CS196285B2 - Method of producing phenylesters of 2-alkoxycarbonylamin - Google Patents
Method of producing phenylesters of 2-alkoxycarbonylamin Download PDFInfo
- Publication number
- CS196285B2 CS196285B2 CS787242A CS724278A CS196285B2 CS 196285 B2 CS196285 B2 CS 196285B2 CS 787242 A CS787242 A CS 787242A CS 724278 A CS724278 A CS 724278A CS 196285 B2 CS196285 B2 CS 196285B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- acid
- ester
- formula
- methoxycarbonylamino
- benzimidazolesulfonic
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- -1 formate ester Chemical class 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 150000004987 o-phenylenediamines Chemical class 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 8
- NMHSXXPZLXHOJO-UHFFFAOYSA-N 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2NC(NC(=O)OC)=NC2=C1 NMHSXXPZLXHOJO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- ROVPGRDMDASARO-UHFFFAOYSA-N phenyl 3,4-diaminobenzenesulfonate Chemical compound C1=C(N)C(N)=CC=C1S(=O)(=O)OC1=CC=CC=C1 ROVPGRDMDASARO-UHFFFAOYSA-N 0.000 description 4
- FKSRSWQTEJTBMI-UHFFFAOYSA-N 3,4-diaminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1N FKSRSWQTEJTBMI-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- JMVOTQMMWZCLEX-UHFFFAOYSA-N phenyl 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC=C1 JMVOTQMMWZCLEX-UHFFFAOYSA-N 0.000 description 3
- NEZIKMJTIOLUGU-UHFFFAOYSA-N phenyl 4-amino-3-nitrobenzenesulfonate Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1S(=O)(=O)OC1=CC=CC=C1 NEZIKMJTIOLUGU-UHFFFAOYSA-N 0.000 description 3
- DXNLDBASBALMSX-UHFFFAOYSA-N phenyl 4-chloro-3-nitrobenzenesulfonate Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(S(=O)(=O)OC=2C=CC=CC=2)=C1 DXNLDBASBALMSX-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- CGWGGQHTSYXUDD-UHFFFAOYSA-N (3-bromophenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=C(N)C(N)=CC=C1S(=O)(=O)OC1=CC=CC(Br)=C1 CGWGGQHTSYXUDD-UHFFFAOYSA-N 0.000 description 2
- XFMINSQCONUQCO-UHFFFAOYSA-N (3-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound CC1=CC=CC(OS(=O)(=O)C=2C=C(N)C(N)=CC=2)=C1 XFMINSQCONUQCO-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000243976 Haemonchus Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001556 benzimidazoles Chemical class 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 244000000013 helminth Species 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- QQODDPGCUGQDHM-UHFFFAOYSA-N (2,4-dimethylphenyl) 3,4-diaminobenzenesulfonate Chemical compound CC1=CC(C)=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 QQODDPGCUGQDHM-UHFFFAOYSA-N 0.000 description 1
- BQPIDRJNXJZWHZ-UHFFFAOYSA-N (2-bromophenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC=C1Br BQPIDRJNXJZWHZ-UHFFFAOYSA-N 0.000 description 1
- TZLGLOTZWNAURF-UHFFFAOYSA-N (2-bromophenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=C(N)C(N)=CC=C1S(=O)(=O)OC1=CC=CC=C1Br TZLGLOTZWNAURF-UHFFFAOYSA-N 0.000 description 1
- CQNCDRXCCSJEPB-UHFFFAOYSA-N (2-chloro-4-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound ClC1=CC(C)=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 CQNCDRXCCSJEPB-UHFFFAOYSA-N 0.000 description 1
- IGESXLVCVIMMAP-UHFFFAOYSA-N (2-chloro-6-methylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=C(C)C=CC=C1Cl IGESXLVCVIMMAP-UHFFFAOYSA-N 0.000 description 1
- GVEUYYJRVRFMDS-UHFFFAOYSA-N (2-chloro-6-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound CC1=CC=CC(Cl)=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 GVEUYYJRVRFMDS-UHFFFAOYSA-N 0.000 description 1
- CWTPUEDXFQHLIR-UHFFFAOYSA-N (2-chlorophenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC=C1Cl CWTPUEDXFQHLIR-UHFFFAOYSA-N 0.000 description 1
- VUPOVZXDFUPZCR-UHFFFAOYSA-N (2-chlorophenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=C(N)C(N)=CC=C1S(=O)(=O)OC1=CC=CC=C1Cl VUPOVZXDFUPZCR-UHFFFAOYSA-N 0.000 description 1
- MWSDQXSORKYRFX-UHFFFAOYSA-N (2-methoxyphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC=C1OC MWSDQXSORKYRFX-UHFFFAOYSA-N 0.000 description 1
- WRNLCFGUAPVTDF-UHFFFAOYSA-N (2-methylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC=C1C WRNLCFGUAPVTDF-UHFFFAOYSA-N 0.000 description 1
- FOPZCEWBOPEBLS-UHFFFAOYSA-N (2-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound CC1=CC=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 FOPZCEWBOPEBLS-UHFFFAOYSA-N 0.000 description 1
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- NXOKKXACBQESEI-UHFFFAOYSA-N (3-bromophenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC(Br)=C1 NXOKKXACBQESEI-UHFFFAOYSA-N 0.000 description 1
- SUVVFPGNNBUFED-UHFFFAOYSA-N (3-bromophenyl) 4-amino-3-nitrobenzenesulfonate Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1S(=O)(=O)OC1=CC=CC(Br)=C1 SUVVFPGNNBUFED-UHFFFAOYSA-N 0.000 description 1
- BTQROPWNFKTNSO-UHFFFAOYSA-N (3-bromophenyl) 4-chloro-3-nitrobenzenesulfonate Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(S(=O)(=O)OC=2C=C(Br)C=CC=2)=C1 BTQROPWNFKTNSO-UHFFFAOYSA-N 0.000 description 1
- UFWGRYUVACXAGJ-UHFFFAOYSA-N (3-chloro-4-methylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=C(C)C(Cl)=C1 UFWGRYUVACXAGJ-UHFFFAOYSA-N 0.000 description 1
- XQYMPPULLSLTTH-UHFFFAOYSA-N (3-chloro-4-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=C(Cl)C(C)=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 XQYMPPULLSLTTH-UHFFFAOYSA-N 0.000 description 1
- XPLMXXAWBCYERB-UHFFFAOYSA-N (3-chlorophenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC(Cl)=C1 XPLMXXAWBCYERB-UHFFFAOYSA-N 0.000 description 1
- MVWMIZKBHIIUJW-UHFFFAOYSA-N (3-chlorophenyl) 4-amino-3-nitrobenzenesulfonate Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1S(=O)(=O)OC1=CC=CC(Cl)=C1 MVWMIZKBHIIUJW-UHFFFAOYSA-N 0.000 description 1
- NPPCVICNVNTDDO-UHFFFAOYSA-N (3-chlorophenyl) 4-chloro-3-nitrobenzenesulfonate Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(S(=O)(=O)OC=2C=C(Cl)C=CC=2)=C1 NPPCVICNVNTDDO-UHFFFAOYSA-N 0.000 description 1
- UMRIXOOKYJPSSR-UHFFFAOYSA-N (3-ethoxyphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound CCOC1=CC=CC(OS(=O)(=O)C=2C=C3NC(NC(=O)OC)=NC3=CC=2)=C1 UMRIXOOKYJPSSR-UHFFFAOYSA-N 0.000 description 1
- BVDJGIMOJFTONF-UHFFFAOYSA-N (3-ethoxyphenyl) 3,4-diaminobenzenesulfonate Chemical compound CCOC1=CC=CC(OS(=O)(=O)C=2C=C(N)C(N)=CC=2)=C1 BVDJGIMOJFTONF-UHFFFAOYSA-N 0.000 description 1
- KRCUXSWQRHFAKL-UHFFFAOYSA-N (3-ethoxyphenyl) 4-amino-3-nitrobenzenesulfonate Chemical compound CCOC1=CC=CC(OS(=O)(=O)C=2C=C(C(N)=CC=2)[N+]([O-])=O)=C1 KRCUXSWQRHFAKL-UHFFFAOYSA-N 0.000 description 1
- ORCRRODNPXBNEA-UHFFFAOYSA-N (3-ethoxyphenyl) 4-chloro-3-nitrobenzenesulfonate Chemical compound CCOC1=CC=CC(OS(=O)(=O)C=2C=C(C(Cl)=CC=2)[N+]([O-])=O)=C1 ORCRRODNPXBNEA-UHFFFAOYSA-N 0.000 description 1
- KKQNCKWAALXEKI-UHFFFAOYSA-N (3-methoxyphenyl) 3,4-diaminobenzenesulfonate Chemical compound COC1=CC=CC(OS(=O)(=O)C=2C=C(N)C(N)=CC=2)=C1 KKQNCKWAALXEKI-UHFFFAOYSA-N 0.000 description 1
- QCCQKSLEMRUDGL-UHFFFAOYSA-N (3-methylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=CC(C)=C1 QCCQKSLEMRUDGL-UHFFFAOYSA-N 0.000 description 1
- HMEHAKJPTXFDAV-UHFFFAOYSA-N (3-methylphenyl) 4-amino-3-nitrobenzenesulfonate Chemical compound CC1=CC=CC(OS(=O)(=O)C=2C=C(C(N)=CC=2)[N+]([O-])=O)=C1 HMEHAKJPTXFDAV-UHFFFAOYSA-N 0.000 description 1
- AGSDJTRUYDYOKC-UHFFFAOYSA-N (3-methylphenyl) 4-chloro-3-nitrobenzenesulfonate Chemical compound CC1=CC=CC(OS(=O)(=O)C=2C=C(C(Cl)=CC=2)[N+]([O-])=O)=C1 AGSDJTRUYDYOKC-UHFFFAOYSA-N 0.000 description 1
- IDECGGBOCHQSGR-UHFFFAOYSA-N (4-bromophenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=C(N)C(N)=CC=C1S(=O)(=O)OC1=CC=C(Br)C=C1 IDECGGBOCHQSGR-UHFFFAOYSA-N 0.000 description 1
- HZLRYBRIYTWVJI-UHFFFAOYSA-N (4-butoxyphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=CC(OCCCC)=CC=C1OS(=O)(=O)C1=CC=C(N=C(NC(=O)OC)N2)C2=C1 HZLRYBRIYTWVJI-UHFFFAOYSA-N 0.000 description 1
- UBQZRGHBKMEVEX-UHFFFAOYSA-N (4-butoxyphenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=CC(OCCCC)=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 UBQZRGHBKMEVEX-UHFFFAOYSA-N 0.000 description 1
- XUMBWVTXGBAVHY-UHFFFAOYSA-N (4-chloro-2-methylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=C(Cl)C=C1C XUMBWVTXGBAVHY-UHFFFAOYSA-N 0.000 description 1
- BHRFFHMJAHRLEX-UHFFFAOYSA-N (4-chloro-3,5-dimethylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC(C)=C(Cl)C(C)=C1 BHRFFHMJAHRLEX-UHFFFAOYSA-N 0.000 description 1
- HFMMTBBMICTONS-UHFFFAOYSA-N (4-chloro-3,5-dimethylphenyl) 3,4-diaminobenzenesulfonate Chemical compound CC1=C(Cl)C(C)=CC(OS(=O)(=O)C=2C=C(N)C(N)=CC=2)=C1 HFMMTBBMICTONS-UHFFFAOYSA-N 0.000 description 1
- JHKXGBVWAIEDJW-UHFFFAOYSA-N (4-chloro-3-methylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=C(Cl)C(C)=C1 JHKXGBVWAIEDJW-UHFFFAOYSA-N 0.000 description 1
- MYBLWLVGPRISIA-UHFFFAOYSA-N (4-chloro-3-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=C(Cl)C(C)=CC(OS(=O)(=O)C=2C=C(N)C(N)=CC=2)=C1 MYBLWLVGPRISIA-UHFFFAOYSA-N 0.000 description 1
- WQIDJNBXBWEBFF-UHFFFAOYSA-N (4-chlorophenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=C(Cl)C=C1 WQIDJNBXBWEBFF-UHFFFAOYSA-N 0.000 description 1
- SWXAXGYVTNHQPF-UHFFFAOYSA-N (4-chlorophenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=C(N)C(N)=CC=C1S(=O)(=O)OC1=CC=C(Cl)C=C1 SWXAXGYVTNHQPF-UHFFFAOYSA-N 0.000 description 1
- XSFRDQWLPLGEPZ-UHFFFAOYSA-N (4-methoxyphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=C(OC)C=C1 XSFRDQWLPLGEPZ-UHFFFAOYSA-N 0.000 description 1
- PMVPZZFOLSZEBG-UHFFFAOYSA-N (4-methoxyphenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=CC(OC)=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 PMVPZZFOLSZEBG-UHFFFAOYSA-N 0.000 description 1
- JJIXFYOIJWXMEQ-UHFFFAOYSA-N (4-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=CC(C)=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 JJIXFYOIJWXMEQ-UHFFFAOYSA-N 0.000 description 1
- MQRYQYNOHRSTMX-UHFFFAOYSA-N (4-propan-2-yloxyphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC=C(OC(C)C)C=C1 MQRYQYNOHRSTMX-UHFFFAOYSA-N 0.000 description 1
- XNKRQJNGYPLTPF-UHFFFAOYSA-N (4-propan-2-yloxyphenyl) 3,4-diaminobenzenesulfonate Chemical compound C1=CC(OC(C)C)=CC=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 XNKRQJNGYPLTPF-UHFFFAOYSA-N 0.000 description 1
- UGCJSPQIFWNLLQ-UHFFFAOYSA-N (5-chloro-2-methylphenyl) 2-(methoxycarbonylamino)-3h-benzimidazole-5-sulfonate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1S(=O)(=O)OC1=CC(Cl)=CC=C1C UGCJSPQIFWNLLQ-UHFFFAOYSA-N 0.000 description 1
- BRUHGWKEMUAJNB-UHFFFAOYSA-N (5-chloro-2-methylphenyl) 3,4-diaminobenzenesulfonate Chemical compound CC1=CC=C(Cl)C=C1OS(=O)(=O)C1=CC=C(N)C(N)=C1 BRUHGWKEMUAJNB-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
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- LJNJJEMEHCBZQQ-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl] 4-chloro-3-nitrobenzenesulfonate Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(S(=O)(=O)OC=2C=C(C=CC=2)C(F)(F)F)=C1 LJNJJEMEHCBZQQ-UHFFFAOYSA-N 0.000 description 1
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Vynález se týká způsobu výroby fenylesterů 2-alkoxykarbonylaminobenzimidazol-5(6)-ylsulfonové kyseliny, které jsou použitelné jako anthelminticky ůčimné látky.The present invention relates to a process for the preparation of 2-alkoxycarbonylaminobenzimidazol-5 (6) -ylsulfonic acid phenyl esters which are useful as anthelmintically active substances.
