公开(公告)号：US06329542B1

公开(公告)日：2001-12-11

申请号：US09689215

申请日：2000-10-12

Applicant: Jollie D. Godfrey, Jr. ,  David R. Kronenthal ,  Mark D. Schwinden ,  Sushil K. Srivastava ,  Keith Ramig ,  John J. Venit ,  Paul A. Jass ,  Saibaba Racha ,  John L. Dillon, Jr. ,  Nachimuthu Soundararajan ,  Gerald L. Powers ,  Atul S. Kotnis

Inventor： Jollie D. Godfrey, Jr. ,  David R. Kronenthal ,  Mark D. Schwinden ,  Sushil K. Srivastava ,  Keith Ramig ,  John J. Venit ,  Paul A. Jass ,  Saibaba Racha ,  John L. Dillon, Jr. ,  Nachimuthu Soundararajan ,  Gerald L. Powers ,  Atul S. Kotnis

IPC: C07C6966

CPC classification number: C07C229/22 ,  C07D317/30

Abstract: The glycinamide of the formula is reacted with the dioxolane of the formula wherein L is a leaving group such as iodo, bromo, alkylsulfonyloxy, or arylsulfonyloxy to give the dioxolane of the formula Treating the dioxolane of formula III under aqueous refluxing conditions followed by exchanging the dioxolane acetal with a dimethoxy acetal and introduction of the methyl ester gives (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester which is an intermediate in the preparation of the dual inhibitor [4S-[4&agr;(R*),7&agr;,10a&bgr;]]-octahydro-4-[(2-mercapto-1-oxo-3-phenylpropyl)-amino]-5-oxo-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid. Also disclosed are storage stable salts of (S)-2-amino-6, 6-dimethoxyhexanoic acid, methyl ester.

Abstract translation: 式中的甘氨酰胺与二氢呋喃的反应是离去基团如碘，溴，烷基磺酰氧基或芳基磺酰氧基，得到下式的二氧戊环：在含水回流条件下，将式III的二氧戊环，然后与二氧戊环缩醛交换， 得到（S）-2-氨基-6,6-二甲氧基己酸甲酯，其是制备双重抑制剂[4S- [4α（R *），7α， 10]] - 八氢-4 - [（2-巯基-1-氧代-3-苯基丙基） - 氨基] -5-氧代-7H-吡啶并[2,1-b] [1,3]硫氮杂-7-羧酸 酸。 还公开了（S）-2-氨基-6,6-二甲氧基己酸甲酯的储存稳定的盐。

公开(公告)号：US5629429A

公开(公告)日：1997-05-13

申请号：US486111

申请日：1995-06-07

Applicant: David R. Kronenthal ,  Richard H. Mueller ,  Jollie D. Godfrey, Jr.

Inventor： David R. Kronenthal ,  Richard H. Mueller ,  Jollie D. Godfrey, Jr.

IPC: C07D233/54 ,  C07D405/12 ,  C07D493/04 ,  C07D233/02 ,  C07D233/04

CPC classification number: C07D405/12 ,  C07D493/04

Abstract: A method of preparing compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof which comprises converting a compound of the formula ##STR2## where the R.sup.2 substituent contains a hydrogen atom which is more acidic than the starred (*) hydrogen atom in formula II, to the corresponding dianion of formula ##STR3## where M is a counterion preferably lithium or magnesium, using two equivalents of a base in an inert solvent such as tetrahydrofuran; then reacting compounds of formula IIA with an epoxide of formula ##STR4## to produce the compounds of formula I.

Abstract translation: 制备式I化合物及其药学上可接受的盐的方法，其包括转化式II化合物，其中R 2取代基含有比在星形（*）氢原子中酸性更高的氢原子 式Ⅱ与相应的式IIA的二价阴离子，其中M为抗衡离子优选为锂或镁，在惰性溶剂如四氢呋喃中使用2当量碱; 然后使式IIA的化合物与式III的环氧化物反应以制备式I的化合物。

公开(公告)号：US5594153A

公开(公告)日：1997-01-14

申请号：US498493

申请日：1995-07-05

Applicant: John K. Thottathil ,  Yadagiri Pendri ,  Wen-Sen Li ,  David R. Kronenthal

Inventor： John K. Thottathil ,  Yadagiri Pendri ,  Wen-Sen Li ,  David R. Kronenthal

IPC: C07C69/675 ,  C07C69/716 ,  C07C319/06 ,  C07D319/06

CPC classification number: C07C319/06 ,  C07C69/675 ,  C07C69/716

Abstract: A novel, overall process for the preparation of a compound of the formula I: ##STR1## where R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group; andR.sup.3 is hydrogen, an alkyl group, or an aryl group, or salts thereof, useful as intermediates in the preparation of HMG-CoA reductase inhibitors; novel methods within the overall process; and novel intermediates produced by those methods.

