CN1337957A - 制备5－氰－2－苯并[c]呋喃酮的方法 - Google Patents
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- 238000002360 preparation method Methods 0.000 title abstract description 4
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims abstract description 9
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 14
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- -1 sulfamide compound Chemical class 0.000 claims description 5
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 2
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 abstract description 6
- 229960001653 citalopram Drugs 0.000 abstract description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract description 6
- 239000000935 antidepressant agent Substances 0.000 abstract description 5
- XEEGWTLAFIZLSF-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carbonitrile Chemical compound N#CC1=CC=C2C(=O)OCC2=C1 XEEGWTLAFIZLSF-UHFFFAOYSA-N 0.000 abstract 2
- QTWUWCFGWYYRRL-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(=O)OCC2=C1 QTWUWCFGWYYRRL-UHFFFAOYSA-N 0.000 abstract 1
- PUIVIZQHTBRFTR-UHFFFAOYSA-N 3-oxo-1h-2-benzofuran-1-carbonitrile Chemical compound C1=CC=C2C(=O)OC(C#N)C2=C1 PUIVIZQHTBRFTR-UHFFFAOYSA-N 0.000 abstract 1
- 239000012024 dehydrating agents Substances 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
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- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
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- 238000007363 ring formation reaction Methods 0.000 description 2
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
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- 238000010533 azeotropic distillation Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
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- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
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Abstract
一种制备5－氰－2－苯并[c]呋喃酮的方法,其中5－羧基－2－苯并[c]呋喃酮与一种脱水剂、诸如亚硫酰氯和一种氨磺酰化合物,具体是硫酰胺,进行反应。氰基－2－苯并[c]呋喃酮可通过方便的实验程序以高收率制得。5－氰－2－苯并[c]呋喃酮是用于抗抑郁药物Citalopram制备中的中间体。
Description
本发明涉及一种新的制备5-氰-2-苯并[c]呋喃酮的方法，后者是制造著名的抗抑郁药物citalopram，即1-[3-(二甲胺基)丙基]-1-(4-氟苯基)-1，3-二氢-5-异苯并呋喃腈的中间体。
发明背景
Citalopram是已在市场上出售多年的著名抗抑郁药物，它具有以下结构式I
结构式I
它是一种选择性的中枢活性血清素(5-羟基色胺；5-HT)重新摄入的抑制剂，因此而具有抗抑郁的活性。这种化合物的抗抑郁活性已在一些出版物中报道过，例如J.Hyttel，Porg.Neuro.Psychopharmacol.&Biol.Psychiat.，1982年，6，277-295页以及A.Gravem，Acta Psychiatr.Scamd.，1987年，75，478-486页。
