Neuroprotective Agent Hydrochloric Acid Repinotan Synthesis

Acute ischemic stroke (AIS) and traumatic brain injury (TBI) are major public health and human life problem. Neuroprotectants play an important role in the treatment of AIS and TBI.5-HT_1A receptor agonists have been reported to exert neuroprotective proterties. Repinotan is a highly potent and selective 5-HT_1A receptor full agonist developed by Bayer Corporation in USA. It is a putative neuroprotective compound in acute ischaemic stroke and traumatic brain injury.Two synthetic routes about the preparation of repinotan were reported. Based on these routes, through theoretically analyzing and practically trying, the target compound was synthesized over 11 steps (and 1 sideway step) operation. Its structure was characterized by the spectra of EI-MS, ¹H-NMR and ¹³C-NMR.N-(4-bromobutyl) saccharine was prepared by sodium saccharine dihydrate reaction with 1,4-dibromobutane. Its melting point and EI-MS spectrum were corrected in this thesis.In order to avoid using expensive LiAlH₄ and deprotecting under high pressures, new routes are designed to prepare the (R)-chroman-2-methanamine. The duration of alkylation of (R)-chroman-2-methanamine with the N-(4-bromobutyl) saccharine was reduced by using K₂CO₃ instead of triethylamine reported by the literature.The EI-MS spectrum of repintan was interpreted, which splitting rule is confirmed by a repinotan's analogue.