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With hydrogenchloride; water; In methanol; for 30h;Heating / reflux; |
Reference Example 11 3-[2-(Trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one 1-[2-(Trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one [Show Image] Diethoxymethyl acetate (15 mL) was added to 2-chloropyridine-3,4-diamine (480 mg) and the resulting mixture was stirred at room temperature for 12 hours. To the mixture was added 1N hydrochloric acid and the precipitate formed was filtered, washed with diethyl ether and then dried to obtain a crude product (400 mg), <strong>[2770-01-6]4-chloro-1H-imidazo[4,5-c]pyridine</strong> as a brown solid. The spectrum of this compound is as follows: 1H NMR (400 MHz, CD3OD) delta 9.45 (s, 1H), 8.51 (d, J = 5.9 Hz, 1H), 7.94 (d, J = 5.9 Hz, 1H). MS (ESI+) 154 (M+ +1, 100%). A hydrochloric acid/methanol solution (25 mL, methanol component 80-90%) was added to this solid (220 mg) and the resulting mixture was heated under reflux for 30 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure, and the resulting residue was washed with diethyl ether and dried to obtain a crude product (150 mg), 3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one as a brown solid. The spectrum of this compound is as follows: 1H NMR (400 MHz, CD3OD) delta 9.40 (s, 1H), 7.58 (d, J = 7.2 Hz, 1H), 6.87 (d, J = 7.2 Hz, 1H). MS (ESI+) 136 (M++1, 100%). Under a nitrogen atmosphere, sodium hydride (134 mg, a 60% oil dispersion) was added to N,N-dimethylformamide (15 mL) and the resulting suspension was cooled to -15C. To the suspension was added 3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (360 mg) and the resulting mixture was stirred at room temperature for 30 minutes. Then, chloro-2-(trimethylsilyl)ethoxymethane (0.550 mL) was added dropwise thereto, followed by stirring at room temperature for 20 hours. Water was added to the reaction solution, followed by extraction with chloroform. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by a silica gel column chromatography (developing solvent: chloroform/methanol = 20/1 to 10/1) to obtain 3-[2-(trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (119 mg) and 1-[2-(trimethyl-silyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one (113 mg) each as a white solid. 3-[2-(Trimethylsilyl)ethoxy]methyl}-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one 1H NMR (400 MHz, CDCl3) delta 11.49 (bs, 1H), 8.03 (s, 1H), 7.16 (m, 1H), 6.77 (d, J = 7.0 Hz, 1H), 5.91 (s, 2H), 3.66 (t, J = 8.2 Hz, 2H), 0.93 (t, J = 8.2 Hz, 2H), - 0.04 (s, 9H). MS (ESI+) 266 (M++1, 100%). 1-[2-(Trimethylsilyl)ethoxy]methyl}-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one 1H NMR (400 MHz, CDCl3) delta 10.97 (bs, 1H), 7.84 (s, 1H), 7.21 (m, 1H), 6.56 (d, J = 7.1 Hz, 1H), 5.45 (s, 2H), 3.51 (t, J = 8.2Hz, 2H), 0.90 (t, J = 8.2 Hz, 2H), - 0.03 (s, 9H). MS (ESI+) 266 (M++1, 100%). |
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