Potential GABAB Receptor Antagonists. VII. The Synthesis of 2-(4-Chlorophenyl)-3-nitropropan-1-amine and Related Analogs of Baclofen

Abstract

3-Nitro-2-phenylpropan-1-amine and 2-(4-chloropenyl)-3-nitropropan-1-amine have been synthesized by the addition of nitrous acid to the corresponding trifluoroacetylaminomethylstyrenes followed by reduction of the double bond with sodium borohydride. A more general and efficient route involves the Michael addition of nitroalkane anions to methyl cinnamates followed by Curtius degradation of the corresponding acids. 2-(4-Chlorophenyl)-3-nitropropan-1-amine is a specific agonist of GABA and the GABAB receptor, with about half the activity of racemic baclofen at the isolated guinea pig ileum. Methylation or dimethylation at C3 decreases activity markedly.