公开(公告)号：US06677462B2

公开(公告)日：2004-01-13

申请号：US09923462

申请日：2001-08-06

申请人： Shoujun Chen ,  Lijun Sun ,  Joel McCleary

发明人： Shoujun Chen ,  Lijun Sun ,  Joel McCleary

IPC分类号： C07D30930

CPC分类号： C07F9/6552 ,  C07C67/31 ,  C07C67/343 ,  C07D309/32 ,  C07C69/732 ,  C07C69/738

摘要： This invention relates to preparation of enantio-enriched compounds, and more particularly to enantio-enriched kavalactone compounds and derivatives thereof. The methods provide compounds that are useful as reagents, or building blocks, in the construction of other enantio-enriched compounds.

摘要翻译： 本发明涉及富含对映体的化合物的制备，更具体地涉及对映体富集的考康内酯化合物及其衍生物。 该方法提供了在构建其它富含烯聚合物的化合物中可用作试剂或构建单元的化合物。

公开(公告)号：US06521762B2

公开(公告)日：2003-02-18

申请号：US09793946

申请日：2001-02-27

申请人： Vilmos Keri ,  Ilona Forgas

发明人： Vilmos Keri ,  Ilona Forgas

IPC分类号： C07D30930

CPC分类号： C07D309/30

摘要： A process reducing the levels of dimeric impurities in a statin to less than 0.08% by treatment of a statin containing more than 0.08% dimeric impurities with a mild base in a suitable solvent mixture.

公开(公告)号：US06376683B1

公开(公告)日：2002-04-23

申请号：US09872849

申请日：2001-06-01

申请人： Pradeep Kumar ,  Rodney Agustinho Fernandes

发明人： Pradeep Kumar ,  Rodney Agustinho Fernandes

IPC分类号： C07D30930

CPC分类号： C07D309/30 ,  Y02P20/582

摘要： The present invention relates to an improved, efficient and enantio-selective process for the synthesis of (4R, 6S)-4-hydroxy-6-hydroxymethyl tetrahydropyran-2-one, employing the Sharpless asymmetric dihydroxylation and regiospecific nucleophilic hydride opening of the cyclic sulfite/sulfate as the key steps. The invention also resides in the intermediates used in the process.

摘要翻译： 本发明涉及一种用于合成（4R，6S）-4-羟基-6-羟甲基四氢吡喃-2-酮的改进的，有效的和对映体选择性方法，采用Sharpless不对称二羟基化和区域特异性亲核氢化物开环的环状 亚硫酸盐/硫酸盐为关键步骤。 本发明也在于该方法中使用的中间体。

公开(公告)号：US06642394B2

公开(公告)日：2003-11-04

申请号：US10363912

申请日：2003-03-10

申请人： Naoshi Murata ,  Kimio Tamura ,  Yasukazu Yoshida ,  Motomu Ohkita

发明人： Naoshi Murata ,  Kimio Tamura ,  Yasukazu Yoshida ,  Motomu Ohkita

IPC分类号： C07D30930

CPC分类号： C07C67/08 ,  C07C51/56 ,  C07C2603/74 ,  C07C57/04 ,  C07C69/54

摘要： (Meth)acrylic acid is reacted with a fatty acid anhydride and the resultant reaction mixture is neutralized and washed with an aqueous alkaline solution having a pH of 7.5 to 13.5. Thus, high-purity (meth)acrylic anhydride can be industrially advantageously produced while avoiding polymerization. This (meth)acrylic anhydride is reacted with a secondary or tertiary alcohol in the presence of a basic compound which in 25° C. water has an acidity (pKa) of 11 or lower. Thus, a high-purity (meth)acrylic ester can be produced in high yield.

摘要翻译： （甲基）丙烯酸与脂肪酸酐反应，中和得到的反应混合物，并用pH为7.5〜13.5的碱性水溶液洗涤。 因此，高纯度（甲基）丙烯酸酐可以在工业上有利地生产，同时避免聚合。 该（甲基）丙烯酸酐在碱性化合物的存在下与仲醇或叔醇反应，其中25℃的水的酸度（pKa）为11或更低。 因此，可以高产率制备高纯度（甲基）丙烯酸酯。

公开(公告)号：US06512006B1

公开(公告)日：2003-01-28

申请号：US09641260

申请日：2000-08-17

申请人： Frederick Earl Boyer, Jr. ,  John Michael Domagala ,  Edmund Lee Ellsworth ,  Christopher Andrew Gajda ,  Elizabeth Ann Lunney ,  Alexander Pavlovsky ,  Vara Prasad Venkata Nagendra Josyula ,  Bradley Dean Tait

发明人： Frederick Earl Boyer, Jr. ,  John Michael Domagala ,  Edmund Lee Ellsworth ,  Christopher Andrew Gajda ,  Elizabeth Ann Lunney ,  Alexander Pavlovsky ,  Vara Prasad Venkata Nagendra Josyula ,  Bradley Dean Tait

IPC分类号： C07D30930

CPC分类号： C07D309/32

摘要： The present invention related to novel dihydropyrones possessing 3-position nitrogen atom, which inhabit the HIV aspartyl protease blocking HIV infectivity. The dihydropyrones are useful in the development of therapies for the treatment of viral infections, and diseases, including AIDS.

