公开(公告)号：US20110034720A1

公开(公告)日：2011-02-10

申请号：US12808829

申请日：2008-12-19

Applicant: Sascha Braune ,  Stefan Steinhofer ,  Peter Poechlauer ,  Rafael Wilhelmus E.G. Reintjens ,  Nicole Theodora W. Linssen ,  Mehul Thathagar

Inventor： Sascha Braune ,  Stefan Steinhofer ,  Peter Poechlauer ,  Rafael Wilhelmus E.G. Reintjens ,  Nicole Theodora W. Linssen ,  Mehul Thathagar

IPC: C07C201/02

CPC classification number: B01J19/0093 ,  B01J2219/0086 ,  B01J2219/00873 ,  B01J2219/00889 ,  B01J2219/00966 ,  B01J2219/00984 ,  C07C201/02 ,  C07C203/04

Abstract: A process for the continuous production of a compound of Formula (II), HO—R1—ONO2 (II) wherein R1 is a straight chain alkyl radical having from 3 to 6 carbon atoms, in a two-phase solvent system, comprising contacting a compound of Formula (I), HO—R1—OH (I) wherein R1 is as defined above, with nitric acid in the presence of a first solvent, wherein the compound of Formula (II) is continuously extracted into a second solvent, and the reaction is carried out in a mixing microreactor which provides a power loss of at least 1.3 times the power loss provided under identical conditions by a circular cross-section straight-channel microreactor having an internal diameter equal to the average hydraulic diameter of the mixing microreactor and a length equal to the length of the mixing microreactor.

Abstract translation: 在二相溶剂系统中连续制备其中R 1为具有3至6个碳原子的直链烷基的式（II）化合物HO-R1-ONO2（Ⅱ）的方法，包括使 式（I）化合物，其中R 1如上定义的HO-R 1 -OH（I）与硝酸在第一溶剂存在下反应，其中将式（II）化合物连续萃取到第二溶剂中， 反应在混合微反应器中进行，该混合微反应器通过圆形截面直通微反应器提供至少1.3相同条件下功率损耗的功率损失，该反应器的内径等于混合微反应器的平均水力直径 长度等于混合微反应器的长度。

公开(公告)号：US20110034719A1

公开(公告)日：2011-02-10

申请号：US12910550

申请日：2010-10-22

Applicant: Aldo BELLI ,  Vincenzo CANNATA ,  Telly FONDUCA ,  Martin HEDBERG ,  Andreas WESTERMARK ,  Marco VILLA

Inventor： Aldo BELLI ,  Vincenzo CANNATA ,  Telly FONDUCA ,  Martin HEDBERG ,  Andreas WESTERMARK ,  Marco VILLA

IPC: C07C201/02

CPC classification number: C07C309/73 ,  A61K31/21 ,  C07C67/08 ,  C07C67/58 ,  C07C201/02 ,  C07C303/28 ,  C07C309/66 ,  C07C309/67 ,  C07C69/734 ,  C07C203/04

Abstract: The present invention relates to a new process for the preparation of the (S)-naproxen 4-nitrooxybutyl ester and to new intermediates obtained and used therein. The invention further relates to the use of the new intermediates for the manufacturing of pharmaceutically active compounds such as (S)-naproxen 4-nitrooxybutyl ester. The invention also relates to the use of (S)-naproxen 4-nitrooxybutyl ester prepared according to the process of the present invention for the manufacturing of a medicament for the treatment of pain.

Abstract translation: 本发明涉及制备（S） - 萘普生4-硝基氧丁基酯的新方法及其中获得和使用的新中间体。 本发明还涉及新中间体用于制备药学活性化合物如（S） - 萘普生4-硝基氧基丁基酯的用途。 本发明还涉及根据本发明的方法制备的（S） - 萘普生4-硝基氧基丁基酯在制备用于治疗疼痛的药物中的用途。

公开(公告)号：US20100312003A1

公开(公告)日：2010-12-09

申请号：US12682479

申请日：2008-10-10

Applicant: Walter Brieden ,  Dominique Michel ,  Wilhelm Quittmann ,  Fabio Rainone ,  Jie-Hui Pan ,  Hang-Bing Fang ,  Ying-Xia Song

Inventor： Walter Brieden ,  Dominique Michel ,  Wilhelm Quittmann ,  Fabio Rainone ,  Jie-Hui Pan ,  Hang-Bing Fang ,  Ying-Xia Song

IPC: C07C203/04 ,  C12P13/00

CPC classification number: C07C201/02 ,  C07C201/12 ,  C07C203/04 ,  C07C205/57

Abstract: The present invention relates to a process for the preparation of organic nitrates having at least one nitryloxy and at least one hydroxy group, wherein the at least one hydroxy group may be present in form of an esterified hydroxy residue, the latter being esterified with an acid other than nitric acid.

Abstract translation: 本发明涉及一种制备具有至少一个硝基氧基和至少一个羟基的有机硝酸盐的方法，其中至少一个羟基可以酯化羟基残基的形式存在，后者用酸酯化 硝酸除外。

公开(公告)号：US07723529B2

公开(公告)日：2010-05-25

申请号：US11632666

申请日：2005-02-02

Applicant: Nicoletta Almirante ,  Massimiliano Ferrario ,  Ennio Ongini

Inventor： Nicoletta Almirante ,  Massimiliano Ferrario ,  Ennio Ongini

IPC: C07D257/00 ,  C07D403/00

CPC classification number: C07D207/46 ,  C07C201/02 ,  C07C203/04 ,  C07C203/10 ,  C07C231/12 ,  C07D207/16 ,  C07D213/89 ,  C07D285/06 ,  C07D285/10 ,  C07D403/10 ,  C07C233/25

Abstract: The present invention relates to a process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates of compounds having at least an hydroxyl or thiol functional group, according to the following reaction scheme The invention also relates to intermediates useful in said process and to their preparation.

Abstract translation: 本发明涉及根据以下反应方案制备具有至少羟基或硫醇官能团的化合物的硝基氧基酯，硝基氧基硫酯，硝基氧基碳酸酯和硝基氧基硫代碳酸酯的方法本发明还涉及可用于所述方法和 他们的准备。

公开(公告)号：US20080293961A1

公开(公告)日：2008-11-27

申请号：US12166739

申请日：2008-07-02

Applicant: Tiziano Scubla ,  Nevio Francescutti ,  Fausto Gorassini ,  Graziano Castaldi

Inventor： Tiziano Scubla ,  Nevio Francescutti ,  Fausto Gorassini ,  Graziano Castaldi

IPC: C07C201/02

CPC classification number: C07C203/04 ,  C07C201/02

Abstract: A process for the purification of 1,4-butanediol mononitrate from 1,4-butanediol dinitrate and 1,4-butanediol, by selective extraction with solvents is herein disclosed.

Abstract translation: 本文公开了通过溶剂选择性萃取从1,4-丁二醇和1,4-丁二醇纯化1,4-丁二醇单硝酸酯的方法。

公开(公告)号：US07238829B2

公开(公告)日：2007-07-03

申请号：US10625558

申请日：2003-07-24

Applicant: Francesca Benedini ,  Erminio Oldani ,  Graziano Castaldi ,  Antonio Tarquini

Inventor： Francesca Benedini ,  Erminio Oldani ,  Graziano Castaldi ,  Antonio Tarquini

IPC: C07C203/10

CPC classification number: C07C201/02 ,  C07C203/04

Abstract: A process for obtaining nitroxyalklesters of the 2(S)(6-methoxy-2-naphthyl)-propanoic acid having an enantiomeric excess higher than or equal to 95%, preferably higher than or equal to 98%, characterized in that an halide of the 2-(S)-(6 methoxy-2-naphthyl)propanoic acid of formula A-Hal, wherein A is the acid acyl residue, is reacted in an inert organic solvent with an aliphatic nitroxyalkanol HO—Y—ONO2, wherein Y is a C2-C20 alkylene or a cycloalkylene from 3 to 8 carbon atoms, or an alkylene as defined containing a cycloalkylene as defined, in the presence of an inorganic base.

