公开(公告)号：WO2006021974A1

公开(公告)日：2006-03-02

申请号：PCT/IN2005/000280

申请日：2005-08-22

Applicant: MOREPEN LABORATORIES LIMITED ,  SURI, Sanjay ,  SARIN, Gurdeep, Singh ,  MAHENDRU, Manu

Inventor： SURI, Sanjay ,  SARIN, Gurdeep, Singh ,  MAHENDRU, Manu

IPC: C07D215/18

CPC classification number: C07D215/18

Abstract: A process comprises preparing benzaldehyde of formula I in a conventional manner, reacting the said benzaldehyde I with Grignard reagent in water miscible etheral solvent to precipitate the alcohol of formula (II) by addition of ammonium salt and water followed by isolating the alcohol thus precipitated by any known methods and then oxidizing directly under "Swern's conditions" to get a ketone of formula m, enolizing the said ketone in presence of a mild base such as alkali metal alkoxide and then reacting it with dialkyl carbonate under conditions effective to yield a β- ketoester of formula IV, benzylating the said β-ketoester so obtained in the preceding step to form the benzoate of formula V in presence of mild inorganic base followed by decarboxylating the said benzoate to a mixture of a ketoester of formula VI and its corresponding acid of formula VIA in the presence of acidic conditions, alkylating the acid VIA present in the mixture in the preceding step to obtain ketoester of formula VI and purifying it if so desired, asymmetrically reducing the ketoester of formula VI, to a chiral alcohol of formula VII using (-) diisopinocamphenylchloroborane (-DIPC1) in presence of less than 4 times v/w aprotic solvent and optionally in presence of Lewis base with respect to the said ketoester of formula VI, treating the said chiral alcohol VII with cerium halo salt, and alkylmagnesium halide followed by isolating the title compound using hyflow supercel and ammonium chloride to get the intermediate diol of formula VIII. Atemately, the said alcohol to Heck coupling with methyl-2-iodobenzoate in presence of Lewis base, acetonitrile, and palladium acetate to yield ketoester (VI), which is converted to diol (VIII) as described herein above.

Abstract translation: 一种方法包括以常规方法制备式I的苯甲醛，使所述苯甲醛I与格氏试剂在水混溶性醚类溶剂中反应，通过加入铵盐和水使式（II）的醇沉淀，然后分离由此沉淀的醇 任何已知的方法，然后在“Swern条件”下直接氧化得到式m的酮，在温和的碱如碱金属醇盐存在下使所述酮烯化，然后在有效产生ß- 式IV的酮酯，使上述步骤中得到的所述β-酮酯苄基化，在温和的无机碱存在下形成式V的苯甲酸酯，随后将所述苯甲酸酯脱羧为式VI的酮酯与其相应的酸 在酸性条件下存在式VIA，在前述步骤中将存在于混合物中的酸VIA烷基化以获得酮酯O 如果需要，可以使用（ - ）二异苯并苯基氯硼烷（-DIPCl）在低于4倍v / w质子惰性溶剂存在下将式VI的酮酯不对称还原为式VII的手性醇，并任选地存在 的路易斯碱相对于所述式VI的酮酯，用铈卤盐处理所述手性醇VII和卤化烷基卤化物，然后使用hyflow超滤和氯化铵分离标题化合物，得到式VIII的中间体二醇。 在路易斯碱，乙腈和乙酸钯的存在下，将所述醇与甲基-2-碘苯甲酸偶合，得到酮酯（VI），如上所述转化为二醇（VIII）。

公开(公告)号：WO2004108679A1

公开(公告)日：2004-12-16

申请号：PCT/IN2003/000214

申请日：2003-06-06

Applicant: MOREPEN LABORATORIES LIMITED ,  SURI, Sanjay ,  SINGH, Jujhhar ,  SARIN, Gurdeep, Singh ,  TANWAR, Madan, Pal ,  MAHENDRU, Manu

Inventor： SURI, Sanjay ,  SINGH, Jujhhar ,  SARIN, Gurdeep, Singh ,  TANWAR, Madan, Pal ,  MAHENDRU, Manu

IPC: C07D215/18

CPC classification number: C07D215/18

Abstract: A method for the preparation of montelukast acid sodium salt thereof in amorphous form has been described. The method comprises of following steps: (a) generating the dilithium dianion of 1-(mercaptomethyl)cyclopropane acetic acid, by reacting with alkyl lithium, (b) coupling the said dianion with wet mesylate to get montelukast acid in crude form, (c) obtaining DCHA salt in crude form by adding dicyclohexylamine (DCHA) to crude acid obtained in the above step (b), (d) purifying and converting the said DCHA salt in crude form, to montelukast acid in pure form, and (e) reacting the pure montelukast acid in a polar protic solvent with a source of sodium ion followed by evaporating the solvent and triturating of the residue with non-polar water immiscible solvent.

