HRP20020405A2 - Method for the preparation of 5-carboxyphthalide - Google Patents
Method for the preparation of 5-carboxyphthalide Download PDFInfo
- Publication number
- HRP20020405A2 HRP20020405A2 HR20020405A HRP20020405A HRP20020405A2 HR P20020405 A2 HRP20020405 A2 HR P20020405A2 HR 20020405 A HR20020405 A HR 20020405A HR P20020405 A HRP20020405 A HR P20020405A HR P20020405 A2 HRP20020405 A2 HR P20020405A2
- Authority
- HR
- Croatia
- Prior art keywords
- carboxyphthalide
- terephthalic acid
- water
- oleum
- equivalents
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 18
- 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 title claims description 17
- 238000002360 preparation method Methods 0.000 title claims description 3
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 claims description 40
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 6
- 229920002866 paraformaldehyde Polymers 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 2
- 235000019256 formaldehyde Nutrition 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- -1 1-[3-(dimethylamino)propyl]-1-(fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile Chemical compound 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 3
- XEEGWTLAFIZLSF-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carbonitrile Chemical compound N#CC1=CC=C2C(=O)OCC2=C1 XEEGWTLAFIZLSF-UHFFFAOYSA-N 0.000 description 3
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 3
- 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 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 229960001653 citalopram Drugs 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- ARCGXLSVLAOJQL-UHFFFAOYSA-N trimellitic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(C(O)=O)=C1 ARCGXLSVLAOJQL-UHFFFAOYSA-N 0.000 description 2
- VUBKPUVOSWVXMI-UHFFFAOYSA-N 3-oxo-1h-2-benzofuran-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2COC(=O)C2=C1 VUBKPUVOSWVXMI-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
- Seasonings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Ovaj se izum odnosi na novi postupak priprave 5-karboksiftalida, početnog materijala za proizvodnju poznatog antidepresiva citaloprama, 1-[3-(dimetilamino)propil]-1-(fluorofenil)-1,3-dihidro-5-izobenzofurankarbonitrila.
Pozadina izuma
Citalopram je selektivni inhibitor ponovne pohrane serotonina, koji se već nekoliko godina uspješno nalazi na tržištu kao antidepresiv. Struktura mu je:
[image]
i može se pripravljati prema postupku opisanom u SAD patentu br. 4,650,884 prema kojemu se 5-cijanoftalid podvrgava dvjema Grignardovim reakcijama za redom, tj. s 4-fluorofenil magnezijevim halogenidom odnosno N,N-dimetil-aminopropil magnezijevim halogenidom, a dobiveni bikarbinolski spoj podvrgava se reakciji zatvaranja prstena dehidracijom. Sam 5-cijanoftalid može se dobiti reakcijom 5-karboksiftalida s dehidrirajućim agensom i sulfonamidom formule H2N-SO2-R u kojoj R predstavlja NH2, alkoksi, opcionalno supstituiran feniloksi ili supstituirani fenil kako bi se dobio 5-cijanoftalid; usp. našu dansku patentnu prijavu u postupku PA 199801718.
5-karboftalid je opisan kao uspješan intermedier u industriji polimera i boja. Međutim, trenutno nema pouzdanog komercijalnog izvora. Poznati postupak je kalalitička hidrogenacija trimelitične kiseline (DE-A1 2630927). Tim se postupkom dobiva mješavina 5- i 6-karboksiftalida, pa je, prema tome, potrebno komplicirano i skupo pročišćavanje. Prema J. Org. Chem. 1970., 35, str. 1695-1696, 5-karboksiftalid se sintetizira reakcijom tereftalne kiseline s trioksanom u tekućem SO3. Tijekom tog postupka trioksan sublimira i taloži se te tako začepljuje uređaj.
Premda je niz drugih metoda bio neuspješan, sada se pokazalo da se 5-karboksiftalid može pripraviti iz tereftalne kiseline u visokom iskorištenju podesnim, rentabilnim postupkom.
Opis izuma
U skladu s time, ovaj izum predstavlja postupak za proizvodnju 5-karboksiftalida
[image]
koji podrazumijeva reakciju tereftalne kiseline
[image]
s paraformaldehidom, HO(CH2)nH, u oleumu.
Postupkom prema ovom izumu dobiva se 5-karfoksiftalid visoke čistoće i visokog iskorištenja (> oko 75%). Osim toga, u usporedbi s ranijim postupcima (J. Org. Chem. 1970., 35, str. 1695-1969), postupak prema ovom izumu odvija se bez taloženja sublimiranog trioksana koje začepljuje uređaj, npr. taloženjem u kondenzatorima.
Korišteni oleum je komercijalno raspoloživ. Sljedeći su proizvodnje Aldrich/Fluka:
12-17%SO3 (dimeća sumporna kiselina) = 15% oleuma
18-24%SO3 (dimeća sumporna kiselina) = 20% oleuma
27-33%SO3 (dimeća sumporna kiselina) = 30% oleuma
Iz drugih izvora 10% ulja sadrži 20-25% SO3
U metodi prema ovom izumu, tereftalna kiselina kondenzira s paraformaldehidom uz oslobađanje vode, koja reagira sa SO3. Kad je reakcija dovršena na sljedeći se način može izolirati 5-karboksiftalid: Mješavina reakcije hidrolizira se s vodom. Kondenzirani proizvod, 5-karboksiftalid uz eventualne nečistoće diftalida može se profiltrirati i 5-karboksiftalid se može otopiti u vodenom mediju uz podešavanje pH na oko 6,7 do 7,3, dok eventualne nečistoće diftalida ostaju u krutoj fazi. Prisutni se diftalid može profiltrirati, nakon čega se 5-karboksiftalid može istaložiti zakiseljavanjem, profiltrirati, isprati vodom i osušiti.
Preferirano se koriste 1,0-1,33 i 1,0-2,5 ekvivalenti CH2O, preferirano 1,0-2,0. Još se više preferirano koriste 1,25-1,5 ekvivalenti SO3 po ekvivalentu tereftalne kiseline. Najviše preferirano, koriste se ekvivalenti oko 1,37 (što je otprilike jednako oko 3,3 kg 20-25% uleuma/kg tereftalne tiseline) po ekvivalentu tereftalne kiseline.
Reakcija tereftalne kiseline s paraformaldehidom obavlja se na povišenoj temperaturi, prikladno na oko 50-148°C, preferirano 115-125°C ili 138-148°C. Vrijeme reakcije nije kritično i stručnjak je može lako odrediti, s time da se za jednu partiju od 210 kg na 115-125°C preferirano koristi vrijeme od 17 - 21 sat. Vrijeme je kraće što je temperatura viša.
Podešavanje pH na 6,3 do 7,3 radi otapanja stvorenog 5-karboksiftalida može se izvršiti pomoću NaOH, npr. oko 10% vodenog NAOH.
Zakiseljavanje u svrhu taloženja 5-karboksiftalida može se obaviti dodavanjem sumporne kiseline sve do pH = 2.
Tereftalna kiselina koja se upotrebljava kao početni materijal komercijalno je raspoloživa.
Primjeri
Ovaj se izum nadalje ilustrira sljedećim primjerima.
Primjer 1
5-Karboksiftalid
Tereftalna kiselina (10 kg) stavlja se u reaktor. Dodaju se oleum (20%(18-24%SO3); 6kg/kg tereftalne kiseline), a zatim paraformaldehid (1,33 ekvivalenta, 0,24 kg/kg tereftalne kiseline). Mješavina se 17 sati trese na 125°C. Dodaje se voda (13 kg/kg tereftalne kiseline) te pomoćno sredstvo za filtriranje, temperatura se podešava na oko 70°C. Talog se profiltrira, ispere vodom i napravi se suspenzija u vodi. pH suspenzije podesi se pomoću NaOH na oko 7, dodaje se aktivni ugljen, 0,07 kg/kg tereftalne kiseline, a zatim se mješavina profiltrira i talog ispere vodom. Temperatura filtrata podesi se na oko 65°C, a pH se pomoću 50% sumporne kiseline podesi na oko 2. Istaloženi 5-karboksilftalid separira se filtriranjem, zatim ispere i osuši. Iskorištenje 83%.
