[EN] NOVEL PROCESS FOR THE PREPARATION OF IMIDAZOLYL COMPOUNDS<br/>[FR] PROCEDE DE PREPARATION DE COMPOSES IMIDAZOLYLE
申请人:SOLVAY PHARM BV
公开号:WO2004046116A1
公开(公告)日:2004-06-03
The present invention relates to a method for the preparation of an imidazolyl compound of the general formula (I), wherein: Ra and Rb each separately are (C1-C6)alkyl, (C1-C6)alkoxyalkyl, optionally substituted aryl or heteroaryl; or wherein Ra and Rb together form a further homocyclic or heterocyclic system comprising one or more rings; Ra’ and Rb’ each are hydrogen or together form a carbon-carbon double bond, said carbon-carbon double bond optionally being part of an aromatic system; Rc is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1,-C6)alkoxyalkyl or halogen; Rd is hydrogen or (C1-C4)aIkyl; Re is hydrogen or (C1-C4)aIkyl; m is 1 or 2; and R1, is hydrogen or (C1-C4)aIkyl; as well as its acid addition salt;characterized in that a compound of the general formula (II) is reacted with a compound of the formula (III), wherein: R is a hydrogen, a (C1-C4)alkyl group optionally substituted with a hydroxygroup or an optionally substituted aryl group, R', R', R'' and R'' each individually are a hydrogen or a (C1-C4)aIkyl group; followed by a reaction with a compound of the formula (IV), wherein R1, Rd and Re have the meanings defined above; and optionally followed by a reaction with a suitable acid. De method according to the present invention is especially useful for the preparation of ondansetron and cilansetron.
本发明涉及一种制备通式(I)的咪唑基化合物的方法,其中:Ra和Rb各自分别为(C1-C6)烷基,(C1-C6)烷氧基烷基,可选择取代的芳基或杂环芳基;或者Ra和Rb一起形成进一步的同环或异环系统,包括一个或多个环;Ra'和Rb'各自为氢或一起形成碳-碳双键,所述碳-碳双键可选择地是芳香系统的一部分;Rc为氢,(C1-C6)烷基,(C1-C6)烷氧基,(C1-C6)烷氧基烷基或卤素;Rd为氢或(C1-C4)烷基;Re为氢或(C1-C4)烷基;m为1或2;R1为氢或(C1-C4)烷基;以及其酸盐;其特征在于通式(II)的化合物与通式(III)的化合物发生反应,其中:R为氢,(C1-C4)烷基,可选择地取代羟基或可选择取代的芳基的基团,R'、R''、R'''和R''''各自为氢或(C1-C4)烷基;随后与通式(IV)的化合物发生反应,其中R1、Rd和Re具有上述定义的含义;并可随后与适当的酸发生反应。根据本发明的方法特别适用于制备昂丹司特龙和西兰司特龙。