product. Silica gel chromatography (gradient of 0 – 100percent ethyl acetate in hexane) provided the product as a colorless oil (0.79g, 79percent yield). 3-Methoxy-2-cyanopyridine (0.88g, 6.5mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) in a 3-neck flask under a nitrogen atmosphere. The reaction was cooled to 0 °C, and a solution of methyl magnesium iodide in tetrahydrofuran (3M, 4.3 ml, 12.8mmol) was added. The reaction was stirred at 0 °C for 2 hours and then quenched with 50 mL of water at 0 °C. The pH was adjusted to 7 with 2N HC1, and the resulting solution was extracted with ethyl acetate (3 x 50 mL)), the combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to provide the crude product. Silica gel chromatography (ISCO RediSep 80 gram column, gradient of 0 - 100percent ethyl acetate in hexane over 26 minutes) provided the product as a colorless oil (0.79g, 79percent yield). 1-(3-methoxy-pyridin-2-yl)-ethanone (0.04 g, 0.26mmol) was dissolved in anhydrous methanol (5 mL) and a solution of lithium hydroxide (1.2 mg, 0.05mmol) in anhydrous methanol (1.75 mL) was added. After 30 minutes, 2-trifluoromethyl-benzaldehyde (0.0356 mL 0.27mmol) was added, and the reaction was allowed to stir for 18 hours. The reaction was then concentrated on a rotary evaporator and the crude product was purified by silica gel chromatography (Isco RediSep 12gram column, gradient of 0 - 100%) ethyl acetate in hexane over 10 minutes) to provide the desired product (0.043 g, 54% yield) as a yellow solid. 1H-NMR (400MZ, CDCI3) delta 8.33 (1H, dd, J = 4.4 and 1.3 Hz), 8.09 (1H, dd, J = 15.9 and 2.1 Hz), 7.90 (1H, d, J = 7.7 Hz), 7.73 (1H, d, J = 7.7 Hz), 7.71 (1H, d, J = 15.9 Hz), 7.60 (1H, t, J = 7.6 Hz), 7.50 (1H, t, J = 7.6 Hz), 7.47, (1H, dd, J = 8.6 and 4.4 Hz), 7.41 (1H, dd, J = 8.6 and 1.3 Hz), 3.96 (3H, s). (M+H): 308.3-Methoxy-2-cyanopyridine (0.88 g, 6.5 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) in a 3-neck flask under a nitrogen atmosphere.The reaction was cooled to 0 C, and a solution of methylmagnesium iodide in tetrahydrofuran (3M, 4.3 ml, 12.8mmol) was added. The reaction was stirred at 0 C for 2 hours and then quenched with 50 mL of water at 0 C. The pH was adjusted to 7 with 2N HCl, and the resulting solution was extracted with ethyl acetate (3 x 50 mL)), the combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to provide the crude product. Silica gel chromatography (gradient of 0 - 100% ethyl acetate in hexane) provided the product as a colorless oil (0.79g, 79% yield). 1H-NMR (CDCl3) delta 8.42 (dd, J = 7.7 and 1.4Hz, 1H), 7.63 (dd, J = 7.6 and 1.4 Hz, 1H), 7.61 (dd, J = 7.7 and 7.6 Hz, 1H), 3.82 (s, 3H), 2.14 (s, 3H), (ESI+): m/z (M+H)+= 152.3-Methoxy-2-cyanopyridine (0.88g, 6.5mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) in a 3-neck flask under a nitrogen atmosphere. The reaction was cooled to 0 C, and a solution of methyl magnesium iodide in tetrahydrofuran (3M, 4.3 ml, 12.8mmol) was added. The reaction was stirred at 0 C for 2 hours and then quenched with 50 mL of water at 0 C. The pH was adjusted to 7 with 2N HC1, and the resulting solution was extracted with ethyl acetate (3 x 50 mL)), the combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to provide the crude product. Silica gel chromatography (ISCO RediSep 80 gram column, gradient of 0 - 100% ethyl acetate in hexane over 26 minutes) provided the product as a colorless oil (0.79g, 79% yield). 1H-NMR (400Mz, CDCI3) delta 8.42 (1H, dd, J = 7.7 and 1.4 Hz), 7.63 (1H, dd, J = 7.6 and 1.4 Hz), 7.61 (1H, dd, J = 7.7 and 7.6 Hz), 3.82 (3H, s), 2.14 (3H, s). Ms (M+H): 152.General procedure: A solution of lithium hydroxide (0.8 mg, 0.03 mmol) and 2'-methoxyacetophenone (26 mg, 0.157 mmol) in absolute methanol (1.5 mL) was stirred at room temperature for 15 min. To the resulting mixture was added a solution of 2-(trifluoromethyl)-3-pyridinecarboxaldehyde (6a, 28 mg, 0.16 mmol) in absolute methanol (15 mL). The reaction was stirred overnight at room temperature (approx. 18 h). The reaction was then concentrated on a rotary evaporator and the resulting oily residue purified by chromatography on silica gel using a gradient of 0-100% ethyl acetate in hexane to provide the desired product (17 mg, 35%) as a light yellow waxy solid. Prepared using the general method from lithium hydroxide (2 mg, 0.05 mmol), 2-(trifluoromethyl)benzaldehyde (47 mg, 0.27 mmol) and (1) 1-(3-Methoxypyridin-2-yl)ethanol (1.0 g) obtained by the method described in the literature () was dissolved in diethyl ether (30 ml), manganese dioxide (2.27 g) was added to the solution, and the resulting mixture was stirred at room temperature for 8 hours. The reaction mixture was filtered through Celite, then the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform to chloroform:methanol = 100:1) to obtain a ketone compound (580 mg).EXAMPLE 10 1-(3-Methoxy-2-pyridyl)-1-ethanone-1-(1-methyl-1H-benzo[d]imidazol-2-yl)-hydrazone (1d-1) A mixture 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