SK287140B6 - Spôsob prípravy citalopramu a medziprodukt na jeho výrobu - Google Patents

Spôsob prípravy citalopramu a medziprodukt na jeho výrobu Download PDF

Info

Publication number: SK287140B6
Authority: SK; Slovakia
Prior art keywords: formula; compound; iii; dimethylamino; mol
Prior art date: 1999-10-25

Application number

SK50008-2009A

Other languages

English (en)

Slovak (sk)

Inventor

Michael Harold Rock

Hans Petersen

Peter Ellegaard

Original Assignee

H. Lundbeck A/S

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-10-25

Filing date

1999-10-25

Publication date

2010-01-07

1999-10-25 Application filed by H. Lundbeck A/S filed Critical H. Lundbeck A/S

1999-10-25 Priority claimed from PCT/DK1999/000581 external-priority patent/WO2000012044A2/en

2010-01-07 Publication of SK287140B6 publication Critical patent/SK287140B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 31
229960001653 citalopram Drugs 0.000 title claims abstract description 29
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 title claims abstract description 27
238000002360 preparation method Methods 0.000 title claims abstract description 12
238000004519 manufacturing process Methods 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 58
-1 3-(N,N-dimethylamino)-propyl magnesium halide Chemical class 0.000 claims abstract description 23
125000002252 acyl group Chemical group 0.000 claims abstract description 9
125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 4
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract 2
150000003839 salts Chemical class 0.000 claims description 11
238000006798 ring closing metathesis reaction Methods 0.000 claims description 5
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
NGPAITITALWALP-UHFFFAOYSA-M magnesium;n,n-dimethylpropan-1-amine;chloride Chemical compound [Mg+2].[Cl-].CN(C)CC[CH2-] NGPAITITALWALP-UHFFFAOYSA-M 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
238000007248 oxidative elimination reaction Methods 0.000 claims description 3
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
230000018044 dehydration Effects 0.000 claims description 2
238000006297 dehydration reaction Methods 0.000 claims description 2
238000010511 deprotection reaction Methods 0.000 claims description 2
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
238000000926 separation method Methods 0.000 claims description 2
WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 claims 3
229960004341 escitalopram Drugs 0.000 claims 3
238000006243 chemical reaction Methods 0.000 abstract description 23
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
239000000243 solution Substances 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 16
238000003756 stirring Methods 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 12
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 10
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical group CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 7
GNULRNVWXYXBQY-UHFFFAOYSA-N 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile Chemical compound C=1C=C(C#N)C=C(CO)C=1C(O)(CCCN(C)C)C1=CC=C(F)C=C1 GNULRNVWXYXBQY-UHFFFAOYSA-N 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
KDVCPEMLEKULTN-UHFFFAOYSA-N [5-cyano-2-(4-fluorobenzoyl)phenyl]methyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCC1=CC(C#N)=CC=C1C(=O)C1=CC=C(F)C=C1 KDVCPEMLEKULTN-UHFFFAOYSA-N 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
150000002576 ketones Chemical class 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000002904 solvent Substances 0.000 description 6
150000001336 alkenes Chemical class 0.000 description 5
239000000935 antidepressant agent Substances 0.000 description 5
239000004310 lactic acid Substances 0.000 description 5
235000014655 lactic acid Nutrition 0.000 description 5
239000007858 starting material Substances 0.000 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 description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
238000003747 Grignard reaction Methods 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
235000011114 ammonium hydroxide Nutrition 0.000 description 4
239000002585 base Substances 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
238000001914 filtration Methods 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
239000000047 product Substances 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
230000001430 anti-depressive effect Effects 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
WSEQXVZVJXJVFP-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound O1CC2=CC(C#N)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 WSEQXVZVJXJVFP-UHFFFAOYSA-N 0.000 description 2
WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical group CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
235000019502 Orange oil Nutrition 0.000 description 2
FFTYWXFRGPBXCG-UHFFFAOYSA-N [5-cyano-2-[(4-fluorophenyl)-hydroxymethyl]phenyl]methyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCC1=CC(C#N)=CC=C1C(O)C1=CC=C(F)C=C1 FFTYWXFRGPBXCG-UHFFFAOYSA-N 0.000 description 2
CRLUMHOSVXEYMY-UHFFFAOYSA-N [5-cyano-2-[4-(dimethylamino)-1-(4-fluorophenyl)but-1-enyl]phenyl]methyl 2,2-dimethylpropanoate Chemical compound C=1C=C(C#N)C=C(COC(=O)C(C)(C)C)C=1C(=CCCN(C)C)C1=CC=C(F)C=C1 CRLUMHOSVXEYMY-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
229940005513 antidepressants Drugs 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
125000001072 heteroaryl group Chemical group 0.000 description 2
125000001041 indolyl group Chemical group 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 2
RYEXTBOQKFUPOE-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].CC[CH2-] RYEXTBOQKFUPOE-UHFFFAOYSA-M 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
239000003826 tablet Substances 0.000 description 2
229960000278 theophylline Drugs 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-UHFFFAOYSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
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
FTHPLWDYWAKYCY-UHFFFAOYSA-N 3,5-dimethoxybenzoyl chloride Chemical group COC1=CC(OC)=CC(C(Cl)=O)=C1 FTHPLWDYWAKYCY-UHFFFAOYSA-N 0.000 description 1
JYLNVJYYQQXNEK-UHFFFAOYSA-N 3-amino-2-(4-chlorophenyl)-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(CN)C1=CC=C(Cl)C=C1 JYLNVJYYQQXNEK-UHFFFAOYSA-N 0.000 description 1
NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 1
JOWBVIAXILQDHG-UHFFFAOYSA-N 4-[(4-fluorophenyl)-hydroxymethyl]-3-(hydroxymethyl)benzonitrile Chemical compound OCC1=CC(C#N)=CC=C1C(O)C1=CC=C(F)C=C1 JOWBVIAXILQDHG-UHFFFAOYSA-N 0.000 description 1
IUSPXLCLQIZFHL-UHFFFAOYSA-N 5-bromo-3h-2-benzofuran-1-one Chemical compound BrC1=CC=C2C(=O)OCC2=C1 IUSPXLCLQIZFHL-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
208000006558 Dental Calculus Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
229910004803 Na2 WO4.2H2 O Inorganic materials 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
ALIGTYPNWJPIKT-UHFFFAOYSA-M [Cl-].FC1=CC=C([Mg+])C=C1 Chemical compound [Cl-].FC1=CC=C([Mg+])C=C1 ALIGTYPNWJPIKT-UHFFFAOYSA-M 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000005129 aryl carbonyl group Chemical group 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical group CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
244000309464 bull Species 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000000969 carrier Substances 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
239000012050 conventional carrier Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000005223 heteroarylcarbonyl group Chemical group 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical group IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
SFLGSKRGOWRGBR-UHFFFAOYSA-N phthalane Chemical class C1=CC=C2COCC2=C1 SFLGSKRGOWRGBR-UHFFFAOYSA-N 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
238000004321 preservation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 1
229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
239000003772 serotonin uptake inhibitor Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000000335 thiazolyl group Chemical group 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/56—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and doubly-bound oxygen atoms bound to the carbon skeleton

