公开(公告)号：US20010027256A1

公开(公告)日：2001-10-04

申请号：US09794762

申请日：2001-02-26

Applicant: H. Lundbeck A/S

Inventor： Hans Petersen ,  Michael Harold Rock ,  Haleh Ahmadian

IPC: C07D307/87

CPC classification number: C07D307/87 ,  A61K31/343

Abstract: The present invention relates to a method for the preparation of citalopram comprising reaction a compound of formula (I) 1 with a compound having the formula 2 wherein X is a suitable leaving group and R is nullCH2nullOnullPg, nullCH2nullNPg1Pg2, nullCHnullN(CH3)2, nullCH(OR1)(OR2) nullC(OR4)(OR5)(OR6), nullCOOR3, nullCH2nullCOnullNH2, nullCHnullCHR7 and nullCONHR8, 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 3 wherein R is as defined above; followed by conversion of the group R to form a dimethylaminomethyl group and isolation of citalopram base or a pharmaceutically acceptable salt thereof.

Abstract translation: 本发明涉及一种制备西酞普兰的方法，其包括使式（I）化合物与具有下式的化合物反应：其中X为合适的离去基团，R为-CH2-O-Pg，-CH2-NPg1Pg2， - CH-N（CH3）2，-CH（OR1）（OR2）-C（OR4）（OR5）（OR6），-COOR3，-CH2-CO-NH2，-CH = CHR7和-CONHR8，其中Pg是 醇基的保护基，Pg1和Pg2是氨基的保护基，R 1和R 2独立地选自烷基，烯基，炔基和任选的烷基取代的芳基或芳烷基，或者R 1和R 2一起形成2至4个的链 碳原子，R 3，R 4，R 5，R 6和R 7各自独立地选自烷基，烯基，炔基和任选烷基取代的芳基或芳烷基，且R 8是氢或甲基; 以形成下式的化合物其中R如上定义; 然后转化基团R以形成二甲基氨基甲基并分离西酞普兰碱或其药学上可接受的盐。

公开(公告)号：US20020025982A1

公开(公告)日：2002-02-28

申请号：US09930107

申请日：2001-08-14

Applicant: H. Lundbeck A/S

Inventor： Hans Petersen ,  Haleh Ahmadian

IPC: A61K031/343 ,  C07D307/93

CPC classification number: C07D307/87

Abstract: Disclosed is a method for the preparation of citalopram comprising conversion of a compound of Formula VIII 1 wherein Z is halogen, to a compound of Formula IV 2 followed by conversion of the compound of Formula IV into citalopram. Methods for the preparation of the compound of Formula IV are also disclosed.

Abstract translation: 公开了一种制备西酞普兰的方法，包括将式VIII的化合物（其中Z为卤素）转化为式IV化合物，随后将式IV化合物转​​化为西酞普兰。 还公开了制备式IV化合物的方法。

公开(公告)号：US20030092761A1

公开(公告)日：2003-05-15

申请号：US10232994

申请日：2002-08-29

Applicant: H. Lundbeck A/S

Inventor： Michael Harold Rock ,  Haleh Ahmadian

IPC: A61K031/343 ,  C07D307/87

CPC classification number: C07D307/87 ,  A61K31/343

Abstract: The invention relates to a method for the preparation of citalopram comprising reaction of a compound of formula II 1 with a compound having the formula 2 wherein R is halogen or nullOnullSO2-X, wherein X is alkyl, alkenyl, alkynyl or optionally alkyl substituted aryl or aralkyl, and R1 is dimethylamino, halogen, nullOnullSO2-X wherein X is as defined above, provided that R is not halogen when R1 is dimethylamino; and if R1 is dimethylamino followed by isolation of citalopram base or a pharmaceutically acceptable acid addition salt thereof, and if R1 is halogen or nullOnullSO2-X, wherein X is as defined above, followed by conversion of the resulting compound of formula 3 wherein R2 is halogen or a group of formula nullOnullSO2-X wherein X is as defined above to citalopram, followed by isolation of citalopram base or a pharmaceutically acceptable acid addition salt thereof.

Abstract translation: 本发明涉及一种制备西酞普兰的方法，包括式II化合物与具有下式的化合物的反应其中R为卤素或-O-SO 2 -X，其中X为烷基，烯基，炔基或任选烷基取代的芳基 或芳烷基，并且R 1是二甲基氨基，卤素，-O-SO 2 -X，其中X如上定义，条件是当R 1是二甲基氨基时R不是卤素; 并且如果R 1是二甲基氨基，然后分离西酞普兰碱或其药学上可接受的酸加成盐，并且如果R 1是卤素或-O-SO 2 -X，其中X如上定义，然后转化所得到的式 R2是卤素或式-O-SO2-X的基团，其中X如上定义为西酞普兰，然后分离西酞普兰碱或其药学上可接受的酸加成盐。

公开(公告)号：US20030083509A1

公开(公告)日：2003-05-01

申请号：US10242804

申请日：2002-09-10

Applicant: H. Lundbeck A/S

Inventor： Hans Petersen ,  Haleh Ahmadian

IPC: C07D307/87

CPC classification number: C07D307/87

Abstract: Methods for manufacture of citalopram through stepwise alkylation of 5-substituted 1-(4-fluorophenyl)-1,3-dihydroisobenzofurans are disclosed.

Abstract translation: 公开了通过5-取代的1-（4-氟苯基）-1,3-二氢异苯并呋喃的逐步烷基化制备西酞普兰的方法。

公开(公告)号：US20020026062A1

公开(公告)日：2002-02-28

申请号：US09930110

申请日：2001-08-14

Applicant: H. Lundbeck A/S

Inventor： Hans Petersen ,  Haleh Ahmadian ,  Robert Dancer

IPC: C07D37/81

CPC classification number: C07D307/87

Abstract: A method for the preparation of citalopram comprising reacting 5-carboxyphthalide successively with a Grignard reagent of 4-halo-fluorophenyl and a Grignard reagent of 3-halo-N,N-dimethyl-propylamine and then effecting ring closure of the resulting compound of Formula XI 1 to a compound of Formula IV 2 followed by conversion of the compound of Formula IV into citalopram is disclosed. Methods for the manufacture and conversion of the compound of Formula IV are also disclosed.

Abstract translation: 一种制备西酞普兰的方法，其包括使5-羧基邻苯二甲酸酯与4-卤代 - 氟苯基的格氏试剂和3-卤代-N，N-二甲基 - 丙胺的格氏试剂依次反应，然后使所得到的式 XI公开了式IV化合物，随后将式IV化合物转​​化为西酞普兰。 还公开了制备和转化式IV化合物的方法。