SK14602002A3 - Spôsob výroby citalopramu a medziprodukty - Google Patents

Spôsob výroby citalopramu a medziprodukty Download PDF

Info

Publication number: SK14602002A3
Authority: SK; Slovakia
Prior art keywords: cyano; group; formula; compound; followed
Prior art date: 2000-03-13

Application number

SK1460-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Hans Petersen

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.)

2000-03-13

Filing date

2001-03-13

Publication date

2003-02-04

2001-03-13 Application filed by H. Lundbeck A/S filed Critical H. Lundbeck A/S

2003-02-04 Publication of SK14602002A3 publication Critical patent/SK14602002A3/sk

Links

229960001653 citalopram Drugs 0.000 title claims abstract description 59
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 57
238000000034 method Methods 0.000 title claims abstract description 53
238000002360 preparation method Methods 0.000 title abstract description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 198
150000001875 compounds Chemical class 0.000 claims description 127
238000006243 chemical reaction Methods 0.000 claims description 110
238000006268 reductive amination reaction Methods 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 34
230000011987 methylation Effects 0.000 claims description 33
238000007069 methylation reaction Methods 0.000 claims description 33
125000000217 alkyl group Chemical group 0.000 claims description 29
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 28
238000006722 reduction reaction Methods 0.000 claims description 28
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 claims description 26
125000003710 aryl alkyl group Chemical group 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 23
125000006239 protecting group Chemical group 0.000 claims description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 20
150000001408 amides Chemical class 0.000 claims description 20
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 18
150000002148 esters Chemical class 0.000 claims description 18
125000003342 alkenyl group Chemical group 0.000 claims description 17
125000000304 alkynyl group Chemical group 0.000 claims description 17
238000004519 manufacturing process Methods 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
150000001412 amines Chemical class 0.000 claims description 12
125000003277 amino group Chemical group 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000003158 alcohol group Chemical group 0.000 claims description 9
150000001540 azides Chemical class 0.000 claims description 9
238000010511 deprotection reaction Methods 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 7
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
125000006241 alcohol protecting group Chemical group 0.000 claims description 5
230000007062 hydrolysis Effects 0.000 claims description 5
238000006460 hydrolysis reaction Methods 0.000 claims description 5
238000002955 isolation Methods 0.000 claims description 5
230000003647 oxidation Effects 0.000 claims description 3
238000007254 oxidation reaction Methods 0.000 claims description 3
230000015572 biosynthetic process Effects 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
238000005576 amination reaction Methods 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
230000001681 protective effect Effects 0.000 claims 1
238000005804 alkylation reaction Methods 0.000 abstract description 3
230000029936 alkylation Effects 0.000 abstract description 2
UFBBMJWPPBNTGA-UHFFFAOYSA-N 1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran Chemical class C1=CC(F)=CC=C1C1C2=CC=CC=C2CO1 UFBBMJWPPBNTGA-UHFFFAOYSA-N 0.000 abstract 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
239000002904 solvent Substances 0.000 description 10
150000002367 halogens Chemical group 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
239000003054 catalyst Substances 0.000 description 7
150000007522 mineralic acids Chemical class 0.000 description 7
239000000243 solution Substances 0.000 description 7
-1 (3-dimethylamino) propyl halide Chemical class 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
125000003118 aryl group Chemical group 0.000 description 6
239000002585 base Substances 0.000 description 6
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
239000000935 antidepressant agent Substances 0.000 description 5
239000003638 chemical reducing agent Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 5
150000007524 organic acids Chemical class 0.000 description 5
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
150000003973 alkyl amines Chemical class 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 4
239000012024 dehydrating agents‎ Substances 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
150000002431 hydrogen Chemical class 0.000 description 4
239000000203 mixture Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
125000001412 tetrahydropyranyl group Chemical group 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-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 group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
230000001430 anti-depressive effect Effects 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
239000008194 pharmaceutical composition Substances 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
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 3
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
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 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 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
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
239000000654 additive Substances 0.000 description 2
150000001335 aliphatic alkanes Chemical class 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 description 2
125000004448 alkyl carbonyl group Chemical group 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
230000009435 amidation Effects 0.000 description 2
238000007112 amidation reaction Methods 0.000 description 2
229940005513 antidepressants Drugs 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
229920001429 chelating resin Polymers 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
230000018044 dehydration Effects 0.000 description 2
238000006297 dehydration reaction Methods 0.000 description 2
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
150000007517 lewis acids Chemical class 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
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
125000005543 phthalimide group Chemical group 0.000 description 2
229910052697 platinum Inorganic materials 0.000 description 2
229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
229920005989 resin Polymers 0.000 description 2
239000011347 resin Substances 0.000 description 2
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
125000003003 spiro group Chemical group 0.000 description 2
239000003826 tablet Substances 0.000 description 2
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
125000002769 thiazolinyl group Chemical group 0.000 description 2
125000004665 trialkylsilyl group Chemical group 0.000 description 2
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 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
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 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
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 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
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
244000309464 bull Species 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000006193 diazotization reaction Methods 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
239000012458 free base Substances 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
125000001072 heteroaryl group Chemical group 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 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
239000008101 lactose Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
239000012022 methylating agents‎ Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000002950 monocyclic group Chemical group 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
150000002825 nitriles Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
230000000379 polymerizing effect Effects 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
230000009103 reabsorption Effects 0.000 description 1
238000007363 ring formation reaction Methods 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
238000000926 separation method Methods 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 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
229960000278 theophylline Drugs 0.000 description 1
CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 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

Landscapes

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

SK1460-2002A 2000-03-13 2001-03-13 Spôsob výroby citalopramu a medziprodukty SK14602002A3 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DKPA200000401		2000-03-13
DKPA200000415		2000-03-14
PCT/DK2001/000168 WO2001068631A1 (en)	2000-03-13	2001-03-13	Method for the preparation of citalopram

Publications (1)

Publication Number	Publication Date
SK14602002A3 true SK14602002A3 (sk)	2003-02-04

Family

ID=26068790

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1460-2002A SK14602002A3 (sk)	2000-03-13	2001-03-13	Spôsob výroby citalopramu a medziprodukty

Country Status (22)

Country	Link
US (2)	US6762308B2 (is)
EP (1)	EP1265883A1 (is)
JP (1)	JP2003527387A (is)
KR (1)	KR20020080481A (is)
CN (1)	CN1429219A (is)
AU (1)	AU2001242298A1 (is)
BG (1)	BG107047A (is)
BR (1)	BR0109176A (is)
CA (1)	CA2402388A1 (is)
CZ (1)	CZ20023384A3 (is)
EA (1)	EA200200969A1 (is)
HR (1)	HRP20020744A2 (is)
HU (1)	HUP0300274A2 (is)
IL (1)	IL151490A0 (is)
IS (1)	IS6529A (is)
MX (1)	MXPA02008869A (is)
NO (1)	NO20024213L (is)
NZ (1)	NZ521201A (is)
PL (1)	PL360110A1 (is)
SK (1)	SK14602002A3 (is)
TR (1)	TR200202166T2 (is)
WO (1)	WO2001068631A1 (is)

