N-HYDROXY-PYRIDINE-2-CARBOXAMIDINE synthesis

Yield:1217430-03-9 72%

Reaction Conditions:

in xylene; for 3 h;Heating / reflux;

Steps:

B.73.1

The title compound was prepared by a modification of a reported method: a) Mylari, B. L. ; Beyer, T. A.; Scott, P. J.; Aldinger, C. E.; Dee, M. F.; Siegel, T. W.; Zembrowski, W. J. J. Med. Chem. 1992,35, 457, and b) Palazzo, G.; Tavella, M.; Strani, G.; SILVESTRINI, B.; J. Med. Pharm. Chem. 1961,4, 351. To a suspension of N'-hydroxypyridine-2-carboximidamide (25.0 g, 0.182 mol) in chloroform (350 mL) was added CHLOROACETYL chloride (20.5 g, 0.182 mol, 1 equiv) and triethylamine (20.23 g, 0.2 mol, 1.1 equiv). When most of the triethylamine had been added, the suspension turned to a clear light-yellow solution. The solution was allowed to stand at room temperature for 1 d. The mixture was extracted with water (3 x 75 mL), resulting in the precipitation of a crystalline solid. The resulting slurry was filtered, and filter cake triturated with ethanol, re-filtered, and dried, affording 29.62 g (73%) of the 0-chloracetyl amidoxime intermediate. This intermediate was refluxed in xylenes (300 mL) for 3 h, and the volatiles removed completely IN VACUO, affording 25.55 g (72% overall) of the pure 1,2, 4-OXADIAZOLE. H NMR (DMSO-d6) 0 5.20 (s, 2H), 7.62 (m, 1H), 8.06 (m, 2H), 8.76 (m, 1H). LC-MS (APCI) calcd FOR C8H6CIN30 : 195.02 ; found (M+H+) : 196.0 m/z.

References:

WO2004/74270,2004,A2 Location in patent:Page 324