摘要翻译： 本发明涉及具有3-位氮原子的新型二氢吡喃酮，其存在HIV天冬氨酰蛋白酶阻断HIV感染性。 二氢吡喃酮可用于开发用于治疗病毒感染和包括艾滋病在内的疾病的治疗。

公开(公告)号：US06472542B1

公开(公告)日：2002-10-29

申请号：US09996664

申请日：2001-11-29

申请人： Edvige Galeazzi ,  Gustavo A. Garcia ,  Fernando Lara ,  Gema Lopez ,  Orestes Martinez ,  Eugenio Tisselli ,  Alicia Trejo

发明人： Edvige Galeazzi ,  Gustavo A. Garcia ,  Fernando Lara ,  Gema Lopez ,  Orestes Martinez ,  Eugenio Tisselli ,  Alicia Trejo

IPC分类号： C07D30930

CPC分类号： C07D309/30 ,  C07C235/30 ,  C07C2602/28 ,  C07F7/1804 ,  C07F7/1892 ,  Y02P20/55

摘要： Simvastatin is produced from lovastatin in high yield and in pharmaceutical purity by forming an amide of lovastatin and protecting the free hydroxyl groups of the lovastatin amide with hexamethyidisilazane (HMDS) to form a protected lovastatin amide. The &agr;-carbon of the 2-methylbutyrate secondary chain of the protected lovastatin amide may be methylated to form a protected simvastatin amide. The protecting groups may be removed therefrom by quenching the methylation reaction with water. The simvastatin amide which is obtained may be hydrolyzed to form simvastatin acid, followed by forming a simvastatin ammonium salt, lactonizing the salt to form simvastatin, and recrystallizing the thus formed crude Simvastatin to a high degree of purity. The HMDS protecting agent for the lactone hydroxyl groups of Lovastatin is selected so as to result in a reaction that does not produce acid so that a base, such as imidazole, is not required to neutralize the acidity of the reaction medium. Another advantage of using HMDS as a protecting agent is that the removal of the protecting agent after the methylation reaction is carried out simply, for example, by water quenching. The lactonization reaction of the present invention may be carried out using a low boiling point solvent, such as methylene chloride, in the presence of inorganic acids such as sulfuric, hydrochloric, methanesulfonic or phosphoric acid as catalyst.

摘要翻译： 辛伐他汀通过形成洛伐他汀的酰胺并以六水合二硅氮烷（HMDS）保护洛伐他汀酰胺的游离羟基，形成受保护的洛伐他汀酰胺，以高产率和药物纯度从洛伐他汀生产。 被保护的洛伐他汀酰胺的2-甲基丁酸二级链的α-碳可被甲基化以形成受保护的辛伐他汀酰胺。 通过用水淬灭甲基化反应可以将保护基除去。 所获得的辛伐他汀酰胺可以水解形成辛伐他汀酸，然后形成辛伐他汀铵盐，将盐内酯化形成辛伐他汀，并将由此形成的粗制辛伐他汀重结晶至高纯度。 选择洛伐他汀的内酯羟基的HMDS保护剂，以产生不产生酸的反应，从而不需要碱例如咪唑来中和反应介质的酸度。 使用HMDS作为保护剂的另一个优点是在甲基化反应后除去保护剂简单地例如通过水淬。 本发明的内酯化反应可以在无机酸如硫酸，盐酸，甲磺酸或磷酸作为催化剂的存在下，使用低沸点溶剂如二氯甲烷进行。

公开(公告)号：US06420569B1

公开(公告)日：2002-07-16

申请号：US09940470

申请日：2001-08-29

申请人： Kazuya Ujihara

发明人： Kazuya Ujihara

IPC分类号： C07D30930

CPC分类号： C07D493/04 ,  C07D309/38

摘要： 4-Hydroxy-6-methyl-3-(4-methyl-2-pentenoyl)-2-pyrone isobtained by allowing 2,3-dihydro-7-methyl-2-(1-methylethyl)-4H,5H-pyrano[4,3-b]pyran-4,5-dione to react with at least one inorganic compound selected from alkali hydroxides, alkaline earth hydroxides, alkali carbonates, alkaline earth carbonates and alkali fluorides in an alcohol, water or a mixture thereof.

