3-Amino-2(1H)-pyridinone

Brown to off-white crystalline powder.

a) 3-Aminopyridin-2-ol; To a 500 mL round bottom flask charged with 2-hydroxy-3-nitro pyridine (2 g, 14.2 mmol) was added 2:1 EtOH:MeOH (120 mL). The mixture was stirred for 10 minutes while flushing with NA yellow solution of the 5-ethyl-6-methyl-3-nitro-2-(1H)-pyidinone (10 g, 55 mmol) in a mixture of methanol and tetrahydrofuran (100 mL, 1:1 v/v) was reduced catalytically in the presence of 7% palladium on charcoal (0.7 g) under an atmosphere of hydrogen (50 psi) at room temperature over a period of 3.5 hours. The resultant mixture was filtered through a small pad of Celite. The filtrate was concentrated under reduced pressure (15 torr) to provide 5.7 g (68%) of the corresponding aminopyridone.A yellow solution of the 5-ethyl-6-methyl-3-nitro-2-(1H)-pyidinone (10 g, 55 mmol) in a mixture of methanol and tetrahydrofuran (100 mL, 1:1 v/v) was reduced catalytically in the presence of 7% palladium on charcoal (0.7 g) under an atmosphere of hydrogen (50 psi) at room temperature over a period of 3.5 hours. The resultant mixture was filtered through a small pad of Celite. The filtrate was concentrated under reduced pressure (15 torr) to provide 5.7 g (68%) of the corresponding aminopyridone.Example 24 EX-24A) 3-Nitro-2-hydroxylpyridine (49.5 g, 0.35 mol) and 10% Pd/C (4.21 g, 4 mmol) in 500 ml ethanol was stirred under an atmosphere of hydrogen introduced via a balloon for 24 hours. After filtering through a pad of Celite 545 and removing the ethanol, a brown solid was obtained as the pure product, To a solution of 1(0.800 g, 6.22 mmol, 1.3 eq) and1.1 (0.527 g, 4.79 mmol, 1.0 eq) in 1, 4-dioxane (8 mE) was added potassium carbonate (1.71 g, 12.44 mmol, 2.0 eq) and degassed with argon for 15 mm. Copper iodide (0.177 g, 0.933 mmol, 0.15 eq) and 1, 2-dimethylethylenediamine (0.164 g, 1.866 mmol, 0.3 eq) was added and reaction mixture again degassed with argon for 5 mm followed by heating at 1150 C. for 6 h. Afier completion of reaction, reaction mixture was cooled to room temperature, transferred into water and product was extracted with ethyl acetate. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by column chromatography and compound was eluted in 1.5% methanol in dichloromethane to obtain pure90b (0.460 g, 47.52%). MS(ES): m/z 203.22 [M+H].To a solution of 41(3.0 g, 17.44 mmol, 1 eq) in1, 4-dioxane (150 mE), 41.1 (2.30 g, 20.92 mmol, 1.2 eq) was added. The reaction mixture was degassed for 10 mm under argon atmosphere followed by addition of potassium carbonate (6.0 g, 43.6 mmol, 2.5 eq), N, N-dimethylethylenediamine (0.384 g, 4.36 mmol, 0.25 eq), and copper iodide (0.497 g, 2.61 mmol, 0.15 eq). The reaction mixture was heated at 115 C. for 12 h. Afier completion of reaction, reaction mixture was transferred to ice cold water and product was extracted with ethylacetate. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by 5% methanol in dichloromethane to obtain 41.2. (1.56 g, Yield: 44.45%). MS (ES): mlz 202.09 [M+H]To a solution of 38 (2 g, 18.18 mmol, 1.0 eq) in 1, 4-dioxane (40 mE), 38.1 (7.2 g, 45.45 mmol, 2.5 eq) was added. The reaction mixture was degassed for 10 mm under argon atmosphere followed by addition of potassium carbonate (7.5 g, 54.54 mmol, 3.0 eq), N, N-dimethylethylenediamine (0.640 g, 7.27 mmol, 0.4 eq), and copper iodide (0.692 g, 3.636 mmol, 0.2 eq). The reaction mixture was heated at 1100 C. for 12 h. After completion of reaction, reaction mixture was transferred to ice cold water and product was extracted with ethyl acetate. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by 3% methanol indichioromethane to obtain 38.2 (2 g, Yield: 58.82%). MS(ES): mlz 188.20 [M+H]To a solution of 28 (1 g, 9.08 mmol, 1 eq) and 28.1 (1.94 g, 10.90 mmol, 1.2 eq) in 1, 4-dioxane (10 mE) was added potassium carbonate (2.50 g, 18.16 mmol, 2.0 eq) and degassed with argon for 15 mm. Copper iodide (0.345 g, 1.81 mmol, 0.2 eq) and 1, 2-dimethylethylenediamine (0.320 g, 3.63 mmol, 0.4 eq) was added and reaction mixture again degassed with argon for 5 mm followed by heating at 1100 C. for 16 h. After completion of reaction, reaction mixture was cooled to room temperature, transferred into water and product was extracted with ethyl acetate. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was further purified by column chromatography and compound was eluted in 1.2% methanol in dichloromethane to obtain pure 28.2 (0.400 g, 2 1.25%). MS(ES): mlz 208.25 [M+H].To a solution of 26.1 (3 g, 13.47 mmol, 1.2 eq) and26.2 (0.989 g, 11.22 mmol, 1.0 eq) in 1, 4-dioxane (30 mE) was added potassium carbonate (3.71 g, 26.94 mmol, 2.0 eq) and degassed with argon for 15 mm. Copper iodide (0.371 g, 2.69 mmol, 0.2 eq) and 1, 2-dimethylethylenediamine (0.474 g, 5.38 mmol, 0.4 eq) was added and reaction mixture again degassed with argon for 5 mm followed by heating at 110 C. for 16 h. After completion of reaction, reaction mixture was cooled to room temperature, transferred into water and product was extracted with ethyl acetate. Organic layer was combined, washed with brine solution, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. This was thrther purified by column chromatography and compound was eluted in 1.5% methanol in dichloromethane to obtain pure 26.3 (1.2 g, 41.24%). MS(ES): mlz 260.27 [M+H].

Molecular Weight:110.11
XLogP3:-0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:110.048012819
Monoisotopic Mass:110.048012819
Topological Polar Surface Area:55.1
Heavy Atom Count:8
Complexity:169
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes