公开(公告)号：EP0001133A1

公开(公告)日：1979-03-21

申请号：EP78200140.8

申请日：1978-08-11

申请人： GIST-BROCADES N.V.

发明人： Henniger, Peter Wolfgang ,  Van Der Drift, Johannes Karel ,  Van Veen, Gerard Joannes

IPC分类号： C07D499/12 ,  C07D499/68

CPC分类号： C07D499/00

摘要： Process for the preparation of / D-a-amino-p- hydrox- yphenylacetamido/ groups containing penicillanic acid and cephalosporanic acid derivatives, comprising the acylation of a compounds of the formulae:
and/or
or
and/or
wherein R 1 , R 2 , and R 3 represent the same or a different group and may be selected from a lower alkyl, benzyl, cycloalkyl or phenyl-group and preferably lower alkyl and more preferably a methyl group and wherein X represents a residue selected from the group consisting of hydrogen, acetoxy or a fivemembered heterocyclic thio residue, containing heteroatoms selected from nitrogen, oxygen and/or sulphur and optionally substituted by lower alkyl and wherein an eventually present -NH- radical has optionally been silylated, which compound is previously prepared by the reaction of -6-aminopenicillanic acid or 7-aminocephalosporanic acid or its 3-methyl modifications with at least one equivalent and preferably about 2 with respect to 6-APA, 7-ACA or 7-ADCA and about 3 equivalents with respect to other 3-methyl modifications of 7-ACA of a tri(lower)alkyl silyl groups supplying agent in a dry inert, water insoluble solvent, such as methylene chloride, by rapid mixing of a pre-cooled solution of the compound of formula I-IV with a pre-cooled reaction mixture of at least an equimolar amount of a compound of the formula
wherein R 4 represents lower alkyl and preferably methyl, R 5 represents hydrogen or lower alkyl and preferably methyl, R 6 represents lower alkoxy and preferably methoxy and R 7 represents lower alkoxy and preferably methoxy, previously prepared from the corresponding Dane salt and an acid chloride under anhydrous conditions in the presence of a tertiary amine as catalyst, such as N-methylmorpholine in a dry, inert, water insoluble, organo solvent such as methylene chloride mixed with a cosolvent or methyl isobutylketone or tetrahydrofuran optionally mixed with a cosolvent, and the continuation of the reactior at a temperature of -10°C or lower and preferably from 2°C to 30°C whereafter the desired compound is recovered by usual methods.

摘要翻译： 制备/ D-氨基 - 对 - 羟基苯基乙酰氨基/含有青霉烷酸和头孢菌酸衍生物的基团的方法，包括下式化合物的酰化：其中R 1，R 2和R 3表示相同或不同的 并且可以选自低级烷基，苄基，环烷基或苯基，优选选自低级烷基，更优选甲基，其中X表示选自氢，乙酰氧基或五元杂环硫代残基的残基，其含有 选自氮，氧和/或硫并且任选被低级烷基取代的杂原子，并且其中最终存在的-NH-基团任选被甲硅烷基化，该化合物预先通过6-氨基青霉烷酸或7-氨基头孢烷酸或其 相对于6-APA，7-ACA或7-ADCA具有至少一个当量，优选约2个的3-甲基修饰和约3当量， 对于三（低级）烷基甲硅烷基供体试剂在干惰性，不溶于水的溶剂如二氯甲烷中的7-ACA的其它3-甲基修饰，通过快速混合式 I-IV与至少等摩尔量的式CHEM化合物的预冷反应混合物，其中R 4表示低级烷基，优选甲基，R 5表示氢或低级烷基，优选甲基，R 6表示低级烷氧基，优选 甲氧基，R7表示低级烷氧基，优选甲氧基，预先由相应的丹烷盐和酰氯在无水条件下，在作为催化剂的叔胺如N-甲基吗啉存在下，在干燥，惰性，不溶于水的有机溶剂 例如与助溶剂混合的二氯甲烷或与共溶剂任选混合的甲基异丁基酮或四氢呋喃，并在-10℃或更低的温度下继续反应 优选为20℃〜30℃，通过常规方法回收所需化合物。

公开(公告)号：EP0001149A1

公开(公告)日：1979-03-21

申请号：EP78200174.7

申请日：1978-09-06

申请人： GIST-BROCADES N.V.

发明人： Bruynes, Cornelis Adrianus ,  De Koning, Jan Jacobus

IPC分类号： C07D501/24 ,  C07D501/00

CPC分类号： C07D501/04 ,  Y02P20/582

摘要： Improved process for the preparation of brominated cephalosporanic derivatives, wherein a desacetoxy-3-cephem sulphoxide of general formula
wherein R 1 represents an acylamido group and R 3 represents a group protecting the carboxy radical, is brominated in manner known per se and a compound of general formula
in the reaction mixture or separated from such a reaction mixture is debrominated in the presence of a hydrogen donor and the 3-bromomethyl-3- cephem derivative of the general formula
thus produced is recovered.

摘要翻译： 制备溴代头孢菌素衍生物的改进方法，其中通式为...的其中R 1表示酰基酰胺基，R 2表示保护羧基的基团的脱乙酸基-3-头孢烯亚砜以本身已知的方式进行溴化， 将反应混合物中的通式为...的化合物或与该反应混合物分离的化合物在氢供体和通式为...的3-溴甲基-3-头孢烯衍生物的存在下脱溴...因此 产生回收。

公开(公告)号：EP0001133B1

公开(公告)日：1982-01-20

申请号：EP78200140.8

申请日：1978-08-11

申请人： GIST-BROCADES N.V.

发明人： Henniger, Peter Wolfgang ,  Van Der Drift, Johannes Karel ,  Van Veen, Gerard Joannes

IPC分类号： C07D499/12 ,  C07D499/68

CPC分类号： C07D499/00

公开(公告)号：EP0001149B1

公开(公告)日：1981-06-03

申请号：EP78200174.7

申请日：1978-09-06

申请人： GIST-BROCADES N.V.

发明人： Bruynes, Cornelis Adrianus ,  De Koning, Jan Jacobus

IPC分类号： C07D501/24 ,  C07D501/00

CPC分类号： C07D501/04 ,  Y02P20/582