Citalopram可按照美国专利No.4,650,884中所描述的方法来制备，按照这一方法，5-氰基-2-苯并[c]呋喃酮相继进行两次Grignard反应，即分别与4-氟苯基卤化镁和N，N-二甲胺基丙基卤化镁反应，并把得到的具有下式II的化合物：
结构式II通过用强酸脱水进行关环反应。
Citalopram的对映异构体可用美国专利No.4,943,590中所描述的方法来制备，即通过分离式II中间体的对映异构体并进行对映选择性的关环反应以获得所需的对映异构体。
这样，5-氰-2-苯并[c]呋喃酮是制造Citalopram的一个重要中间体，以适当的量，通过一种方便的方法以及成本适当的方式来生产这一物质就是一件重要的事情。
以前在Bull.Soc.Sci.Bretagne，1951，26，35以及Levy和Stephen在J.Chem.Soc.，1931，867页曾描述过一种制备5-氰-2-苯并[c]呋喃酮的方法。用这种方法时，是把5-氨基-2-苯并[c]呋喃酮通过重氮化接着与CuCN反应而转化成5-氰-2-苯并[c]呋喃酮。而5-氨基-2-苯并[c]呋喃酮是通过两步还原操作从4-氨基邻苯二甲酰亚胺制得的。
由酸的酰氯合成一些烷基-和苯基腈被描述于TetrahedronLetters，1982，23，(14)1505-1508页以及Tetrahedron，1998，54，9281页。
虽然一些别的方法失败了，但现已发现5-氰-2-苯并[c]呋喃酮可用一种方便的、成本合适的单罐程序从5-羧基-2-苯并[c]呋喃酮以高收率制得。
发明描述
按此，本发明提供了一种新的制备5-氰-2-苯并[c]呋喃酮(式IV)的方法
结构式IV它包括把5-羧基-2-苯并[c]呋喃酮(式III)
结构式III与一种脱水剂和一种通式为H2NSO2-R(式V)的磺酰胺进行反应，式(V)中的R是：
a)NH2、C1-6烷氧基、苯氧基，
b)被卤素、C1-4烷基、氰基、羟基、C1-4烷氧基、三氟甲基、硝基、氨基、C1-4烷基氨基或二-C1-4烷基氨基所取代的苯氧基，
c)被一个或多个吸电子基团取代的苯基，以获得5-氰-2-苯并[c]呋喃酮。
可以用任何合适的脱水剂，并且最适宜的试剂可由本领域的技术人员容易地决定。合适的脱水剂的实例有SOCl2、POCl3、PCl5、SOBr2、POBr3、PBr5、SOI2、POI3、PI5以及草酰氯。优选含氯的试剂，最优选用SOCl2。
术语吸电子取代基打算用来指任何具有足够吸电子力使反应能够进行的取代基，诸如硝基、氰基、卤素、三氟甲基、氨基磺酰基。3，5-二硝基苯基是这类苯基上被吸电子取代基所取代的一个实例。
在本发明方法中，5-羧基-2-苯并[c]呋喃酮与脱水剂反应以形成相应的5-卤甲酰基衍生物，后者再与具有式V的磺酰胺反应从而形成5-氰-2-苯并[c]呋喃酮。在进行后面反应的过程中，必需有催化量的酸存在。如果需要，5-卤甲酰衍生物可在进一步反应之前被析离。然而，最好是反应作为单罐类型的程序来进行，而不同析离5-卤甲酰基中间体。最好是反应经由5-氯甲酰-2-苯并[c]呋喃酮进行。
用于本方法中的具有式V的磺酰胺优选硫酰胺，即式V中R是NH2的化合物。
反应可不用溶剂来进行，或者用一种合适的溶剂，诸如环丁砜或乙腈。任选环丁砜被用作溶剂。
这样，在本发明一个优选的实施方案中，5-羧基-2-苯并[c]呋喃酮是在SOCl2存在的条件下在环丁砜溶液中与硫酰胺进行反应。
反应是在升高温度的条件下进行。当环丁砜被用作溶剂时，反应优选在约120-150℃进行。
5-氰-2-苯并[c]呋喃酮可用通常的方法来析离，例如加入水、过滤、接着洗涤结晶。如果需要，可通过实施重结晶进一步提纯。
方便地，可分别将1.0至2.0当量的硫酰胺和脱水剂与1.0当量的5-羧基-2-苯并[c]呋喃酮进行反应。优选用1.0-1.2当量的硫酰胺。
通过本发明，可以高收率(＞约70％)制得5-氰-2-苯并[c]呋喃酮。这种方法比已知的方法方便得多，并且使用更方便和更便宜的反应物和反应条件。还有，由于这种方法是单罐型操作程序，使生产能力大为增加，由此成本得以大为降低。
用作原料的5-羧基-2-苯并[c]呋喃酮可通过在US专利No.3,607,884或德国专利No.2630927中所描述的方法获得，即把对苯二甲酸的浓溶液在液体SO3中与甲醛反应，或者通过1，2，4-苯三酸的电化学氢化反应。
实施例
本发明将通过以下实施例进一步说明。
实施例1
5-氰-2-苯并[c]呋喃酮
把5-羧基-2-苯并[c]呋喃酮(50克，0.28摩尔)和硫酰胺(31克，0.32摩尔)悬浮在环丁砜(150毫升)中。加入亚硫酰氯(41克，0.34摩尔)并把温度升高到130-140℃两小时。在浊这到约90℃时，有气体发生。让混合物冷却到90℃，加入水(150毫升)。把温度维持在85-90℃15分钟，然后把溶液冷却到35℃。滤出结晶并用水(250毫升)洗涤。标题化合物可由醋酸中结晶。产量34.5克，77％。DSC开始：203℃。纯度98.5％(按hplc峰面积)。1H NMR(DMSO-d6，500MHz)：5.48(2H，s)，8.03(2H，s)，8.22(1H.s).13C NMR (DMSO-d6，125MHz)：70.0，116.1，188.O，126.0，127.5，129.0，132.8，147.7，169.3.
