t-butyl(3S,4S)-1-(2,4-dimethoxybenzyl)-4-formyl-2-oxo-3-azetidinecarbamate | 89605-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: t-butyl(3S,4S)-1-(2,4-dimethoxybenzyl)-4-formyl-2-oxo-3-azetidinecarbamate
• 英文别名: tert-butyl N-[(2S,3S)-1-[(2,4-dimethoxyphenyl)methyl]-2-formyl-4-oxoazetidin-3-yl]carbamate
• CAS: 89605-21-0
• 化学式: C₁₈H₂₄N₂O₆
• 分子量: 364.398
• InChiKey: CRCFDYFRVMGFKK-HIFRSBDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  t-butyl(3S,4S)-1-(2,4-dimethoxybenzyl)-4-formyl-2-oxo-3-azetidinecarbamate 、 2-三(苯基)膦亚基乙酰胺 在 二氯甲烷 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以There are obtained 3.6 g (81%) of t-butyl(3R,4S)-1-(2,4-dimethoxybenzyl)-4-[(E)-2-carbamoylvinyl]-2-oxo-3-azetidinecarbamate of melting point 270° C.的产率得到t-butyl(3R,4S)-1-(2,4-dimethoxybenzyl)-4-[(E)-2-carbamoylvinyl]-2-oxo-3-azetidinecarbamate
  参考文献：
  名称：

  Process for the manufacture of 1-sulpho-2-oxoazetidine derivatives

  摘要：

  制备公式为##STR1##的1-磺酸基-2-噁唑烷衍生物，其中Het是一个含有1或2个氮原子和可选的氧原子或硫原子的5或6元芳环，可选地氨基取代，R.sup.1是氢，低烷基，苯基-低烷基，低酰基，低烷氧羰基，低烯基-低烷基，低烷氧羰基-低烷基，苯基-低-烷氧羰基-低烷基，硝基苯基-低-烷氧羰基-低烷基或羧基-低烷基，R.sup.2是氢，低烷基，低烯基，低炔基，低烷氧羰基，低酰氧基-低烷基，低烷氧羰基-低烯基，羟亚胺甲基，低烷氧亚胺甲基，氨基甲酰基，氨基甲酰基-低烯基或氨基甲氧羰基-低烷基，.dbd.NOR.sup.1基团至少部分以syn-形式存在，以外消旋体形式或3S对映体形式存在，以及这些化合物的易水解酯和药学兼容盐的制备方法，通过用公式##STR2##的化合物与公式##STR3##的硫代酯进行酰化，其中Het如上所述，R.sup.10具有除羧基-低烷基以外的任何R.sup.1值，也可以表示为三低烷基硅烷基-低烷氧羰基-低烷基或转化为易水解酯基的羧基-低烷基，.dbd.NOR.sup.10基团至少部分以syn-形式存在，以及进行后续步骤（N-磺酸化，将R.sup.20转化为R.sup.2，将R.sup.10转化为R.sup.1），其中一些步骤是可选的。该发明还提供了公式I和公式III的苯并噻唑硫代酯的某些新产品以及通过酯化相应的羧酸制备苯并噻唑硫代酯的方法。最后，该发明提供了一种制备R.sup.1为t-烷氧羰基甲基的羧酸的方法。公式I化合物具有抗微生物活性。

  公开号：

  US04948898A1

文献信息

• Process for the manufacture of 1-sulpho-2-oxoazetidine carboxylic acid
  申请人：Hoffmann-La Roche Inc.

  公开号：US04652651A1

  公开（公告）日：1987-03-24

  The manufacture of 1-sulpho-2-oxazetidine derivatives of the formula ##STR1## in which Het is an optionally amino-substituted, 5- or 6-membered, aromatic heterocycle containing 1 or 2 nitrogen atoms and optionally also an oxygen or sulphur atom, R.sup.1 is hydrogen, lower alkyl, phenyl-lower alkyl, lower alkanoyl, lower alkoxycarbonyl, lower alkenyl-lower alkyl, lower alkoxycarbonyl-lower alkyl, phenyl-lower-alkoxycarbonyl-lower alkyl, nitrophenyl-lower-alkoxycarbonyl-lower alkyl or carboxy-lower alkyl and R.sup.2 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxycarbonyl, lower alkanoyloxy-lower alkyl, lower alkoxycarbonyl-lower alkenyl, hydroxyiminomethyl, lower alkoxyiminomethyl, carbamoyl, carbamoyl-lower alkenyl or carbamoyloxy-lower alkyl, the group .dbd.NOR.sup.1 being present at least partially in the syn-form, in racemic form or in the form of the 3S-enantiomer, and of readily hydrolyzable esters and pharmaceutically compatible salts of these compounds, by acylating a compound of the formula ##STR2## in which R.sup.20 equals R.sup.2 or can also represent a 2,2-dimethyl-1,3-dioxolan-4-yl group and R.sup.3 is hydrogen or sulpho, or a salt thereof with a thioester of the formula ##STR3## in which Het is as above and R.sup.10 has any of the values of R.sup.1 except carboxy-lower alkyl, and can also represent a tri-lower alkyl-silyl-lower-alkoxycarbonyl-lower alkyl group or a carboxy-lower alkyl group converted into a readily hydrolyzable ester group, and the group .dbd.NOR.sup.10 is present at least partially in the syn-form, and carrying out subsequent steps (N-sulphonation, conversion of R.sup.20 into R.sup.2, R.sup.10 into R.sup.1), some of which are optional. The invention also provides certain novel products of formula I and benzthiazolyl thioesters of formula III per se and the preparation of the benzthiazolyl thioesters by esterifying corresponding carboxylic acids. Finally, the invention provides a process for the preparation of carboxylic acids in which R.sup.1 is t-alkoxycarbonylmethyl. The compounds of formula I have antimicrobial activity.

  该专利描述了一种制备1-磺酸-2-噁唑环丙烷衍生物的方法，其化学式为##STR1##其中Het是一个含有1或2个氮原子和可能还有一个氧原子或硫原子的可选氨基取代的5或6元芳香杂环，R.sup.1是氢、低烷基、苯基-低烷基、低烷酰、低烷氧羰基、低烯基-低烷基、低烷氧羰基-低烷基、苯基-低烷氧羰基-低烷基、硝基苯基-低烷氧羰基-低烷基或羧基-低烷基，R.sup.2是氢、低烷基、低烯基、低炔基、低烷氧羰基、低烷酰氧基-低烷基、低烷氧羰基-低烯基、羟基亚胺甲基、低烷氧亚胺甲基、氨甲酰基、氨甲酰基-低烯基或氨甲酰氧基-低烷基，.dbd.NOR.sup.1基团至少部分以syn-形式存在，是外消旋形式或3S-对映体形式，以及这些化合物的易水解酯和药用兼容盐的制备方法。
• 1-Carba-(dethia)-Cephalosporin Derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0831093A1

  公开（公告）日：1998-03-25

  1-carba-(dethia)-cephalosporin derivatives of the general formula I wherein R1is hydrogen, optionally fluoro substituted lower alkyl, aralkyl, cycloalkyl, -COR4 or -C(R5R6)CO2R7 -C(R5R6)CONHR7; where R5 and R6 are each independently hydrogen or lower alkyl, or R5 and R6 taken together form a cycloalkyl group; R4 is hydrogen or lower alkyl and R7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group; R2is hydrogen, hydroxy, lower alkyl-Qm, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl-Qm, aryl-Qm, aryloxy, aralkoxy, a heterocyclic ring or heterocyclyl lower alkyl, the lower alkyl, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl, aryl, aryloxy, aralkoxy and the heterocyclic ring being unsubstituted or substituted with at least one group selected from carboxy, amino, nitro, cyano, optionally fluoro substituted lower alkyl, lower alkoxy, hydroxy, halogen, -COR6, -C(R5R6)CO2R7, -C(R5R6)CONR5R8, -CONR5R6, -N(R6)COOR10, R6OCO- or R6COO- where R5 and R6 are hydrogen or lower alkyl; R7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group; R8 is hydrogen, lower alkyl or optionally substituted phenyl; R10 is lower alkyl, lower alkenyl or a carboxylic acid protecting group; Qis -CHR-, -CO- or -SO2-; Ris hydrogen or lower alkyl R3is hydroxy, lower-alkoxy, or -O-, when R2 has a positive charge, or -OM and M represents an alkali metal; mis 0 or 1; nis 0, 1 or 2; Xis CH or N as well as readily hydrolysable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts.

  通式 I 的 1-羧基-(去甲)-头孢菌素衍生物 其中 R1 是氢、任选被氟取代的低级烷基、芳基、环烷基、-COR4 或 -C(R5R6)CO2R7 -C(R5R6)CONHR7；其中 R5 和 R6 各自独立地是氢或低级烷基，或 R5 和 R6 共同形成环烷基；R4 是氢或低级烷基，R7 是氢、低级烷基、低级烯基或羧酸保护基； R2是氢、羟基、低级烷基-Qm、环烷基、低级烷氧基、低级烯基、环烯基、低级炔基、芳基-Qm、芳氧基、芳烷氧基、杂环或杂环低级烷基、低级烷基、环烷基、低级烷氧基、低级烯基、环烯基、低级炔基、芳基、芳氧基、芳烷氧基和杂环低级烷基、杂环未被取代或被至少一个基团取代，这些基团选自羧基、氨基、硝基、氰基、任选被氟取代的低级烷基、低级烷氧基、羟基、卤素、-COR6、-C(R5R6)CO2R7、-C(R5R6)CONR5R8、-CONR5R6、-N(R6)COOR10、R6OCO- 或 R6COO-，其中 R5 和 R6 为氢或低级烷基；R7 是氢、低级烷基、低级烯基或羧酸保护基； R8 是氢、低级烷基或任选取代的苯基； R10 是低级烷基、低级烯基或羧酸保护基； Q是-CHR-、-CO-或-SO2-； R2是氢或低级烷基 当 R2 带正电荷时，R3 是羟基、低级烷氧基或-O-，或-OM，M 代表碱金属； mis为 0 或 1； n为 0、1 或 2； X 是 CH 或 N 及其易于水解的酯、所述化合物的药学上可接受的盐以及式 I 化合物及其酯和盐的水合物。
• Process for the manufacture of 1-sulpho-2-oxoazetidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US04948898A1

