Synthesis Of The Ethyl [1-(Pyridine-2-Yl) Ethoxy] Acetic Acid And Its Derivatives And The Effects On Learning And Memory In Mice

Learning and memory are one of the most important fuctions of brain.With the growing proportion of older people in our population all over the world,the holdback of human memory facilitation has been the most serious problem in the field of medicine.The development of the medicine promoting learning and memory are worldwidely concerned.Mingzhu Li.etc.discovered that ethyl 2-(benzyloxy) aryl actecate has strong learning and memory facilitation in mice.In order to find out the best medicine of promoting learning and memory,we synthesized(1-Pyridin-2-yl-ethoxy)-acetic acid and its derivatives on the base of a mass of literature search.This paper we select 2-(dimethylamine) ethyl-2-(1-(pyridine -2-yl)ethoxy) acetate hydrochloride(5) which was used to do phamarcological experiment by swimming maze test.And the results showed that the compound 5 could obviously improve learning and memory in mice which were given 400 mL/L alcohol(p＜0.001).With the dosage growing,the effect of improving learning and memory in mice became more better.The phamarcological experimental results show that 2-(dimethyl amino)ethyl 2-(1-(pyridin-2-yl)ethoxy)acetate hydrochloride has strong learning and memory facilitation in mice,and start a new field of the medicine of improving learning and memory facilitation and got a breakthrough for finding out more better medicine.2-(1-bromoethyl) pynidine(2) was obtained by 2-ethylpyridine through Whol-Ziegl er reaction.The compound 2 and sodium 2-ethoxy-2-oxo-ethanolate responded to ethyl[2-(1-(pyridine-2-yl)ethoxy)]acetate(3).The compound 3 was esterified to meth yl[2-(1-(pyridine-2-yl)ethoxy)]acetate(4).The compound 3 and 2-(dimethylamino) ethanol reacted,and then gave the gas of dry HCl in dry ethoxyethane to get 2-(dimethylamine) ethyl-2-(1-(pyridine-2-yl)ethoxy) acetate hydrochloride(5).The same way to get 2-(diethylamine)ethyl2-(1-(pyridine-2-yl)ethoxy)acetate hydrochlo ride(6).2-(1-(pyridine-2-yl)ethoxy)aceticacid(7)was obtained by the hydrolyzation of compound 3 under the alkaline condition.The compound 8 was got by the reaction of the compound 7 and sulfuryl dichloride.2-[1-(pyridine-2-yl)ethoxy]acetamindes(9) ～(14)were obtained by the ammonolysis of the compound 8.The compound 3 and ta mide responded to 2-(1-(pyridine-2-yl)ethoxy)acetamide(15).The compound 3 and hydrazide responded to 2-(1-(pyridine-2-yl)ethoxy) acetohydrazide(16).The compou -nd 3 and ethyl formate responded to ethyl(2-(1-(pyridine-2-yl)ethoxy)-3-hydroxya cr ylate(17) through Claisen reaction.The compound 17 and hydrazide responded to 4-((1-(pyridine-2yl)ethoxy)methyl)-1H-pyrazol-5(4H)-one(18).The structures of the sixteen new compounds(3～18) were confirmed by IR,1HNMR spectrum.