公开(公告)号：US07371868B2

公开(公告)日：2008-05-13

申请号：US11691740

申请日：2007-03-27

Applicant: Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Taro Kiyoto

Inventor： Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Taro Kiyoto

IPC: C07D231/00 ,  C07D209/02 ,  C07D209/54

CPC classification number: C07D401/04 ,  A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07F5/025 ,  Y02P20/55

Abstract: Process for producing a 7-bromoquinolone-carboxylic acid derivative of the following formula or its salt by reacting a 2,4-dibromo-3-hydroxybenzoic acid ester compound of the formula R7a-x to obtain a 3-alkoxy-2,4-dibromobenzoic acid ester, subjecting the 3-alkoxy-2,4-dibromobenzoic acid ester to elimination reaction of the carboxyl-protecting group to obtain a 3-alkoxy-2,4-dibromobenzoic acid, subjecting the 3-alkoxy-2,4-dibromobenzoic acid to ketoesterification reaction to obtain a 3-alkoxy-2,4-dibromobenyolacetic acid ester, reacting the 3-alkoxy-2,4-dibromobenzoylacetic acid ester with an orthoester or an acetal, then reacting the reaction product with a compound of the formula R2—NH or its salt to obtain a 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester and subjecting the 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester to ring-closing reaction, and products thereof.

Abstract translation: 制备下式的7-溴喹诺酮 - 羧酸衍生物或其盐的方法，其通过使式<β的在线式描述的2,4-二溴-3-羟基苯甲酸酯化合物=“在线式 “end =”lead“？> R 7a -x <？in-line-formula description =”In-line Formulas“end =”tail“？>以获得3-烷氧基-2， 4-二溴苯甲酸酯，使3-烷氧基-2,4-二溴苯甲酸酯与羧基保护基进行消去反应，得到3-烷氧基-2,4-二溴苯甲酸，将3-烷氧基-2,4-二溴苯甲酸 4-二溴苯甲酸进行酮酯化反应，得到3-烷氧基-2,4-二溴苯乙醇酸乙酯，使3-烷氧基-2,4-二溴苯甲酰基乙酸酯与原酸酯或缩醛反应，然后使反应产物与化合物 的式R 2 -NH或其盐，得到2-（3-烷氧基-2,4-二溴苯甲酰基）-3-取代的氨基丙烯酸酯，并使2-（3-烷氧基 - 3,4-二溴苯甲酰基）-3-取代基 氨基丙烯酸酯进行闭环反应，其产物。

公开(公告)号：US20050203301A1

公开(公告)日：2005-09-15

申请号：US10209078

申请日：2002-08-01

Applicant: Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Taro Kiyoto

Inventor： Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Taro Kiyoto

IPC: A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07D401/04 ,  C07D471/02 ,  C07D43/02

CPC classification number: C07D401/04 ,  A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07F5/025 ,  Y02P20/55

Abstract: Process for producing a 7-bromoquinolone-carboxylic acid derivative of the following formula or its salt by reacting a 2,4-dibromo-3-hydroxybenzoic acid ester compound of the formula R7a-x to obtain a 3-alkoxy-2,4-dibromobenzoic acid ester, subjecting the 3-alkoxy-2,4-dibromobenzoic acid ester to elimination reaction of the carboxyl-protecting group to obtain a 3-alkoxy-2,4-dibromobenzoic acid, subjecting the 3-alkoxy-2,4-dibromobenzoic acid to ketoesterification reaction to obtain a 3-alkoxy-2,4-dibromobenyolacetic acid ester, reacting the 3-alkoxy-2,4-dibromobenzoylacetic acid ester with an orthoester or an acetal, then reacting the reaction product with a compound of the formula R2a—NH or its salt to obtain a 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester and subjecting the 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester to ring-closing reaction, and products thereof.

Abstract translation: 制备下式的7-溴喹诺酮 - 羧酸衍生物或其盐的方法，其通过使式<β的在线式描述的2,4-二溴-3-羟基苯甲酸酯化合物=“在线式 “end =”lead“？> R 7a -x <？in-line-formula description =”In-line Formulas“end =”tail“？>以获得3-烷氧基-2， 4-二溴苯甲酸酯，使3-烷氧基-2,4-二溴苯甲酸酯与羧基保护基进行消去反应，得到3-烷氧基-2,4-二溴苯甲酸，将3-烷氧基-2,4-二溴苯甲酸 4-二溴苯甲酸进行酮酯化反应，得到3-烷氧基-2,4-二溴苯乙醇酸乙酯，使3-烷氧基-2,4-二溴苯甲酰基乙酸酯与原酸酯或缩醛反应，然后使反应产物与化合物 的式R 2a -NH或其盐，得到2-（3-烷氧基-2,4-二溴苯甲酰基）-3-取代的氨基丙烯酸酯，并使2-（3-烷氧基 - 3,4-二溴苯甲酰基）-3-取代基 叔氨基丙烯酸酯进行闭环反应，及其产物。

公开(公告)号：US06337399B1

公开(公告)日：2002-01-08

申请号：US09529407

申请日：2000-04-26

Applicant: Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

Inventor： Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

IPC: C07D21516

CPC classification number: C07D401/04 ,  A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07F5/025 ,  Y02P20/55

