FI85694C - Foerfarande foer framstaellning av terapeutiskt anvaendbara 2-aryl-3-(karbamoyl eller tiokarbamoyl)-1-(1h -1,2,4-triazol-1-yl)-propan-2-olderivat. - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara 2-aryl-3-(karbamoyl eller tiokarbamoyl)-1-(1h -1,2,4-triazol-1-yl)-propan-2-olderivat. Download PDFInfo
- Publication number
- FI85694C FI85694C FI833496A FI833496A FI85694C FI 85694 C FI85694 C FI 85694C FI 833496 A FI833496 A FI 833496A FI 833496 A FI833496 A FI 833496A FI 85694 C FI85694 C FI 85694C
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- FI
- Finland
- Prior art keywords
- formula
- compound
- preparation
- group
- ethyl
- Prior art date
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- -1 thiocarbamoyl Chemical group 0.000 title claims description 51
- 238000002360 preparation method Methods 0.000 title claims description 47
- 238000000034 method Methods 0.000 title claims description 13
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 title claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 103
- 239000000460 chlorine Substances 0.000 claims description 62
- 239000000203 mixture Substances 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 24
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 18
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- SIOVKLKJSOKLIF-UHFFFAOYSA-N bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)OC(C)=N[Si](C)(C)C SIOVKLKJSOKLIF-UHFFFAOYSA-N 0.000 claims description 4
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 4
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 150000001649 bromium compounds Chemical class 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 5
- 239000007795 chemical reaction product Substances 0.000 claims 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 239000006188 syrup Substances 0.000 claims 1
- 235000020357 syrup Nutrition 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
- 239000000243 solution Substances 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 34
- 238000004458 analytical method Methods 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 239000011347 resin Substances 0.000 description 9
- 229920005989 resin Polymers 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- IDZFQCBUBYYJKE-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butanamide Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(CC(=O)N)CN1C=NC=N1 IDZFQCBUBYYJKE-UHFFFAOYSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000222122 Candida albicans Species 0.000 description 4
- 206010017533 Fungal infection Diseases 0.000 description 4
- 208000031888 Mycoses Diseases 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 229940095731 candida albicans Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 239000004533 oil dispersion Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
- UYDJMLXCRXWDHY-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butanenitrile Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(CC#N)(O)CN1C=NC=N1 UYDJMLXCRXWDHY-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 230000000855 fungicidal effect Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000002596 lactones Chemical class 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 2
- QDFUAELUIBGRPW-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-3-hydroxy-2,2-dimethyl-4-(1,2,4-triazol-1-yl)butanamide Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(C(C)(C(N)=O)C)CN1C=NC=N1 QDFUAELUIBGRPW-UHFFFAOYSA-N 0.000 description 2
- JOKCRTQSVAOBSG-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-3-hydroxy-2-methyl-4-(1,2,4-triazol-1-yl)butanenitrile Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(C(C#N)C)CN1C=NC=N1 JOKCRTQSVAOBSG-UHFFFAOYSA-N 0.000 description 2
