公开(公告)号：US06858747B2

公开(公告)日：2005-02-22

申请号：US10819910

申请日：2004-04-08

Applicant: Daqing Che ,  Bhaskar Reddy Guntoori ,  K. S. Keshava Murthy

Inventor： Daqing Che ,  Bhaskar Reddy Guntoori ,  K. S. Keshava Murthy

IPC: C07D211/90 ,  C07C69/79 ,  C07C205/00

CPC classification number: C07D211/90

Abstract: An improved catalyst is disclosed for a process involving the preparation of benzylidene intermediates useful in the preparation of 1,4-dihydropyridine compounds and derivatives thereof useful as medicines such as for example felodipine. This is accomplished by the condensation of an aldehyde and an acetoacetate in the presence of a novel catalyst system that includes a pyridyl carboxylic acid and a secondary amine. It has been found that through the use of the present invention the purity and yield of the desired isomer of the benzylidene intermediate can be maximized, thus avoiding the requirement of additional purification steps. The use of these intermediates can then be further reacted to form the required dihydropyridines, again having a very high purity and yield compared with the prior art.

Abstract translation: 公开了一种改进的催化剂，其用于制备可用作制备1,4-二氢吡啶化合物及其衍生物的亚苄基中间体的方法，其用作药物，例如非洛地平。 这可以通过醛和乙酰乙酸酯在包含吡啶羧酸和仲胺的新型催化剂体系的存在下缩合来实现。 已经发现，通过使用本发明，可以使亚苄基中间体的所需异构体的纯度和产率最大化，从而避免了额外的纯化步骤的需要。 然后可以将这些中间体的使用进一步反应以形成所需的二氢吡啶，与现有技术相比，再次具有非常高的纯度和产率。

公开(公告)号：US09394251B2

公开(公告)日：2016-07-19

申请号：US14365638

申请日：2012-07-27

Applicant: Bin Zhang ,  Xiaowei Hu ,  Pucha Yan ,  Xianyi Zhang ,  Hongjun Gao ,  Yuanqiang Li ,  Daqing Che

Inventor： Bin Zhang ,  Xiaowei Hu ,  Pucha Yan ,  Xianyi Zhang ,  Hongjun Gao ,  Yuanqiang Li ,  Daqing Che

IPC: C07D209/08 ,  C07F7/00 ,  C07F7/02 ,  C07F7/18 ,  C07F9/6539

CPC classification number: C07D209/08 ,  C07F7/00 ,  C07F7/02 ,  C07F7/18 ,  C07F9/65397 ,  Y02P20/55

Abstract: Disclosed are a silodosin intermediate and a preparation method thereof. The silodosin intermediate has the structure shown by the formula (A). X is hydrogen or bromide and R1 is hydrogen. The formyl group may be a group having the structure shown by the formula I. R7 is a protecting group of carboxyl, and R2 is 3-hydroxypropyl or a group having the structure shown by the formula II. W is a protecting group of hydroxyl. A compound of the formula (A) according to the present invention may further be used for preparing a compound having the structure shown by the formula (D). By means of the intermediate and the preparation method therefor provided by the present invention, high-purity optically pure silodosin can be obtained, and the optical purity is above 99%.

Abstract translation: 公开了一种西洛多辛中间体及其制备方法。 西洛德辛中间体具有式（A）所示的结构。 X是氢或溴，R 1是氢。 甲酰基可以是具有式I所示结构的基团.R 7是羧基的保护基，R 2是3-羟丙基或具有式II所示结构的基团。 W是羟基的保护基。 根据本发明的式（A）化合物还可用于制备具有式（D）所示结构的化合物。 通过本发明提供的中间体及其制备方法，可以得到高纯度的光学纯的芝麻酮，光学纯度高于99％。

公开(公告)号：US08829226B2

公开(公告)日：2014-09-09

申请号：US13579065

申请日：2011-01-28

Applicant: Xianyi Zhang ,  Shaoqing Ge ,  Daqing Che

Inventor： Xianyi Zhang ,  Shaoqing Ge ,  Daqing Che

IPC: C07C271/22 ,  C07C269/06 ,  C07C231/02

CPC classification number: C07C231/02 ,  C07C269/06 ,  C07C271/22 ,  C07C237/06

Abstract: A new compound is provided, which is used for preparing lacosamide. A novel method for preparing lacosamide is also provided. During the reaction, iodomethane and silver oxide that are cost expensive are not used, nor a Pd-c catalyst is used, so the production cost is low, the raw materials and accessory materials are cheap and easily available, and the process is simple, so that industrial production is easy to realize; and moreover, the yield is high, and good economic efficiency can be achieved.