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* Cited by examiner, † Cited by third party
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DK1173431T4 (da)	1999-04-14	2010-01-04	Lundbeck & Co As H	Fremgangsmåde til fremstilling af citalopram
NL1017417C1 (nl)	2000-03-03	2001-03-16	Lundbeck & Co As H	Werkwijze voor de bereiding van Citalopram.
IES20010206A2 (en)	2000-03-13	2002-03-06	Lundbeck & Co As H	Method for the preparation of citalopram
KR20020080481A (ko)	2000-03-13	2002-10-23	하. 룬트벡 아크티에 셀스카브	시탈로프람의 제조 방법
CN1427835A (zh)	2000-03-13	2003-07-02	H·隆德贝克有限公司	5－取代的1－(4－氟苯基)－1,3－二氢异苯并呋喃的分步烷基化
TR200202155T2 (tr)	2000-03-14	2002-12-23	H. Lundbeck A/S	Sitalopramin 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
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
WO2004085416A1 (en) *	2003-03-24	2004-10-07	Hetero Drugs Limited	Novel crystalline forms of (s)-citalopram oxalate
TWI339651B (en)	2004-02-12	2011-04-01	Lundbeck & Co As H	Method for the separation of intermediates which may be used for the preparation of escitalopram
US7613106B2 (en) *	2005-01-04	2009-11-03	Avaya Inc.	Dial plan transparency for fragmented networks
GB0601286D0 (en)	2006-01-23	2006-03-01	Sandoz Ag	Asymmetric synthesis

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GB1143703A (is)	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
ES2148120T3 (es)	1997-07-08	2002-01-16	Lundbeck & Co As H	Metodo para la preparacion de citalopram.
UA62985C2 (en)	1997-11-10	2004-01-15	Lunnbeck As H	A method for the preparation of citalopram
EA002770B1 (ru)	1997-11-11	2002-08-29	Х.Лундбекк А/С	Способ получения циталопрама
PL199423B1 (pl)	1998-10-20	2008-09-30	Lundbeck & Co As H	Sposób wytwarzania citalopramu
IL143422A0 (en)	1998-12-23	2002-04-21	Lundbeck & Co As H	Method for the preparation of 5-cyanophthalide
AR022329A1 (es)	1999-01-29	2002-09-04	Lundbeck & Co As H	Metodo para la preparacion de 5-cianoftalida
DK1173431T4 (da)	1999-04-14	2010-01-04	Lundbeck & Co As H	Fremgangsmåde til fremstilling af 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
AR026063A1 (es)	1999-11-01	2002-12-26	Lundbeck & Co As H	Metodo para la preparacion de 5-carboxiftalida.
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
HUP0203635A3 (en)	1999-12-28	2005-02-28	Lundbeck & Co As H	Method for the preparation of citalopram
PT1246813E (pt)	1999-12-30	2004-02-27	Lundbeck & Co As H	Metodo para a preparacao de citalopram
CN1195749C (zh)	2000-01-14	2005-04-06	H.隆德贝克有限公司	制备5－氰基2－苯并[c]呋喃酮的方法
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.
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
KR20020080481A (ko)	2000-03-13	2002-10-23	하. 룬트벡 아크티에 셀스카브	시탈로프람의 제조 방법
IES20010206A2 (en)	2000-03-13	2002-03-06	Lundbeck & Co As H	Method for the preparation of citalopram
TR200202155T2 (tr)	2000-03-14	2002-12-23	H. Lundbeck A/S	Sitalopramin preparasyon metodu
DE10190485T1 (de)	2000-03-16	2002-03-21	Lundbeck & Co As H	Verfahren zur Herstellung von 5-Cyano-1-(4-fluorphenyl)-1,3-dihydroisobenzofuranen
CA2383963A1 (en)	2000-07-06	2002-01-17	Eva Bolzonella	Method for the preparation of citalopram
CA2354877C (en)	2000-08-18	2006-05-02	H. Lundbeck A/S	Method for the preparation of citalopram
WO2001045483A2 (en)	2000-12-22	2001-06-28	H. Lundbeck A/S	Method for the preparation of pure 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