- KLDBXGOSXRMDNN-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-3-hydroxy-2-methyl-4-(1,2,4-triazol-1-yl)butanoic acid Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(C(C(O)=O)C)CN1C=NC=N1 KLDBXGOSXRMDNN-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
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- 241001225321 Aspergillus fumigatus Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
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- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 241000223238 Trichophyton Species 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 229940091771 aspergillus fumigatus Drugs 0.000 description 2
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- 239000002775 capsule Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- WSGYTEYSRFXUHA-UHFFFAOYSA-N ethyl 3-(2,4-dichlorophenyl)-3-hydroxy-2,2-dimethyl-4-(1,2,4-triazol-1-yl)butanoate Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(C(C)(C)C(=O)OCC)CN1C=NC=N1 WSGYTEYSRFXUHA-UHFFFAOYSA-N 0.000 description 2
- XIGUOIMMTSPWBB-UHFFFAOYSA-N ethyl 3-(2,4-dichlorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butanimidate dihydrochloride Chemical compound Cl.Cl.CCOC(=N)CC(O)(Cn1cncn1)c1ccc(Cl)cc1Cl XIGUOIMMTSPWBB-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
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- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000005544 phthalimido group Chemical group 0.000 description 2
- 229960000380 propiolactone Drugs 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
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- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- NYRWCQVYWCNIFP-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-3-hydroxy-2-methyl-4-(1,2,4-triazol-1-yl)butanamide Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(C(C(N)=O)C)CN1C=NC=N1 NYRWCQVYWCNIFP-UHFFFAOYSA-N 0.000 description 1
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- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910001513 alkali metal bromide Inorganic materials 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
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- 239000000908 ammonium hydroxide Substances 0.000 description 1
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- 125000004069 aziridinyl group Chemical group 0.000 description 1
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- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
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- 201000003984 candidiasis Diseases 0.000 description 1
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- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
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- 239000008187 granular material Substances 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
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- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- QHBBPEKPMLHVBC-UHFFFAOYSA-N methyl n-[3-(2,4-dichlorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butanoyl]-n-methoxycarbonylcarbamate Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(CC(=O)N(C(=O)OC)C(=O)OC)CN1C=NC=N1 QHBBPEKPMLHVBC-UHFFFAOYSA-N 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
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- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical class [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 description 1
- XPVIQDHGDUHXNF-UHFFFAOYSA-N n-acetyl-3-(2,4-dichlorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butanamide Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(O)(CC(=O)NC(=O)C)CN1C=NC=N1 XPVIQDHGDUHXNF-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 230000001590 oxidative effect Effects 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 239000003755 preservative agent Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
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- 235000012045 salad Nutrition 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
- A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dentistry (AREA)
- Agronomy & Crop Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8227978 | 1982-09-30 | ||
| GB8227978 | 1982-09-30 | ||
| GB838302888A GB8302888D0 (en) | 1983-02-02 | 1983-02-02 | Antifungal agents |
| GB8302888 | 1983-02-02 | ||
| GB838312624A GB8312624D0 (en) | 1983-05-07 | 1983-05-07 | Triazole antifungal agents |
| GB8312624 | 1983-05-07 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI833496A0 FI833496A0 (fi) | 1983-09-28 |
| FI833496A7 FI833496A7 (fi) | 1984-03-31 |
| FI85694B FI85694B (fi) | 1992-02-14 |
| FI85694C true FI85694C (fi) | 1992-05-25 |
Family
ID=27261761
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI833496A FI85694C (fi) | 1982-09-30 | 1983-09-28 | Foerfarande foer framstaellning av terapeutiskt anvaendbara 2-aryl-3-(karbamoyl eller tiokarbamoyl)-1-(1h -1,2,4-triazol-1-yl)-propan-2-olderivat. |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP0106515B1 (OSRAM) |
| KR (1) | KR880002208B1 (OSRAM) |
| AU (1) | AU542694B2 (OSRAM) |
| DD (1) | DD218098A5 (OSRAM) |
| DE (1) | DE3378764D1 (OSRAM) |
| DK (1) | DK166622B1 (OSRAM) |
| ES (1) | ES526066A0 (OSRAM) |
| FI (1) | FI85694C (OSRAM) |
| GR (1) | GR81270B (OSRAM) |
| HU (1) | HU194837B (OSRAM) |
| IE (1) | IE56019B1 (OSRAM) |
| IL (1) | IL69825A (OSRAM) |
| NO (1) | NO164168C (OSRAM) |
| NZ (1) | NZ205795A (OSRAM) |
| PT (1) | PT77430B (OSRAM) |
| YU (4) | YU195683A (OSRAM) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4610716A (en) * | 1982-12-14 | 1986-09-09 | Ciba-Geigy Corporation | Fluorinated azolyl ethanol growth regulators and microbicides |
| JPS6025990A (ja) * | 1983-07-20 | 1985-02-08 | Shionogi & Co Ltd | トリアゾ−ル系ジオキソラン誘導体 |
| GB8322983D0 (en) * | 1983-08-26 | 1983-09-28 | Pfizer Ltd | Triazole antifungal agents |
| CN1008735B (zh) * | 1984-11-02 | 1990-07-11 | 拜尔公司 | 以取代的氮杂茂基甲基-环丙基-甲醇衍生物为活性成分的组合物 |
| GB8510195D0 (en) * | 1985-04-22 | 1985-05-30 | Ici Plc | Heterocyclic compounds |
| GB8601952D0 (en) * | 1986-01-28 | 1986-03-05 | Ici Plc | Heterocyclic compounds |
| WO1989004829A1 (en) * | 1987-11-20 | 1989-06-01 | Schering Corporation | Tri- and tetra-substituted-oxetanes and tetrahydrofurans and intermediates thereof |
| DE3839170A1 (de) * | 1988-11-19 | 1990-05-31 | Bayer Ag | Cyclopropyl-substituierte azolylmethylcarbinole, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US5134152A (en) * | 1989-12-07 | 1992-07-28 | Sankyo Company, Limited | Oxetane derivatives and their use as anti-fungal or fungicidal agents |
| EP0481405B1 (de) * | 1990-10-17 | 1997-06-11 | Hoechst Schering AgrEvo GmbH | Pyrimidin-Derivate, Verfahren zu ihrer Herstellung sie enthaltende Mittel und ihre Verwendung als Fungizide |
| GB9107055D0 (en) * | 1991-04-04 | 1991-05-22 | Pfizer Ltd | Triazole antifungal agents |
| JP3471831B2 (ja) * | 1991-12-09 | 2003-12-02 | 富山化学工業株式会社 | 新規なトリアゾール誘導体およびその塩 |
| DE4206529A1 (de) * | 1992-03-02 | 1993-09-09 | Bayer Ag | Azolylmethyl-cyclopropyl-derivate |
| CN1054853C (zh) * | 1995-01-11 | 2000-07-26 | 上海三维制药公司 | 氟康唑中间体1－[2－(2,4－二氟苯基)2,3－环氧丙基]－1h－1,2,4－三氮唑及其甲磺酸盐的制备方法 |
| DE29914119U1 (de) | 1999-08-09 | 1999-12-16 | Maschinen- und Anlagenservice GmbH, 03172 Guben | Bürstenwelle zur Reinigung von Gleisanlagen |
| AU2012268211B2 (en) | 2011-06-07 | 2015-10-15 | Kureha Corporation | Azole derivative, method for producing same, intermediate compound, and agricultural or horticultural chemical agent and industrial material protecting agent |
