公开(公告)号：US20020128497A1

公开(公告)日：2002-09-12

申请号：US10096149

申请日：2002-03-06

Applicant: H. Lundbeck A/S

Inventor： Eva Bolzonella ,  Andrea Castellin ,  Andrea Nicole

IPC: C07D307/87

CPC classification number: C07D307/87

Abstract: A method for the manufacture of citalopram characterized in (i) reaction of 1-(4-fluorophenyl)-1-(3-dimethylaminopropyl)-5-halophthalane with an activated magnesium to form the Grignard reagent null3-null1-(4-fluorophenyl)-1,3 dihydro-isobenzofuran-1-ylnullpropylnulldimethylamine 5-magnesium halide followed by (ii) reaction of null3-null1-(4-fluorophenyl)-1,3 dihydro-isobenzofuran-1-ylnullpropyl)dimethylamine 5-magnesium halide with a compound containing a nullCN group bound to a leaving group to form citalopram.

Abstract translation: 一种制备西酞普兰的方法，其特征在于（i）1-（4-氟苯基）-1-（3-二甲基氨基丙基）-5-卤代酞菁与活化镁反应形成格利雅试剂[3- [1-（4 - 氟苯基）-1,3-二氢 - 异苯并呋喃-1-基]丙基]二甲胺5-卤化镁，然后（ⅱ）[3- [1-（4-氟苯基）-1,3-二氢 - 异苯并呋喃-1-基] 吡啶-2-基]丙基）二甲胺5-卤化镁与包含与离去基团结合的-CN基团的化合物形成西酞普兰。

公开(公告)号：US20030178295A1

公开(公告)日：2003-09-25

申请号：US10361800

申请日：2003-02-10

Applicant: H. LUNDBECK A/S

Inventor： Andrea Castellin ,  Giulio Volpe ,  Federico Sbrogio

IPC: B01D003/28

CPC classification number: C07D307/87

Abstract: A process for the preparation of citalopram of formula (I) 1 in which a compound of formula (II) 2 wherein Z is iodo, bromo, chloro or CF3null(CF2)nnullSO2nullOnull n being 0, 1, 2, 3, 4, 5, 6, 7 or 8, is subjected to a cyanide exchange reaction in which the group Z is exchanged with cyanide by reaction with a cyanide source; the resultant crude citalopram product is optionally subjected to some initial purification and the crude citalopram base is subsequently subjected to a film distillation process; the resulting citalopram product is then optionally further purified and worked up and isolated as the base or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20020087012A1

公开(公告)日：2002-07-04

申请号：US10035005

申请日：2001-12-20

Applicant: H. Lundbeck A/S

Inventor： Andrea Castellin ,  Giulio Volpe ,  Federico Sbrogio

IPC: C07D307/87

CPC classification number: C07D307/87

Abstract: A process for the preparation of citalopram of formula (I) 1 in which a compound of formula (II) 2 wherein Z is iodo, bromo, chloro or CF3null(CF2)nnullSO2nullOnull n being 0, 1, 2, 3, 4, 5, 6, 7 or 8, is subjected to a cyanide exchange reaction in which the group Z is exchanged with cyanide by reaction with a cyanide source; the resultant crude citalopram product is optionally subjected to some initial purification and the crude citalopram base is subsequently subjected to a film distillation process; the resulting citalopram product is then optionally further purified and worked up and isolated as the base or a pharmaceutically acceptable salt thereof.

Abstract translation: 制备式（I）西酞普兰的方法，其中Z为碘，溴，氯或CF 3 - （CF 2）n -SO 2 -O-的式（II）化合物为0,1,2,3 ，4，5，6，7或8进行氰化物交换反应，其中基团Z与氰化物通过与氰化物源反应而与氰化物进行交换; 所得粗制西酞普兰产品任选进行一些初步纯化，随后对粗制西酞普兰碱进行膜蒸馏处理; 然后任选地将所得西酞普兰产物进一步纯化和处理并分离为碱或其药学上可接受的盐。