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Neurology (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Epidemiology (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Steroid Compounds (AREA)

SK50008-2009A 1999-10-25 1999-10-25 Spôsob prípravy citalopramu a medziprodukt na jeho výrobu SK287140B6 (sk)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PCT/DK1999/000581 WO2000012044A2 (en)	1999-10-25	1999-10-25	Method for the preparation of citalopram

Publications (1)

Publication Number	Publication Date
SK287140B6 true SK287140B6 (sk)	2010-01-07

Family

ID=8157164

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK50008-2009A SK287140B6 (sk)	1999-10-25	1999-10-25	Spôsob prípravy citalopramu a medziprodukt na jeho výrobu

Country Status (25)

Country	Link
US (1)	US6566540B2 (de)
EP (1)	EP1298124B1 (de)
KR (1)	KR100505820B1 (de)
AR (1)	AR024518A1 (de)
AT (2)	ATE277032T1 (de)
CA (1)	CA2291133C (de)
CY (1)	CY1107635T1 (de)
CZ (1)	CZ292894B6 (de)
DE (3)	DE69920526T2 (de)
DK (2)	DK1298124T3 (de)
EA (1)	EA002801B1 (de)
ES (1)	ES2282365T3 (de)
HK (1)	HK1043129B (de)
HR (1)	HRP20020344B1 (de)
HU (1)	HUP0200169A3 (de)
IL (3)	IL143875A0 (de)
IS (1)	IS2260B (de)
NO (1)	NO20071311L (de)
NZ (1)	NZ512406A (de)
PL (1)	PL201056B1 (de)
PT (2)	PT1298124E (de)
SI (2)	SI1298124T1 (de)
SK (1)	SK287140B6 (de)
TR (1)	TR200401456T1 (de)
UA (1)	UA72238C2 (de)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AR034612A1 (es) *	2001-06-25	2004-03-03	Lundbeck & Co As H	Proceso para la preparacion del citalopram racemico y/o del s- o r-citalopram mediante la separacion de una mezcla de r- y s-citalopram
AR040970A1 (es) *	2002-08-12	2005-04-27	Lundbeck & Co As H	Metodo para la separacion de intermediarios que pueden ser utilizados para la preparacion de escitalopram
US20050137255A1 (en) *	2002-12-23	2005-06-23	H. Lundbeck A/S	Crystalline escitalopram hydrobromide and methods for preparing the same
NZ540281A (en) *	2002-12-23	2008-07-31	Lundbeck & Co As H	Escitalopram hydrobromide and a method for the preparation thereof
AU2003223105A1 (en) *	2003-03-24	2004-10-18	Hetero Drugs Limited	Novel crystalline forms of (s)-citalopram oxalate
US20050196453A1 (en) *	2004-03-05	2005-09-08	H. Lundbeck A/S	Crystalline composition containing escitalopram
KR20080080094A (ko) *	2005-10-14	2008-09-02	하. 룬트벡 아크티에 셀스카브	에스시탈로프람 및 부프로피온의 저용량 조합물을 이용한중추신경계 장애의 치료 방법
AU2006304889A1 (en) *	2005-10-14	2007-04-26	H. Lundbeck A/S	Stable pharmaceutical formulations containing escitalopram and bupropion
ES2653852T3 (es) *	2007-08-03	2018-02-09	Richter Gedeon Nyrt.	Composiciones farmacéuticas que contienen ligandos del receptor de dopamina y procedimientos de tratamiento usando ligandos del receptor de dopamina

