公开(公告)号：US06346610B1

公开(公告)日：2002-02-12

申请号：US09445240

申请日：1999-12-03

申请人： Noriyasu Kataoka ,  Kenzo Tanaka ,  Masanobu Yatagai

发明人： Noriyasu Kataoka ,  Kenzo Tanaka ,  Masanobu Yatagai

IPC分类号： C07M100

CPC分类号： C07H17/08 ,  Y02P20/55

摘要： An industrially suitable process for preparing V-28-3M useful as an antimycotic agent by conducting methyl esterification of V-28-3 efficiently. V-28-2 is efficiently converted into V-28-3M by protecting the amino group of the amino sugar of V-28-3 with an appropriate protecting group, subjecting the carboxyl group of V-28-3 to methyl esterification with methyl methanesulfonate or methyl p-toluenesulfonate in the presence of a base, and deprotecting the N-protected intermediate.

摘要翻译： 通过有效地进行V-28-3的甲基酯化，可以制备适用于抗真菌剂的V-28-3M的工业上合适的方法。 通过用合适的保护基保护V-28-3的氨基糖的氨基，V-28-2的羧基被甲基酯化，V-28-2被有效地转化成V-28-3M 甲磺酸酯或对甲苯磺酸甲酯在碱的存在下脱保护，并保护N-保护的中间体。

公开(公告)号：US20100204505A1

公开(公告)日：2010-08-12

申请号：US12766178

申请日：2010-04-23

申请人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

发明人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

IPC分类号： C07C229/52

CPC分类号： C07D239/96 ,  C07C233/87

摘要： The present invention provides a method for producing a phenylalanine derivative(s) having a quinazolinedione ring of formula (5), including steps comprising of reacting an acylphenylalanine derivative(s) of formula (1) with a carbonyl group-introducing reagent(s) and a derivative(s) of anthranilic acid to form an asymmetric urea intermediate(s); making the asymmetric urea intermediate(s) into a quinazolinedione compound(s) of formula (4) in the presence of a base(s); and N-alkylating quinazolinedione ring amide of the obtained quinazolinedione compounds with N-alkylation agents. This production method is an industrially applicable method for producing phenylalanine derivatives having a quinazolinedione skeleton, which are compounds highly useful as drugs having α 4 integrin inhibiting activity. In the formulae (1) and (5), R1 represents a phenyl group having a substituent(s) and the like, R2 represents an alkyl group and the like, R3 represents a dialkylamino group and the like, and R4 represents an alkyl group and the like.

摘要翻译： 本发明提供了具有式（5）喹唑啉二酮环的苯丙氨酸衍生物的制备方法，包括使式（1）的酰基苯丙氨酸衍生物与羰基引入试剂反应的步骤， 和邻氨基苯甲酸的衍生物以形成不对称脲中间体; 在碱的存在下使不对称脲中间体转化为式（4）的喹唑啉二酮化合物; 和得到的喹唑啉二酮化合物的N-烷基化喹唑啉二酮环酰胺与N-烷基化剂。 该制造方法是用于生产具有喹唑啉二酮骨架的苯丙氨酸衍生物的工业上适用的方法，其是作为具有α4整联蛋白抑制活性的药物高度有用的化合物。 在式（1）和（5）中，R 1表示具有取代基等的苯基，R 2表示烷基等，R 3表示二烷基氨基等，R 4表示烷基 等等。

公开(公告)号：US5900492A

公开(公告)日：1999-05-04

申请号：US982458

申请日：1997-12-02

申请人： Katsutoshi Sakata ,  Takashi Tsuji ,  Noriyasu Kataoka ,  Masanobu Yatagai

发明人： Katsutoshi Sakata ,  Takashi Tsuji ,  Noriyasu Kataoka ,  Masanobu Yatagai

IPC分类号： C07C69/757 ,  C07C211/27 ,  C07D307/93 ,  C07D307/00

CPC分类号： C07C69/757 ,  C07C211/27 ,  C07D307/93

摘要： A method for resolving optically impure 3-oxa-2-oxobicyclo�3.1.0!hexane-1-carboxylic acid esters. A method is provided for producing a 1-alkoxycarbonyl-2-hydroxymethylcyclopropane-1-carboxylic acid.N-benzyl-.alpha.-phenylethylamine diastereomer salt. An enantiomer of N-benzyl-.alpha.-phenylethylamine is reacted with a 1-alkoxycarbonyl-2-hydroxymethylcyclopropane-1-carboxylic acid to produce a precipitate that is enriched in one diastereomer of the salt. After isolating the optically active salt, the N-benzyl-.alpha.-phenylethylamine may be separated to produce the corresponding 1-alkoxycarbonyl-2-hydroxymethylcyclopropane-1-carboxylic acid. Under acidic conditions, the carboxylic acid and hydroxyl groups undergo ring closure to afford the optically active 3-oxa-2-oxobicyclo�3.1.0!hexane-1-carboxylic acid ester.