Abstract translation: 一种获得具有高于或等于95％，优选高于或等于98％的对映异构体过量的2（S）（6-甲氧基-2-萘基） - 丙酸的硝基螺旋体的方法，其特征在于， 其中A是酸酰基残基的式A-Hal的2-（S） - （6甲氧基-2-萘基）丙酸在惰性有机溶剂中与脂族硝基链烷醇HO-Y-ONO 2，其中Y是C 2 -C 20亚烷基或3至8个碳原子的亚环烷基，或如所定义的含有如所定义的亚环烷基的亚烷基 在无机碱存在下进行。

公开(公告)号：US20070112194A1

公开(公告)日：2007-05-17

申请号：US10522986

申请日：2003-08-06

Applicant: Piero Del Soldato ,  Giancarlo Santus ,  Francesca Benedini

Inventor： Piero Del Soldato ,  Giancarlo Santus ,  Francesca Benedini

IPC: C07D241/04 ,  C07C201/04

CPC classification number: C07C269/06 ,  C07C67/10 ,  C07C69/734 ,  C07C201/02 ,  C07C203/04 ,  C07C271/28 ,  C07C303/28 ,  C07C309/73

Abstract: The present invention refers to a process for preparing a compound of general formula (A), as reported in the description, wherein R is a radical of a drug and R1-R12 are hydrogen or alkyl groups, m, n, o, q, r and s are each independently an integer from 0 to 6, and p is 0 or 1, and X is O, S, SO, SO2, NR13 or PR13 or an aryl, heteroaryl group, said process comprising reacting a compound of formula (B) R—COOZ (B) wherein R is as defined above and Z is hydrogen or a cation selected from: Li+, Na+, K+, Ca++, Mg++, tetralkylammonium, tetralkylphosphonium, with a compound of formula (C), as reported in the description, wherein R1-R12 and m, n, o, p, q, r, s are as defined above and Y is a suitable leaving group.

Abstract translation: 本发明涉及制备通式（A）化合物的方法，如说明书所述，其中R为药物基团，R 1 -R 12为氢或烷基，m，n，o，q， r和s各自独立地为0〜6的整数，p为0或1，X为O，S，SO，SO 2，NR 13或PR 13或芳基杂芳基，所述方法包括使式 B）R-COOZ（B）其中R如上所定义，Z是氢或选自：Li +，Na +，K +，Ca ++，Mg ++，四烷基铵，四烷基鏻与式（C）化合物的阳离子，如 其描述其中R1-R12和m，n，o，p，q，r，s如上所定义，Y是合适的离去基团。

公开(公告)号：US20060128983A1

公开(公告)日：2006-06-15

申请号：US10534868

申请日：2003-11-06

Applicant: Nevio Francescutti ,  Tiziano Scubla ,  Fausto Gorassini ,  Graziano Castaldi

Inventor： Nevio Francescutti ,  Tiziano Scubla ,  Fausto Gorassini ,  Graziano Castaldi

IPC: C07C201/02

CPC classification number: C01B21/46 ,  C07C201/02 ,  C07C203/04

Abstract: A process for the preparation of compounds of formula HO-A-ONO2  (I) wherein A is a C2-C6 alkylene chain by nitration of the corresponding alkanediols with “stabilised” nitric acid is herein disclosed. The process is safer to operators and allows to obtain advantageous yields on an industrial scale.