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GB1143703A (de)	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
DE3926765A1 (de)	1989-08-12	1991-02-14	Hoechst Ag	Verfahren zur verminderung von primaerem und sekundaerem amin in einem tertiaeren amin
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
JP3526581B2 (ja)	1997-07-08	2004-05-17	ハー・ルンドベック・アクティーゼルスカブ	シタロプラムの製造方法
UA62985C2 (en)	1997-11-10	2004-01-15	Lunnbeck As H	A method for the preparation of citalopram
CN1286687A (zh) *	1997-11-11	2001-03-07	H·隆德贝克有限公司	制备西酞普兰的方法
WO2000023431A1 (en)	1998-10-20	2000-04-27	H. Lundbeck A/S	Method for the preparation of citalopram
HK1043130B (zh)	1998-12-23	2005-03-04	H‧隆德贝克有限公司	制备5-氰基2-苯并[c]呋喃酮的方法
AR022329A1 (es)	1999-01-29	2002-09-04	Lundbeck & Co As H	Metodo para la preparacion de 5-cianoftalida
IL145615A0 (en)	1999-04-14	2002-06-30	Lundbeck & Co As H	Method for the preparation of 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
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
IL144816A (en)	2000-08-18	2005-09-25	Lundbeck & Co As H	Method for the preparation of citalopram
JP2003519121A (ja)	2000-12-28	2003-06-17	ハー・ルンドベック・アクチエゼルスカベット	純粋なシタロプラムの製造方法

1999
- 1999-10-25 HK HK02105036.3A patent/HK1043129B/zh not_active IP Right Cessation
- 1999-10-25 CA CA002291133A patent/CA2291133C/en not_active Expired - Fee Related
- 1999-10-25 KR KR10-2001-7008100A patent/KR100505820B1/ko not_active Expired - Fee Related
- 1999-10-25 SI SI9930960T patent/SI1298124T1/sl unknown
- 1999-10-25 PT PT02028326T patent/PT1298124E/pt unknown
- 1999-10-25 AT AT99950511T patent/ATE277032T1/de active
- 1999-10-25 DK DK02028326T patent/DK1298124T3/da active
- 1999-10-25 DE DE69920526T patent/DE69920526T2/de not_active Expired - Lifetime
- 1999-10-25 UA UA2001075224A patent/UA72238C2/uk unknown
- 1999-10-25 SI SI9930703T patent/SI1228056T1/xx unknown
- 1999-10-25 NZ NZ512406A patent/NZ512406A/xx not_active IP Right Cessation
- 1999-10-25 HU HU0200169A patent/HUP0200169A3/hu unknown
- 1999-10-25 SK SK50008-2009A patent/SK287140B6/sk not_active IP Right Cessation
- 1999-10-25 DE DE19983836A patent/DE19983836C1/de not_active Expired - Fee Related
- 1999-10-25 DE DE69935355T patent/DE69935355T2/de not_active Expired - Lifetime
- 1999-10-25 HR HR20020344A patent/HRP20020344B1/xx not_active IP Right Cessation
- 1999-10-25 EA EA200100593A patent/EA002801B1/ru not_active IP Right Cessation
- 1999-10-25 EP EP02028326A patent/EP1298124B1/de not_active Expired - Lifetime
- 1999-10-25 PT PT99950511T patent/PT1228056E/pt unknown
- 1999-10-25 DK DK99950511T patent/DK1228056T3/da active
- 1999-10-25 ES ES02028326T patent/ES2282365T3/es not_active Expired - Lifetime
- 1999-10-25 AT AT02028326T patent/ATE355268T1/de active
- 1999-10-25 PL PL349440A patent/PL201056B1/pl not_active IP Right Cessation
- 1999-10-25 IL IL14387599A patent/IL143875A0/xx active IP Right Grant
- 1999-10-25 TR TR2004/01456T patent/TR200401456T1/xx unknown
- 1999-11-10 AR ARP990105703A patent/AR024518A1/es active IP Right Grant
2001
- 2001-06-15 IS IS5970A patent/IS2260B/is unknown
- 2001-06-20 IL IL143875A patent/IL143875A/en not_active IP Right Cessation
2002
- 2002-05-03 US US10/138,811 patent/US6566540B2/en not_active Expired - Fee Related
- 2002-08-29 CZ CZ20022925A patent/CZ292894B6/cs not_active IP Right Cessation
2006
- 2006-07-18 IL IL176943A patent/IL176943A0/en unknown
2007
- 2007-03-09 NO NO20071311A patent/NO20071311L/no unknown
- 2007-05-21 CY CY20071100690T patent/CY1107635T1/el unknown