Abstract translation: 提供了一种新的化合物，用于制备lacosamide。 还提供了一种制备lacosamide的新方法。 在反应过程中，不使用成本昂贵的碘甲烷和氧化银，也不使用Pd-c催化剂，因此生产成本低，原材料和辅助材料便宜且易于使用，工艺简单， 使工业生产容易实现; 而且产量高，可以实现良好的经济效益。

公开(公告)号：US07935817B2

公开(公告)日：2011-05-03

申请号：US12059321

申请日：2008-03-31

Applicant: Peter Garth Blazecka ,  Daqing Che ,  Cameron L. McPhail ,  Allan W. Rey

Inventor： Peter Garth Blazecka ,  Daqing Che ,  Cameron L. McPhail ,  Allan W. Rey

IPC: C07F9/6561 ,  A61K31/675

CPC classification number: C07F9/65616

Abstract: Provided are a cocrystal of Adefovir dipivoxil and nicotinamide as well as a cocrystal of Adefovir dipivoxil and salicylamide cocrystal and processes for the preparation thereof.

Abstract translation: 提供了阿德福韦酯和烟酰胺的共结晶，以及阿德福韦酯和水杨酰胺共晶体的共结晶体及其制备方法。

公开(公告)号：US20100324298A1

公开(公告)日：2010-12-23

申请号：US12855667

申请日：2010-08-12

Applicant: Fan Wang ,  Laura Kaye Montemayor ,  Daqing Che ,  Stephen E. Horne

Inventor： Fan Wang ,  Laura Kaye Montemayor ,  Daqing Che ,  Stephen E. Horne

IPC: C07D401/12

CPC classification number: C07D401/12 ,  Y02P20/55

Abstract: A novel process for the preparation of omeprazole and its enantiomers, such as esomeprazole, as well as the preparation of related 2-(2-pyridinylmethyl-sulphinyl)-1H-benzimidazoles, including pantoprazole, lansoprazole and rabeprazole, as recemates or single enantiomers, and their alkali or alkaline salts has been developed. The novel process involves the surprising discovery that protection of the free-base benzimidazole sulfoxide (e.g. omeprazole or esomeprazole), by reaction with an alkyl, aryl or aralkyl chloroformate following oxidation of the corresponding sulfide, eliminates the need for its direct isolation. Subsequent removal of the protecting group with a solution of alkali or alkaline earth alkoxide in a C1-C4 alcohol directly provides the corresponding salt. By eliminating the need to handle the free-base benzimidazole sulfoxide, this advantageous procedure provides increased chemical yields over processes described in the art.

Abstract translation: 一种用于制备奥美拉唑及其对映异构体的新方法，例如艾美拉唑，以及相关的2-（2-吡啶基甲基 - 亚磺酰基）-1H-苯并咪唑（包括泮托拉唑，兰索拉唑和雷贝拉唑）作为受体或单一对映异构体的制备， 并开发了它们的碱金属盐或碱金属盐。 该新方法涉及令人惊奇的发现：在相应的硫化物氧化后，通过与烷基，芳基或氯甲酸烷基酯反应来保护游离碱性苯并咪唑亚砜（例如奥美拉唑或埃索美拉唑）消除了对其直接分离的需要。 随后用碱金属或碱土金属醇溶液在C1-C4醇中除去保护基团直接提供相应的盐。 通过消除处理游离碱性苯并咪唑亚砜的需要，与本领域中描述的方法相比，该有利的方法提供了增加的化学产率。

公开(公告)号：US07709634B2

公开(公告)日：2010-05-04

申请号：US11902211

申请日：2007-09-20

Applicant: Kiran Kumar Kothakonda ,  Daqing Che

Inventor： Kiran Kumar Kothakonda ,  Daqing Che

IPC: C07D498/22

CPC classification number: C07D498/22

Abstract: A stable amorphous form of rifaximin is disclosed. This form is chemically and polymorphically stable on storage and can be prepared by dissolving rifaximin in a solvent to form a solution, which is precipitated by adding an anti-solvent and isolating of the precipitated amorphous rifaximin as an end product.