摘要翻译： 一种拆分光学上不纯的3-氧杂-2-氧代双环[3.1.0]己烷-1-羧酸酯的方法。 提供了制备1-烷氧基羰基-2-羟甲基环丙烷-1-羧酸N-苄基-α-苯乙胺非对映体盐的方法。 N-苄基-α-苯乙基胺的对映异构体与1-烷氧基羰基-2-羟甲基环丙烷-1-羧酸反应，产生富含一种盐的非对映异构体的沉淀物。 分离光学活性盐后，可以分离N-苄基-α-苯乙胺，生成相应的1-烷氧基羰基-2-羟甲基环丙烷-1-羧酸。 在酸性条件下，羧酸和羟基发生闭环，得到光学活性3-氧杂-2-氧代双环[3.1.0]己烷-1-羧酸酯。

公开(公告)号：US08318975B2

公开(公告)日：2012-11-27

申请号：US12766178

申请日：2010-04-23

申请人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

发明人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

IPC分类号： C07C63/04

CPC分类号： C07D239/96 ,  C07C233/87

摘要： The present invention provides a method for producing a phenylalanine derivative(s) having a quinazolinedione ring of formula (5), including steps comprising of reacting an acylphenylalanine derivative(s) of formula (1) with a carbonyl group-introducing reagent(s) and a derivative(s) of anthranilic acid to form an asymmetric urea intermediate(s); making the asymmetric urea intermediate(s) into a quinazolinedione compound(s) of formula (4) in the presence of a base(s); and N-alkylating quinazolinedione ring amide of the obtained quinazolinedione compounds with N-alkylation agents. This production method is an industrially applicable method for producing phenylalanine derivatives having a quinazolinedione skeleton, which are compounds highly useful as drugs having α 4 integrin inhibiting activity. In the formulae (1) and (5), R1 represents a phenyl group having a substituent(s) and the like, R2 represents an alkyl group and the like, R3 represents a dialkylamino group and the like, and R4 represents an alkyl group and the like.

摘要翻译： 本发明提供了具有式（5）喹唑啉二酮环的苯丙氨酸衍生物的制备方法，包括使式（1）的酰基苯丙氨酸衍生物与羰基引入试剂反应的步骤， 和邻氨基苯甲酸的衍生物以形成不对称脲中间体; 在碱的存在下使不对称脲中间体转化为式（4）的喹唑啉二酮化合物; 和得到的喹唑啉二酮化合物的N-烷基化喹唑啉二酮环酰胺与N-烷基化剂。 该制造方法是用于生产具有喹唑啉二酮骨架的苯丙氨酸衍生物的工业上适用的方法，其是作为具有α4整联蛋白抑制活性的药物高度有用的化合物。 在式（1）和（5）中，R 1表示具有取代基等的苯基，R 2表示烷基等，R 3表示二烷基氨基等，R 4表示烷基 等等。

公开(公告)号：US07737274B2

公开(公告)日：2010-06-15

申请号：US11207751

申请日：2005-08-22

申请人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

发明人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

IPC分类号： A61K31/517 ,  C07D239/80 ,  C07D239/88 ,  C07C61/08 ,  C07C63/06 ,  C07C229/56

CPC分类号： C07D239/96 ,  C07C233/87

摘要： The present invention provides a method for producing a phenylalanine derivative(s) having a quinazolinedione ring of formula (5), including steps comprising of reacting an acylphenylalanine derivative(s) of formula (1) with a carbonyl group-introducing reagent(s) and a derivative(s) of anthranilic acid to form an asymmetric urea intermediate(s); making the asymmetric urea intermediate(s) into a quinazolinedione compound(s) of formula (4) in the presence of a base(s); and N-alkylating quinazolinedione ring amide of the obtained quinazolinedione compounds with N-alkylation agents. This production method is an industrially applicable method for producing phenylalanine derivatives having a quinazolinedione skeleton, which are compounds highly useful as drugs having α 4 integrin inhibiting activity. In the formulae (1) and (5), R1 represents a phenyl group having a substituent(s) and the like, R2 represents an alkyl group and the like, R3 represents a dialkylamino group and the like, and R4 represents an alkyl group and the like.

