Organic Communications

Year: 2017  Volume: 10   Issue: 2



An optimized and very detailed, grams scale synthesis of CTEP, through a complete characterization of all the isolated and purified intermediates

Silvana Alfei and Irum Baig

Dipartimento di Farmacia (DIFAR), Università di Genova, Viale Cembrano, 4 16147, Genova, Italia

Abstract: Glutamate is the major excitatory neurotransmitter in the brain. 2-Chloro-4-[2,5-dimethyl-1-(4-trifluoromethoxyphenyl)-1H-imidazol-4-ylethynyl]pyridine (5) (CTEP) is the first reported negative allosteric modulator of the metabotropic glutamate receptor 5 (mGlu5NAM) with a biological half-life of 48 hours in rodents and therefore considered an ideal tool for chronic studies in rats and mice. In this work an optimized protocol for the synthesis and purification of CTEP is reported. Through the developed new work up scrupulously described in detail, CTEP was obtained in 63 % yield, with a significant improvement in comparison with the methods reported in literature (27%) and in a tripled overall yield (27% versus 9%). Furthermore, all the intermediates between which the unreported multifunctional and appealing compound 8 as well as the final compound 5 were isolated, purified and fully characterized by IR, NMR ( 1H NMR and 13C NMR), melting point, except for the oily 7, and Elemental analysis.

 Keywords: Acetylene-type mGlu5 NAMs; optimization; isolation; purification; NMR; characterization; conformational investigation. © 2017 ACG Publications. All rights reserved.