Abstract: This invention relates to processes for producing a 7-isoindoline-quinolonecarboxylic acid derivative represented by the general formula [1] which is useful as an antibacterial agent, and an intermediate thereof: wherein R1 represents a hydrogen atom or a carboxyl-protecting group; R2 represents a substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aryl or heterocyclic group; R3 represents at least one group selected from hydrogen atom, halogen atoms, substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aryl, alkoxy or alkylthio groups, nitro group, cyano group, acyl groups, protected or unprotected hydroxyl groups and protected or unprotected or substituted or unsubstituted amino groups; R4 represents at least one group selected from hydrogen atom, halogen atoms, substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aralkyl, aryl, alkoxy or alkylthio groups, protected or unprotected hydroxyl or imino groups, protected or unprotected or substituted or unsubstituted amino groups, alkylidene groups, oxo group and groups each forming a cycloalkane group together with the carbon atom to which R4 bonds; R5 represents a hydrogen atom, an amino-protecting group, a substituted or unsubstituted alkyl, cycloalkyl, alkylsulfonyl, arylsulfonyl, acyl or aryl group; R6 represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, alkoxy or alkylthio group, a protected or unprotected hydroxyl or amino group or a nitro group; and A represents CH or C—R7 in which R7 represents a halogen atom, a substituted or unsubstituted alkyl, alkoxy or alkylthio group or a protected or unprotected hydroxyl group, and to a salt of a 7-isoindoline-quinolonecarboxylic acid represented by the general formula [1], a hydrate thereof and a composition comprising them as an active ingredient.

公开(公告)号：US20070225506A1

公开(公告)日：2007-09-27

申请号：US11691740

申请日：2007-03-27

Applicant: Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

Inventor： Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

IPC: C07D209/04

CPC classification number: C07D401/04 ,  A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07F5/025 ,  Y02P20/55

Abstract: Process for producing a 7-bromoquinolone-carboxylic acid derivative of the following formula or its salt by reacting a 2,4-dibromo-3-hydroxybenzoic acid ester compound of the formula R7a-x to obtain a 3-alkoxy-2,4-dibromobenzoic acid ester, subjecting the 3-alkoxy-2,4-dibromobenzoic acid ester to elimination reaction of the carboxyl-protecting group to obtain a 3-alkoxy-2,4-dibromobenzoic acid, subjecting the 3-alkoxy-2,4-dibromobenzoic acid to ketoesterification reaction to obtain a 3-alkoxy-2,4-dibromobenyolacetic acid ester, reacting the 3-alkoxy-2,4-dibromobenzoylacetic acid ester with an orthoester or an acetal, then reacting the reaction product with a compound of the formula R2— NH or its salt to obtain a 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester and subjecting the 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester to ring-closing reaction, and products thereof.

Abstract translation: 制备下式的7-溴喹诺酮 - 羧酸衍生物或其盐的方法，其通过使式<β的在线式描述的2,4-二溴-3-羟基苯甲酸酯化合物=“在线式 “end =”lead“？> R 7a -x <？in-line-formula description =”In-line Formulas“end =”tail“？>以获得3-烷氧基-2， 4-二溴苯甲酸酯，使3-烷氧基-2,4-二溴苯甲酸酯与羧基保护基进行消去反应，得到3-烷氧基-2,4-二溴苯甲酸，将3-烷氧基-2,4-二溴苯甲酸 4-二溴苯甲酸进行酮酯化反应，得到3-烷氧基-2,4-二溴苯乙醇酸乙酯，使3-烷氧基-2,4-二溴苯甲酰基乙酸酯与原酸酯或缩醛反应，然后使反应产物与化合物 的式R 2 -O-NH或其盐，得到2-（3-烷氧基-2,4-二溴苯甲酰基）-3-取代的氨基丙烯酸酯，并使2-（3-烷氧基 - 3,4-二溴苯甲酰基）-3-取代基 叔氨基丙烯酸酯进行闭环反应，及其产物。

公开(公告)号：US06482835B2

公开(公告)日：2002-11-19

申请号：US09961364

申请日：2001-09-25

Applicant: Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

Inventor： Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

IPC: A61K3147

CPC classification number: C07D401/04 ,  A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07F5/025 ,  Y02P20/55

Abstract: Processes for producing a 7-isoindoline-quinolonecarboxylic acid derivative represented by the general formula [1] which is useful as an antibacterial agent, and an intermediate thereof: comprising reacting, in the presence of metallic palladium, an isoindoline-5-boronic acid, or of a 5-halogenoisoindoline, in the presence of a palladium catalyst, with a dialkoxyborane or an alkoxydiborane.

Abstract translation: 制备可用作抗菌剂的通式[1]表示的7-异二氢吲哚 - 喹诺酮羧酸衍生物的方法及其中间体：包括在金属钯存在下，异二氢吲哚-5-硼酸， 或5-卤代异吲哚啉，在钯催化剂存在下，与二烷氧基硼烷或烷氧基二硼烷。