摘要翻译： 通过使2,3-二氢-7-甲基-2-（1-甲基乙基）-4H，5H-吡喃并[2,3-b]吡唑并[1,2-a]所示的4-羟基-6-甲基-3-（4-甲基-2-戊烯酰基） 4,3-b]吡喃-4,5-二酮与醇，水或其混合物中的至少一种选自碱金属氢氧化物，碱土金属氢氧化物，碱金属碳酸盐，碱土金属碳酸盐和碱金属氟化物的无机化合物反应。

公开(公告)号：US06278001B1

公开(公告)日：2001-08-21

申请号：US08875446

申请日：1997-10-08

申请人： Guy Solladie ,  Claude Bauder

发明人： Guy Solladie ,  Claude Bauder

IPC分类号： C07D30930

CPC分类号： C07D309/30

摘要： A novel method for preparing (+)compactin and (+)mevinolin analog compounds having a &bgr;-hydroxy-&dgr;-lactone grouping is disclosed. The method for preparing said compounds uses novel reaction intermediates. Said reaction intermediates and the respective methods for preparing same are also disclosed.

摘要翻译： 公开了一种制备（+）压缩物和（+）具有β-羟基-δ-内酯基团的美维林类似物的新颖方法。 制备所述化合物的方法使用新的反应中间体。 还公开了所述反应中间体及其制备方法。

公开(公告)号：US06833461B2

公开(公告)日：2004-12-21

申请号：US10468852

申请日：2003-08-25

申请人： Chung Il Hong ,  Jung Woo Kim ,  Hee Jong Shin ,  Tae Won Kang ,  Dong Ock Cho

发明人： Chung Il Hong ,  Jung Woo Kim ,  Hee Jong Shin ,  Tae Won Kang ,  Dong Ock Cho

IPC分类号： C07D30930

CPC分类号： C07D309/30 ,  Y02P20/55

摘要： The present invention relates to an improved process for preparing simvastatin and more particularly, the improved process for preparing simvastatin expressed by formula 1 with high yield and high purity by performing the following sequential processes comprising: (i) hydrolysis of lovastatin as starting material with potassium t-butoxide in an organic solvent and small amount of water under a mild reaction condition, followed by lactonization of the obtained solid intermediate with preventing from formation of by-products; (ii) protection of an alcohol group with t-butyldimethylsilyl group which can be easily removed with concentrated hydrochloric acid without the formation of by-products; (iii) acylation of the obtained protected intermediate with acyloxytriphenyl phosphonium salt as an acylating agent under a mild reaction condition; and (iv) removal of the silyl protective group with a concentrated hydrochloric acid. The present invention is to provide the improved process of preparing simvastatin expressed by formula 1 environmentally sound, economically efficient, and industrially useful.

摘要翻译： 本发明涉及一种制备辛伐他汀的改进方法，更具体地说，涉及通过进行以下顺序方法制备具有高产率和高纯度的式1所表达的辛伐他汀的改进方法，包括：（i）将洛伐他汀作为原料与钾 叔丁醇在有机溶剂和少量水中，在温和的反应条件下，然后将所得固体中间体内酯化，防止副产物的形成; （ii）用叔丁基二甲基甲硅烷基保护醇基，其可以用浓盐酸容易地除去而不形成副产物; （iii）在温和的反应条件下用酰氧基三苯基鏻盐作为酰化剂酰化所得保护的中间体; 和（iv）用浓盐酸除去甲硅烷基保护基。 本发明提供了由式1表达的辛伐他汀的改进方法，其在环境无害，经济有效和工业上有用。

公开(公告)号：US06797831B2

公开(公告)日：2004-09-28

申请号：US10440537

申请日：2003-05-19

申请人： Ramesh Dandala ,  Sonny Sebastian ,  Sanapureddy Jagan Mohan Reddy ,  Meenakshisunderam Sivakumaran

发明人： Ramesh Dandala ,  Sonny Sebastian ,  Sanapureddy Jagan Mohan Reddy ,  Meenakshisunderam Sivakumaran

IPC分类号： C07D30930

CPC分类号： C07D309/30

摘要： There is disclosed a process for the manufacture of simvastatin of Formula I which comprises heating a compound, namely acid or ammonium salt of compound of Formula II, where Z is H or NH4 in an organic solvent at a temperature of 130-140° C.

摘要翻译： 公开了制备式I的辛伐他汀的方法，其包括在130-140℃的温度下，在有机溶剂中加热化合物即式II化合物的酸或铵盐，其中Z是H或NH 4。