UA72238C2 - A method for the preparation of citalopram (variants), s-citalopram, intermediary ketones and a method for the preparation of racemic compounds - Google Patents

A method for the preparation of citalopram (variants), s-citalopram, intermediary ketones and a method for the preparation of racemic compounds Download PDF

Info

Publication number: UA72238C2
Authority: UA; Ukraine
Prior art keywords: formula; compound; citalopram; acyl; dimethylamino
Prior art date: 1999-10-25

Application number

UA2001075224A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Lundbeck & Co As H

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

2005-02-15

1999-10-25 Application filed by Lundbeck & Co As H filed Critical Lundbeck & Co As H

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

2005-02-15 Publication of UA72238C2 publication Critical patent/UA72238C2/uk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 85
238000000034 method Methods 0.000 title claims abstract description 52
229960001653 citalopram Drugs 0.000 title claims abstract description 35
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 31
238000002360 preparation method Methods 0.000 title claims abstract description 6
150000002576 ketones Chemical class 0.000 title claims description 10
238000006243 chemical reaction Methods 0.000 claims abstract description 24
125000002252 acyl group Chemical group 0.000 claims abstract description 16
-1 4-fluorophenylmagnesium halide Chemical class 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 8
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 claims description 8
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
230000015572 biosynthetic process Effects 0.000 claims description 7
150000004820 halides Chemical class 0.000 claims description 7
RYEXTBOQKFUPOE-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].CC[CH2-] RYEXTBOQKFUPOE-UHFFFAOYSA-M 0.000 claims description 7
238000007248 oxidative elimination reaction Methods 0.000 claims description 7
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
230000018044 dehydration Effects 0.000 claims description 6
238000006297 dehydration reaction Methods 0.000 claims description 6
230000003647 oxidation Effects 0.000 claims description 6
238000007254 oxidation reaction Methods 0.000 claims description 6
XEEGWTLAFIZLSF-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carbonitrile Chemical compound N#CC1=CC=C2C(=O)OCC2=C1 XEEGWTLAFIZLSF-UHFFFAOYSA-N 0.000 claims description 5
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 4
230000003993 interaction Effects 0.000 claims description 4
238000006798 ring closing metathesis reaction Methods 0.000 claims description 4
238000000926 separation method Methods 0.000 claims description 4
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 claims description 3
BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 claims description 3
FTHPLWDYWAKYCY-UHFFFAOYSA-N 3,5-dimethoxybenzoyl chloride Chemical compound COC1=CC(OC)=CC(C(Cl)=O)=C1 FTHPLWDYWAKYCY-UHFFFAOYSA-N 0.000 claims description 2
125000003158 alcohol group Chemical group 0.000 claims description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
238000002955 isolation Methods 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims 3
MYLBTCQBKAKUTJ-UHFFFAOYSA-N 7-methyl-6,8-bis(methylsulfanyl)pyrrolo[1,2-a]pyrazine Chemical compound C1=CN=CC2=C(SC)C(C)=C(SC)N21 MYLBTCQBKAKUTJ-UHFFFAOYSA-N 0.000 claims 2
150000001263 acyl chlorides Chemical class 0.000 claims 1
150000001336 alkenes Chemical class 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 8
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 abstract description 3
239000011777 magnesium Substances 0.000 abstract description 2
229910052749 magnesium Inorganic materials 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 29
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
239000011541 reaction mixture Substances 0.000 description 16
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 15
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
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
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000000935 antidepressant agent Substances 0.000 description 6
235000019439 ethyl acetate Nutrition 0.000 description 6
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
239000002904 solvent Substances 0.000 description 6
238000003747 Grignard reaction Methods 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
150000001344 alkene derivatives Chemical class 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
239000000126 substance Substances 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
238000001816 cooling Methods 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
239000007787 solid Substances 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
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-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
239000004480 active ingredient Substances 0.000 description 3
239000000654 additive Substances 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
230000001430 anti-depressive effect Effects 0.000 description 3
229940005513 antidepressants Drugs 0.000 description 3
239000002585 base Substances 0.000 description 3
238000000921 elemental analysis Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
150000003891 oxalate salts Chemical class 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 3
239000007858 starting material Substances 0.000 description 3
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 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 compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
239000013078 crystal Substances 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
125000001072 heteroaryl group Chemical group 0.000 description 2
125000001041 indolyl group Chemical group 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
125000002950 monocyclic group Chemical group 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
230000002269 spontaneous effect Effects 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
YXCRMKYHFFMNPT-UHFFFAOYSA-N 1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound C1=CC(F)=CC=C1C1C2=CC=C(C#N)C=C2CO1 YXCRMKYHFFMNPT-UHFFFAOYSA-N 0.000 description 1
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 1
AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
238000004265 3D NMR spectra Methods 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
244000144725 Amygdalus communis Species 0.000 description 1
235000011437 Amygdalus communis Nutrition 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
244000223760 Cinnamomum zeylanicum Species 0.000 description 1
235000005979 Citrus limon Nutrition 0.000 description 1
244000131522 Citrus pyriformis Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000007818 Grignard reagent Substances 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
241000220225 Malus Species 0.000 description 1
235000011430 Malus pumila Nutrition 0.000 description 1
235000015103 Malus silvestris Nutrition 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
101100412856 Mus musculus Rhod gene Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
101100242191 Tetraodon nigroviridis rho gene Proteins 0.000 description 1
244000111306 Torreya nucifera Species 0.000 description 1
235000006732 Torreya nucifera Nutrition 0.000 description 1
241000256856 Vespidae Species 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
150000007513 acids Chemical class 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
235000020224 almond Nutrition 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 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 compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
239000002775 capsule Substances 0.000 description 1
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208000026106 cerebrovascular disease Diseases 0.000 description 1
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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
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IGABGQDRDPWCGR-UHFFFAOYSA-N cyanide;hydrate Chemical compound O.N#[C-] IGABGQDRDPWCGR-UHFFFAOYSA-N 0.000 description 1
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239000000975 dye Substances 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
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238000011141 high resolution liquid chromatography Methods 0.000 description 1
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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
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239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 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
229940076279 serotonin Drugs 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
229910052682 stishovite Inorganic materials 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 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
230000001256 tonic effect Effects 0.000 description 1
229910052905 tridymite Inorganic materials 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)

