5,6-DIMETHYL-2-OXO-1,2-DIHYDRO-PYRIDINE-3-CARBONITRILE

To a solution of 480mL of water (E / Z) -2- methyl-3-oxo-1-ene-1-ol Sodium (77.6g, 0.64mol) was added cyanoacetamide (49.0g, 0.70mol). To this mixture was added a solution of piperidine-acetic acid(From acetic acid (9.16g, 8.75mL, 0.15mol), 21.2mL of water and pyridine (13.0g, 15.1mL, 0.15mol) was obtained), and the mixture was heated at reflux through 4h, then stirred at room temperature for 16h. Acetic acid (75.5g, 72mL, 1.26mol) was added to the reaction mixture, the precipitated pale yellow solid. The latter was filtered off with suction, washed with water and dried under reduced pressure at 2h at 55 . To give 66.4 g of (70percent of theory) of a pale yellow solid.General procedure: A substituted alkyl methyl ketone or cyclic ketone (1 equiv) and ethyl formate or ethyl acetic(1 equiv) was added dropwise to absolute ether solution of sodium metal (1 equiv) for 1 h whilemaintained below 20 C. After the addition, the reaction was allowed to stir in an ice bath untilthe sodium metal had disappeared. The precipitate was filtered, washed with absolute ether anddried to give the corresponding compound which was directly used for the next step without further purification. To a solution of previous product (1 equiv), and cyanoacetamide (1.05 equiv) in water was stirred6 min at room temperature. The mixture was added dropwise piperidine acetate solution (0.3 equiv), which was prepared from piperidine (1 equiv), acetic acid (1 equiv) and water (5 equiv). The solutionwas heated to reflux for 2 h. Then, the reactor was cooled to room temperature, and adjusted to pH 4 by 4 N hydrochloric acid. The resulting solid was filtered, respectively washed with water and ether, and dried to give the corresponding compound which was purified by recrystallizing using menthol as solvent.Water (546 mL) was added to 2-methyl-3-oxobutanal sodium salt (1-013-01) (34.73 g), and to the reaction mixture was added 2-cyanoacetamide (23.91 g) and 1.76 mol/L piperidinium acetate (119.4 mL), and the reaction mixture was stirred under reflux in an oil bath at 127 °C. After 21 h, to the reaction mixture was added gradually dropwise acetic acid (42.7 mL) at 65 °C as internal temperature for 15 min. After the stirring was continued until internal temperature became to 24 °C, the resulting crystal was filtered, and washed with water to give 3-cyano-5, 6-dimethyl-2-pyridone (1-013-02) (27.76 g, 65.9percent, m.p. 258-263 °C).1H NMR (300 MHz, DMSO): δ 1.98 (s, 3H), 2.23 (s, 3H), 7.95 (s, 1H), 12.45 (br s, 1H).Water was added to 2-methyl-3-oxobutanal sodium salt (1-013-01) (34.73 g), and to the reaction mixture was added 2-cyanoacetamide (23.91 g) and 1.76 mol/L piperidinium acetate (119.4 mL), and the reaction mixture was stirred under reflux in an oil bath at 127 DEG C. After 21 h, to the reaction mixture was added gradually dropwise acetic acid (42.7 mL) at 65 DEG C as internal temperature for 15 min. After the stirring was continued until internal temperature became to 24 DEG C, the resulting crystal was filtered, and washed with water to give 3-cyano-5, 6-dimethyl-2-pyridone (1-013-02) (27.76 g, 65.9percent, m.p. 258-263 DEG C).<1>H NMR (300 MHz, DMSO): delta 1.98 (s, 3H), 2.23 (s, 3H), 7.95 (s, 1H), 12.45 (br s, 1H).Step (ii): Synthesis of 2-oxo-l, 2, dihydro-5, 6-dimethyl pyridine-3-carbonitrile; Cyano acetamide (3.78 g, 0.237 mol) was added to a solution of the sodium salt of 3-formyl-2-butanone (5.00 g, 40.9 mmol) in water (100 niL), and this reaction was allowed to stir at room temperature for 1 h. Afterwards, a 2 M solution of piperidine acetate in water (10 mL) was added, and the reaction mixture was allowed to reflux for 24 h. This mixture was allowed to cool and was acidified with acetic acid. The suspension was filtered and the precipitate was washed with toluene. The filtrate was collected and was concentrated to afford a sticky residue, which was washed with diethyl ether followed by ethyl acetate, to afford the title compound (2.00 g), yield: 33 percent, as a light brown solid. Mp: 103

An intermediate in the preparation of HIV-1 specific reverse transcriptase inhibitors, antiallergic agents, and Omeprazole metabolites.

Molecular Weight:148.16
XLogP3:-0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:148.063662883
Monoisotopic Mass:148.063662883
Topological Polar Surface Area:52.9
Heavy Atom Count:11
Complexity:314
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes