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With phosphorus(V) oxybromide; In chloroform; at 140℃; for 4.5h;
Reference Example 5: Synthesis of 2,4-dibromo-6-methylpyridine A mixture of 2,4-dihydroxy-6-methylpyridine (5.0 g) and phosphorus oxybromide (68.7 g) was stirred at 140C for 4.5 h. The reaction mixture was cooled to room temperature, followed by addition of chloroform, and then the mixture was poured into ice water. The layers were separated, and then aqueous layer was extracted with chloroform. The organic layer was washed with water and saturated aqueous sodium hydrogencarbonate and dried with anhydrous sodium sulfate, then the desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting solids were recrystallized with methanol and ethyl acetate to obtain 2,4-dibromo-6-methylpyridine (2.2 g). MS: CI+ (m/z) 250 (M++1) 1H-NMR (200 MHz, CDCl3): delta7.80-7.84 (m, 1H), 7.63-7.67 (m, 1H), 2.45 (s, 3H)
To a solution of 4-hydroxy-6-methyl-2-oxo-l,2-dihydropyridine (3-2; 20.1 g; 161 mmol) in NMP (1.6 L) was added <strong>[327056-73-5]3-chloro-5-fluorobenzonitrile</strong> (3-1; 25 g; 161 mmol) and potassium carbonate (44.4 g; 321 mmol). The resulting solution stirred at 12O0C overnight. The reaction mixture was cooled to ambient temperature and diluted with 4 L of ice- water. The aqueous layer was acidified to pH 5 to precipitate out the product. The precipitate was collected via filtration, washed with water, and air dried. The crude solid product was triturated in 5% methanol/dichloromethane and filtered to give a solid. The solid was triturated with 1 : 1 ethyl acetate :hexane, stirred, and filtered to afford the title product as a tan solid. MS M+l = 261.0. lH NMR (CD3OD): 2.30 (s, 3H), 5.62 (s, IH), 6.05 (s, IH), 7.55 (s, IH), 7.0 (s, IH), 7.76 (s, IH).
With sodium acetate; In ethanol; at 78℃; for 1h;Green chemistry;
General procedure: Isatin 1 (3 mmol), malononitrile (3 mmol), 4-hydroxy-6-methylpyridin-2(1H)-one 2 (3 mmol) were refluxed for 60 minin ethanol (5 ml) with sodium acetate (10 mol%) or in pyridine (without any catalyst). After the reaction was finished, the solid was filtered,washed with ice ethanol and dried to isolate pure products 3. For their characteristics, see Online Supplementary Materials.
2-amino-4-(2-hydroxy-3,5-diiodophenyl)-7-methyl-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]pyridine-3-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With sodium acetate; In ethanol; for 1h;Reflux;
General procedure: Aldehyde 1 (3 mmol), malononitrile (3 mmol), 4-hydroxy-6-methylpyridin-2(1H)-one (3 mmol) and AcONa (0.3 mmol) were refluxed in 5 mL of ethanol for 1 h. After the reaction was finished, the solid was filtered, washed with cold ethanol and dried to isolate pure substituted 2-amino-7-methyl-5-oxo-4-phenyl-5,6-dihydro-4H-pyrano[3,2-c]pyridine-3-carbonitriles 2a-i.
Chemistry
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