Abstract translation: 公开了稳定的无定形形式的利福昔明。 这种形式在储存时是化学上和多晶型稳定的，并且可以通过将利福昔明溶解在溶剂中以形成溶液来制备，所述溶液通过加入抗溶剂和分离沉淀的无定形的利福昔明作为最终产物而沉淀。

公开(公告)号：US20080319189A1

公开(公告)日：2008-12-25

申请号：US11976978

申请日：2007-10-30

Applicant: Kiran Kumar Kothakonda ,  Daqing Che ,  Bhaskar Reddy Guntoori

Inventor： Kiran Kumar Kothakonda ,  Daqing Che ,  Bhaskar Reddy Guntoori

IPC: C07D243/10

CPC classification number: C07D495/04

Abstract: There is provided a process for the preparation of olanzapine comprising: i) reacting 4-amino-2-methyl-10H-thieno-[2,3-b][1,5]benzodiazepine and N-methylpiperazine in a C1 to C4 alcoholic solvent or mixture thereof at suitable temperature and for a suitable time, ii) cooling the reaction mixture, and iii) isolating the precipitated olanzapine.

Abstract translation: 提供了一种制备奥氮平的方法，其包括：i）使4-氨基-2-甲基-10H-噻吩并[2,3-b] [1,5]苯并二氮杂和N-甲基哌嗪在C1至C4醇中反应 溶剂或其混合物在合适的温度和合适的时间，ii）冷却反应混合物，和iii）分离沉淀的奥氮平。

公开(公告)号：US20060194867A1

公开(公告)日：2006-08-31

申请号：US11099624

申请日：2005-04-06

Applicant: Fan Wang ,  Daqing Che ,  Bhaskar Guntoori ,  Yajun Zhao ,  Aaron Kinsman ,  Jody Faught ,  Alan Chow

Inventor： Fan Wang ,  Daqing Che ,  Bhaskar Guntoori ,  Yajun Zhao ,  Aaron Kinsman ,  Jody Faught ,  Alan Chow

IPC: A61K31/401 ,  C07D207/34

CPC classification number: C07D207/34

Abstract: A process is provided for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 comprising: (a) reacting the aldehyde 1 with the enolate form of (S)-2-hydroxy-1,2,2-triphenylethyl acetate substituent in a chelating co-solvent; (b) hydrolysis of (R,S)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (S)-2-hydroxy-1,2,2-triphenylethyl ester (2a and 2b) using a base, preferably an alkali metal base, preferably in a solvent to form the carboxylic acid 7; (c) treating the acid 7 with a chiral base to form a salt and purifying the salt to obtain enantiomerically enriched (R)-7 chiral base salt; (d) alkylation of the (R)-7 chiral base salt or the free base derived from (R)-7, forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 and atorvastatin calcium 6, wherein R is a C1 to C6 alkyl, C6 to C9 aryl or C7 to C10 aralkyl.

Abstract translation: 提供了制备（R）-5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基] -5-羟基-3-氧代-1-庚酸，R-取代的酯9，其包含：（a）使醛1与烯醇化形式的（S）-2-羟基-1,2,2-三苯基乙基乙酸酯取代基 在螯合助溶剂中; （b）（R，S）-5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基 ] -3-羟基-1-戊酸，（S）-2-羟基-1,2,2-三苯基乙酯（2a和2b），使用碱，优选碱金属碱，优选在溶剂中形成羧酸 酸7; （c）用手性碱处理酸7以形成盐并纯化该盐以获得对映体富集的（R）-7手性碱盐; （d）（R）-7手性碱盐或衍生自（R）-7的游离碱的烷基化，形成（R）-5- [2-（4-氟苯基）-5-（1-甲基乙基） 3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基] -5-羟基-3-氧代-1-庚酸，R-取代的酯9和阿托伐他汀钙6，其中R是C1 C6烷基，C6〜C9芳基或C7〜C10芳烷基。