摘要翻译： 本发明提供了具有式（5）喹唑啉二酮环的苯丙氨酸衍生物的制备方法，包括使式（1）的酰基苯丙氨酸衍生物与羰基引入试剂反应的步骤， 和邻氨基苯甲酸的衍生物以形成不对称脲中间体; 在碱的存在下使不对称脲中间体转化为式（4）的喹唑啉二酮化合物; 和得到的喹唑啉二酮化合物的N-烷基化喹唑啉二酮环酰胺与N-烷基化剂。 该制造方法是用于生产具有喹唑啉二酮骨架的苯丙氨酸衍生物的工业上适用的方法，其是作为具有α4整联蛋白抑制活性的药物高度有用的化合物。 在式（1）和（5）中，R 1表示具有取代基等的苯基，R 2表示烷基等，R 3表示二烷基氨基等，R 4表示烷基 等等。

公开(公告)号：US20060009476A1

公开(公告)日：2006-01-12

申请号：US11207751

申请日：2005-08-22

申请人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

发明人： Noriyasu Kataoka ,  Akinori Tatara ,  Masanobu Yatagai ,  Junko Yamanaka

IPC分类号： A61K31/517 ,  C07D239/91

CPC分类号： C07D239/96 ,  C07C233/87

摘要： The present invention provides a method for producing a phenylalanine derivative(s) having a quinazolinedione ring of formula (5), including steps comprising of reacting an acylphenylalanine derivative(s) of formula (1) with a carbonyl group-introducing reagent(s) and a derivative(s) of anthranilic acid to form an asymmetric urea intermediate(s); making the asymmetric urea intermediate(s) into a quinazolinedione compound(s) of formula (4) in the presence of a base(s); and N-alkylating quinazolinedione ring amide of the obtained quinazolinedione compounds with N-alkylation agents. This production method is an industrially applicable method for producing phenylalanine derivatives having a quinazolinedione skeleton, which are compounds highly useful as drugs having α 4 integrin inhibiting activity. In the formulae (1) and (5), R1 represents a phenyl group having a substituent(s) and the like, R2 represents an alkyl group and the like, R3 represents a dialkylamino group and the like, and R4 represents an alkyl group and the like.

摘要翻译： 本发明提供了具有式（5）喹唑啉二酮环的苯丙氨酸衍生物的制备方法，包括使式（1）的酰基苯丙氨酸衍生物与羰基引入试剂反应的步骤， 和邻氨基苯甲酸的衍生物以形成不对称脲中间体; 在碱的存在下使不对称脲中间体转化为式（4）的喹唑啉二酮化合物; 和得到的喹唑啉二酮化合物的N-烷基化喹唑啉二酮环酰胺与N-烷基化剂。 该制造方法是用于生产具有喹唑啉二酮骨架的苯丙氨酸衍生物的工业上适用的方法，其是作为具有α4整联蛋白抑制活性的药物高度有用的化合物。 在式（1）和（5）中，R 1表示具有取代基等的苯基，R 2表示烷基等，R 3表示二烷基氨基等，R 4表示烷基 等等。

公开(公告)号：US06172224B2

公开(公告)日：2001-01-09

申请号：US09263999

申请日：1999-03-08

申请人： Noriyasu Kataoka ,  Toshihiro Matsuzawa ,  Masanobu Yatagai

发明人： Noriyasu Kataoka ,  Toshihiro Matsuzawa ,  Masanobu Yatagai

IPC分类号： C07D47332

CPC分类号： C07D473/00

摘要： A process for purifying 2-amino-6-chloro-9-[(1′S,2′R)-1′,2′-bis(hydroxymethyl) cycdopropane-1′-yl]methylpurine represented by the following formula (5) comprises the step of selectively isolating 2-amino-6-chloro-9-[(1′S,2′R)-1′,2′-bis(hydroxymethyl) cyclopropane-1′-yl]methylpurine from a mixture of 2-amino-6-chloro-9-[(1′S,2′R)-1′,2′-bis(hydroxymethyl)cyclopropane-1′-yl]methylpurine and 2-amino-6-chloro-7-[(1′S,2′R)-1′,2′-bis(hydroxymethyl)cyclopropane-1′-yl]methylpurine represented by the following formula (6) by the crystallization. This process has a satisfactory medicinal quality on an industrial scale without necessitating complicated operations such as chromatographic purification.