Primjer 2
5-Karboksiftalid
Oleum (20-25% SO3 43 kg) se stavlja u reaktor. Dodaje se tereftalna kiselina (13 kg), a zatim paraformaldehid (3,8 kg). Mješavina se 41⁄2 sata trese na 138-148°C. Dodaje se voda (87 l), a temperatura podešava na oko 100°C. Talog se profiltrira, ispere vodom i napravi se suspenzija u vodi. pH suspenzije podesi se pomoću NaOH (oko 10%) na oko 7, dodaje se aktivni ugljen, 0,5 kg, a zatim se mješavina profiltrira i talog ispere vodom. Temperatura filtrata podesi se na oko 85°C, a pH se pomoću 96% sumporne kiseline podesi na oko 2. Istaloženi 5-karboksiftalid separira se filtriranjem, ispere i osuši. Iskorištenje 82%.
Claims (5)
1. Način priprave 5-karboksiftalida
[image]
naznačen time da uključuje reakciju tereftalne kiseline
[image]
s paraformaldehidom HO(CH2)nH u oleumu.
2. Način prema patentnom zahtjevu 1, naznačen time da se koriste 1,0-1,33 ekvivalenti CH2O i 1,0-2,5 ekvivalenti SO3 po ekvivalentu tereftalne kiseline.
3. Način prema patentnim zahtjevu 2, naznačen time da se koriste 1,0-2,0, posebno 1,25-1,5 ekvivalenti SO3 po ekvivalentu tereftalne kiseline.
4. Način prema patentnom zahtjevu 3, naznačen time da se koriste ekvivalenti od oko 1,37 SO3 po ekvivalentu tereftalne kiseline.
5. Način prema patentnom zahtjevu 3, naznačen time da se koristi oko 3,3 kg 20-25% oleuma po kg tereftalne kiseline.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA199901569 | 1999-11-01 | ||
| PCT/DK2000/000585 WO2001032642A1 (en) | 1999-11-01 | 2000-10-19 | Method for the preparation of 5-carboxyphthalide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20020405A2 true HRP20020405A2 (en) | 2004-02-29 |
Family
ID=8106151
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20020405A HRP20020405A2 (en) | 1999-11-01 | 2002-05-10 | Method for the preparation of 5-carboxyphthalide |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6403813B1 (hr) |
| EP (1) | EP1235819A1 (hr) |
| JP (1) | JP2003513084A (hr) |
| CN (1) | CN1187348C (hr) |
| AR (1) | AR026063A1 (hr) |
| AU (1) | AU7902400A (hr) |
| BR (1) | BR0015471A (hr) |
| CA (1) | CA2389379C (hr) |
| HK (1) | HK1052702A1 (hr) |
| HR (1) | HRP20020405A2 (hr) |
| IT (1) | IT1319251B1 (hr) |
| MX (1) | MXPA02004313A (hr) |
| WO (1) | WO2001032642A1 (hr) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL198024B1 (pl) | 1999-04-14 | 2008-05-30 | Lundbeck & Co As H | Sposób wytwarzania citalopramu, związki pośrednie i ich zastosowanie do wytwarzania citalopramu |
| ITMI991581A1 (it) * | 1999-06-25 | 2001-01-15 | Lundbeck & Co As H | Metodo per la preparazione di citalopram |
| AR026063A1 (es) * | 1999-11-01 | 2002-12-26 | Lundbeck & Co As H | Metodo para la preparacion de 5-carboxiftalida. |
| PL355532A1 (en) | 1999-12-28 | 2004-05-04 | H.Lundbeck A/S | Method for the preparation of citalopram |
| CZ20022627A3 (cs) | 1999-12-30 | 2002-10-16 | H. Lundbeck A/S | Způsob výroby citalopramu |
| SK286879B6 (sk) * | 2000-01-14 | 2009-07-06 | H. Lundbeck A/S | Spôsob prípravy 5-kyanoftalidu |
| IT1317729B1 (it) | 2000-01-18 | 2003-07-15 | Norpharma S P A | Procedimento per la preparazione della 5-carbossiftalide. |
