反应详情

Scheme IX shows the presently preferred method of synthesis for compounds of Formula I where A-B is --CH=N--. 2-chloro-3-nitropyridine is suspended in methanol and reacted with 2 molar equivalents of sodium methoxide at reflux temperature to provide 2-methoxy-3-nitropyridine 38, which is precipitated by diluting the reaction mixture with about 4 volumes of water (with respect to the reaction mixture volume) to provide compound 38 as a white solid. Compound 38 is then dissolved in ethanol and hydrogenated over palladium on carbon to provide compound 39, which is concentrated from the reaction solution and reacted with arylaldehyde 46 in benzene at reflux for about 3 to 5 hours or more in the presence of a molecular seive having a pore size preferably about 4 Angstroms in diameter. (The synthesis of arylaldehyde 46 is described hereafter with reference to Scheme X.) The reaction mixture is then cooled to room temperature and stirred for about 12 to about 24 hours and then filtered and dried under vacuum. The crude dried product is dissolved in ethanol and treated with sodium borohydride for between about 18 and about 36 hours, cooled to room temperature and quenched with water. The aqueous solution of compound 40 is then extracted with methylene chloride, filtered and concentrated. Compound 40 is then treated with hydrochloric acid in dioxane to provide 41. Compound 41 is suspended in THF/ether (1/3) and chloroacetyl chloride is added and the resulting mixture is stirred at room temperature to provide compound 42. Treatment of compound 42 in THF with sodium hydride provides 43 which is a compound of Formula I, wherein A-B is --CH=N--. ##STR15## Scheme X depicts the synthesis of arylaldehydes (ArCHO) 46, which are useful reactants in the method depicted in Scheme IX. Halomethylbenzamides may be prepared as described herein with reference to any of Schemes III through V. By way of example, haloalkylbenzamide 44 in DMF is treated with sodium acetate at 80° C.-85° C. for about 4-8 hours and cooled to room temperature and stirred overnight. The reaction mixture is then treated with saturated aqueous potassium carbonate and stirred at room temperature for one to two days or more to provide the 4-hydroxymethyl compound 45. A solution of compound 45 in methylene chloride is then added to a suspension of pyridinium chlorochromate in methylene chloride and the reaction is carried out with stirring for about 2-3 hours to provide arylaldhyde 46.

1. customthe presently preferred method of synthesis for compounds of Formula I where A-B
2. temperatureat reflux temperature