| CN104961693A (zh) | 2011-11-25 | 2015-10-07 | 株式会社吴羽 | 唑衍生物及其应用 |
| WO2015083436A1 (ja) | 2013-12-05 | 2015-06-11 | 株式会社クレハ | 農園芸用薬剤、植物病害防除方法および植物病害防除用製品 |
| EP3078265B1 (en) | 2013-12-05 | 2017-06-07 | Kureha Corporation | Agricultural and horticultural chemical, plant disease control method and plant disease control product |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0046633A1 (en) * | 1980-08-22 | 1982-03-03 | Imperial Chemical Industries Plc | Heterocyclic compounds useful as pesticides and processes for making them |
| DE3048267A1 (de) * | 1980-12-20 | 1982-07-15 | Bayer Ag, 5090 Leverkusen | Substituierte 1-azolyl-butan-2-ole, verfahren zu ihrer herstellung und ihre verwendung als pflanzenschutzmittel sowie als zwischenprodukte |
| GR78234B (OSRAM) * | 1981-03-10 | 1984-09-26 | Ciba Geigy Ag | |
| EP0084236A3 (en) * | 1981-12-22 | 1983-08-03 | Fbc Limited | Fungicidal heterocyclic compounds and compositions containing them |
| GB2120235A (en) * | 1982-03-23 | 1983-11-30 | Ici Plc | Triazole and imidazole derivatives having fungicidal and plant-growth regulating activity |
| GB8301699D0 (en) * | 1983-01-21 | 1983-02-23 | Pfizer Ltd | Antifungal agents |
-
1983
- 1983-09-09 EP EP83305278A patent/EP0106515B1/en not_active Expired
- 1983-09-09 DE DE8383305278T patent/DE3378764D1/de not_active Expired
- 1983-09-26 KR KR1019830004490A patent/KR880002208B1/ko not_active Expired
- 1983-09-27 IL IL69825A patent/IL69825A/xx not_active IP Right Cessation
- 1983-09-28 NZ NZ205795A patent/NZ205795A/en unknown
- 1983-09-28 FI FI833496A patent/FI85694C/fi not_active IP Right Cessation
- 1983-09-28 DK DK443683A patent/DK166622B1/da not_active IP Right Cessation
- 1983-09-29 IE IE2302/83A patent/IE56019B1/en not_active IP Right Cessation
- 1983-09-29 GR GR72582A patent/GR81270B/el unknown
- 1983-09-29 AU AU19771/83A patent/AU542694B2/en not_active Ceased
- 1983-09-29 PT PT77430A patent/PT77430B/pt not_active IP Right Cessation
- 1983-09-29 HU HU833388A patent/HU194837B/hu not_active IP Right Cessation
- 1983-09-29 NO NO833549A patent/NO164168C/no unknown
- 1983-09-29 DD DD83255229A patent/DD218098A5/de unknown
- 1983-09-29 YU YU01956/83A patent/YU195683A/xx unknown
- 1983-09-29 ES ES526066A patent/ES526066A0/es active Granted
-
1985
- 1985-08-14 YU YU01296/85A patent/YU129685A/xx unknown
- 1985-08-14 YU YU01295/85A patent/YU129585A/xx unknown
- 1985-08-14 YU YU01297/85A patent/YU129785A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HU194837B (en) | 1988-03-28 |
| DK166622B1 (da) | 1993-06-21 |
| NO164168C (no) | 1990-09-05 |
| PT77430B (en) | 1986-04-17 |
| IE832302L (en) | 1984-03-30 |
| KR840006221A (ko) | 1984-11-22 |
| KR880002208B1 (ko) | 1988-10-18 |
| IE56019B1 (en) | 1991-03-27 |
| EP0106515A2 (en) | 1984-04-25 |
| NO164168B (no) | 1990-05-28 |
| YU195683A (en) | 1986-02-28 |
| ES8504150A1 (es) | 1985-04-16 |
| DK443683A (da) | 1984-03-31 |
| FI833496A7 (fi) | 1984-03-31 |
| IL69825A (en) | 1986-12-31 |
| GR81270B (OSRAM) | 1984-12-11 |
| AU542694B2 (en) | 1985-03-07 |
| YU129585A (en) | 1986-02-28 |
| EP0106515B1 (en) | 1988-12-28 |
| EP0106515A3 (en) | 1985-12-04 |
| DD218098A5 (de) | 1985-01-30 |
| ES526066A0 (es) | 1985-04-16 |
| NZ205795A (en) | 1985-09-13 |
| PT77430A (en) | 1983-10-01 |
| IL69825A0 (en) | 1983-12-30 |
| YU129785A (en) | 1986-02-28 |
| DE3378764D1 (en) | 1989-02-02 |
| DK443683D0 (da) | 1983-09-28 |
| FI833496A0 (fi) | 1983-09-28 |
| YU129685A (en) | 1986-02-28 |
| NO833549L (no) | 1984-04-02 |
| AU1977183A (en) | 1984-04-05 |
| FI85694B (fi) | 1992-02-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: PFIZER CORPORATION |