R. N. Shakhmaev, A. Sunagatullina, V. Zorin
Sep 28, 2016
Citations
0
Influential Citations
10
Citations
Journal
Russian Journal of General Chemistry
Abstract
Flunarizine {Sibelium, 1-[bis(4-fluorophenyl)methyl]4-[(2E)-3-phenylprop-2-en-1-yl]piperazine} is a wellknown drug belonging to calcium channel blockers. It exhibits vasodilating effect, improves cerebral blood circulation, and shows antihistamine activity. Flunarizine is used to treat migraines, dizziness, vestibular disorders, and epilepsy [1–4]. Industrial production of flunarizine is based on condensation of N-cynnamylpiperazine with bis(4-fluorophenyl)chloromethane or of cynnamyl chloride with 1-[bis(4-fluorophenyl)methyl]piperazine [5, 6]. Flunarizine can be obtained by regioselective metal-catalyzed amination of cinnamyl alcohol with 1-[bis(4-fluorophenyl)methyl]piperazine using Pt(cod)2Cl2–DPEPhos [7] and Pd(OAc)2–1,10phenanthroline catalysts [8]. (E)and (Z)-isomers of 1[bis(4-fluorophenyl)methyl]-4-(3-phenylprop-2-en-1yl)piperazine (E : Z = 1 : 7.4) have been also prepared via Wittig reaction involving {4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}acetaldehyde and benzyltriphenylphosphonium chloride, followed by isomers separation by column chromatography [9].