Abstract translation: 一种制备式<β的化合物的方法在线式描述=“在线式”中=“铅”→HO-A-ONO 2（I）<α -line-formula description =“In-line Formulas”end =“tail”？>其中A是C 2 -C 6 -C 6亚烷基链，硝化相应的链烷二醇 本文公开了“稳定”硝酸。 该过程对操作员更安全，并允许在工业规模上获得有利的产量。

公开(公告)号：US20060122402A1

公开(公告)日：2006-06-08

申请号：US10527647

申请日：2003-09-18

Applicant: Johan Andersson ,  Aldo Belli ,  Vincenzo Cannata ,  Martin Hedberg ,  Andreas Palmgren ,  Sigrid Schuldei ,  Marika Strom ,  Marco Villa

Inventor： Johan Andersson ,  Aldo Belli ,  Vincenzo Cannata ,  Martin Hedberg ,  Andreas Palmgren ,  Sigrid Schuldei ,  Marika Strom ,  Marco Villa

IPC: C07D333/32 ,  C07D209/82 ,  C07D209/44 ,  C07C201/02

CPC classification number: C07C303/28 ,  A61K31/216 ,  C07C67/08 ,  C07C201/02 ,  C07C203/04 ,  C07C227/16 ,  C07C227/20 ,  C07C229/42 ,  C07C309/66 ,  C07C69/738

Abstract: The present invention relates to a new process for the preparation of NO-donating compounds using a sulfonated intermediate. The invention relates to new intermediates prepared therein suitable for large scale manufacturing of NO-donating compounds. The invention further relates to the use of the new intermediates for the manufacturing of pharmaceutically active NO-donating compounds. The invention further relates to a substantially crystalline form of NO-donating NSAIDs, especially 2-[2-(nitrooxy)ethoxy]ethyl {2-[(2,6-dichlorophenyl)amino]phenyl}acetate, the preparation thereof and to pharmaceutical formulations containing said crystalline form and to the use of said crystalline form in the preparation of a medicament.

Abstract translation: 本发明涉及使用磺化中间体制备供给NO的化合物的新方法。 本发明涉及其中制备的适用于大量制备供体化合物的新中间体。 本发明还涉及新的中间体用于制备药物活性的供体化合物的用途。 本发明进一步涉及一种基本上呈结晶形式的给予NO的NSAID，尤其是{2 - [（2,6-二氯苯基）氨基]苯基}乙酸酯的2- [2-（硝基氧基）乙氧基]乙酯，其制备方法和药物 含有所述结晶形式的制剂以及所述结晶形式在制备药物中的用途。

公开(公告)号：US06700011B1

公开(公告)日：2004-03-02

申请号：US10031412

申请日：2002-01-18

Applicant: Francesca Benedini ,  Erminio Oldani ,  Graziano Castaldi ,  Antonio Tarquini

Inventor： Francesca Benedini ,  Erminio Oldani ,  Graziano Castaldi ,  Antonio Tarquini

IPC: C07C20304

CPC classification number: C07C201/02 ,  C07C203/04

Abstract: A process for obtaining nitroxyalkylesters of the 2-(S)-(6-methoxy-2-naphthyl)-propanoic acid having an enantiomeric excess higher than or equal to 95%, preferably higher than or equal to 98%, characterized in that an halide of the 2-(S)-(6-methoxy-2-naphthyl)-propanoic acid of formula A-Hal, wherein A is the acid acyl residue, is reacted in an inert organic solvent with an aliphatic nitroxyalkanol HO—Y—ONO2, wherein Y is a C2-C20 alkylene or a cycloalkylene from 3 to 8 carbon atoms, or an alkylene as defined containing a cycloalkylene as defined, in the presence of an inorganic base.

Abstract translation: 一种获得具有高于或等于95％，优选高于或等于98％的对映体过量的2-（S） - （6-甲氧基-2-萘基） - 丙酸的硝基烷基酯的方法，其特征在于， 其中A是酸酰基残基的式A-Hal的2-（S） - （6-甲氧基-2-萘基） - 丙酸的卤化物在惰性有机溶剂中与脂族硝基链烷醇HO-Y- ONO 2，其中Y是C 3 -C 20亚烷基或3至8个碳原子的亚环烷基，或在无机碱存在下含有如定义的亚环烷基的亚烷基。