An efficient eight step synthesis of 2-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine (I) starting from glyoxalic acid was developed. A process involving condensation of glyoxalic acid with N,N-dimethylamine followed by reductive amination and BOC protection of the 2-(2-dimethylamino)ethylamino)acetic acid provided intermediate 2-(tert-butoxycarbonyl-(2-(dimethylamino)ethyl)amino)acetic acid. Activation of the latter using carbonyl diimidazole followed by treatment with methoxymethylamine led to the formation of tert-butyl-2-(dimethylamino)ethyl-(2-methoxy(methyl)amino)-2-oxoethyl)carbamate which upon reaction with in-situ generated (4-fluoro-3-(trifluoromethyl)phenyl) magnesium bromide followed by BOC de-protection provided N-(2-(4-(2-fluoro-3-(trifluoromethyl)phenyl)-2-oxoethyl)-N,N-dimethylethane-1,2-diamine dihydrochloride. The coupling of the amine with activated 1-(tert-butoxycarbonyl)-piperidine-4-carboxylic acid provided tert-butyl-4-((2-dimethylamino)ethyl)-(2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(oxoethyl)carbamoyl)piperidine-1-carboxylate. Treatment of the latter with NH4OAc in ethanol led to the formation of tert-butyl-4-(1-(2-dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)-piperidine-1-carboxylate which upon in-situ BOC de-protection followed by neutralization provided the title compound. This poster entails the work completed toward the development of the title compound.

Efficient synthesis of 2-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1<i>H</i>-imidazol-1-yl)-N,N-dimethylethanamine

244th National Meeting (2012)

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Efficient synthesis of 2-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine