WO2005116011A1 - A novel stereoselective synthesis of benzimidazole sulfoxides - Google Patents
A novel stereoselective synthesis of benzimidazole sulfoxides Download PDFInfo
- Publication number
- WO2005116011A1 WO2005116011A1 PCT/IN2004/000143 IN2004000143W WO2005116011A1 WO 2005116011 A1 WO2005116011 A1 WO 2005116011A1 IN 2004000143 W IN2004000143 W IN 2004000143W WO 2005116011 A1 WO2005116011 A1 WO 2005116011A1
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- WIPO (PCT)
- Prior art keywords
- formula
- solvent
- salt
- methoxy
- acid
- Prior art date
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- -1 benzimidazole sulfoxides Chemical class 0.000 title claims abstract description 74
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 12
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 9
- 230000000707 stereoselective effect Effects 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 124
- 239000000203 mixture Substances 0.000 claims abstract description 39
- 150000003462 sulfoxides Chemical class 0.000 claims abstract description 30
- SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 claims abstract description 16
- 238000001640 fractional crystallisation Methods 0.000 claims abstract description 16
- 229960004770 esomeprazole Drugs 0.000 claims abstract description 14
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims abstract description 8
- XURCIPRUUASYLR-UHFFFAOYSA-N Omeprazole sulfide Chemical compound N=1C2=CC(OC)=CC=C2NC=1SCC1=NC=C(C)C(OC)=C1C XURCIPRUUASYLR-UHFFFAOYSA-N 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 79
- 239000002904 solvent Substances 0.000 claims description 76
- 150000001875 compounds Chemical class 0.000 claims description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- 239000002585 base Substances 0.000 claims description 26
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- DSSYKIVIOFKYAU-OIBJUYFYSA-N (S)-camphor Chemical compound C1C[C@]2(C)C(=O)C[C@H]1C2(C)C DSSYKIVIOFKYAU-OIBJUYFYSA-N 0.000 claims description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 17
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 16
- 150000008282 halocarbons Chemical class 0.000 claims description 16
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 238000007254 oxidation reaction Methods 0.000 claims description 15
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 14
- 238000010511 deprotection reaction Methods 0.000 claims description 14
- 229930007886 (R)-camphor Natural products 0.000 claims description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 13
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 150000002576 ketones Chemical class 0.000 claims description 12
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 12
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 11
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 230000003647 oxidation Effects 0.000 claims description 11
- 239000008096 xylene Substances 0.000 claims description 11
- 150000001298 alcohols Chemical class 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 150000004965 peroxy acids Chemical class 0.000 claims description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 10
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims description 9
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 239000007800 oxidant agent Substances 0.000 claims description 9
- 239000011734 sodium Substances 0.000 claims description 9
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 8
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 8
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 8
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 8
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 8
- 229940011051 isopropyl acetate Drugs 0.000 claims description 8
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 8
- 239000011591 potassium Substances 0.000 claims description 8
- 229910052700 potassium Inorganic materials 0.000 claims description 8
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims description 7
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 7
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 7
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 7
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 125000003375 sulfoxide group Chemical group 0.000 claims description 7
- 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 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 claims description 6
- 150000002170 ethers Chemical class 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 6
- 229960000381 omeprazole Drugs 0.000 claims description 6
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 claims description 6
- 229940086542 triethylamine Drugs 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 5
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims description 5
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 5
- 239000005456 alcohol based solvent Substances 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 150000003863 ammonium salts Chemical class 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229950005499 carbon tetrachloride Drugs 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 229960001701 chloroform Drugs 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- YGIYXPDSUCRWCW-QPQWKYTISA-N ClS(Cl)(=O)=O.C1C[C@@]2(C)C(=O)CC1C2(C)C Chemical compound ClS(Cl)(=O)=O.C1C[C@@]2(C)C(=O)CC1C2(C)C YGIYXPDSUCRWCW-QPQWKYTISA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 150000004679 hydroxides Chemical class 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 239000012452 mother liquor Substances 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- MFWFDRBPQDXFRC-LNTINUHCSA-N (z)-4-hydroxypent-3-en-2-one;vanadium Chemical group [V].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O MFWFDRBPQDXFRC-LNTINUHCSA-N 0.000 claims description 3
- INOGLHRUEYDAHX-UHFFFAOYSA-N 1-chlorobenzotriazole Chemical compound C1=CC=C2N(Cl)N=NC2=C1 INOGLHRUEYDAHX-UHFFFAOYSA-N 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical group O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- FVJIUYMDPPZODN-UHFFFAOYSA-N [Br].C1CC2C(=[N+]=[N-])CC1CC2 Chemical compound [Br].C1CC2C(=[N+]=[N-])CC1CC2 FVJIUYMDPPZODN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001980 alanyl group Chemical group 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 3
- WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 claims description 3
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 claims description 3
- 239000005453 ketone based solvent Substances 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 150000002976 peresters Chemical class 0.000 claims description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 3
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 claims description 3
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical class CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 2
- 150000003568 thioethers Chemical class 0.000 claims description 2
- 229940073584 methylene chloride Drugs 0.000 claims 12
- 159000000003 magnesium salts Chemical class 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000003944 tolyl group Chemical group 0.000 claims 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 125000003158 alcohol group Chemical group 0.000 claims 2
- 150000001340 alkali metals Chemical class 0.000 claims 2
- 229960000846 camphor Drugs 0.000 claims 2
- 229910017053 inorganic salt Inorganic materials 0.000 claims 2
- 229940074411 xylene Drugs 0.000 claims 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- SUBDBMMJDZJVOS-XMMPIXPASA-N (R)-omeprazole Chemical compound C([S@@](=O)C=1NC2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-XMMPIXPASA-N 0.000 description 5
- 0 **S(c1nc2c(*)c(*)c(*)c(*)c2[n]1)=O Chemical compound **S(c1nc2c(*)c(*)c(*)c(*)c2[n]1)=O 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000027119 gastric acid secretion Effects 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- DYTUAOUIQFNOIH-HTQZYQBOSA-L (2s,3s)-2,3-diethyl-2,3-dihydroxybutanedioate Chemical compound CC[C@@](O)(C([O-])=O)[C@@](O)(CC)C([O-])=O DYTUAOUIQFNOIH-HTQZYQBOSA-L 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000006165 cyclic alkyl group Chemical group 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- FOFFPEFVSRGLOZ-JIDHJSLPSA-N potassium;5-methoxy-2-[(s)-(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-1-ide Chemical compound [K+].C([S@](=O)C=1[N-]C2=CC=C(C=C2N=1)OC)C1=NC=C(C)C(OC)=C1C FOFFPEFVSRGLOZ-JIDHJSLPSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
- HJHJWKIIHRCOHJ-QFIPXVFZSA-N 1-[(S)-(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazole Chemical compound CC=1C(=NC=C(C=1OC)C)C[S@](=O)N1C=NC2=C1C=CC=C2 HJHJWKIIHRCOHJ-QFIPXVFZSA-N 0.000 description 1
- NVUJWPQINQUNNM-UHFFFAOYSA-N 1h-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1.C1=CC=C2NC=NC2=C1 NVUJWPQINQUNNM-UHFFFAOYSA-N 0.000 description 1
- HBDKFZNDMVLSHM-UHFFFAOYSA-N 2-(pyridin-2-ylmethylsulfinyl)-1h-benzimidazole Chemical class N=1C2=CC=CC=C2NC=1S(=O)CC1=CC=CC=N1 HBDKFZNDMVLSHM-UHFFFAOYSA-N 0.000 description 1
- ILMHAGCURJPNRZ-UHFFFAOYSA-N 6-methoxy-1h-benzimidazole Chemical class COC1=CC=C2N=CNC2=C1 ILMHAGCURJPNRZ-UHFFFAOYSA-N 0.000 description 1
- LELDJUYQEMKHJH-UHFFFAOYSA-N Cc1cnc(C)c(C)c1OC Chemical compound Cc1cnc(C)c(C)c1OC LELDJUYQEMKHJH-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 125000000815 N-oxide group Chemical group 0.000 description 1
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001339 alkali metal compounds Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001341 alkaline earth metal compounds Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960003174 lansoprazole Drugs 0.000 description 1
- SIXIIKVOZAGHPV-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=C[CH]C2=N1 SIXIIKVOZAGHPV-UHFFFAOYSA-N 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960005019 pantoprazole Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- YREYEVIYCVEVJK-UHFFFAOYSA-N rabeprazole Chemical compound COCCCOC1=CC=NC(CS(=O)C=2NC3=CC=CC=C3N=2)=C1C YREYEVIYCVEVJK-UHFFFAOYSA-N 0.000 description 1
- 229960004157 rabeprazole Drugs 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 150000003609 titanium compounds Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the present invention provides a stereoselective synthesis for preparing a benzimidazoie sulfoxide of formula I or a salt thereof either as a single enantiomer or in an enantiomerically enriched form:
- Example 1 5-Methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methylthio]-1H- benzimidazole (15 gm) was dissolved in methylene chloride (150 ml) and N,N- diisopropylethylamine (9.0 gm) was added to the solution. The solution was cooled to 0°C - 5°C.
- Example 7 Potassium salt of (S)-5-Methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl) methylsulfinyrj-1 H-benzimidazole (Esomeprazole potassium) (6.2 gm) was dissolved in water ( 80 ml). To this solution, was added magnesium chloride solution (1.8 gm in 50 ml water), and then the contents were stirred for 1 hour at 25°C. The solid precipitated was filtered, washed with water and dried under vacuum for 12 hours at 40°C to obtain 4.5 gm of esomeprazole magnessium df ⁇ ydrate (enantiomeric excess: 99.5%).
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IN2004/000143 WO2005116011A1 (en) | 2004-05-28 | 2004-05-28 | A novel stereoselective synthesis of benzimidazole sulfoxides |
DK04735319.8T DK1748998T3 (en) | 2004-05-28 | 2004-05-28 | New stereoselective synthesis of benzimidazole sulfoxides |
AT04735319T ATE456566T1 (en) | 2004-05-28 | 2004-05-28 | NEW STEREOSELECTIVE SYNTHESIS OF BENZIMIDAZOLE SULFOXIDES |
US10/503,846 US7365206B2 (en) | 2004-05-28 | 2004-05-28 | Stereoselective synthesis of benzimidazole sulfoxides |
DE602004025386T DE602004025386D1 (en) | 2004-05-28 | 2004-05-28 | NEW STEREOSELECTIVE SYNTHESIS OF BENZIMIDAZOLSULFOXIDEN |
PT04735319T PT1748998E (en) | 2004-05-28 | 2004-05-28 | A novel stereoselective synthesis of benzimidazole sulfoxides |
EP04735319A EP1748998B1 (en) | 2004-05-28 | 2004-05-28 | A novel stereoselective synthesis of benzimidazole sulfoxides |
ES04735319T ES2338556T3 (en) | 2004-05-28 | 2004-05-28 | NOVEDOUS STEREOSELECTIVE SYNTHESIS OF SULFOXIDES OF BENZIMIDAZOL. |
US11/865,295 US7928241B2 (en) | 2004-05-28 | 2007-10-01 | Stereoselective synthesis of benzimidazole sulfoxides |
US11/865,312 US8173817B2 (en) | 2004-05-28 | 2007-10-01 | Stereoselective synthesis of benzimidazole sulfoxides |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IN2004/000143 WO2005116011A1 (en) | 2004-05-28 | 2004-05-28 | A novel stereoselective synthesis of benzimidazole sulfoxides |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/865,295 Division US7928241B2 (en) | 2004-05-28 | 2007-10-01 | Stereoselective synthesis of benzimidazole sulfoxides |
US11/865,312 Division US8173817B2 (en) | 2004-05-28 | 2007-10-01 | Stereoselective synthesis of benzimidazole sulfoxides |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005116011A1 true WO2005116011A1 (en) | 2005-12-08 |
Family
ID=35450822
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2004/000143 WO2005116011A1 (en) | 2004-05-28 | 2004-05-28 | A novel stereoselective synthesis of benzimidazole sulfoxides |
Country Status (8)
Country | Link |
---|---|
US (3) | US7365206B2 (en) |
EP (1) | EP1748998B1 (en) |
AT (1) | ATE456566T1 (en) |
DE (1) | DE602004025386D1 (en) |
DK (1) | DK1748998T3 (en) |
ES (1) | ES2338556T3 (en) |
PT (1) | PT1748998E (en) |
WO (1) | WO2005116011A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1801110A1 (en) | 2005-12-22 | 2007-06-27 | KRKA, tovarna zdravil, d.d., Novo mesto | Esomeprazole arginine salt |
WO2010003974A3 (en) * | 2008-07-09 | 2010-07-01 | Lek Pharmaceuticals D.D. | Process for preparation of esomeprazole sodium of high chemical purity and new forms of esomeprazole sodium |
WO2010095144A2 (en) * | 2009-02-04 | 2010-08-26 | Msn Laboratories Limited | Process for the preparation of proton pump inhibitors |
WO2011121594A1 (en) * | 2010-04-01 | 2011-10-06 | Neuland Laboratories Ltd. | A process for the preparation of itraconazole |
US8354541B2 (en) | 2008-11-18 | 2013-01-15 | Hetero Research Foundation | Optical purification of esomeprazole |
US8394963B2 (en) | 2007-02-21 | 2013-03-12 | Cipla Limited | Process for the preparation of esomeprazole magnesium dihydrate |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004111029A2 (en) * | 2003-06-10 | 2004-12-23 | Teva Pharmaceutical Industries Ltd. | Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole |
ES2441970T3 (en) * | 2004-09-13 | 2014-02-07 | Takeda Pharmaceutical Company Limited | Method of producing lansoprazole |
CN102886045A (en) | 2005-02-03 | 2013-01-23 | 综合医院公司 | Method for treating gefitinib resistant cancer |
EP2195309A4 (en) * | 2007-10-08 | 2013-04-24 | Hetero Drugs Ltd | Polymorphs of esomeprazole salts |
US8022216B2 (en) * | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
EP3135285B1 (en) | 2008-06-17 | 2018-08-15 | Wyeth LLC | Antineoplastic combinations containing hki-272 and vinorelbine |
WO2011058569A1 (en) | 2009-11-12 | 2011-05-19 | Hetero Research Foundation | Process for the resolution of omeprazole |
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EP0221041A2 (en) * | 1985-10-29 | 1987-05-06 | Aktiebolaget Hässle | Benzimidazole derivatives, process for their preparation and their pharmaceutical use |
DE4035455A1 (en) * | 1990-11-08 | 1992-05-14 | Byk Gulden Lomberg Chem Fab | ENANTIOMER SEPARATION |
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SE7804231L (en) | 1978-04-14 | 1979-10-15 | Haessle Ab | Gastric acid secretion |
SE8301182D0 (en) * | 1983-03-04 | 1983-03-04 | Haessle Ab | NOVEL COMPOUNDS |
SE9301830D0 (en) * | 1993-05-28 | 1993-05-28 | Ab Astra | NEW COMPOUNDS |
US5877192A (en) * | 1993-05-28 | 1999-03-02 | Astra Aktiebolag | Method for the treatment of gastric acid-related diseases and production of medication using (-) enantiomer of omeprazole |
SE504459C2 (en) * | 1994-07-15 | 1997-02-17 | Astra Ab | Process for the preparation of substituted sulfoxides |
NZ510180A (en) * | 1998-08-10 | 2002-11-26 | Univ California | Prodrugs of the pyridyl-methylsulphonyl-benzimidazole type proton pump inhibitors |
WO2004002982A2 (en) | 2002-06-27 | 2004-01-08 | Dr. Reddy's Laboratories Limited | A process for preparation of optically pure or optically enriched sulfoxide compounds, including amorphous esomeprazole and salts thereof |
DK1740571T3 (en) * | 2004-04-28 | 2009-11-02 | Hetero Drugs Ltd | Process for Preparation of Pyridinyl Methyl-1H-Benzimidazole Compounds in Enantiomerically Enriched Form or as Single Enantiomers |
-
2004
- 2004-05-28 PT PT04735319T patent/PT1748998E/en unknown