Abstract translation: 已经描述了制备无定形形式的孟鲁司他酸钠盐的方法。 该方法包括以下步骤：（a）通过与烷基锂反应生成1-（巯基甲基）环丙烷乙酸的二锂二阴离子，（b）将所述二价阴离子与湿甲磺酸酯偶联得到粗制形式的孟鲁司特酸，（c 通过向上述步骤（b）中获得的粗酸加入二环己基胺（DCHA），（d）以粗制形式将所述DCHA盐纯化并转化成纯形式的孟鲁司特酸，得到粗制形式的DCHA盐，和（e） 使极性质子溶剂中的纯孟鲁司特酸与钠离子源反应，然后蒸发溶剂并用非极性水不混溶溶剂研磨残余物。

公开(公告)号：WO2006018807A8

公开(公告)日：2006-08-10

申请号：PCT/IB2005052691

申请日：2005-08-15

Applicant: RANBAXY LAB LTD ,  MAHENDRU MANU ,  ARYAN RAM CHANDER ,  KUMAR SATISH ,  PANDYA BHARGAV ,  DUGGAL SANJAM ,  GADE SANJAY ,  KUMAR YATENDRA

Inventor： MAHENDRU MANU ,  ARYAN RAM CHANDER ,  KUMAR SATISH ,  PANDYA BHARGAV ,  DUGGAL SANJAM ,  GADE SANJAY ,  KUMAR YATENDRA

IPC: C07D501/00 ,  A61K31/546 ,  A61P31/04

CPC classification number: C07D501/00

Abstract: The invention relates to processes for the preparation of crystalline polymorphic forms of cefdinir of formula I. More particularly, it relates to the preparation of crystalline polymorphic forms of cefdinir designated as Forms B and C. The invention also relates to pharmaceutical compositions that include the polymorphic forms B and C, and the use of the compositions for treating bacterial infections.

Abstract translation: 本发明涉及用于制备式I的头孢地尼的结晶多晶形式的方法。更具体地说，本发明涉及被称为形式B和C的头孢地尼的结晶多晶形式的制备。本发明还涉及药物组合物，其包括多晶型物 形式B和C，以及组合物用于治疗细菌感染的用途。

公开(公告)号：WO2006018807A1

公开(公告)日：2006-02-23

申请号：PCT/IB2005/052691

申请日：2005-08-15

Applicant: RANBAXY LABORATORIES LIMITED ,  MAHENDRU, Manu ,  ARYAN, Ram, Chander ,  KUMAR, Satish ,  PANDYA, Bhargav ,  DUGGAL, Sanjam ,  GADE, Sanjay ,  KUMAR, Yatendra

Inventor： MAHENDRU, Manu ,  ARYAN, Ram, Chander ,  KUMAR, Satish ,  PANDYA, Bhargav ,  DUGGAL, Sanjam ,  GADE, Sanjay ,  KUMAR, Yatendra

IPC: C07D501/00 ,  A61K31/546 ,  A61P31/04

CPC classification number: C07D501/00

Abstract: The invention relates to processes for the preparation of crystalline polymorphic forms of cefdinir of formula (I). More particularly, it relates to the preparation of crystalline polymorphic forms of cefdinir designated as Forms B and C. The invention also relates to pharmaceutical compositions that include the polymorphic forms B and C, and the use of the compositions for treating bacterial infections.

Abstract translation: 本发明涉及制备式（I）的头孢地尼的结晶多晶形式的方法。 更具体地说，本发明涉及被称为形式B和C的头孢地尼的晶体多晶形式的制备。本发明还涉及包含多晶型B和C的药物组合物，以及该组合物用于治疗细菌感染的用途。

公开(公告)号：WO2007029155A3

公开(公告)日：2007-08-30

申请号：PCT/IB2006053073

申请日：2006-09-01

Applicant: RANBAXY LAB LTD ,  KUMAR NARESH ,  NAYYAR SANDEEP ,  MAHENDRU MANU

Inventor： KUMAR NARESH ,  NAYYAR SANDEEP ,  MAHENDRU MANU

IPC: C07C273/18 ,  C07C275/42

CPC classification number: C07C273/189 ,  C07C275/42

Abstract: The present invention relates to an improved process for preparing pure celiprolol base in monohydrate form by crystallizing crude celiprolol base in one or more carboxylic acid ester solvents and its conversion to pharmaceutically acceptable acid addition salts, for example, celiprolol hydrochloride Form I in high purity.

Abstract translation: 本发明涉及一种通过在一种或多种羧酸酯溶剂中结晶粗硅藻土碱基并将其转化为药学上可接受的酸加成盐（例如，高纯度的盐酸赛立洛尔盐酸盐形式I）来制备一水合物形式的纯赖洛洛尔碱的改进方法。

公开(公告)号：WO2007029155A2

公开(公告)日：2007-03-15

申请号：PCT/IB2006/053073

申请日：2006-09-01

Applicant: RANBAXY LABORATORIES LIMITED ,  KUMAR, Naresh ,  NAYYAR, Sandeep ,  MAHENDRU, Manu

Inventor： KUMAR, Naresh ,  NAYYAR, Sandeep ,  MAHENDRU, Manu

CPC classification number: C07C273/189 ,  C07C275/42

Abstract: The present invention relates to an improved process for preparing pure celiprolol base in monohydrate form by crystallizing crude celiprolol base in one or more carboxylic acid ester solvents and its conversion to pharmaceutically acceptable acid addition salts, for example, celiprolol hydrochloride Form I in high purity.

Abstract translation: 本发明涉及通过在一种或多种羧酸酯溶剂中结晶粗塞利洛尔碱并将其转化为药学上可接受的酸加成盐来制备一水合物形式的纯塞利吡咯碱的改进方法，例如， 塞利洛尔盐酸盐晶型I，高纯度。