UA2001075224A 1999-10-25 1999-10-25 A method for the preparation of citalopram (variants), s-citalopram, intermediary ketones and a method for the preparation of racemic compounds UA72238C2 (en)

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
UA72238C2 true UA72238C2 (en)	2005-02-15

Family

ID=8157164

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2001075224A UA72238C2 (en)	1999-10-25	1999-10-25	A method for the preparation of citalopram (variants), s-citalopram, intermediary ketones and a method for the preparation of racemic compounds

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
SK287140B6 (sk)	2010-01-07
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
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

Publication	Publication Date	Title
AU742554B2 (en)	2002-01-03	Method for the preparation of citalopram
UA62984C2 (en)	2004-01-15	A method for the preparation of citalopram
JP4315637B2 (ja)	2009-08-19	シタロプラムの製造方法
KR20010112421A (ko)	2001-12-20	시탈로프람의 제조방법
UA70987C2 (uk)	2004-11-15	Спосіб одержання 5-ціанофталіду
JP2003012663A6 (ja)	2006-10-12	シタロプラムの製造方法
BG107015A (bg)	2003-05-30	Метод за получаване на циталопрам
KR100505820B1 (ko)	2005-08-03	시탈로프람의 제조방법
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
FI118765B (fi)	2008-03-14	Menetelmä sitalopraamin valmistamiseksi
KR100821912B1 (ko)	2008-04-16	시탈로프람의 제조 방법
MXPA01006361A (en)	2001-12-13	Method for the preparation of citalopram
BG65425B1 (bg)	2008-07-31	Метод за получаване на циталопрам
CZ20012246A3 (cs)	2001-09-12	Způsob výroby citalopramu
BG65271B1 (bg)	2007-11-30	Метод за получаване на циталопрам
JPH0570630B2 (de)	1993-10-05