公开(公告)号：US07834201B2

公开(公告)日：2010-11-16

申请号：US11425522

申请日：2006-06-21

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： C07D307/87

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

摘要翻译： 本发明涉及众所周知的抗抑郁药物依他普仑S-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃甲腈的结晶碱，所述制剂为 碱，使用碱，草酸盐的纯化盐的制备方法，通过所述方法获得的盐和含有这些盐的制剂的方法，以及制备纯化的依他普仑游离碱或依他普仑的盐的方法， 例如草酸盐，使用氢溴酸盐，通过所述方法获得的盐和含有这些盐的制剂。 最后，本发明涉及硬度至少为22N，口服崩解时间小于120秒的可分散片剂，其包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点为 40-100℃的范围，以及制造这种可分散片剂的方法。

公开(公告)号：US20110046218A1

公开(公告)日：2011-02-24

申请号：US12916750

申请日：2010-11-01

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： A61K31/343 ,  C07D307/87 ,  A61P25/24

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

摘要翻译： 本发明涉及众所周知的抗抑郁药物依他普仑S-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃甲腈的结晶碱，所述制剂为 碱，使用碱，草酸盐的纯化盐的制备方法，通过所述方法获得的盐和含有这些盐的制剂的方法，以及制备纯化的依他普仑游离碱或依他普仑的盐的方法， 例如草酸盐，使用氢溴酸盐，通过所述方法获得的盐和含有这些盐的制剂。 最后，本发明涉及硬度至少为22N，口服崩解时间小于120秒的可分散片剂，其包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点为 40-100℃的范围，以及制造这种可分散片剂的方法。

公开(公告)号：US06566540B2

公开(公告)日：2003-05-20

申请号：US10138811

申请日：2002-05-03

申请人： Michael Harold Rock ,  Hans Petersen ,  Peter Ellegaard

发明人： Michael Harold Rock ,  Hans Petersen ,  Peter Ellegaard

IPC分类号： C07D30787

CPC分类号： C07D307/87

摘要： A method for the preparation of S-citalopram comprising reaction of a compound of Formula (IV), wherein R is C1-6 alkyl, acyl, C1-6 alkylsulfonyl or arylsulfonyl, with 3-(N,N-dimethylamino)-propyl magnesium halide, to prepare citalopram.

摘要翻译： 一种制备S-西酞普兰的方法，其包括其中R为C 1-6烷基，酰基，C 1-6烷基磺酰基或芳基磺酰基的式（IV）化合物与3-（N，N-二甲基氨基） - 丙基镁 卤化物，以制备西酞普兰。

公开(公告)号：US07560576B2

公开(公告)日：2009-07-14

申请号：US12046984

申请日：2008-03-12

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： C07D307/00 ,  A61K31/34

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

摘要翻译： 本发明涉及众所周知的抗抑郁药物依他普仑S-1- [3-（二甲基氨基）丙基] -1-（4-氟苯基）-1,3-二氢-5-异苯并呋喃腈的结晶碱，其制剂 的所述碱的方法，使用碱，通过所述方法获得的盐以及含有这些盐的制剂来制备依他普仑的纯化盐如草酸盐的方法，以及制备纯化的依他普仑游离碱或其盐的方法 使用氢溴酸盐，通过所述方法获得的盐和含有这些盐的制剂，例如草酸盐。 最后，本发明涉及硬度至少为22N，口服崩解时间小于120秒的可分散片剂，其包含吸附在水溶性填料上的活性药物成分，其中活性药物成分的熔点为 40-100℃的范围，以及制造这种可分散片剂的方法。

公开(公告)号：US20080161584A1

公开(公告)日：2008-07-03

申请号：US12046999

申请日：2008-03-12

申请人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

发明人： Robert Dancer ,  Hans Petersen ,  Ole Nielsen ,  Michael Harold Rock ,  Helle Eliasen ,  Ken Liljegren

IPC分类号： C07D307/87

CPC分类号： C07D307/81

摘要： The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100° C., as well as a method for making such an orodispersible tablet.

公开(公告)号：US07271273B2

公开(公告)日：2007-09-18

申请号：US11285922

申请日：2005-11-23

申请人： Hans Petersen ,  Michael Harold Rock

发明人： Hans Petersen ,  Michael Harold Rock

IPC分类号： C07D307/54

CPC分类号： C07D307/88

摘要： The invention provides a new and improved method for the preparation of 5-cyano-phtalid, which is a key intermediate in the preparation of the antidepressant compound citalopram.