Abstract translation: 一种用于制备式I化合物的新颖的总体方法：其中R 1和R 2各自独立地为氢，烷基，环烷基，芳基或与碳原子一起 它们相连，形成环烷基; 和R3是氢，烷基或芳基，或其盐，可用作制备HMG-CoA还原酶抑制剂的中间体; 整体过程中的新颖方法; 和由这些方法生产的新型中间体。

公开(公告)号：US07968718B2

公开(公告)日：2011-06-28

申请号：US12548809

申请日：2009-08-27

Applicant: Nachimuthu Soundararajan ,  Yuping Qiu ,  Wenhao Hu ,  David R. Kronenthal ,  Pierre Sirard ,  Jean Lajeunesse ,  Robert Droghini ,  Ramakrishnan Chidambaram ,  Xinhua Qian ,  Kenneth J. Natalie ,  Shawn K. Pack ,  Nathan Reising ,  Erqing Tang ,  Michael G. Fakes ,  Qi Gao ,  Feng Qian ,  Blisse J. Vakkalagadda ,  Chiajen Lai ,  Shan-Ming Kuang

Inventor： Nachimuthu Soundararajan ,  Yuping Qiu ,  Wenhao Hu ,  David R. Kronenthal ,  Pierre Sirard ,  Jean Lajeunesse ,  Robert Droghini ,  Ramakrishnan Chidambaram ,  Xinhua Qian ,  Kenneth J. Natalie ,  Shawn K. Pack ,  Nathan Reising ,  Erqing Tang ,  Michael G. Fakes ,  Qi Gao ,  Feng Qian ,  Blisse J. Vakkalagadda ,  Chiajen Lai ,  Shan-Ming Kuang

IPC: C07D471/02

CPC classification number: C07D471/04 ,  C07C311/49 ,  C07D213/26

Abstract: A process is provided for preparing triazole substituted azaindoleoxoacetic piperazine derivative. Novel intermediates produced in the above process, and novel N-1 and amorphous forms of a 1,2,3-triazole substituted azaindoloxoacetic piperazine derivatives and processes for producing such novel forms are also provided.

Abstract translation: 提供制备三唑取代的氮杂糊精乙酸哌嗪衍生物的方法。 还提供了在上述方法中制备的新型中间体和新的N-1和无定形形式的1,2,3-三唑取代的氮杂寡脱氧乙酸哌嗪衍生物及其制备方法。

公开(公告)号：US07034152B2

公开(公告)日：2006-04-25

申请号：US10734012

申请日：2003-12-11

Applicant: Yadagiri R. Pendri ,  Chung-Pin H. Chen ,  Sunil S. Patel ,  Jeffrey M. Evans ,  Jing Liang ,  David R. Kronenthal ,  Gerald L. Powers ,  Siva Josyula Prasad ,  Jeffrey T. Bien ,  Zhongping Shi ,  Ramesh N. Patel ,  Amit Banerjee ,  Yeung Yu Chan ,  Sushil K. Rijhwani ,  Ambarish K. Singh ,  Shaopeng Wang ,  Milan Stojanovic ,  David J. Kucera ,  Richard P. Polniaszek ,  Charles Lewis ,  John Thottathil ,  Dhileepkumar Krishnamurty ,  Maotang X. Zhou ,  Purushotham Vemishetti

Inventor： Yadagiri R. Pendri ,  Chung-Pin H. Chen ,  Sunil S. Patel ,  Jeffrey M. Evans ,  Jing Liang ,  David R. Kronenthal ,  Gerald L. Powers ,  Siva Josyula Prasad ,  Jeffrey T. Bien ,  Zhongping Shi ,  Ramesh N. Patel ,  Amit Banerjee ,  Yeung Yu Chan ,  Sushil K. Rijhwani ,  Ambarish K. Singh ,  Shaopeng Wang ,  Milan Stojanovic ,  David J. Kucera ,  Richard P. Polniaszek ,  Charles Lewis ,  John Thottathil ,  Dhileepkumar Krishnamurty ,  Maotang X. Zhou ,  Purushotham Vemishetti

IPC: C07D473/18 ,  C07D7/08 ,  C07D473/40 ,  C07F7/10 ,  C07F7/18

CPC classification number: C07F7/083 ,  C07D473/18 ,  C07F7/081 ,  C07F7/0812 ,  C07F7/0814 ,  C07F7/0827 ,  C07F7/1804

Abstract: Processes are disclosed for preparing the antiviral agent entecavir. A resin adsorption process for the isolation and purification of entecavir is also disclosed. Various intermediates useful in the preparation of entecavir are also disclosed.

Abstract translation: 公开了制备抗病毒剂恩替卡韦的方法。 还公开了用于恩替卡韦的分离和纯化的树脂吸附方法。 还公开了可用于制备恩替卡韦的各种中间体。

公开(公告)号：US5616775A

公开(公告)日：1997-04-01

申请号：US596811

申请日：1996-02-05

Applicant: David R. Kronenthal ,  Jollie D. Godfrey, Jr.

Inventor： David R. Kronenthal ,  Jollie D. Godfrey, Jr.

IPC: A61K38/00 ,  C07C315/02 ,  C07C317/50 ,  C07C319/14 ,  C07C319/20 ,  C07C323/59 ,  C07C327/34 ,  C07D513/04 ,  C07K5/078 ,  C07C381/00

CPC classification number: C07D513/04 ,  C07C315/02 ,  C07C319/14 ,  C07C319/20 ,  C07C327/34 ,  C07K5/06139 ,  A61K38/00 ,  Y02P20/55

Abstract: Homocysteine analogs of the formula ##STR1## wherein P.sub.1 is a nitrogen protecting group and R.sub.6 is alkyl, substituted alkyl or benzyl are prepared by esterifying N-protected L-methionine, oxidizing, treating the resulting sulfoxide with an acid anhydride, treating the resulting product with an alkali metal hydroxide followed by removal of formaldehyde and the treatment with an acid anhydride or acid halide. The L-homocysteine analogs are useful as intermediates in the preparation of compounds containing a fused bicyclic ring.

Abstract translation: 其中P1为氮保护基，R6为烷基，取代的烷基或苄基的式为“IMAGE”的同型半胱氨酸类似物通过酯化N-保护的L-甲硫氨酸，用酸酐氧化，处理所得亚砜，制备所得产物 用碱金属氢氧化物除去甲醛，用酸酐或酰卤处理。 L-同型半胱氨酸类似物可用作制备含有稠合双环的化合物的中间体。

公开(公告)号：US5436347A

公开(公告)日：1995-07-25

申请号：US247825

申请日：1994-05-20

Applicant: Sharon D. Real ,  David R. Kronenthal

Inventor： Sharon D. Real ,  David R. Kronenthal

IPC: C07D493/18 ,  C07D493/08

CPC classification number: C07D493/18

Abstract: A method is provided for preparing a chiral benzaldehyde of the structure ##STR1## by acylating an anhydride of the structure ##STR2## with a chiral oxazolidine of the structure ##STR3## where Q is MgHal or Li, and X, Y and Z are as described herein, to form a keto acid which is reduced and cyclized. The resulting benzaldehyde may be used in making the final anti-thrombotic--anti-vasospastic compounds. Novel intermediates are also provided.

Abstract translation: 提供了一种制备具有结构“IMAGE”结构的手性苯甲醛的方法，其中使用结构式“IMAGE”的手性恶唑烷，其中Q为MgHal或Li，X，Y和Z为 以形成还原和环化的酮酸。 所得苯甲醛可用于制备最终的抗血栓形成 - 抗血管痉挛性化合物。 还提供了新的中间体。

公开(公告)号：US5332840A

公开(公告)日：1994-07-26

申请号：US67885

申请日：1993-05-27

Applicant: Sharon D. Real ,  David R. Kronenthal

Inventor： Sharon D. Real ,  David R. Kronenthal

IPC: C07D493/18 ,  C07D493/08

CPC classification number: C07D493/18

Abstract: A method is provided for preparing a chiral benzaldehyde of the structure ##STR1## by acylating an anhydride of the structure ##STR2## with a chiral oxazolidine of the structure ##STR3## where Q is MgHal or Li, and X, Y and Z are as described herein, to form a keto acid which is reduced and cyclized. The resulting benzaldehyde may be used in making the final anti-thrombotic - anti-vasospastic compounds. Novel intermediates are also provided.

Abstract translation: 提供了一种制备具有结构“IMAGE”结构的手性苯甲醛的方法，其中使用结构式“IMAGE”的手性恶唑烷，其中Q为MgHal或Li，X，Y和Z为 以形成还原和环化的酮酸。 所得苯甲醛可用于制备最终的抗血栓形成 - 抗血管痉挛型化合物。 还提供了新的中间体。

公开(公告)号：US07074921B2

公开(公告)日：2006-07-11

申请号：US10292093

申请日：2002-11-12

Applicant: David R. Kronenthal ,  Rao S. Bhandaru ,  Zhongping Shi ,  Boguslaw M. Mudryk

Inventor： David R. Kronenthal ,  Rao S. Bhandaru ,  Zhongping Shi ,  Boguslaw M. Mudryk

IPC: C07D243/14 ,  A61K31/55 ,  A61P35/00

CPC classification number: C07D233/64 ,  C07C255/58 ,  C07C255/61 ,  C07D243/14 ,  C07D333/34 ,  C07D403/06 ,  C07D409/12 ,  C07D409/14 ,  C07F7/1804

Abstract: Methods for the synthesis of benzodiazepine compounds having farnesyl protein transferase inhibitory activity.

公开(公告)号：US06486315B2

公开(公告)日：2002-11-26

申请号：US09993872

申请日：2001-11-16

Applicant: David R. Kronenthal ,  Rajendra P. Deshpande ,  James Simpson

Inventor： David R. Kronenthal ,  Rajendra P. Deshpande ,  James Simpson

IPC: C07D22302

CPC classification number: C07D513/04 ,  C07D223/12

Abstract: Mercaptoalkanoylamino lactam acids are recrystallized by treatment with an agent that minimizes the formation of disulfides. Suitable agents are bismercaptans, phosphine or phosphite reducing agents, zinc metal powder, and sodium hydrosulfite.

Abstract translation: 巯基乙酰氨基内酰胺酸通过用最小化二硫化物形成的试剂处理来重结晶。 合适的试剂是双硫醇，膦或亚磷酸酯还原剂，锌金属粉末和连二亚硫酸钠。