实施例2
5-氰-2-苯并[c]呋喃酮
把湿的5-羧基-2-苯并[c]呋喃酮(14公斤，干重约6.3公斤，35摩尔)悬浮于环丁砜(23.5公斤)中。用甲苯进行恒沸蒸馏以除去水。加入硫酰胺(3.9公斤，41摩尔)和亚硫酰氯(5.8公斤，48摩尔)并把温度升到135-140℃5小时。在约90℃时有气体发生。让混合物冷却到90℃并加入水(21.3公斤)。把温度维持在85-90℃15分钟，然后将溶液冷却到35℃。滤出结晶并用水(14.2公斤)洗涤。标题化合物可由醋酸中结晶。产量3.8公斤，68％。纯度99.5％(按hplc峰面积)。
实施例3
5-氰-2-苯并[c]呋喃酮
把5-氯羰基-2-苯并[c]呋喃酮(24.3克，0.124摩尔)溶解于环丁砜(51克)中。加入硫酰胺(13.8克，0.144摩尔)并把温度升到135℃3小时。在约90℃时有气体发生。让混合物冷却并加入水(100克)。把温度维持在85-90℃5分钟，然后把溶液冷却到60℃。滤出结晶并用水(60克)和醋酸(30克)洗涤。然后把标题化合物在真空中干燥。产量19克，95％。纯度98.2％(按hplc的峰面积)。
Claims (10)
1.一种制备5-氰-2-苯并[c]呋喃酮(式IV)的方法
结构式IV它包括把5-羧基-2-苯并[c]呋喃酮(式III)
结构式III与一种脱水剂和通式为H2NSO2-R(式V)的磺酰胺类化合物进行反应，其中R是：
a)NH2、C1-6烷氧基、苯氧基，
b)被卤素、C1-4烷基、氰基、羟基、C1-4烷氧基、三氟甲基、硝基、氨基、C1-4烷基氨基或二C1-4-烷基氨基所取代的苯氧基，
c)被一个或多个吸电子取代基所取代的苯基。
2.权利要求1的方法，其中所用的脱水剂是SOCl2、POCl3、PCl5、SOBr2、POBr3、PBr5、SOI2、POI3、PI5或草酰氯。
3.权利要求2的方法，其中所用的脱水剂是SOCl2、POCl3或PCl5，优选SOCl2。
4.权利要求1-3中任意一项的方法，其中所用的磺酰胺是一种式V化合物，其中的R是NH2。
5.权利要求1-4中任意一项的方法，其中在进行反应时不用析离5-卤甲酰基-2-苯并[c]呋喃酮中间体。
6.权利要求1或5的方法，其中反应可在没有溶剂存在的条件下进行。
7.权利要求1或5的方法，其中反应是在环丁砜或乙腈中进行的，优选在环丁砜中进行。
8.权利要求5的方法，其中5-羧基-2-苯并[c]呋喃酮与硫酰胺是在环丁砜溶液中，在SOCl2存在的条件下进行反应的。
9.权利要求1-4中任意一面的方法，其中由5-羧基-2-苯并[c]呋喃酮与脱水剂反应得到的5-卤甲酰基-2-苯并[c]呋喃酮中间体，被析离出来以后再与磺酰胺进行反应。
10.权利要求9的方法，其中反应是在环丁砜中进行的。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA199900128 | 1999-01-29 | ||
| DKPA199900128 | 1999-01-29 |
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| Publication Number | Publication Date |
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| CN1337957A true CN1337957A (zh) | 2002-02-27 |
| CN1158271C CN1158271C (zh) | 2004-07-21 |
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| CNB008030480A Expired - Fee Related CN1158271C (zh) | 1999-01-29 | 2000-01-26 | 制备5-氰-2-苯并[c]呋喃酮的方法 |
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| Country | Link |
|---|---|
| US (1) | US6441201B1 (zh) |
| EP (1) | EP1150966B1 (zh) |
| JP (1) | JP2002535397A (zh) |
| KR (1) | KR100430327B1 (zh) |
| CN (1) | CN1158271C (zh) |
| AR (1) | AR022329A1 (zh) |
| AT (1) | ATE222900T1 (zh) |
| AU (1) | AU763666B2 (zh) |
| BG (1) | BG64924B1 (zh) |
| BR (1) | BR0008978A (zh) |
| CA (1) | CA2361395C (zh) |
| CZ (1) | CZ300257B6 (zh) |
| DE (1) | DE60000364T2 (zh) |
| DK (1) | DK1150966T3 (zh) |
| EA (1) | EA003257B1 (zh) |
| ES (1) | ES2180508T3 (zh) |
| HK (1) | HK1044342B (zh) |
| HU (1) | HUP0104976A3 (zh) |
| IL (2) | IL144114A0 (zh) |
| IS (1) | IS2223B (zh) |
| IT (1) | IT1317741B1 (zh) |
| NO (1) | NO326532B1 (zh) |
| NZ (1) | NZ512775A (zh) |
| PL (1) | PL198385B1 (zh) |
| PT (1) | PT1150966E (zh) |
| SI (1) | SI1150966T1 (zh) |
| SK (1) | SK284367B6 (zh) |
| TR (1) | TR200102135T2 (zh) |
| UA (1) | UA70987C2 (zh) |
| WO (1) | WO2000044738A1 (zh) |
| ZA (1) | ZA200105549B (zh) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2189502T3 (es) | 1998-10-20 | 2003-07-01 | Lundbeck & Co As H | Metodo para la prevencion de citalopram. |
| NZ512073A (en) | 1998-12-23 | 2003-10-31 | H | Method for the preparation of 5-cyanophthalide and citalopram |