2-alkoxykarbonylaminobenzimidazolyl-deriváty s alkylovými, acylovými, fenoxylovými zbytky a fenylthíoskupinami v poloze 5(6) jísou již jako anthelmintika známé [P. Actor a další, Nátuře 215, 321 (1967), DOS 2 029 637, DOS 2 164 690, DOS 2 363 348].The 2-alkoxycarbonylaminobenzimidazolyl derivatives with alkyl, acyl, phenoxy and phenylthio groups in the 5-position (6) are already known as anthelmintics [P. Actor et al., Nature 215, 321 (1967), DOS 2,029,637, DOS 2,164,690, DOS 2,363,348].
Předmětem vynálezu jsou anthelminticky účinné fenylestery 2-alkoxykarbonylamiinobenzimidazolyl-5(6)-sulfonové kyseliny obecného vzorce 1The present invention provides anthelmintically active 2-alkoxycarbonylamino-benzimidazolyl-5 (6) -sulfonic acid phenyl esters of Formula 1
v němžin which
Ri znamená alkylový zbytek s 1 až 4 atomy uhlíku,R 1 represents an alkyl radical having 1 to 4 carbon atoms,
Rz a Rs znamenají vždy nezávisle na sobě vodík, aikoxyskupinu s 1 až 4 atomy uhlíku, halogen, trifluormethylovou skupinu, alkylovou skupinu s 1 až 4 atomy uhlíku, alko2 xykarbonylovou skupimu s 1 až 4 atomy uhlíku v alkoxylové části nebo kyanoskupinu.R 2 and R 5 are each independently hydrogen, C 1 -C 4 -alkoxy, halogen, trifluoromethyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxycarbonyl or cyano.
Jako alkylové zbytky v substituentech Ri, Rz a R3 přicházejí v úvahu: methyl, ethyl, propyl, isopropyl, butyl, sek.butyl, terc.butyl. Jako alkoxyskupiny v substituentech R2 a Rj přicházejí v úvahu: methoxyskupina, ethoxyskupina, propoxyskupina, isopropoxyskupina a butoxyskupina. Jako atomy halogenu v substituentech Rz a R3 přicházejí v úvahu: fluor,· chlor, brom a jod. Jako alkoxykarbonylové skupiny v substituentech Rz a R3 přicházejí v úvahu methoxykarbonylová skupina, ethoxykarbonylová skupina, propoxykarbonylová skupina nebo butoxykarbonylová skupina.Suitable alkyl radicals in the substituents R1, R2 and R3 are: methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl. Suitable alkoxy groups in R2 and R1 are: methoxy, ethoxy, propoxy, isopropoxy and butoxy. Suitable halogen atoms in the substituents R2 and R3 are: fluorine, chlorine, bromine and iodine. Suitable alkoxycarbonyl groups in substituents R2 and R3 are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl.
Zvláště výhodné jsou sloučeniny vzorce 1, v němž Ri znamená methyl, Rz znamená vodík a R3 znamená vodík, chlor, brom, trifluormethyl, methyl, ethyl,, methoxyskupinu nebo ethoxyskupinu, přičemž R3 je se zvláštní výhodou v poloze 3 fenylového kruhu.Particularly preferred are compounds of formula 1 wherein R 1 is methyl, R 2 is hydrogen and R 3 is hydrogen, chloro, bromo, trifluoromethyl, methyl, ethyl, methoxy or ethoxy, with R 3 being particularly preferred at the 3-position of the phenyl ring.
Předmětem vynálezu je způsob výroby fenylesterů 2-alkoxykarbonylaminobenzimidazol-5(6)-yl-sulfonové kyseliny vzorce 1, v němž Ri, Rz a R3 mají shora uvedený vý196285 znám, který spočívá v tom, že se derivát o-fenylendiaminu obecného vzorce 2The present invention provides a process for the preparation of 2-alkoxycarbonylaminobenzimidazol-5 (6) -ylsulfonic acid phenyl esters of formula 1, wherein R 1, R 2 and R 3 have the aforementioned 196285, characterized in that the o-phenylenediamine derivative of formula 2
v němžin which
Rž a R3 mají shora uvedený význam, nechá reagovat s esterem bis-alkyl- nebo bis-arylthio-methylenaminomravenčí kyseliny obecného vzorce 6R 2 and R 3 are as defined above, reacted with a bis-alkyl- or bis-arylthiomethyleneaminic acid ester of formula 6
RiSRiS
C=N—C—ORi /11 RsS O (6), v němžC = N — C — ORi / 11 RsS O (6) wherein
Ri má význam uvedený pod vzorcem 1 aR 1 is as defined in formula 1 a
Rá a Rs jsou buď stejné něho vzájemně rozdílné a znamenají alkylový zbytek s i až 4 atomy uhlíku, alkenylový zbytek se 3 až 5 atomy uhlíku, cyklohexylový zbytek nebo popřípadě substituovaný fenylový, popřípadě benzylový zbytek vzorců 7, popřípadě 8 * jSVcwv (X)n . ...Ra and Rs are either identical to him different and each represent an alkyl radical a to 4 carbon atoms, an alkenyl radical having 3-5 carbon atoms, a cyclohexyl radical or an optionally substituted phenyl or benzyl radical of formula 7 or 8 * JSV CW in (X) n. ...
přičemžwhereas
X znamená nezávisle na sobě atom halogenu, methylovou skupinu nebo nitroskupinu, neboX is independently halogen, methyl or nitro, or
Ri a Rs mohou být spojeny také do kruhu, který obsahuje 2 nebo 3 methylenové skupiny a n znamená číslo 0, 1 nebo 2.R 1 and R 5 can also be joined to a ring containing 2 or 3 methylene groups and n is 0, 1 or 2.
Průběh reakcí lze znázornit následujícími réakčními schématy:The course of reactions can be illustrated by the following reaction schemes:
0)0)
Za účelem provádění reakce podle vynálezu. se nechá reagovat účelně 1 mol derivátu o-fenylendiaminu vzorce 2 s 1 mol esteru kyseliny bis-alkyl- nebo bis-arylthiomethylenaminomravenčí vzorce 6 v inertním rozpouštědle, jako je tetrahydrofuran, dioxan, isopropylether nebo chloroform při zvýšené teplotě, účelně při teplotě teploty varu použitého rozpouštědla.For carrying out the reaction according to the invention. 1 mol of the o-phenylenediamine derivative of formula 2 is suitably reacted with 1 mol of the bis-alkyl- or bis-arylthiomethyleneamine-formic acid ester of formula 6 in an inert solvent such as tetrahydrofuran, dioxane, isopropyl ether or chloroform at elevated temperature, conveniently at boiling point. solvents.
Je možno při postupu podle vynálezu vyrábět ester kyseliny bis-alkyl- nebo bis-arylthiomethylenaminomravenčí také teprve v reakční nádobě z hydrochloridu esteru kyseliny ixninodlthiouhličité přidáním esteru kyseliny chlormravenčí vzorce 10.In the process according to the invention, the bis-alkyl- or bis-arylthiomethyleneaminic formate can also be produced only in the reaction vessel from the mono-lithium carbonate ester hydrochloride by addition of the chloroformic acid ester of formula 10.
Jako estery kyseliny chlormravenčí vzorce 10 přicházejí v úvahu například:Suitable chloroformic acid esters of formula (10) are, for example:
methýlester kyseliny chlormravenčí, ethylester kyseliny chlormravenčí, propylester kyseliny chlormravenčí, isopropylester kyseliny chlormravenčí, butylester kyseliny chlormravenčí, isobutylester kyseliny. chlormravenčí a terč.butylester kyseliny chlormravenčí.methyl chloroformate, ethyl chloroformate, propyl chloroformate, isopropyl chloroformate, butyl chloroformate, isobutyrate. chloroformate and tert-butyl chloroformate.
V tomto případě se musí přidávat činidlo, které váže kyselinu, kterým může být- organická nebo anorganická báze, jako hydroxid sodný, kyselý uhličitan sodný nebo triethylamin. Jako reakční prostředí jsou vhodná polární a nepolární rozpouštědla jako ether, aceton, dioxan, voda, dimethylformamid, benzen nebo cyklohexan, přičemž se teplota reakční směsi nechá výhodně vystoupit nad 20°C.In this case, an acid binding agent, which may be an organic or inorganic base, such as sodium hydroxide, sodium bicarbonate or triethylamine, must be added. Suitable reaction media are polar and non-polar solvents such as ether, acetone, dioxane, water, dimethylformamide, benzene or cyclohexane, the temperature of the reaction mixture preferably being allowed to rise above 20 ° C.
Estery bis-alkyl- nebo bis-arylthiomethylenaminomravenčí kyseliny se dají připravit z odpovídajících esterů dithioiminouhličité kyseliny reakcí s estery kyseliny chlormravenčí vzorce 10 podle amerického patentního spisu 3 562 290.Bis-alkyl- or bis-arylthiomethyleneaminic form esters can be prepared from the corresponding dithioiminocarboxylic acid esters by reaction with chloroformic acid esters of formula 10 according to U.S. Pat. No. 3,562,290.
Jako příklady esterů bis-alkyl- nebo bis-arylthiomethylenaminomravenčí kyseliny vzorce 6 lze uvést:Examples of bis-alkyl- or bis-arylthiomethyleneaminic acid esters of formula 6 include:
methýlester bis-methylthiomethylenaminomravenčí kyseliny, ethylester bis-methylthiomethylenaminomravenčí kyseliny, propylester bis-methylthiomethylenaminomravenčí kyseliny, isopropylester bis-methylthiomethylenaminomravenčí kyseliny, butylester bis-methylthiomethylenaminomravenčí kyseliny, sek.butylester bis-methylthiomethylenaminomravenčí kyseliny, methýlester bis-butylthiomethylenaminomravemčí kyseliny, methýlester methylthiobutylthiomethylenaminomravenčí kyseliny, methýlester allylthiocyklohexylthiomethylenaminomravenčí kyseliny, methýlester methylthiofenylthiomethylenaminomravenčí kyseliny, methýlester methylthio-(3,4-dichlorbenzylthio) methylenaminomravenčí kyseliny nebo methýlester methylthio- (2-chlor-4-methylthio) methylenaminomravenčí kyseliny.Methyl bis methylthiomethylenaminomravenčí acid ethyl ester bis-methylthiomethylenaminomravenčí, propyl bis methylthiomethylenaminomravenčí ester, isopropyl bis-methylthiomethylenaminomravenčí acid ethyl ester, bis-methylthiomethylenaminomravenčí acid sec.-bis methylthiomethylenaminomravenčí acid, methyl bis butylthiomethylenaminomravemčí acid methyl methylthiobutylthiomethylenaminomravenčí acid methyl allylthiocyklohexylthiomethylenaminomravenčí acids, methylthiophenylthiomethyleneaminic acid methyl ester, methylthio- (3,4-dichlorobenzylthio) methyleneaminic acid methyl ester, or methylthio- (2-chloro-4-methylthio) methyleneaminic acid methyl ester.
Jako deriváty o-fenylendiamino vzorce 2 přicházejí v úvahu například:Examples of suitable o-phenylenediamino derivatives of formula (2) are:
fenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid phenyl ester,
4-chlorfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 4-chlorophenyl ester,
3- chlorfenylester 3,4-diaminobenzensulfonové kyseliny,3-Chlorophenyl 3,4-diaminobenzenesulfonic acid ester
2- chlorf enylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 2-chlorophenyl ester,
2.5- dichlorfenylester 3,4-diaminobenzensulfonové kyseliny,2,5-diaminobenzenesulfonic acid 2,5-dichlorophenyl ester,
3.5- dichlorf enylester 3,4-dlaminobemzensulfonové kyseliny,3,4-Dlaminobenzenesulfonic acid 3,5-dichlorophenyl ester,
4- bromfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 4-bromophenyl ester,
3- bromfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 3-bromophenyl ester,
2- bromf enylester 3,4-díaminobenzemšulfonové kyseliny,3,4-diamino-benzenesulfonic acid 2-bromophenyl ester,
4- methylfenylester 3,4-diáminobenzensulfonové kyseliny3,4-diamino-benzenesulfonic acid 4-methyl-phenyl ester
3- methylf enylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 3-methylphenyl ester,
2-methylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 2-methylphenyl ester,
4- terc.butylfenylester 3,4-diaminóbenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 4- tert -butyl phenyl ester,
2.4- dimethylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 2,4-dimethylphenyl ester,
2-chlor-4-methylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 2-chloro-4-methylphenyl ester,
2- chlor-6-meithylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 2-chloro-6-methylphenyl ester,
3- chlor-4-methylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 3-chloro-4-methylphenyl ester,
3-chlor-6-methylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 3-chloro-6-methylphenyl ester,
3- chlor-4-karbethoxyfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 3-chloro-4-carbethoxyphenyl ester,
4- chlor-2-methylfenylester 3,4-diaminoberizensulfonové kyseliny,3,4-diaminoberizenesulfonic acid 4-chloro-2-methylphenyl ester,
4-chIor-3-methylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 4-chloro-3-methylphenyl ester,
4-chlor-3,5-dimethylfenylester 3,4-diaminobsnzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 4-chloro-3,5-dimethylphenyl ester,
3.5- bistrifluo.rmethylfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 3,5-bistrifluoro-methylphenyl ester,
4-methoxyfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 4-methoxyphenyl ester,
3- methoxyfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 3-methoxyphenyl ester,
2-methoxyfe,nylester 3,4-diaminobenzensulfonové kyseliny,2-methoxyphenyl, 3,4-diaminobenzenesulfonic acid ester,
4- propo.xyf enylester 3,4-diaipinobenzensulfonové kyseliny,3,4-diaipinobenzenesulfonic acid 4-propoxyxyphenyl ester,
4-isopropoxyfenylester 3,4-diaminobenzensulfonové kyseliny,3,4-diaminobenzenesulfonic acid 4-isopropoxyphenyl ester,
4-butoxyfenyleister 3,4-diaminobenzensulfonové kyseliny a3,4-diaminobenzenesulfonic acid 4-butoxyphenyl ester a
4-isobuto:xyfenylester 3,4-diaminobenzensulfonové kyseliny.3,4-diaminobenzenesulfonic acid 4-isobutoxyphenyl ester.
Tímto způsobem se získají následující sloučeniny:The following compounds are obtained in this way:
fenylester 2-methoxyikarbonylamino-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid phenyl ester,
4-chlorfenylesteir 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 4-chlorophenyl ester,
3- chlorfenyles,ter 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,3-chlorophenyl, ter 2-methoxycarbonylamino-5-benzimidazolesulfonic acid,
2- chlorfenylester 2-methoxykarbonylamino-5-benzímidazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazolesulfonic acid 2-chlorophenyl ester,
2.5- dichlorfenylesteř 2-methoxykarbonylamlno-5-benzimidazolsulfonové kyseliny,2.5-Dichloro-phenyl ester of 2-methoxycarbonylamino-5-benzimidazolesulfonic acid,
3.5- dichlorfe.nylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,3,5-Dichlorophenyl 2-methoxycarbonylamino-5-benzimidazolesulfonic acid ester,
4- bromfenylester 2-methoxykarbonylamino-5-benzímidazolsulfonové kyseliny,4-Bromophenyl 2-methoxycarbonylamino-5-benzimidazolesulfonic acid ester,
3- bromfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,3-Bromophenyl 2-methoxycarbonylamino-5-benzimidazolesulfonic acid ester,
2- bromfenyJ.ester 2-methoxykarbonylamino-5-benzimldazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazole sulfonic acid 2-bromophenyl ester
4- methylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,4-Methylphenyl ester of 2-methoxycarbonylamino-5-benzimidazolesulfonic acid,
3- methylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,3-Methoxyphenyl ester of 2-methoxycarbonylamino-5-benzimidazolesulfonic acid,
2-methylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazolesulfonic acid 2-methylphenyl ester,
4- terc.butylfenylester 2-methoxykarbonylamino-5-benzimídazolsuIfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazole sulfonic acid 4- tert -butyl phenyl ester,
2.4- dimethyHenylester 2-methoxykarbonylamlno-5-benzimidazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazolesulfonic acid 2,4-dimethyl ester,
2-chlor-4-methylfenylester 2-methoxykarbonylamlno-5-benzlmidazolsulfonové kyseliny,2-Chloro-4-methylphenyl 2-methoxycarbonylamino-5-benzimidazole sulfonic acid ester,
2- chlor-6-methylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 2-chloro-6-methylphenyl ester,
3- chlor-4-methylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazolesulfonic acid 3-chloro-4-methylphenyl ester,
3-chlor-6-methylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 3-chloro-6-methylphenyl ester,
3- chlor-4-karbethoxyfenylester 2-methoxykarbonylamino-5-benzimídazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazolesulfonic acid 3-chloro-4-carbethoxyphenyl ester,
4- chlor-2-methylfenylester 2-methoxykarbonylamino-5-benzimldazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazole sulfonic acid 4-chloro-2-methylphenyl ester,
4-chlor-3-methylfenylester 2-meithoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-Methoxycarbonylamino-5-benzimidazolesulfonic acid 4-chloro-3-methylphenyl ester,
4-chlor-3,5-dimethylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 4-chloro-3,5-dimethylphenyl ester,
3.5- bistrifluormethylfenylester 2-methoxykarbo,nylamino-5-benzimidazolsulfonové kyseliny,3,5-bistrifluoromethylphenyl ester of 2-methoxycarbonylamino-5-benzimidazolesulfonic acid,
4-methoxyfenylester 2-methoxykarbonylamino-5-benzlmidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 4-methoxyphenyl ester,
3- methoxyfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,3-Methoxyphenyl 2-methoxycarbonylamino-5-benzimidazolesulfonic acid ester,
2-methoxyfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 2-methoxyphenyl ester,
4- propoxyfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,4-Propoxyphenyl 2-methoxycarbonylamino-5-benzimidazolesulfonic acid ester
4-lsopropoxyfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 4-isopropoxyphenyl ester,
4-butoxyfenylester 2-methoxykarbonylamlno-5-benzimidazolsulfonové kyseliny,2-methoxycarbonylamino-5-benzimidazolesulfonic acid 4-butoxyphenyl ester,
4-isobutoxyfenylester 2-methoxykarbonylaimino-5-benzimidazolsulfonové kyseliny, fenylester 2-ethoxykarbonylamino-5-benzimidazolsulfonové kyseliny, fenylester 2-propoxykarbonylamino-5-benzimidazolsulfonové kyseliny, fenylester 2-isopropoxykarbonylamino-5-benzimidazolsulfonové kyseliny, fenylester 2-isobutoxykarbonylamino-5-benzimidazolsulfonové kyseliny, fenylester 2-butoxykarbonylamino-5-benzimidazolsulfonové kyseliny a fenylester 2-terc.butoxykarbonylamino-5-benzimidazolsulfonové kyseliny.2-Methoxycarbonylaminoimino-5-benzimidazolesulfonic acid 4-isobutoxyphenyl ester, 2-ethoxycarbonylamino-5-benzimidazolesulfonic acid phenyl ester, 2-propoxycarbonylamino-5-benzimidazolesulfonic acid phenyl ester, 2-isopropoxycarbonylamino-5-benzimidazolesulfonic acid phenylester, 2-isopropoxycarbonylamino-5-benzyl ester, acids, 2-butoxycarbonylamino-5-benzimidazolesulfonic acid phenyl ester, and 2-tert-butoxycarbonylamino-5-benzimidazolesulfonic acid phenyl ester.
Derivát o-fenylendiamino vzorce 2, který slouží jako výchozí látka pro reakci podle vynálezu se získává redukcí odpovídajícího aminonitroderivátu vzorce 12, v němž Rž a R3 mají stejný význam jako ve vzorci 1. Redukce se může provádět například hydrogenací v přítomnosti Raneyova niklu a rozpouštědla jako methanolu nebo dimethylformamidu při teplotách mezí 20 a 60 °C nebo působením redukčních činidel jako dithioničitanu sodného.The o-phenylenediamino derivative of formula (2), which serves as the starting material for the reaction according to the invention, is obtained by reduction of the corresponding amino nitro derivative of formula (12) in which R1 and R3 have the same meaning as in formula 1. of methanol or dimethylformamide at temperatures between 20 and 60 ° C or by treatment with reducing agents such as sodium dithionite.
Aminonitroderiváty vzorce 12 se získávají reakcí odpovídajících chlornitroderivátů vzorce 13, v němž Rz a R3 mají stejný význam jako ve vzorci i, s amoniakem ve vhodném rozpouštědle, jako je dioxan nebo methanol při zvýšené teplotě a zvýšeném tlaku. Chlornitroderiváty vzorce 13 se získávají tím, že se uvádí v reakci chlorid kyseliny 3-nitro-4-chlorbenzensulfonové vzorce 15 s fenolem vzorce 14, v němž Rž a R3 mají stejný význam jako ve vzorci 1, v inertním rozpouštědle v přítomnosti báze, jako je triethylamin.The amino nitro derivatives of formula 12 are obtained by reacting the corresponding chloro nitro derivatives of formula 13 in which R 2 and R 3 have the same meaning as in formula i with ammonia in a suitable solvent such as dioxane or methanol at elevated temperature and elevated pressure. The chloronitroderivatives of formula 13 are obtained by reacting 3-nitro-4-chlorobenzenesulfonic acid chloride of formula 15 with a phenol of formula 14, wherein R 2 and R 3 have the same meaning as in formula 1, in an inert solvent in the presence of a base such as triethylamine.
Fenylestery ’ 2-alkoxykarbonylaminobenzi.midazol-5( 6 j-ylsulfonové kyseliny podle vynálezu jsou cennými chemoterapeutiky a jsou vhodné k potírání parazitárních chorob u lidí a zvířat, jako helminthů a motolice jaterní.The 2-alkoxycarbonylaminobenzimidazol-5 (6-ylsulfonic acids) phenyl esters of the present invention are valuable chemotherapeutic agents and are useful in combating parasitic diseases in humans and animals, such as helminths and liver fluke.
Účinné látky podle vynálezu jsou zvlášť účinné proti velkému počtu helminthů, jako je například vlasovka (Haemonchus), vlasovka (Trichostró.ngylus), vlasovka (Ostertagia), hádě (Strongyloides), vlasovka (Cooperia), zubovka (Chabertia), zubovka (Oesophagostomum), vlasovka (Hyostrongylus), měchovec (Ancylostoma), škrkavka (Askaris) a roup (Heterakisj, Zvláště výrazná je účinnost sloučenin podle vynálezu proti háděti napadajícímu žaludeční a střevní trakt, a to především přežvýkavců. Napadení zvířat těmito parazity vede k velkým hospodářským škodám, v důsledku čehož nacházejí sloučeniny podle vynálezu použití zejména ve zvěrolékařství.The active compounds according to the invention are particularly effective against a large number of helminths, such as, for example, Haemonchus, Trichostromus, Ostertagia, Strongyloides, Cooperia, Chabertia, Oesophagostomum ), lineworm (Hyostrongylus), hookworm (Ancylostoma), roundworm (Askaris) and roup (Heterakisj). As a result, the compounds of the invention find particular use in veterinary medicine.
Účinné látky vzorce 1 se podle povahyThe active substances of the formula 1 are, depending on the nature of the active ingredient
198285 napadení aplikují v dávkách mezi 0,5 a 50 miligramy na 1 kg tělesné hmotnosti po dobu 1 až 14 dnů.198285 infections are administered at doses between 0.5 and 50 milligrams per kg body weight for 1 to 14 days.
K orální aplikaci přicházejí v úvahu tablety, dražé, kapsle, prášky, granuláty nebo pasty, které obsahují účinné látky spolu s obvyklými pomocnými látkami a nosnými látkami, jako je škrob, prášková celulóza, mastek, stearan hořečnatý, cukr, želatina, uhličitan vápenatý, jemně disperzní kyselina křemičitá, karboxymethylcelulóza nebo podobné látky.For oral administration, tablets, coated tablets, capsules, powders, granules or pastes which contain the active substances together with the usual excipients and carriers such as starch, powdered cellulose, talc, magnesium stearate, sugar, gelatin, calcium carbonate, finely dispersed silicic acid, carboxymethylcellulose or the like.
Pro parentetální aplikaci přicházejí v úvahu roztoky, které se připravují za použití sezamového oleje, ricinového oleje nebo syntetických triglyceridů, popřípadě za přídavku tokoferolu jako antioxidačně účinné látky nebo/a za použití povrchově aktivních látek, jako jsou estery sorbitanu s mastnými kyselinami. Vedle toho přicházejí v úvahu vodné suspenze, které se připravují za použití efhoxylovaných esterů sorbitanu s mastnými kyselinami, popřípadě za přídavku zahušťovadel, jako je polyethylenglykol nebo karboxymethylcelulóza.For parenteral administration, solutions which are prepared using sesame oil, castor oil or synthetic triglycerides, optionally with the addition of tocopherol as an antioxidant and / or with surfactants such as sorbitan fatty acid esters, are suitable. In addition, aqueous suspensions are prepared which are prepared by using ethoxylated sorbitan fatty acid esters, optionally with the addition of thickeners, such as polyethylene glycol or carboxymethylcellulose.
Koncentrace účinných látek podle vynálezu v přípravcích připravených z těchto látek, se pohybují účelně pro potřeby veterinárních léčiv mezi 2 a 20 hmotnostními procenty. Pro účely humánních léčiv se koncentrace účinných látek pohybuje mezi 20 a 80 hmotnostními °/o.The concentrations of the active compounds according to the invention in the preparations prepared from these compounds are suitably between 2 and 20% by weight for the purposes of veterinary medicines. For the purpose of human medicines, the concentration of the active ingredients is between 20 and 80% by weight.
Za účelem zjištění účinku sloučenin podle vynálezu byly prováděny chemoterapeutické pokusy na jehňatech o hmotnosti asi 30 kg, kterým byly za účelem infekce experimentálně aplikovány larvy vlasovky slezové (Haemonchuš contortusj, popřípadě vlasovky kozí (Trichostrongylus colubriformisj. Pokusná zvířata byla udržována v boxech, které byly denně důkladně čištěny. Po uplynutí prepatenční doby (čas mezi infekcí a pohlavní dospělostí parazitů s počínajícím se vylučováním vajíček nebo larev) byl modifikovaným McMasterovým postupem podle Wetzela [TierSrztliche Umschau, 6, 209 až 210 (1951)] určován počet vajíček na 1 g výkalu. Bezprostředně potom bylo provedeno ošetření ovcí (obecně 4 až 8 zvířat na 1 účinnou látku, nejméně však 2 zvířata). Zvířatům byly aplikovány dávky sloučenin podle vynálezu ve formě suspenze, a to vždy v 10 ml 1% suspenze tylózy. Vždy 7., 14. a 28. den po ošetření byl znovu shora uvedeným způsobem zjišťován počet vajíček na 1 g výkalu a bylo vypočteno procentuální snížení ve srovnání s výchozí hodnotou před ošetřením.In order to investigate the effect of the compounds of the invention, chemotherapeutic experiments were carried out on lambs weighing about 30 kg which were injected experimentally with larvae of Haemonchus contortusj and Trichostrongylus colubriformisj for infection. After the pre-retention time (time between infection and sexual maturity of parasites beginning with egg or larvae secretion), the number of eggs per g of faeces was determined by a modified McMaster procedure according to Wetzel (TierSrztliche Umschau, 6, 209-210 (1951)). Immediately thereafter, sheep were treated (generally 4 to 8 animals per active ingredient, but at least 2 animals). and on day 28 after treatment was again sh The number of eggs per g of faeces was determined in this manner and the percentage reduction compared to the pre-treatment baseline was calculated.
Sloučeniny podle vynálezu jsou výtečně účinné nejen při orální aplikaci, nýbrž jsou účinné také při parenterální aplikaci v dávkách až do 2 mg/kg. Tím zdaleka převyšují srovnatelné deriváty benzimidazolu, zejména všechny známé 5(6j-substituované 2-benzimidazolkarbamáty. z The compounds of the invention are excellent not only for oral administration, but also for parenteral administration at doses up to 2 mg / kg. This far exceeds the comparable benzimidazole derivatives, in particular all known 5 (6J-2-substituted benzimidazole. From
Postup přípravy sloučenin podle vynálezu je blíže objasněn v následujících príkla10 dech. Teploty jsou uváděny ve stupních Celsia.The preparation of the compounds of the invention is illustrated in the following examples. Temperatures are given in degrees Celsius.