摘要翻译： 本发明提供了一种新的改进的制备5-氰基 - 邻苯二甲酸的方法，该方法是制备抗抑郁化合物西酞普兰的关键中间体。

公开(公告)号：US06420574B1

公开(公告)日：2002-07-16

申请号：US09794762

申请日：2001-02-26

申请人： Hans Petersen ,  Michael Harold Rock ,  Haleh Ahmadian

发明人： Hans Petersen ,  Michael Harold Rock ,  Haleh Ahmadian

IPC分类号： C07D30778

摘要： The present invention relates to a method for the preparation of citalopram comprising reaction a compound of formula (I) with a compound having the formula wherein X is a suitable leaving group and R is —CH2—O—Pg, —CH2—NPg1Pg2, —CO—N(CH3)2, —CH(OR1)(OR2), —C(OR4)(OR5)(OR6), —COOR3, —CH2—CO—NH2, —CH═CHR7 and —CONHR8, wherein Pg is a protection group for an alcohol group, Pg1 and Pg2 are protection groups for an amino group, R1 and R2 are independently selected from alkyl, alkenyl, alkynyl and optionally alkyl substituted aryl or aralkyl groups or R1 and R2 together form a chain of 2 to 4 carbon atoms, each of R3, R4, R5, R6 and R7 are independently selected from alkyl, alkenyl, alkynyl and optionally alkyl substituted aryl or aralkyl and R8 is hydrogen or methyl; to form a compound of the formula wherein R is as defined above; followed by conversion of the R group and isolation of citalopram base or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20090088469A1

公开(公告)日：2009-04-02

申请号：US12329750

申请日：2008-12-08

申请人： Hans Petersen ,  Michael Harold Rock ,  Henrik Svane

发明人： Hans Petersen ,  Michael Harold Rock ,  Henrik Svane

IPC分类号： A61K31/343 ,  C07D307/81 ,  C07D307/80 ,  A61P25/24

CPC分类号： C07D307/87 ,  C07D307/81

摘要： Method for the preparation of citalopram comprising reaction of a compound of Formula (IV) wherein R is halogen, or CF3—(CF2)n—SO2—, n being 0 to 8, with a cyanide source in the presence of a palladium catalyst and a catalytic amount of Cu+ or Zn2+, or with Zn(CN)2 in the presence of a palladium catalyst.

摘要翻译： 制备西酞普兰的方法，其包括其中R为卤素的式（IV）化合物或CF 3 - （CF 2）n -SO 2 - ，n为0至8的化合物与氰化物源在钯催化剂存在下反应， 催化量的Cu +或Zn2 +，或与Zn（CN）2在钯催化剂存在下反应。

公开(公告)号：US06750358B2

公开(公告)日：2004-06-15

申请号：US10012025

申请日：2001-11-06

申请人： Hans Petersen ,  Michael Harold Rock

发明人： Hans Petersen ,  Michael Harold Rock

IPC分类号： C07D30787

CPC分类号： B01J31/2295 ,  A61K31/34 ,  B01J31/2404 ,  B01J2231/4205 ,  B01J2531/847 ,  C07D307/87

摘要： Method for the preparation of citalopram comprising reaction of a compound of Formula (IV) wherein R is Cl or Br with a cyanide source in the presence of a nickel catalyst and isolation of the corresponding 5-cyano compound, i.e. citalopram.

摘要翻译： 制备西酞普兰的方法，包括在镍催化剂存在下，R为Cl或Br与氰化物源的式（Ⅳ）化合物和相应的5-氰基化合物（即西酞普兰）的分离反应。

公开(公告)号：US06407267B1

公开(公告)日：2002-06-18

申请号：US09891874

申请日：2001-06-25

申请人： Michael Harold Rock ,  Hans Petersen ,  Peter Ellegaard

发明人： Michael Harold Rock ,  Hans Petersen ,  Peter Ellegaard

IPC分类号： C07D30787

CPC分类号： C07D307/87

摘要： A method for the preparation of citalopram comprising reaction of a compound of Formula (IV), wherein R is C1-6 alkyl, acyl, C1-6 alkylsulfonyl or arylsulfonyl, with 3-(N,N-dimethylamino)-propyl magnesium halide, to prepare citalopram.

摘要翻译： 一种制备西酞普兰的方法，包括其中R为C 1-6烷基，酰基，C 1-6烷基磺酰基或芳基磺酰基的式（Ⅳ）化合物与3-（N，N-二甲基氨基） - 丙基卤化镁反应， 准备西酞普兰。