申请人:——
公开号:US20030055269A1
公开(公告)日:2003-03-20
The present invention provides a process for producing an intermediate for thienopyrimidine derivatives having the GnRH antagonistic activity at an industrial large scale.
The process for production of the present invention relates to a process for producing a compound represented by the formula (III):
1
wherein respective symbols have the same meanings as those described below, or a salt thereof, which comprises subjecting a compound represented by the formula (I):
2
wherein R
1
denotes hydrogen, nitro, halogen, phthalimido, mono- or di-(alkylcarbonyl)amino or alkoxy, or a salt thereof, to an acid halogenating reaction, which is successively reacted with malonic acid ester and magnesium alkoxide, treated with an acid, and reacted with sulfur and a compound represented by the formula: NCCH
2
COOR
2
[wherein R
2
denotes alkyl or aryl], or a salt thereof, in the presence of primary amine. According to the process of production of the present invention, thienopyrimidine derivatives having the GnRH antagonistic activity can be produced effectively and at an industrial large scale by a high yield and simple method.
本发明提供了一种在工业大规模下生产具有GnRH拮抗活性的噻唑嘧啶衍生物中间体的方法。本发明的生产方法涉及生产以下化合物的方法(III):其中各符号具有以下所述的相同含义,或其盐,包括将化合物(I):其中R1表示氢,硝基,卤素,邻苯二甲酰亚胺,单个或二个(烷基羰基)氨基或烷氧基,或其盐,经过酸卤化反应,随后与丙二酸酯和镁烷氧化物反应,用酸处理,然后与硫和化合物(II):NCCH2COOR2(其中R2表示烷基或芳基),或其盐,在原始胺的存在下反应。根据本发明的生产方法,通过高产率和简单的方法,可以有效地在工业大规模下生产具有GnRH拮抗活性的噻唑嘧啶衍生物。