  公开（公告）日：1990-08-14

  The manufacture of 1-sulpho-2-oxazetidine derivatives of the formula ##STR1## in which Het is an optionally amino-substituted, 5- or 6-membered, aromatic heterocycle containing 1 or 2 nitrogen atoms and optionally also an oxygen or sulphur atom, R.sup.1 is hydrogen, lower alkyl, phenyl-lower alkyl, lower alkanoyl, lower alkoxycarbonyl, lower alkenyl-lower alkyl, lower alkoxycarbonyl-lower alkyl, phenyl-lower-alkoxycarbonyl-lower alkyl, nitrophenyl-lower-alkoxycarbonyl-lower alkyl or carboxy-lower alkyl and R.sup.2 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxycarbonyl, lower alkanoyloxy-lower alkyl, lower alkoxycarbonyl-lower alkenyl, hydroxyiminomethyl, lower alkoxyiminomethyl, carbamoyl, carbamoyl-lower alkenyl or carbamoyloxy-lower alkyl, the group .dbd.NOR.sup.1 being present at least partially in the syn-form, in racemic form or in the form of the 3S-enantiomer, and of readily hydrolyzable esters and pharmaceutically compatible salts of these compounds, by acylating a compound of the formula ##STR2## in which R.sup.20 equals R.sup.2 or can also represent a 2,2-dimethyl-1,3-dioxolan-4-yl group and R.sup.3 is hydrogen or sulpho, or a salt thereof with a thioester of the formula ##STR3## in which Het is as above and R.sup.10 has any of the values of R.sup.1 except carboxy-lower alkyl, and can also represent a tri-lower alkyl-silyl-lower-alkoxycarbonyl-lower alkyl group or a carboxy-lower alkyl group converted into a readily hydrolyzable ester group, and the group .dbd.NOR.sup.10 is present at least partially in the syn-form, and carrying out subsequent steps (N-sulphonation, conversion of R.sup.20 into R.sup.2, R.sup.10 into R.sup.1), some of which are optional. The invention also provides certain novel products of formula I and benzthiazolyl thioesters of formula III per se and the preparation of the benzthiazolyl thioesters by esterifying corresponding carboxylic acids. Finally, the invention provides a process for the preparation of carboxylic acids in which R.sup.1 is t-alkoxycarbonylmethyl. The compounds of formula I have antimicrobial activity.

  制备公式为##STR1##的1-磺酸基-2-噁唑烷衍生物，其中Het是一个含有1或2个氮原子和可选的氧原子或硫原子的5或6元芳环，可选地氨基取代，R.sup.1是氢，低烷基，苯基-低烷基，低酰基，低烷氧羰基，低烯基-低烷基，低烷氧羰基-低烷基，苯基-低-烷氧羰基-低烷基，硝基苯基-低-烷氧羰基-低烷基或羧基-低烷基，R.sup.2是氢，低烷基，低烯基，低炔基，低烷氧羰基，低酰氧基-低烷基，低烷氧羰基-低烯基，羟亚胺甲基，低烷氧亚胺甲基，氨基甲酰基，氨基甲酰基-低烯基或氨基甲氧羰基-低烷基，.dbd.NOR.sup.1基团至少部分以syn-形式存在，以外消旋体形式或3S对映体形式存在，以及这些化合物的易水解酯和药学兼容盐的制备方法，通过用公式##STR2##的化合物与公式##STR3##的硫代酯进行酰化，其中Het如上所述，R.sup.10具有除羧基-低烷基以外的任何R.sup.1值，也可以表示为三低烷基硅烷基-低烷氧羰基-低烷基或转化为易水解酯基的羧基-低烷基，.dbd.NOR.sup.10基团至少部分以syn-形式存在，以及进行后续步骤（N-磺酸化，将R.sup.20转化为R.sup.2，将R.sup.10转化为R.sup.1），其中一些步骤是可选的。该发明还提供了公式I和公式III的苯并噻唑硫代酯的某些新产品以及通过酯化相应的羧酸制备苯并噻唑硫代酯的方法。最后，该发明提供了一种制备R.sup.1为t-烷氧羰基甲基的羧酸的方法。公式I化合物具有抗微生物活性。