公开(公告)号：US20050203302A1

公开(公告)日：2005-09-15

申请号：US10800741

申请日：2004-03-16

Applicant: Bhaskar Guntoori ,  Daqing Che ,  Fan Wang ,  Yajun Zhao ,  K.S. Murthy ,  Stephen Horne

Inventor： Bhaskar Guntoori ,  Daqing Che ,  Fan Wang ,  Yajun Zhao ,  K.S. Murthy ,  Stephen Horne

IPC: C07D207/34 ,  C07D207/416 ,  C07D27/36

CPC classification number: C07D207/416 ,  C07D207/34

Abstract: A process for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, tert-butylester comprising: (a) reduction of 5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-oxo-1-pentanoic acid, (R)-2-hydroxy-1,2,2-triphenylethyl ester; (b) hydrolysis of (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (R)-2-hydroxy-1,2,2-triphenylethyl ester using an alkali base in a solvent to form the acid; (c) alkylation of the acid forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, tert-butylester.

Abstract translation: 制备（R）-5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基] 包括：（a）还原5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（ 苯基氨基）羰基] -1H-吡咯-1-基] -3-氧代-1-戊酸，（R）-2-羟基-1,2,2-三苯乙基酯; （b）（R）-5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基] -3-羟基-1-戊酸，（R）-2-羟基-1,2,2-三苯基乙基酯，使用碱在溶剂中形成酸; （c）酸形成（R）-5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1 - 基] -5-羟基-3-氧代-1-庚酸叔丁酯。

公开(公告)号：US07812179B2

公开(公告)日：2010-10-12

申请号：US12222690

申请日：2008-08-14

Applicant: Fan Wang ,  Daqing Che ,  Bhaskar Reddy Guntoori ,  Yajun Zhao ,  Aaron C. Kinsman ,  Jody Faught ,  Alan Chow

Inventor： Fan Wang ,  Daqing Che ,  Bhaskar Reddy Guntoori ,  Yajun Zhao ,  Aaron C. Kinsman ,  Jody Faught ,  Alan Chow

IPC: C07D207/333

CPC classification number: C07D207/34

Abstract: A process is provided for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 comprising: (a) reacting the aldehyde 1 with the enolate form of (S)-2-hydroxy-1,2,2-triphenylethyl acetate substituent in a chelating co-solvent; (b) hydrolysis of (R,S)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (S)-2-hydroxy-1,2,2-triphenylethyl ester (2a and 2b) using a base, preferably an alkali metal base, preferably in a solvent to form the carboxylic acid 7; (c) treating the acid 7 with a chiral base to form a salt and purifying the salt to obtain enantiomerically enriched (R)-7 chiral base salt; (d) alkylation of the (R)-7 chiral base salt or the free base derived from (R)-7, forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 and atorvastatin calcium 6, wherein R is a C1 to C6 alkyl, C6 to C9 aryl or C7 to C10 aralkyl.

Abstract translation: 提供了制备（R）-5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基] -5-羟基-3-氧代-1-庚酸，R-取代的酯9，其包含：（a）使醛1与烯醇化形式的（S）-2-羟基-1,2,2-三苯基乙基乙酸酯取代基 在螯合助溶剂中; （b）（R，S）-5- [2-（4-氟苯基）-5-（1-甲基乙基）-3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基 ] -3-羟基-1-戊酸，（S）-2-羟基-1,2,2-三苯基乙酯（2a和2b），使用碱，优选碱金属碱，优选在溶剂中形成羧酸 酸7; （c）用手性碱处理酸7以形成盐并纯化该盐以获得对映体富集的（R）-7手性碱盐; （d）（R）-7手性碱盐或衍生自（R）-7的游离碱的烷基化，形成（R）-5- [2-（4-氟苯基）-5-（1-甲基乙基） 3-苯基-4 - [（苯基氨基）羰基] -1H-吡咯-1-基] -5-羟基-3-氧代-1-庚酸，R-取代的酯9和阿托伐他汀钙6，其中R是C1 C6烷基，C6〜C9芳基或C7〜C10芳烷基。