2-(Acetylamino)isonicotinic acid

b) 2-Acetamidopyridine-4-carboxylic acid (3); 214.0 g of (2) are introduced in portions with stirring into an aqueous solution of 160 g of potassium permanganate at 50214.0 g of (2) are introduced in portions with stirring into an aqueous solution of 160 g of potassium permanganate at 50°C. A further 360 g of potassium permanganate are added in portions over the course of one hour. The temperature of the reaction mixture should not exceed 90°C during this. The mixture is then stirred for 1.5 h and filtered hot, and the filtrate is adjusted to pH 3-4 with conc. HCl. The white precipitate of (3) which separates out is filtered off and dried in vacuum over P(A) (B) N4-[4-(tert-Butyl)-1, 3-thiazol-2-yl]-2-(acetylamino)isonicotinamide 2-(Acetylamino)isonicotinic acid (500 mg, 2.8 mmol) was added dropwise with thionyl chloride (15 ml, 68.5 mmol) at room temperature, warmed to 80° C. and stirred for 30 minutes. The reaction solution was returned to room temperature, concentrated under reduced pressure, and the residue was subjected to azeotropy with toluene to evaporate excessive thionyl chloride. The resulting yellow crystals was added to a mixed solution of pyridine (0.25 ml), dichloromethane (5 ml) and 4-(tert-butyl)-1, 3-thiazol-2-amine (525 mg, 3.35 mmol) under ice cooling. The mixture was stirred at 0° C. for 30 minutes, then warmed to room temperature, and further stirred for 2 hours and 30 minutes. The reaction solution was added with water and extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform-->chloroform:methanol=80:1-->50:1) to obtain 545.8 mg (61percent) of the title compound. 1H-NMR (CDCl3) delta: 1.31 (9H, s), 2.26 (3H, s), 6.61 (1H, s), 7.63 (1H, dd, J=0.49, 5.14 Hz), 8.44 (1H, d, J=5.14 Hz), 8.51 (1H, brd), 8.72 (1H, s) EI/MS; m/z: 319 (M++1)2-Amino-isonicotinic Acid Methyl Ester (2-3) 2-Acetylamino-isonicotinic acid (3.10 g, 17.2 mmol) was stirred in 35 mL MeOH at 0° C. HCl (g) was bubbled through the solution for 10 minutes and then the reaction was heated to reflux. After 16 hours the reaction was concentrated in vacuo. The residue was diluted with water and the pH was adjusted to 7 with Na2CO3 (s). A white precipitate formed which was filtered to afford a portion of pure desired product. The aqueous phase was extracted three times with 95:5 dichloromethane (DCM)/nBuOH. The organic phases were dried over Na2SO4, filtered and concentrated to afford more of the pure product as a white solid. 1H NMR (CDCl3) delta 8.19 (d, 1H, J=5.3 Hz), 7.17 (dd, 1H, J=1.4, 5.3 Hz), 7.07 (d, 1H, J=1.3 Hz), 4.64 (bs, 2H), 3.92 (s, 3H). MS [M+H]+=153.0.2-Amino-isonicotinic acid methyl ester (8-3) 2-Acetylamino-isonicotinic acid (3.10 g, 17.2 mmol) was stirred in 35 mL MeOH at 0° C. HCl (g) was bubbled through the solution for 10 min and then the reaction was heated to reflux. After 16 h the reaction was concentrated in vacuo. The residue was diluted with water and the pH was adjusted to 7 with Na2CO3 (s). A white precipitate formed which was filtered to afford a portion of pure desired product. The aqueous phase was extracted three time with 95:5 DCM/nBuOH. The organic phases were dried over Na2SO4, filtered and concentrated to afford more of the pure desired product as a white solid. 1H NMR (CDCl3) delta 8.19 (d, 1H, J=5.3 Hz), 7.17 (dd, 1H, J=1.4, 5.3 Hz), 7.07 (d, 1H, J=1.3 Hz), 4.64 (bs, 2H), 3.92 (s, 3H). MS [M+H]+=153.0.

Molecular Weight:180.16
XLogP3:-0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:180.05349212
Monoisotopic Mass:180.05349212
Topological Polar Surface Area:79.3
Heavy Atom Count:13
Complexity:217
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes