公开(公告)号：US5164494A

公开(公告)日：1992-11-17

申请号：US327977

申请日：1989-03-23

申请人： Hendrik A. Witkamp ,  Jan J. DeKoning ,  Jan Verwej ,  Herman H. Grootveld ,  Everardus J. A. M. Leenderts

发明人： Hendrik A. Witkamp ,  Jan J. DeKoning ,  Jan Verwej ,  Herman H. Grootveld ,  Everardus J. A. M. Leenderts

IPC分类号： A61K31/545 ,  C07D20060101 ,  C07D499/00 ,  C07D501/00 ,  C07D501/04 ,  C07D501/16 ,  C07D501/18 ,  C07D501/46

CPC分类号： C07D501/04 ,  C07D499/00 ,  C07D501/18

摘要： Process for the preparation of 7.beta.-amino-3-substituted methyl-3-cephem-4-carboxylic acid derivatives, new intermediates comprising 7.beta.-(cyclo)alkylideneammonio-3-halomethyl-3-cephem-4-carboxylic acid derivatives and 7.beta.-amino/ammonio-3-bromomethyl-3-cephem-4-carboxylic acid derivatives and the processes for the preparation of these intermediates.

公开(公告)号：US4985554A

公开(公告)日：1991-01-15

申请号：US337525

申请日：1989-02-15

申请人： Jan Verweij ,  Jan J. De Koning ,  Hendrik A. Witkamp

发明人： Jan Verweij ,  Jan J. De Koning ,  Hendrik A. Witkamp

IPC分类号： A61K31/545 ,  C07D20060101 ,  C07D501/00 ,  C07D501/04 ,  C07D501/14 ,  C07D501/18 ,  C07D501/22 ,  C07D501/24 ,  C07D501/40 ,  C07F9/28 ,  C07F9/54 ,  C07F9/547 ,  C07F9/6547

CPC分类号： C07D501/04 ,  C07D501/14

摘要： A process is provided for the preparation of 3-methylene and 3-halomethylene cepham derivatives via 3-phosphoniomethyl-3-cephem derivatives, which in turn can be prepared from 3-halomethyl-3-cephem derivatives. The preparation can be carried out with or without isolating the intermediate phosphonium cephem compounds. The 3-methylene and 3-halomethylene cepham derivatives and in particular the 1-oxo and 1,1-dioxo cepham compounds are also prepared by reducing a 3-halomethyl-3-cephem derivative with activated metal, preferably zinc or magnesium.

公开(公告)号：US4921954A

公开(公告)日：1990-05-01

申请号：US216877

申请日：1988-07-08

申请人： Hendrik A. Witkamp ,  Jan Verweij ,  Jan J. DeKoning ,  Herman H. Grootveld ,  Everardus J. A. M. Leenderts

发明人： Hendrik A. Witkamp ,  Jan Verweij ,  Jan J. DeKoning ,  Herman H. Grootveld ,  Everardus J. A. M. Leenderts

IPC分类号： A61K31/545 ,  C07D20060101 ,  C07D499/00 ,  C07D501/00 ,  C07D501/04 ,  C07D501/16 ,  C07D501/18 ,  C07D501/46

CPC分类号： C07D501/04 ,  C07D499/00 ,  C07D501/18

摘要： Process for the preparation of 7.beta.-amino-3-substituted methyl-3-cephem-4-carboxylic acid derivatives, new intermediates comprising 7.beta.-(cyclo)alkylideneammonio-3-halomethyl-3-cephem-4-carboxylic acid derivatives and 7.beta.-amino/ammonio-3-bromomethyl-3-cephem-4-carboxylic acid derivatives and the processes for the preparation of these intermediates.

