Search

The preparation of pyrimidine analogs of the 2,6-di-tert-butylphenol antiinflammatory agents Prifelone (R-830), Tebufelone (NE-11740) and Ym-13,162 is described. Grignard addition to the N-methoxy-N-methylamide derived from 4,6-bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinecarboxylic acid yielded a series of 2-pyrimidinyl ketones. Further elaboration of an ethyl ketone and cyclization with sodium cyanate gave a pyrimidinylimidazole.

The preparation of 1,2,4-thiadiazoles with a di-tert-butylphenol substituent at the thiadiazole 3-position is described. A thermally generated nitrile sulfide was reacted with tosyl cyanide in a 1,3-dipolar cyclization reaction to provide a thiadiazole intermediate containing a labile 5-tosyl substituent.

The preparation of 1,2,4-thiadiazoles with a di-tert-butylphenol substituent at the thiadiazole 3-position is described. A thermally generated nitrile sulfide was reacted with tosyl cyanide in a 1,3-dipolar cyclization reaction to provide a thiadiazole intermediate containing a labile 5-tosyl substituent.