| PT1173431E (pt) | 1999-04-14 | 2003-09-30 | Lundbeck & Co As H | Metodo de preparacao do citalopram |
| ITMI991581A1 (it) * | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
| ITMI991579A1 (it) | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
| DK1298124T3 (da) | 1999-10-25 | 2007-07-09 | Lundbeck & Co As H | Fremgangsmåde til fremstilling af citalopram |
| GB2360281B (en) | 1999-10-25 | 2002-01-16 | Lundbeck & Co As H | Method for the preparation of citalopram |
| AR026063A1 (es) | 1999-11-01 | 2002-12-26 | Lundbeck & Co As H | Metodo para la preparacion de 5-carboxiftalida. |
| EA004742B1 (ru) | 1999-12-28 | 2004-08-26 | Х.Лундбекк А/С | Способ получения циталопрама |
| AU1858400A (en) | 1999-12-30 | 2001-07-16 | H. Lundbeck A/S | Method for the preparation of citalopram |
| WO2001051477A1 (en) | 2000-01-14 | 2001-07-19 | H. Lundbeck A/S | Method for the preparation of 5-cyanophthalide |
| NL1017415C1 (nl) | 2000-02-24 | 2001-05-18 | Lundbeck & Co As H | Werkwijze voor de bereiding van Citalopram. |
| NL1017417C1 (nl) | 2000-03-03 | 2001-03-16 | Lundbeck & Co As H | Werkwijze voor de bereiding van Citalopram. |
| KR20020080485A (ko) * | 2000-03-13 | 2002-10-23 | 하. 룬트벡 아크티에 셀스카브 | 5-치환 1-(4-플루오로페닐)-1,3-디히드로이소벤조푸란의단계적 알킬화 |
| IES20010206A2 (en) | 2000-03-13 | 2002-03-06 | Lundbeck & Co As H | Method for the preparation of citalopram |
| TR200202166T2 (tr) | 2000-03-13 | 2002-12-23 | H. Lndbeck A/S | Sitalopramın preparasyon metodu |
| TR200202155T2 (tr) | 2000-03-14 | 2002-12-23 | H. Lundbeck A/S | Sitalopramin preparasyon metodu |
| WO2001068632A1 (en) * | 2000-03-16 | 2001-09-20 | H. Lundbeck A/S | Method for the preparation of 5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofurans |
| AR032455A1 (es) | 2000-05-12 | 2003-11-12 | Lundbeck & Co As H | Metodo para la preparacion de citalopram, un intermediario empleado en el metodo, un metodo para la preparacion del intermediario empleado en el metodo y composicion farmaceutica antidepresiva |
| CA2354880C (en) | 2000-08-18 | 2003-06-03 | H. Lundbeck A/S | Method for the preparation of citalopram |
| TR200201166T1 (tr) | 2000-12-22 | 2002-10-21 | H.Lundbecks A/S | Saf sitalopram hazırlanması için yöntem |
| AU2001100399B4 (en) | 2000-12-28 | 2002-03-21 | H Lundbeck As | Process for the preparation of pure citalopram |
| GR1004635B (el) * | 2001-08-14 | 2004-07-14 | H@Αlundbeckαa@Sαα | Μεθοδοσαπαρασκευησατησασιταλοπραμης@αα |
| EP1321464A1 (en) * | 2001-12-21 | 2003-06-25 | ICROM S.p.A. | Process for the preparation of 5-cyanophthalide and intermediates useful therein |
| TWI306846B (en) | 2002-08-12 | 2009-03-01 | Lundbeck & Co As H | Method for the separation of intermediates which may be used for the preparation of escitalopram |
| CA2519629A1 (en) | 2003-03-21 | 2004-09-30 | H. Lundbeck A/S | Intermediates for the preparation of citalopram and escitalopram |