摘要翻译： 制备7β-氨基-3-取代的甲基-3-头孢烯-4-羧酸衍生物的方法，包含7β-（环）亚烷基氨基-3-卤代甲基-3-头孢烯-4-羧酸衍生物的新中间体和 7β-氨基/氨基-3-溴甲基-3-头孢烯-4-羧酸衍生物及其制备方法。

公开(公告)号：US4994454A

公开(公告)日：1991-02-19

申请号：US457253

申请日：1989-12-27

申请人： Jan Verweij ,  Jan J. DeKoning ,  Hendrik A. Witkamp

发明人： Jan Verweij ,  Jan J. DeKoning ,  Hendrik A. Witkamp

IPC分类号： A61K31/545 ,  C07D20060101 ,  C07D501/00 ,  C07D501/04 ,  C07D501/14 ,  C07D501/18 ,  C07D501/22 ,  C07D501/24 ,  C07D501/40 ,  C07F9/28 ,  C07F9/54 ,  C07F9/547 ,  C07F9/6547

CPC分类号： C07D501/04 ,  C07D501/14

摘要： A process is provided for the preparation of 3-methylene and 3-halomethylene cepham derivatives via 3-phosphoniomethyl-3-cephem derivatives, which in turn can be prepared from 3-halomethyl-3-cephem derivatives. The preparation can be carried out with or without isolating the intermediate phosphonium cephem compounds. The 3-methylene and 3-halomethylene cephem derivatives and in particular the 1-oxo and 1,1-dioxo cephem compounds are also prepared by reducing a 3-halomethyl-3-cephem derivative with activated metal, preferably zinc or magnesium.

公开(公告)号：US5359058A

公开(公告)日：1994-10-25

申请号：US874738

申请日：1992-04-27

申请人： Jan Verweij ,  Henri G. J. Hirs ,  Hendrik A. Witkamp ,  Everardus J. A. M. Leenderts ,  Jan J. Dekoning ,  Herman H. Grootveld

发明人： Jan Verweij ,  Henri G. J. Hirs ,  Hendrik A. Witkamp ,  Everardus J. A. M. Leenderts ,  Jan J. Dekoning ,  Herman H. Grootveld

IPC分类号： A61K31/545 ,  C07D20060101 ,  C07D499/00 ,  C07D501/00 ,  C07D501/04 ,  C07D501/16 ,  C07D501/18 ,  C07D501/46

CPC分类号： C07D501/04 ,  C07D499/00 ,  C07D501/18

摘要： A cephalosporin compound substituted in the 7-position with a (cyclo)alkylideneammonio group of formula (II) ##STR1## wherein X' is an anion from an acid HX, R.sub.1 and R.sub.2 are individually a C.sub.1 -C.sub.16 alkyl group, or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a cycloalkylidene ring with up to 8 carbon atoms and a process for the preparation which compounds are useful intermediates.

摘要翻译： 在7-位上用式（II）的（环）亚烷基氨基取代的头孢菌素化合物其中X'是酸HX的阴离子，R1和R2分别是C1-C16烷基， 或R 1和R 2与它们所连接的碳原子一起形成具有至多8个碳原子的亚环烷基环，以及这些化合物是有用的中间体的方法。

公开(公告)号：US5109132A

公开(公告)日：1992-04-28

申请号：US581518

申请日：1990-09-10

申请人： Jan Verweij ,  Jan J. De Koning ,  Hendrik A. Witkamp

发明人： Jan Verweij ,  Jan J. De Koning ,  Hendrik A. Witkamp

IPC分类号： A61K31/545 ,  C07D20060101 ,  C07D501/00 ,  C07D501/04 ,  C07D501/14 ,  C07D501/18 ,  C07D501/22 ,  C07D501/24 ,  C07D501/40 ,  C07F9/28 ,  C07F9/54 ,  C07F9/547 ,  C07F9/6547

CPC分类号： C07D501/04 ,  C07D501/14

摘要： A process is provided for the preparation of 3-methylene and 3-halomethylene cepham derivatives via 3-phosphoniomethyl-3-cephem derivatives, which in turn can be prepared from 3-halomethyl-3-cephem derivatives. The preparation can be carried out with or without isolating the intermediate phosphonium cephem compounds. The 3-methylene and 3-halomethylene cepham derivatives and in particular the 1-oxo and 1,1-dioxo cepham compounds are also prepared by reducing a 3-halomethyl-3-cepham derivative with activated metal, preferably zinc or magnesium.