Process for Preparing Amorphous Rosuvastatin Calcium of Impurities
    1.
    发明申请
    Process for Preparing Amorphous Rosuvastatin Calcium of Impurities 有权
    制备无定形罗苏伐他汀钙杂质的方法

    公开(公告)号:US20090111839A1

    公开(公告)日:2009-04-30

    申请号:US11922532

    申请日:2006-06-22

    CPC分类号: C07D239/42

    摘要: A pure amorphous form of rosuvastatin calcium substantially free from alkali metal impurities is disclosed. A process of preparing a pure amorphous form of rosuvastatin calcium is disclosed, which comprises hydrolysis of C1-C5 alkyl esters of rosuvastatin, preferably tert-butyl ester of rosuvastatin, with an organic nitrogen base, e.g. guanidines, amidines, amines and quaternary ammonium hydroxides, in the presence of water, optionally containing aprotic solvent, following the conversion of thus obtained rosuvastatin salt with a source of calcium to obtain rosuvastatin calcium, which is then isolated. An alternative process is disclosed, which comprises the conversion of numerous novel ammonium salts of rosuvastatin, preferably tert-octylammonium salt of rosuvastatin, with the source of calcium to desired commercial rosuvastatin calcium. Rosuvastatin calcium is an inhibitor of HMG CoA reductase, useful in the treatment of hyperlipidemia, hypercholesterolemia and atherosclerosis.

    摘要翻译: 公开了一种基本上不含碱金属杂质的纯粹无定形的瑞舒伐他汀钙。 公开了一种制备纯无定形形式的瑞舒伐他汀钙的方法,其包括将瑞舒伐他汀的C 1 -C 5烷基酯,优选罗苏伐他汀的叔丁酯与有机氮碱例如水解。 胍,脒,胺和季铵氢氧化物,在水存在下,任选地含有非质子溶剂,随后将得到的瑞舒伐他汀盐与钙源转化,得到瑞舒伐他汀钙,然后将其分离。 公开了一种替代方法,其包括将瑞舒伐他汀的许多新型铵盐,优选罗苏伐他汀的叔辛基铵盐与钙源转化为所需的商业罗苏伐他汀钙。 罗苏伐他汀钙是HMG CoA还原酶的抑制剂,可用于治疗高脂血症,高胆固醇血症和动脉粥样硬化。

    Process for preparing amorphous rosuvastatin calcium of impurities
    2.
    发明授权
    Process for preparing amorphous rosuvastatin calcium of impurities 有权
    制备无定形罗苏伐他汀钙杂质的方法

    公开(公告)号:US09150518B2

    公开(公告)日:2015-10-06

    申请号:US11922532

    申请日:2006-06-22

    IPC分类号: C07D239/42

    CPC分类号: C07D239/42

    摘要: A pure amorphous form of rosuvastatin calcium substantially free from alkali metal impurities is disclosed. A process of preparing a pure amorphous form of rosuvastatin calcium is disclosed, which comprises hydrolysis of C1-C5 alkyl esters of rosuvastatin, preferably tert-butyl ester of rosuvastatin, with an organic nitrogen base, e.g. guanidines, amidines, amines and quaternary ammonium hydroxides, in the presence of water, optionally containing aprotic solvent, following the conversion of thus obtained rosuvastatin salt with a source of calcium to obtain rosuvastatin calcium, which is then isolated. An alternative process is disclosed, which comprises the conversion of numerous novel ammonium salts of rosuvastatin, preferably tert-octylammonium salt of rosuvastatin, with the source of calcium to desired commercial rosuvastatin calcium. Rosuvastatin calcium is an inhibitor of HMG CoA reductase, useful in the treatment of hyperlipidemia, hypercholesterolemia and atherosclerosis.

    摘要翻译: 公开了一种基本上不含碱金属杂质的纯粹无定形的瑞舒伐他汀钙。 公开了一种制备纯无定形形式的瑞舒伐他汀钙的方法,其包括将瑞舒伐他汀的C 1 -C 5烷基酯,优选罗苏伐他汀的叔丁酯与有机氮碱例如水解。 胍,脒,胺和季铵氢氧化物,在水存在下,任选地含有非质子溶剂,随后将得到的瑞舒伐他汀盐与钙源转化,得到瑞舒伐他汀钙,然后将其分离。 公开了一种替代方法,其包括将瑞舒伐他汀的许多新型铵盐,优选罗苏伐他汀的叔辛基铵盐与钙源转化为所需的商业罗苏伐他汀钙。 罗苏伐他汀钙是HMG CoA还原酶的抑制剂,可用于治疗高脂血症,高胆固醇血症和动脉粥样硬化。

    Process for preparing pure amorphous rosuvastatin calcuim
    3.
    发明授权
    Process for preparing pure amorphous rosuvastatin calcuim 有权
    制备纯无定形罗苏伐他汀的方法

    公开(公告)号:US08207333B2

    公开(公告)日:2012-06-26

    申请号:US11916599

    申请日:2006-06-22

    IPC分类号: C07D239/02

    CPC分类号: C07D239/42

    摘要: A new process for preparing pure amorphous rosuvastatin calcium, substantially free of impurities, is disclosed. A process comprising hydrolysing a C1 to C5 alkyl ester of rosuvastatin, preferably methyl rosuvastatin or tert-butyl rosuvastatin, with a base, e.g. sodium hydroxide, in the presence of an aprotic solvent, preferably tetrahydrofuran and N,N-dimethyl acetamide, or in the presence of a mixture of an aprotic solvent and water, to obtain a solution of rosuvastatin salt, which may be converted to another rosuvastatin salt using another cation, e.g. with calcium cation to obtain rosuvastatin calcium. Rosuvastatin amine salts may be obtained as well.In another preferred aspect of the invention rosuvastatin free acid may be converted to various rosuvastatin salts, e.g. to rosuvastatin calcium, rosuvastatin sodium or various rosuvastatin amine salts, including rosuvastatin solvates, e.g. rosuvastatin calcium hydrate.Rosuvastatin calcium is useful in the treatment of hyperlipidemia, hypercholesterolemia and atherosclerosis.