- 2004-05-28 ES ES04735319T patent/ES2338556T3/en active Active
- 2004-05-28 WO PCT/IN2004/000143 patent/WO2005116011A1/en not_active Application Discontinuation
- 2004-05-28 AT AT04735319T patent/ATE456566T1/en active
- 2004-05-28 DK DK04735319.8T patent/DK1748998T3/en active
- 2004-05-28 EP EP04735319A patent/EP1748998B1/en not_active Not-in-force
- 2004-05-28 DE DE602004025386T patent/DE602004025386D1/en active Active
- 2004-05-28 US US10/503,846 patent/US7365206B2/en not_active Expired - Fee Related
-
2007
- 2007-10-01 US US11/865,312 patent/US8173817B2/en not_active Expired - Fee Related
- 2007-10-01 US US11/865,295 patent/US7928241B2/en not_active Expired - Fee Related
Patent Citations (2)
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EP0221041A2 (en) * | 1985-10-29 | 1987-05-06 | Aktiebolaget Hässle | Benzimidazole derivatives, process for their preparation and their pharmaceutical use |
DE4035455A1 (en) * | 1990-11-08 | 1992-05-14 | Byk Gulden Lomberg Chem Fab | ENANTIOMER SEPARATION |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1801110A1 (en) | 2005-12-22 | 2007-06-27 | KRKA, tovarna zdravil, d.d., Novo mesto | Esomeprazole arginine salt |
US8394963B2 (en) | 2007-02-21 | 2013-03-12 | Cipla Limited | Process for the preparation of esomeprazole magnesium dihydrate |
EP2842953A1 (en) | 2007-02-21 | 2015-03-04 | Cipla Limited | Process for the preparation of esomeprazole magnesium dihydrate |
WO2010003974A3 (en) * | 2008-07-09 | 2010-07-01 | Lek Pharmaceuticals D.D. | Process for preparation of esomeprazole sodium of high chemical purity and new forms of esomeprazole sodium |
CN102089296A (en) * | 2008-07-09 | 2011-06-08 | 力奇制药公司 | Process for preparation of esomeprazole sodium of high chemical purity and new forms of esomeprazole sodium |
US8614331B2 (en) | 2008-07-09 | 2013-12-24 | Lek Pharmaceuticals D.D. | Process for preparation of esomeprazole sodium of high chemical purity and new forms of esomeprazole sodium |
US8354541B2 (en) | 2008-11-18 | 2013-01-15 | Hetero Research Foundation | Optical purification of esomeprazole |
WO2010095144A2 (en) * | 2009-02-04 | 2010-08-26 | Msn Laboratories Limited | Process for the preparation of proton pump inhibitors |
WO2010095144A3 (en) * | 2009-02-04 | 2010-11-04 | Msn Laboratories Limited | Process for preparation of proton pump inhibitors |
WO2011121594A1 (en) * | 2010-04-01 | 2011-10-06 | Neuland Laboratories Ltd. | A process for the preparation of itraconazole |
Also Published As
Publication number | Publication date |
---|---|
DE602004025386D1 (en) | 2010-03-18 |
EP1748998A1 (en) | 2007-02-07 |
ES2338556T3 (en) | 2010-05-10 |
DK1748998T3 (en) | 2010-05-10 |
US7928241B2 (en) | 2011-04-19 |
ATE456566T1 (en) | 2010-02-15 |
US7365206B2 (en) | 2008-04-29 |
US20060166986A1 (en) | 2006-07-27 |
US8173817B2 (en) | 2012-05-08 |
EP1748998B1 (en) | 2010-01-27 |
US20080076930A1 (en) | 2008-03-27 |
PT1748998E (en) | 2010-03-24 |
US20080076929A1 (en) | 2008-03-27 |
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