2001
- 2001-03-13 KR KR1020027011863A patent/KR20020080481A/ko not_active Withdrawn
- 2001-03-13 JP JP2001567723A patent/JP2003527387A/ja not_active Withdrawn
- 2001-03-13 BR BR0109176-0A patent/BR0109176A/pt not_active IP Right Cessation
- 2001-03-13 SK SK1460-2002A patent/SK14602002A3/sk not_active Application Discontinuation
- 2001-03-13 HR HRP20020744 patent/HRP20020744A2/hr not_active Application Discontinuation
- 2001-03-13 PL PL36011001A patent/PL360110A1/xx not_active Application Discontinuation
- 2001-03-13 AU AU2001242298A patent/AU2001242298A1/en not_active Abandoned
- 2001-03-13 IL IL15149001A patent/IL151490A0/xx unknown
- 2001-03-13 CA CA002402388A patent/CA2402388A1/en not_active Abandoned
- 2001-03-13 HU HU0300274A patent/HUP0300274A2/hu unknown
- 2001-03-13 NZ NZ521201A patent/NZ521201A/xx unknown
- 2001-03-13 EP EP01915098A patent/EP1265883A1/en not_active Withdrawn
- 2001-03-13 CN CN01809338A patent/CN1429219A/zh active Pending
- 2001-03-13 EA EA200200969A patent/EA200200969A1/ru unknown
- 2001-03-13 CZ CZ20023384A patent/CZ20023384A3/cs unknown
- 2001-03-13 TR TR2002/02166T patent/TR200202166T2/xx unknown
- 2001-03-13 MX MXPA02008869A patent/MXPA02008869A/es unknown
- 2001-03-13 WO PCT/DK2001/000168 patent/WO2001068631A1/en not_active Ceased
2002
- 2002-08-27 IS IS6529A patent/IS6529A/is unknown
- 2002-09-02 BG BG107047A patent/BG107047A/xx unknown
- 2002-09-04 NO NO20024213A patent/NO20024213L/no not_active Application Discontinuation
- 2002-09-05 US US10/237,145 patent/US6762308B2/en not_active Expired - Fee Related
2004
- 2004-05-21 US US10/851,595 patent/US6992198B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US20040215025A1 (en)	2004-10-28
EA200200969A1 (ru)	2003-02-27
MXPA02008869A (es)	2003-02-10
CZ20023384A3 (cs)	2003-01-15
BR0109176A (pt)	2003-04-22
KR20020080481A (ko)	2002-10-23
CN1429219A (zh)	2003-07-09
TR200202166T2 (tr)	2002-12-23
CA2402388A1 (en)	2001-09-20
AU2001242298A1 (en)	2001-09-24
JP2003527387A (ja)	2003-09-16
IS6529A (is)	2002-08-27
BG107047A (en)	2003-04-30
WO2001068631A1 (en)	2001-09-20
NO20024213L (no)	2002-11-13
IL151490A0 (en)	2003-04-10
EP1265883A1 (en)	2002-12-18
NO20024213D0 (no)	2002-09-04
HRP20020744A2 (en)	2004-12-31
NZ521201A (en)	2004-02-27
PL360110A1 (en)	2004-09-06
US6992198B2 (en)	2006-01-31
US20030092919A1 (en)	2003-05-15
US6762308B2 (en)	2004-07-13
HUP0300274A2 (hu)	2003-06-28

Legal Events

Date	Code	Title	Description
2010-03-08	FC9A	Refused patent application

Publication	Publication Date	Title
SK13672002A3 (sk)	2003-03-04	Spôsob prípravy citalopramu, antidepresívny farmaceutický prostriedok s obsahom citalopramu a medziprodukty
SK32000A3 (en)	2000-07-11	Method for the preparation of citalopram, a pharmaceutical composition containing the same and intermediates
SK14602002A3 (sk)	2003-02-04	Spôsob výroby citalopramu a medziprodukty
US6768011B2 (en)	2004-07-27	Method for the preparation of citalopram
SK14512002A3 (sk)	2003-03-04	Spôsob výroby citalopramu, medziprodukt a citalopram výrobený týmto spôsobom
SK14522002A3 (sk)	2003-03-04	Spôsob prípravy citalopramu a citalopram pripravený týmto spôsobom
SK14592002A3 (sk)	2003-03-04	Spôsob prípravy citalopramu, antidepresívny farmaceutický prostriedok s jeho obsahom a medziprodukty
HK1055744A (en)	2004-01-21	Method for the preparation of citalopram