    摘要翻译: 公开了一种制备基本上不含杂质的纯无定形罗苏伐他汀钙的新方法。 一种方法包括将瑞舒伐他汀,优选甲基瑞舒伐他汀或叔丁基瑞舒伐他汀的C1至C5烷基酯与碱例如 氢氧化钠,在非质子溶剂,优选四氢呋喃和N,N-二甲基乙酰胺的存在下,或在非质子溶剂和水的混合物存在下,得到可以转化为另一种瑞舒伐他汀的罗苏伐他汀盐溶液 盐使用另一种阳离子,例如 用钙阳离子获得瑞舒伐他汀钙。 也可以获得罗苏伐他汀胺盐。 在本发明的另一个优选方面,瑞舒伐他汀游离酸可以转化成各种瑞舒伐他汀盐,例如 罗苏伐他汀钙,罗苏伐他汀钠或各种瑞舒伐他汀胺盐,包括瑞舒伐他汀溶剂化物, 瑞舒伐他汀钙水合物 罗苏伐他汀钙可用于治疗高脂血症,高胆固醇血症和动脉粥样硬化。

    Catalyzed carbonylation in the synthesis of angiotensin II antagonists
    6.
    发明授权
    Catalyzed carbonylation in the synthesis of angiotensin II antagonists 失效
    在血管紧张素II拮抗剂的合成中催化羰基化

    公开(公告)号:US08445693B2

    公开(公告)日:2013-05-21

    申请号:US12933585

    申请日:2009-03-19

    IPC分类号: C07D235/08

    摘要: One embodiment disclosed in the invention is the efficient synthesis of halogenated biaryl starting material via Grignard chemistry and the use thereof. Another embodiment of the invention is the reaction of catalyzed carbonylation of the 3′-(2′-halo-biphenyl-4-ylmethyl)-1,7′-dimethyl-2′-propyl-1H,3′H-[2,5′]bibenzoimidazolyl (TLMH) using either gaseous carbon monoxide in a solvent mixture containing water; or formic acid salts optionally together with acetic acid in anhydrous solvent.

    摘要翻译: 本发明公开的一个实施方案是通过格利雅化学及其用途有效地合成卤化联芳基原料。 本发明的另一个实施方案是3' - (2'-卤代 - 联苯-4-基甲基)-1,7'-二甲基-2'-丙基-1H,3'H- [2, 5']联苯并咪唑基(TLMH),使用气态一氧化碳在含水的溶剂混合物中; 或甲酸盐任选地与乙酸一起在无水溶剂中。

    Processes for the preparation of key intermediate for the synthesis of rosuvastatin or pharmaceutically acceptable salts thereof
    8.
    发明授权
    Processes for the preparation of key intermediate for the synthesis of rosuvastatin or pharmaceutically acceptable salts thereof 有权
    制备用于合成罗苏伐他汀或其药学上可接受的盐的关键中间体的方法

    公开(公告)号:US09067895B2

    公开(公告)日:2015-06-30

    申请号:US13515782

    申请日:2010-12-15

    摘要: The present invention relates in general to the field of organic chemistry and in particular to a process for the preparation of 5-((E)-2-((2S,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethanesulfonylamino)pyrimidine (RSVL) as well as a process for preparing crystalline 5-((E)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethanesulfonylamino)pyrimidine (RSVLTBS) useful as key intermediates for the preparation of rosuvastatin or pharmaceutically acceptable salts thereof.

    摘要翻译: 本发明一般涉及有机化学领域,特别涉及一种制备5 - ((E)-2 - ((2S,4R)-4-羟基-6-氧代四氢-2H-吡喃-2-基) 吡啶-2-基)乙烯基)-4-(4-氟苯基)-6-异丙基-2-(N-甲基甲磺酰基氨基)嘧啶(RSVL)的方法,以及制备5 - ((E)-2 - ((2S ,4R)-4-(叔丁基二甲基甲硅烷氧基)-6-氧代四氢-2H-吡喃-2-基)乙烯基)-4-(4-氟苯基)-6-异丙基-2-(N-甲基甲磺酰基氨基)嘧啶(RSVLTBS) 可用作制备瑞舒伐他汀或其药学上可接受的盐的关键中间体。

    Process for the Synthesis of Hmg-Coa Reductase Inhibitors
    9.
    发明申请
    Process for the Synthesis of Hmg-Coa Reductase Inhibitors 有权
    合成Hmg-Coa还原酶抑制剂的方法

    公开(公告)号:US20080300406A1

    公开(公告)日:2008-12-04

    申请号:US12088019

    申请日:2006-10-04

    申请人: Zdenko Casar

    发明人: Zdenko Casar

    IPC分类号: C07D239/02

    摘要: A novel synthesis of statins uses Wittig reaction of a heterocyclic core of statin with a lactonized side chain already possessing needed stereochemistry. Any separation of diastereoisomers is performed early in the course of synthesis.

    摘要翻译: 他汀类药物的新型合成使用他汀类药物的核心与具有所需立体化学的内酯化侧链的Wittig反应。 非对映异构体的任何分离在合成过程中进行。