| NL1017417C1 (nl) | 2000-03-03 | 2001-03-16 | Lundbeck & Co As H | Werkwijze voor de bereiding van Citalopram. |
| GB0005477D0 (en) | 2000-03-07 | 2000-04-26 | Resolution Chemicals Limited | Process for the preparation of citalopram |
| JP2003527387A (ja) | 2000-03-13 | 2003-09-16 | ハー・ルンドベック・アクチエゼルスカベット | シタロプラムの製造方法 |
| NL1017500C1 (nl) | 2000-03-13 | 2001-04-26 | Lundbeck & Co As H | Werkwijze voor de bereiding van Citalopram. |
| JP2003527385A (ja) * | 2000-03-13 | 2003-09-16 | ハー・ルンドベック・アクチエゼルスカベット | ５−置換された１−（４−フルオロフェニル）−１，３−ジヒドロイソベンゾフランの段階的アルキル化法 |
| PT1265882E (pt) | 2000-03-14 | 2004-06-30 | Lundbeck & Co As H | Metodo para preparacao de citalopram; composto e citalopram |
| TR200202168T2 (tr) * | 2000-03-16 | 2002-12-23 | H. Lundbeck A/S | 5-Siyano-1-(4-Florofenil)-1,3-Dihidroizobenzofuranların preparasyon metodu |
| 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 |
| US7687645B2 (en) * | 2003-03-21 | 2010-03-30 | H. Lundbeck A/S | Intermediates for the preparation of citalopram and escitalopram |
| US20050154052A1 (en) * | 2003-03-24 | 2005-07-14 | Hetero Drugs Limited | Novel crystalline forms of (s)-citalopram oxalate |
| WO2006090409A1 (en) * | 2005-02-28 | 2006-08-31 | Kekule Pharma Ltd., | An improved process for the preparation of 5 - carboxyphthalide |
| CN106632183A (zh) * | 2016-12-07 | 2017-05-10 | 万全万特制药（厦门）有限公司 | 一种草酸艾司西酞普兰杂质的制备方法 |
| CN112062741A (zh) * | 2019-06-11 | 2020-12-11 | 太仓市茜泾化工有限公司 | 一种5-羧酸苯酞的制备方法 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1143703A (hr) | 1965-03-18 | |||
| US3607884A (en) * | 1969-03-11 | 1971-09-21 | Mobil Oil Corp | Preparation of 5-carboxyphthalide in liquid sodium trioxide |
| DE2242007A1 (de) * | 1972-08-26 | 1974-03-14 | Basf Ag | Verfahren zur herstellung von phthalimidinen |
| GB1526331A (en) | 1976-01-14 | 1978-09-27 | Kefalas As | Phthalanes |
| DE2630927A1 (de) * | 1976-07-09 | 1978-01-19 | Basf Ag | Verfahren zur herstellung von phthalidcarbonsaeure-(5) |
| 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 |
| DE59003859D1 (de) | 1989-08-23 | 1994-01-27 | Alusuisse Lonza Services Ag | Sterilisierfähiger Verpackungsbehälter aus Kunststoff-Metall-Kunststoff-Verbundmaterial und Verfahren zu dessen Herstellung. |
| 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 |
| EA001728B1 (ru) | 1997-07-08 | 2001-08-27 | Х.Лундбекк А/С | Способ получения циталопрама |
| UA62985C2 (en) | 1997-11-10 | 2004-01-15 | Lunnbeck As H | A method for the preparation of citalopram |
| SK283907B6 (sk) | 1997-11-11 | 2004-04-06 | H. Lundbeck A/S | Spôsob výroby citalopramu a medziprodukty |
| AU746665B2 (en) | 1998-10-20 | 2002-05-02 | H. Lundbeck A/S | Method for the preparation of citalopram |
| BR9916955A (pt) | 1998-12-23 | 2001-09-11 | Lundbeck & Co As H | Método para preparação de 5-cianoftalida |
| AR022329A1 (es) | 1999-01-29 | 2002-09-04 | Lundbeck & Co As H | Metodo para la preparacion de 5-cianoftalida |
| PL198024B1 (pl) | 1999-04-14 | 2008-05-30 | Lundbeck & Co As H | Sposób wytwarzania citalopramu, związki pośrednie i ich zastosowanie do wytwarzania citalopramu |
