Studies On The Synthesis Of Antipsychotic Drug 3-(1-[3-{(4-pyrimidin-2-yl) Piperazin-1-yl}] Propyl) Amino-2H-1, 4-benzoxazine And Anticoccidial Nicarb

The first part Antipsychotic drugs are used to treat schizophrenia and other mental blockade. Conventional antipsychotic drugs have, after a long-time taking, extrapyramindal side effects, bad treatment compliance, and also the increasing danger of relapse, even the permanent disability. The second-generation antipsychotic drugs, superior to the conventional ones, are mainly used to treat cognitive deficits, to control masculine symptom, to improve attention blockade and to better neuropsychological function. However, the tendency of blockading dopamine of limbic brain system may bring adverse effects to cognitive function.As a new antipsychotic drug, 3-(1-[3-{(4-pyrimidin-2-yl) piperazin-l-yl}]propyl)amino-2H-l,4-benzoxazine has high affinity and selectivity in binding the D4 receptor. It is therefore useful in the treatment of a variety of neuropsychological or affective disorders, dopaminergic blockade disorders and extrapyramindal side effects caused by the use of conventional neuroleptic agents.We synthesized the target compound by six steps based on the patent and made great improvements in the key steps and got the satisfied results. In the second step, the hydrolysis with acid or base was used instead of the hydrazinolysis. Thus, we avoided using toxic hydrazine hydrate and Kugelrohr apparatus and at the same time improved the yields in the best hydrolysis conditions. In the fifth and sixth steps, the target compound was obtained by changing the reaction temperature and adding a little of base as catalyst. By doing so, we made the yield improved dramatically.The second part Anticoccidials, mainly used to control animal diseases caused by coccidis, are extensively applied to the current animal feed as an additive. However, under the circumstances of high-density and large-mass produce, adding anticoccidials to animal feed as feed additive to prevent livestock coccidiosis is an efficient and worldwide method.Nicarb has high or mediate activity to almost all chicken Eimeria. It is mainly used to control the second-generation schizont of coccidis with the activity peak to coccidis on the forth day. In other words, it has the strongest activity to the second-generation schizont. The results of tissue culture show that Nicarb has inhabitation function to the first-generation schizont. Such a product also has the function of inhabitation and kill. That is to say, it has the function of prevention and treatment. Even if it is used at 48h or 72h after infection, nicarb can also efficiently inhabitate coccidis. It has been efficient since it came out in 1955.The previous synthesis of Nicarb in industry usually included four steps, this paper mainly made improvement in the first and second steps. We adopted cheap triphosgene as material instead of high-cost dibutyl phthalate. As a result, we could shorten the synthesis routes, improve the yield and easily transform from preparation to manufacture.