Also Published As

Publication number	Publication date
IL176943A0 (en)	2006-12-10
ES2282365T3 (es)	2007-10-16
PL349440A1 (en)	2002-07-29
PL201056B1 (pl)	2009-03-31
CA2291133C (en)	2003-06-17
PT1298124E (pt)	2007-05-31
HUP0200169A3 (en)	2002-11-28
HUP0200169A2 (en)	2002-06-29
US20020177722A1 (en)	2002-11-28
PT1228056E (pt)	2005-02-28
TR200401456T1 (tr)	2005-04-21
IL143875A (en)	2008-03-20
US6566540B2 (en)	2003-05-20
IL143875A0 (en)	2002-04-21
AR024518A1 (es)	2002-10-16
DK1228056T3 (da)	2005-01-24
SI1298124T1 (sl)	2007-08-31
EP1298124B1 (de)	2007-02-28
HRP20020344B1 (hr)	2010-10-31
HK1043129A1 (en)	2002-09-06
KR100505820B1 (ko)	2005-08-03
NZ512406A (en)	2004-01-30
IS2260B (is)	2007-06-15
CZ292894B6 (cs)	2003-12-17
DE19983836C1 (de)	2003-10-23
CY1107635T1 (el)	2013-04-18
SI1228056T1 (en)	2005-02-28
KR20010092799A (ko)	2001-10-27
CA2291133A1 (en)	2001-04-25
HK1043129B (zh)	2004-10-21
DE69920526T2 (de)	2006-02-23
EA200100593A1 (ru)	2001-10-22
DK1298124T3 (da)	2007-07-09
EA002801B1 (ru)	2002-10-31
DE69920526D1 (de)	2004-10-28
EP1298124A1 (de)	2003-04-02
ATE355268T1 (de)	2006-03-15
DE69935355D1 (de)	2007-04-12
UA72238C2 (en)	2005-02-15
HRP20020344A2 (en)	2004-02-29
NO20071311L (no)	2001-08-24
ATE277032T1 (de)	2004-10-15
IS5970A (is)	2001-06-15
DE69935355T2 (de)	2007-11-08

Legal Events

Date	Code	Title	Description
2013-07-02	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20121025

Publication	Publication Date	Title
US6407267B1 (en)	2002-06-18	Method for the preparation of citalopram
EP1173431B2 (de)	2009-08-26	Verfahren zur herstellung von citalopram
SK285813B6 (sk)	2007-08-02	Spôsob prípravy citalopramu, farmaceutický prostriedok s obsahom citalopramu a medziprodukt
JP4315637B2 (ja)	2009-08-19	シタロプラムの製造方法
KR20030022378A (ko)	2003-03-15	시탈로프람의 제조 방법
JP2003012663A6 (ja)	2006-10-12	シタロプラムの製造方法
US6566540B2 (en)	2003-05-20	Method for the preparation of citalopram or S-citalopram
SK17542002A3 (sk)	2003-04-01	Spôsob prípravy citalopramu, medziprodukt a antidepresívny farmaceutický prostriedok s obsahom citalopramu
JP3365764B2 (ja)	2003-01-14	シタロプラムの製造方法
CN1133633C (zh)	2004-01-07	西酞普兰的制备方法
FI118765B (fi)	2008-03-14	Menetelmä sitalopraamin valmistamiseksi
CZ292992B6 (cs)	2004-01-14	Způsob výroby citalopramu
BG65271B1 (bg)	2007-11-30	Метод за получаване на циталопрам
BG65425B1 (bg)	2008-07-31	Метод за получаване на циталопрам
MXPA01006361A (en)	2001-12-13	Method for the preparation of citalopram