| 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 |
| CH692421A5 (de) | 1999-10-25 | 2002-06-14 | Lundbeck & Co As H | Verfahren zur Herstellung von Citalopram. |
| WO2001032643A1 (en) | 1999-11-01 | 2001-05-10 | H. Lundbeck A/S | Method for the preparation of 5-carboxyphthalide |
| 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 |
| AR026063A1 (es) | 1999-11-01 | 2002-12-26 | Lundbeck & Co As H | Metodo para la preparacion de 5-carboxiftalida. |
| IT1317729B1 (it) * | 2000-01-18 | 2003-07-15 | Norpharma S P A | Procedimento per la preparazione della 5-carbossiftalide. |
| US6433196B1 (en) * | 2000-02-17 | 2002-08-13 | Sumika Fine Chemicals Co., Ltd. | Production method of citalopram, intermediate therefor and production method of the intermediate |
| IES20010143A2 (en) | 2000-02-24 | 2001-07-25 | Lundbeck & Co As H | Method for the preparation of citalopram |
| NL1017415C1 (nl) | 2000-02-24 | 2001-05-18 | Lundbeck & Co As H | Werkwijze voor de bereiding van Citalopram. |
| GB0005477D0 (en) | 2000-03-07 | 2000-04-26 | Resolution Chemicals Limited | Process for the preparation of citalopram |
| FI20011622A (fi) | 2000-08-18 | 2002-02-19 | Lundbeck & Co As H | Menetelmä sitalopraamin valmistamiseksi |
| KR100430746B1 (ko) | 2000-12-28 | 2004-05-10 | 하. 룬트벡 아크티에 셀스카브 | 순수한 시탈로프람의 제조방법 |
-
2000
- 2000-10-17 AR ARP000105451A patent/AR026063A1/es unknown
- 2000-10-19 JP JP2001534793A patent/JP2003513084A/ja not_active Withdrawn
- 2000-10-19 BR BR0015471-7A patent/BR0015471A/pt not_active IP Right Cessation
- 2000-10-19 US US09/692,653 patent/US6403813B1/en not_active Expired - Fee Related
- 2000-10-19 CA CA002389379A patent/CA2389379C/en not_active Expired - Fee Related
- 2000-10-19 AU AU79024/00A patent/AU7902400A/en not_active Abandoned
- 2000-10-19 MX MXPA02004313A patent/MXPA02004313A/es unknown
- 2000-10-19 WO PCT/DK2000/000585 patent/WO2001032642A1/en active Application Filing
- 2000-10-19 CN CNB008151431A patent/CN1187348C/zh not_active Expired - Fee Related
- 2000-10-19 EP EP00969234A patent/EP1235819A1/en not_active Withdrawn
- 2000-10-27 IT IT2000MI002342A patent/IT1319251B1/it active
-
2002
- 2002-05-06 US US10/140,361 patent/US6888009B2/en not_active Expired - Fee Related
- 2002-05-10 HR HR20020405A patent/HRP20020405A2/hr not_active Application Discontinuation
-
2003
- 2003-07-10 HK HK03104993A patent/HK1052702A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1235819A1 (en) | 2002-09-04 |
| BR0015471A (pt) | 2002-07-09 |
| HK1052702A1 (en) | 2003-09-26 |
| US6888009B2 (en) | 2005-05-03 |
| JP2003513084A (ja) | 2003-04-08 |
| AR026063A1 (es) | 2002-12-26 |
| CN1391567A (zh) | 2003-01-15 |
| US6403813B1 (en) | 2002-06-11 |
| CN1187348C (zh) | 2005-02-02 |
| US20020165403A1 (en) | 2002-11-07 |
| MXPA02004313A (es) | 2002-11-07 |
| WO2001032642A1 (en) | 2001-05-10 |
| CA2389379A1 (en) | 2001-05-10 |
| IT1319251B1 (it) | 2003-09-26 |
| CA2389379C (en) | 2007-04-10 |
| ITMI20002342A1 (it) | 2002-04-27 |
| AU7902400A (en) | 2001-05-14 |
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