| TR200504022T1 (tr) * | 2003-03-24 | 2006-08-21 | Hetero Drugs Limited | (S)-sitalopram oksalatın yeni sıvı kristal formları. |
| EP1777221A1 (en) * | 2005-10-14 | 2007-04-25 | Adorkem Technology SpA | Process for the preparation of 5-cyanophthalide starting from 5-carboxyphthalide |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1143703A (zh) | 1965-03-18 | |||
| GB1526331A (en) | 1976-01-14 | 1978-09-27 | Kefalas As | Phthalanes |
| GB8419963D0 (en) * | 1984-08-06 | 1984-09-12 | Lundbeck & Co As H | Intermediate compound and method |
| GB8814057D0 (en) | 1988-06-14 | 1988-07-20 | Lundbeck & Co As H | New enantiomers & their isolation |
| US5296507A (en) | 1990-09-06 | 1994-03-22 | H.Lundbeck A/S | Treatment of cerbrovascular disorders |
| DE19626659A1 (de) | 1996-07-03 | 1998-01-08 | Basf Ag | Verfahren zur Herstellung von Phthaliden |
| DE19627697A1 (de) | 1996-07-10 | 1998-01-15 | Basf Ag | Verfahren zur Herstellung von Phthaliden |
| SK283309B6 (sk) * | 1997-07-08 | 2003-05-02 | H. Lundbeck A/S | Spôsob výroby citalopramu a medziprodukty |
| UA62985C2 (en) * | 1997-11-10 | 2004-01-15 | Lunnbeck As H | A method for the preparation of citalopram |
| EP1042310B1 (en) | 1997-11-11 | 2002-07-31 | H. Lundbeck A/S | Method for the preparation of citalopram |
| ES2189502T3 (es) | 1998-10-20 | 2003-07-01 | Lundbeck & Co As H | Metodo para la prevencion de citalopram. |
| NZ512073A (en) * | 1998-12-23 | 2003-10-31 | H | Method for the preparation of 5-cyanophthalide and citalopram |
| PT1173431E (pt) | 1999-04-14 | 2003-09-30 | Lundbeck & Co As H | Metodo de preparacao do citalopram |
| ITMI991579A1 (it) | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
| ITMI991581A1 (it) | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
| GB2360281B (en) | 1999-10-25 | 2002-01-16 | Lundbeck & Co As H | Method for the preparation of citalopram |
| US6310222B1 (en) | 1999-11-01 | 2001-10-30 | Sumika Fine Chemicals Co., Ltd. | Production method of 5-phthalancarbonitrile compound, intermediate therefor and production method of the intermediate |
| NL1017415C1 (nl) | 2000-02-24 | 2001-05-18 | Lundbeck & Co As H | Werkwijze voor de bereiding van Citalopram. |
| IES20010143A2 (en) | 2000-02-24 | 2001-07-25 | Lundbeck & Co As H | Method for the preparation of citalopram |
| GB0005477D0 (en) | 2000-03-07 | 2000-04-26 | Resolution Chemicals Limited | Process for the preparation of citalopram |
| CA2354880C (en) | 2000-08-18 | 2003-06-03 | H. Lundbeck A/S | Method for the preparation of citalopram |
| TR200201166T1 (tr) | 2000-12-22 | 2002-10-21 | H.Lundbecks A/S | Saf sitalopram hazırlanması için yöntem |
| AU2001100399B4 (en) | 2000-12-28 | 2002-03-21 | H Lundbeck As | Process for the preparation of pure citalopram |
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- 2000-01-26 JP JP2000595994A patent/JP2002535397A/ja active Pending
- 2000-01-26 CN CNB008030480A patent/CN1158271C/zh not_active Expired - Fee Related
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