摘要翻译： 用于纯化由下式（5）表示的2-氨基-6-氯-9 - [（1'S，2'R）-1'，2'-双（羟甲基）环丙烷-1'-基]甲基嘌呤的方法包括 从2-氨基-6-氯-9 - [（1'S，2'R）-1'，2'-双（羟甲基）环丙烷-1'-基]甲基嘌呤的2-氨基-6- 6-氯-9 - [（1'S，2'R）-1'，2'-双（羟甲基）环丙烷-1'-基]甲基嘌呤和2-氨基-6-氯-7 - [（1'S，2' R）-1'，2'-双（羟甲基）环丙烷-1'-基]甲基嘌呤通过结晶表示。 该方法在工业规模上具有令人满意的药用质量，而不需要色谱纯化等复杂操作。

公开(公告)号：US20070032658A1

公开(公告)日：2007-02-08

申请号：US11498752

申请日：2006-08-04

申请人： Takayuki Hamada ,  Masayuki Oshita ,  Masanobu Yatagai

发明人： Takayuki Hamada ,  Masayuki Oshita ,  Masanobu Yatagai

IPC分类号： C07D213/56 ,  C07C311/45

CPC分类号： C07C233/47 ,  C07C227/34 ,  C07C271/22 ,  C07C229/36

摘要： Optically active diphenylalanine compounds may be conveniently prepared in a good yield by reacting a diphenylalanine compound represented by formula (1) with an optically active amine compound represented by formula (2) in the presence of an organic solvent to give a diastereomeric salt represented by formula (5) and then treating the diastereomeric salt under acidic conditions to give an optically active diphenylalanine compound represented by formula (3): wherein each symbol is as defined in the specification.

摘要翻译： 通过使由式（1）表示的二苯基丙氨酸化合物与由式（2）表示的光学活性胺化合物在有机溶剂的存在下反应，可以以良好的收率方便地制备光活性二苯丙氨酸化合物，得到式 （5），然后在酸性条件下处理非对映体盐，得到由式（3）表示的光学活性二苯丙氨酸化合物：其中每个符号如说明书中所定义。

公开(公告)号：US07217835B2

公开(公告)日：2007-05-15

申请号：US10937345

申请日：2004-09-10

申请人： Takayuki Hamada ,  Masanobu Yatagai

发明人： Takayuki Hamada ,  Masanobu Yatagai

IPC分类号： C07C229/00

CPC分类号： C07C227/16 ,  C07C229/36

摘要： The present invention relates to a method of producing a compound represented by the formula [I] or a salt thereof, which comprises reacting a compound represented by the formula [II] or a salt thereof with a compound represented by the formula [III] or a salt thereof, in the presence of a base, in alcohol, and provides a production method of an O-substituted tyrosine compound, which is superior in productivity, versatility and safety, and economically and industrially useful: wherein each symbol is as defined in the specification.

摘要翻译： 本发明涉及制备由式[I]表示的化合物或其盐的方法，该方法包括使式[Ⅱ]表示的化合物或其盐与式[Ⅲ]表示的化合物或式 其盐，在碱的存在下，在醇中，并且提供了生产率，通用性和安全性优异的O取代的酪氨酸化合物的制备方法，并且在经济和工业上有用：其中每个符号如 规格。

公开(公告)号：US6114525A

公开(公告)日：2000-09-05

申请号：US113509

申请日：1998-07-10

申请人： Toshihiro Matsuzawa ,  Tohru Nishiwaki ,  Seiichi Nishi ,  Masanobu Yatagai

发明人： Toshihiro Matsuzawa ,  Tohru Nishiwaki ,  Seiichi Nishi ,  Masanobu Yatagai

IPC分类号： C07D473/18 ,  C07D473/00

CPC分类号： C07D473/00

摘要： A pure (-)-9-[1'S, 2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine is prepared by:suspending or dissolving a mixture comprising (-)-9-[1'S, 2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine and (7-[1'S,2'R-bis(hydroxymethyl)cyclopropan-1'-yl]methylguanine in an alcohol or a hydrous alcohol, reacting the resulting suspension or solution with an alkali metal hydroxide or alkoxide, and selectively precipitating crystals of nucleic acid derivatives of formula (I) ##STR1## wherein M represents an alkali metal.

摘要翻译： 通过以下方法制备纯的（ - ） - 9- [1'S，2'R-双（羟甲基）环丙烷-1'-基]甲基鸟嘌呤：悬浮或溶解包含（ - ） - 9- [1'S，2'R- 双（羟甲基）环丙烷-1'-基]甲基鸟嘌呤和（7- [1'S，2'R-双（羟甲基）环丙烷-1'-基]甲基鸟嘌呤在醇或含水醇中反应，使得到的悬浮液或溶液与 碱金属氢氧化物或醇盐，并且选择性地沉淀式（I）的核酸衍生物的晶体，其中M表示碱金属。