PřikladlHe did
17,9 g methylesteru kyseliny bis-methylthiomethylenamínomravenčí se přidá k 26,4 gramu fenylesteru 3,4-diaminobenzensulfonové kyseliny v 200 ml tetrahydrofuranu a směs se zahřívá k váru 3 hodiny pod zpětným chladičem. Potom se nechá reakční směs vychladnout a vyloučený fenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny se odfiltruje a čistí se rozpuštěním v dioxanu, filtrací roztoku přes aktivní uhlí a vysrážením vodou. Výtěžek 12 g, teplota rozkladu 242 °C.17.9 g of methyl bis-methylthiomethyleneamine formate were added to 26.4 g of 3,4-diaminobenzenesulfonic acid phenyl ester in 200 ml of tetrahydrofuran and the mixture was refluxed for 3 hours. The reaction mixture is then allowed to cool and the precipitated 2-methoxycarbonylamino-5-benzimidazolesulfonic acid phenyl ester is filtered off and purified by dissolving in dioxane, filtering the solution through activated carbon and precipitating with water. Yield 12 g, decomposition temperature 242 ° C.
Fenylester kyseliny 3,4-diaminobe,nzensulfonové se připravuje tím, že se hydrogenuje 27 g fenylesteru kyseliny 3-nitro-4-aminobenzensulfonové v 300 ml methylglykolu za přítomnosti Raneyova niklu při atmosférickém tlaku a teplotě místnosti. Katalyzátor se odfiltruje a po zahuštění filtrátu se získá fenylester 3,4-diaminobenzensulfonové kyseliny ve formě surového produktu. Tímto produktem je 25 g tmavého oleje, který se může přímo používat k cyklizaci.3,4-Diaminobenzenesulfonic acid phenyl ester is prepared by hydrogenating 27 g of 3-nitro-4-aminobenzenesulfonic acid phenyl ester in 300 ml of methyl glycol in the presence of Raney nickel at atmospheric pressure and room temperature. The catalyst was filtered off and the filtrate was concentrated to give 3,4-diaminobenzenesulfonic acid phenyl ester as a crude product. This product is 25 g of a dark oil which can be used directly for cyclization.
Za účelem přípravy fenylesteru 3-nitro-4-aminobenzensulfonové kyseliny se 54 g fenylesteru 3-nitro-4-chlorbenzensulfonové kyseliny udržuje v 500 ml dioxanu při přetlaku 0,5 MPa plynného amoniaku po dobu 5 hodin při teplotě 50°C a potom se rozpouštědlo odstraní ve vakuu. Ke zbytku se přidá 200 ml směsi stejných- dílů methanolu a vody, přičemž po krátké době vznikne pevná sraženina, která se odfiltruje.In order to prepare 3-nitro-4-aminobenzenesulfonic acid phenyl ester, 54 g of 3-nitro-4-chlorobenzenesulfonic acid phenyl ester is held in 500 ml of dioxane under a pressure of 0.5 MPa of ammonia gas for 5 hours at 50 ° C and then the solvent removed under vacuum. 200 ml of a mixture of equal parts of methanol and water are added to the residue, and after a short time a solid precipitate is formed which is filtered off.
Po několikanásobném překrystalování z methanolu a potom z benzenu se získá 28 g fenylesteru 3-nitro-4-aminobenzensulfonové kyseliny o bodu tání 104 °C.Recrystallization several times from methanol and then from benzene gave 28 g of 3-nitro-4-aminobenzenesulfonic acid phenyl ester, m.p. 104 ° C.
Fenylester 3-nitro-4-chlorbenzensulfonové kyseliny se získá tím, že se 51 g chloridu3-Nitro-4-chlorobenzenesulfonic acid phenyl ester is obtained by taking 51 g of chloride
3-nitro-4-chlorbenzensulfonové kyseliny smísí s 18,8 g fenolu ve 120 ml acetonu a za chlazení se pří vnitřní teplotě nepřesahující 10 °C přikape 28 ml triéthylaminu. Směs se míchá ještě několik hodin při teplotě místnosti a potom se přidá voda, přičemž se vyloučí olej, který se zpracuje za použití etheru.3-Nitro-4-chlorobenzenesulfonic acid is mixed with 18.8 g of phenol in 120 ml of acetone and 28 ml of triethylamine are added dropwise while cooling at an internal temperature not exceeding 10 ° C. The mixture was stirred for several hours at room temperature, and then water was added, leaving an oil which was treated with ether.
Po překrystalování z methanolu se vyloučí 54 g fenylesteru 3-nitro-4-chlorbenzensulfonové kyseliny o teplotě tání 71 °C.After recrystallization from methanol, 54 g of 3-nitro-4-chlorobenzenesulfonic acid phenyl ester, m.p. 71 DEG C., precipitated.
P ř í k 1 a d 2Example 1 a d 2
K ochlazenému roztoku 19,7 g hydrochloridu methylesteru iminodithiouhličité kyseliny a 12,5 g methylesteru kyseliny chlormravenčí v 50 ml vody se přikape 10% roztok hydroxidu sodného, přičemž teplota nemá přesáhnout 10 °C. Jakmile se dosáhne hodnoty pH 7,5, přidá se 26,4 g fenylesteruTo a cooled solution of 19.7 g of iminodithium carbonate methyl ester hydrochloride and 12.5 g of methyl chloroformate in 50 ml of water was added dropwise a 10% sodium hydroxide solution, the temperature not to exceed 10 ° C. Once pH 7.5 is reached, 26.4 g of the phenyl ester is added
3,4-diaminobenzensulfonové kyseliny v 50 mililitrech ledové kyseliny octové a směs3,4-diaminobenzenesulfonic acid in 50 ml glacial acetic acid and mixture
198 285 se zahřívá 2 hodiny za míchání pod zpětným chladičem. Potom se nechá reakční směs vychladnout a vzniklý fenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny sě odfiltruje. Tento produkt je ve svých vlastnostech shodný s reakčním produktem popsaným v příkladu 1.198 285 was heated under reflux for 2 hours. The reaction mixture was then allowed to cool and the resulting 2-methoxycarbonylamino-5-benzimidazolesulfonic acid phenyl ester was filtered off. This product is identical in nature to the reaction product described in Example 1.
Analogickým způsobem se za použití příslušně modifikovaných výchozích látek připraví následující sloučeniny:The following compounds were prepared in an analogous manner using appropriately modified starting materials:
3. přes 3-chlorfenylester 3-nitro-4-chlorbenzensulfonové kyseliny (t. t,68°C) a 3-chlorfenylester 3-nitro-4-aminobenzensulfonové kyseliny (t. t. 138 °C), a 3-chlorfenylester 3,4-diaminobenzensulfonové kyseliny (t. t. 84 °C) se získá 3-chlorfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny (teplota tání 234 C) (rozklad);3. via 3-nitro-4-chlorobenzenesulfonic acid 3-chlorophenyl ester (mp, 68 ° C) and 3-nitro-4-aminobenzenesulfonic acid 3-chlorophenyl ester (mp 138 ° C), and 3,4-chlorophenyl ester 3,4- diaminobenzenesulfonic acid (mp 84 ° C) gave 2-methoxycarbonylamino-5-benzimidazolesulfonic acid 3-chlorophenyl ester (m.p. 234 C) (dec.);
4. přes 3-bromfenylester 3-nitro-4-chlorbenzensulfonové kyseliny (t. t. 72 °C), a 3-b'romfenylester 3-nitro-4-aminobenzensulfonové kyseliny (t. t. 141 °C) a 3-bromfenylester 3,4-diaminobenzensulfonové kyseliny (t. t. 94 °C) se získá 3-bromfenyl ester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny (t. t. 242 °C) (rozklad);4. via 3-nitro-4-chlorobenzenesulfonic acid 3-bromophenyl ester (mp 72 ° C), and 3-nitro-4-aminobenzenesulfonic acid 3-bromophenyl ester (mp 141 ° C) and 3,4-diaminobenzenesulfonic acid 3-bromophenyl ester acid (mp 94 ° C) to give 2-methoxycarbonylamino-5-benzimidazolesulfonic acid 3-bromophenyl ester (mp 242 ° C) (dec);
5. pres 3-methylfenylester 3-nitro-4-chlorbenzensulfonové kyseliný (t. t. 60 °C), a 3-methylfenylester 3-nitro-4-aminobenzensulfonové kyseliny (t. t. 138 °C), a 3-methylfenylester 3,4-diaminobenzensulfonové kyseliny (t. t. 84 °C), se získá 3-methylfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny (t. t. 234° Celsia) (rozklad);5. via 3-nitro-4-chlorobenzenesulfonic acid 3-methylphenyl ester (mp 60 ° C), and 3-nitro-4-aminobenzenesulfonic acid 3-methylphenyl ester (mp 138 ° C), and 3,4-diaminobenzenesulfonic acid 3-methylphenyl ester (mp 84 ° C), 2-methoxycarbonylamino-5-benzimidazolesulfonic acid 3-methylphenyl ester (mp 234 ° C) (dec);
6. přes 3-methoxyfenylester 3-nitro-4-chlorbenzensulfonové kyseliny (olej), a 3-methoxyfenylester 3-niťřo-4-aminobenzensulfonové kyseliny (t. t. 116 C'C), a 3-methoxyfenylester 3,4-diaminobenzensulfonové kyseliny (olej) se získá 3-methoxyfenylester 2-methoxykarbonylamino-5-benzimidiazolsulfonové kyseliny (t. t. 227° Celsia) (rozklad);6. Through the methoxyphenyl 3-3-nitro-4-methylphenyl ester (oil) and the methoxyphenyl 3-3-nitro-4-aminobenzenesulfonic acid (mp 116 C ° C), and the methoxyphenyl 3-3,4-diaminobenzenesulphonic acid (oil ) to give 2-methoxycarbonylamino-5-benzimidiazolesulfonic acid 3-methoxyphenyl ester (mp 227 ° C) (dec.);
7. přes 3-ethoxyfenylester 3-nitro-4-chlorbenzensulfonové kyseliny (olej), a 3-ethoxyfenylester 3-nitro-4-aminobenzensulfonové kyseliny (t. t. 86 °C), a 3-ethoxyfenylester 3,4-diaminobenzensulfonové kyseliny (olej) se získá 3-ethoxyfenylester 2-methoxykarbonylamino-5-benzimidazolsulfonové kyseliny (t. t. 212 °C) (rozklad);7. via 3-nitro-4-chlorobenzenesulfonic acid 3-ethoxyphenyl ester (oil), and 3-nitro-4-aminobenzenesulfonic acid 3-ethoxyphenyl ester (mp 86 ° C), and 3,4-diaminobenzenesulfonic acid 3-ethoxyphenyl ester (oil) to give 2-methoxycarbonylamino-5-benzimidazolesulfonic acid 3-ethoxyphenyl ester (mp 212 ° C) (dec.);
8. přes 3-trifluormethylfenylester 3-nltro-4-chlorbenzensulfonové kyseliny (t. t.- 65° Celsia), a 3-trifluormethylfenylester 3-nitro-4-aminobenzensulfonové kyseliny (t. t. 132°C), a 3-trifluormethylfenylester 3,4-diaminobenzensulfonové kyseliny se zíáká 3-trifluormethylfenylester 2-methoxykarbonylamíno-5-benzimidazolsulfonové kyseliny (t. t. 250° Celsia) (rozklad).8. via 3-nitro-4-chlorobenzenesulfonic acid 3-trifluoromethylphenyl ester (mp 65 ° C), and 3-nitro-4-aminobenzenesulfonic acid 3-trifluoromethylphenyl ester (mp 132 ° C), and 3,4-diaminobenzenesulfonic acid 3-trifluoromethylphenyl ester 2-methoxycarbonylamino-5-benzimidazolesulfonic acid 3-trifluoromethylphenyl ester (mp 250 ° C) decomposes.
PREDMETSUBJECT
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS787242A CS196285B2 (en) | 1974-08-28 | 1978-11-06 | Method of producing phenylesters of 2-alkoxycarbonylamin |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2441202A DE2441202C2 (en) | 1974-08-28 | 1974-08-28 | 2-Carbalkoxyamino-benzimidazolyl-5 (6) -sulfonic acid-phenyl ester, process for their preparation and anthelmintic compositions containing them |
| CS755620A CS196282B2 (en) | 1974-08-28 | 1975-08-15 | Method of producing phenylesters of 2-alkoxycarbonyl aminobenzimidazol-5/6/-ylsulphonic acid |
| CS787242A CS196285B2 (en) | 1974-08-28 | 1978-11-06 | Method of producing phenylesters of 2-alkoxycarbonylamin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS196285B2 true CS196285B2 (en) | 1980-03-31 |
Family
ID=25746218
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS787242A CS196285B2 (en) | 1974-08-28 | 1978-11-06 | Method of producing phenylesters of 2-alkoxycarbonylamin |
| CS787240A CS196283B2 (en) | 1974-08-28 | 1978-11-06 | Method of producing phenylesters of 2-alkoxycarbonyl aminobenzimidazol-5/6/-ylsulphonic acid |
| CS787241A CS196284B2 (en) | 1974-08-28 | 1978-11-06 | Method of producing phenylesters of 2-alkoxycarbonyl aminobenzimidazol-5/6/-ylsulphonic acid |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS787240A CS196283B2 (en) | 1974-08-28 | 1978-11-06 | Method of producing phenylesters of 2-alkoxycarbonyl aminobenzimidazol-5/6/-ylsulphonic acid |
| CS787241A CS196284B2 (en) | 1974-08-28 | 1978-11-06 | Method of producing phenylesters of 2-alkoxycarbonyl aminobenzimidazol-5/6/-ylsulphonic acid |
Country Status (1)
| Country | Link |
|---|---|
| CS (3) | CS196285B2 (en) |
-
1978
- 1978-11-06 CS CS787242A patent/CS196285B2/en unknown
- 1978-11-06 CS CS787240A patent/CS196283B2/en unknown
- 1978-11-06 CS CS787241A patent/CS196284B2/en unknown
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| Publication number | Publication date |
|---|---|
| CS196283B2 (en) | 1980-03-31 |
| CS196284B2 (en) | 1980-03-31 |
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