HUE026357T2 - Eljárás 1-triazol-2-butanol-származék elõállítására - Google Patents
Eljárás 1-triazol-2-butanol-származék elõállítására Download PDFInfo
- Publication number
- HUE026357T2 HUE026357T2 HUE11821851A HUE11821851A HUE026357T2 HU E026357 T2 HUE026357 T2 HU E026357T2 HU E11821851 A HUE11821851 A HU E11821851A HU E11821851 A HUE11821851 A HU E11821851A HU E026357 T2 HUE026357 T2 HU E026357T2
- Authority
- HU
- Hungary
- Prior art keywords
- methylenepiperidine
- acid
- reaction
- production
- mmol
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 28
- 239000002253 acid Substances 0.000 claims description 31
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical group [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 25
- LPKIGDXRQSIQBA-UHFFFAOYSA-N 4-methylidenepiperidine Chemical compound C=C1CCNCC1 LPKIGDXRQSIQBA-UHFFFAOYSA-N 0.000 description 60
- 238000000034 method Methods 0.000 description 47
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 31
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- NFEZZTICAUWDHU-RDTXWAMCSA-N efinaconazole Chemical compound N1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)CCC(=C)CC1 NFEZZTICAUWDHU-RDTXWAMCSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 229960003937 efinaconazole Drugs 0.000 description 19
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 239000013078 crystal Substances 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- HJKPRGHQSIXXBX-UHFFFAOYSA-N 4-methylidenepiperidine;hydrobromide Chemical compound Br.C=C1CCNCC1 HJKPRGHQSIXXBX-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
- 239000007810 chemical reaction solvent Substances 0.000 description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 7
- 238000007142 ring opening reaction Methods 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 6
- 238000007259 addition reaction Methods 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 150000001340 alkali metals Chemical class 0.000 description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
- 150000001342 alkaline earth metals Chemical class 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 229940071870 hydroiodic acid Drugs 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
- ZNVPSVHFBUNDNS-UHFFFAOYSA-N 4-methylidenepiperidine;hydroiodide Chemical compound I.C=C1CCNCC1 ZNVPSVHFBUNDNS-UHFFFAOYSA-N 0.000 description 5
- 150000002924 oxiranes Chemical class 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- QANJLSHZDUOBBP-QPUJVOFHSA-N 1-[[(2r,3s)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl]methyl]-1,2,4-triazole Chemical compound C[C@@H]1O[C@]1(C=1C(=CC(F)=CC=1)F)CN1N=CN=C1 QANJLSHZDUOBBP-QPUJVOFHSA-N 0.000 description 4
- XGMSENVPQPNOHF-UHFFFAOYSA-N 4-methylidenepiperidine;hydrochloride Chemical compound Cl.C=C1CCNCC1 XGMSENVPQPNOHF-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- VLJSVVSFBYEJHA-UHFFFAOYSA-N 4-methylidenepiperidine;2,2,2-trifluoroacetic acid Chemical compound C=C1CCNCC1.OC(=O)C(F)(F)F VLJSVVSFBYEJHA-UHFFFAOYSA-N 0.000 description 3
- LWAOMUXXYAPKOZ-UHFFFAOYSA-N 4-methylidenepiperidine;nitric acid Chemical compound O[N+]([O-])=O.C=C1CCNCC1 LWAOMUXXYAPKOZ-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QLSWIGRIBOSFMV-UHFFFAOYSA-N 1h-pyrrol-2-amine Chemical class NC1=CC=CN1 QLSWIGRIBOSFMV-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- -1 4-Methylenpiperidin 4-Methylenpiperidin-hydrobromid Chemical compound 0.000 description 1
- GGIHIQLARXTWLC-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;4-methylidenepiperidine Chemical compound C=C1CCNCC1.CC1=CC=C(S(O)(=O)=O)C=C1 GGIHIQLARXTWLC-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N Sec-butyl alcohol Natural products CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- GKMQWTVAAMITHR-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O.CCC(C)O GKMQWTVAAMITHR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- UUCCCPNEFXQJEL-UHFFFAOYSA-L strontium dihydroxide Chemical compound [OH-].[OH-].[Sr+2] UUCCCPNEFXQJEL-UHFFFAOYSA-L 0.000 description 1
- 229910001866 strontium hydroxide Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (4)
- igPs>ÿps>«tok 1 « Eprâs {SR|^-2^{2;4^iuof%nsi)'3»{4-meit!#pplpafMn-14$$ ~{W~1 <22l4riakoM $smùdÏ£iô$ MjénâH eiMSÜséra, orpely fârtâ!mae^<2R^S)»2^#^ii|forf^|h^m«]gr2'î0#‘'l?2^4-tri^4•f^|8stâ^''4^^^p|s«»Â sa^arfslfeiôs p^âval egy pakddkdsagbers a kpgp èà làfcipm gpl slkaiati y&gy ajkéipidiPm-hjProxid Ivagy ahnak hklràpnaR jéfmféiétm.
- 2, Μ1. igèriypoai $z&nnti «îjéréa, ahot as aîkâlifénv vagy aikélrlôldîfevhidroxid a liîium-hidroxid.
- 3, Aa 1 vagy 2, igéhypoal osarintl Iprês, ahoi a 4~-mat|paglpofibjn pavaddiPida §φ b 4-?aatâtepipoAdh^^osdrotoîîkl vagy 4 motiiéppipaddîo-ôidfojodid.
- 4, A 3, sgèoypôot sæeonP après, ahoi a 4-matilérpperklin savaddlsiôa sôja 4-metiièopiparkiio·· hidfopromid, 1. &z 1-4, igénypontok bâmtspks mmM après, ahoi a raatePkôitsg sgafeolhi!, 12-dpstoxietih, OlRiopantirdiehlPler, doglppahoh iPuhsnoi vsgy Α'-ίΡΡΙΙίϊ-ροηΐοηορ, f> Aa 3. igdpypb# saadpd si||f% shot a raakciokozag açatpnkhi vagy cpoperdlhmstibêts?.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010194068 | 2010-08-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUE026357T2 true HUE026357T2 (hu) | 2016-06-28 |
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Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090175810A1 (en) | 2008-01-03 | 2009-07-09 | Gareth Winckle | Compositions and methods for treating diseases of the nail |
| US8039494B1 (en) | 2010-07-08 | 2011-10-18 | Dow Pharmaceutical Sciences, Inc. | Compositions and methods for treating diseases of the nail |
| JP6516759B2 (ja) | 2013-10-03 | 2019-05-22 | ダウ ファーマシューティカル サイエンシーズ，インコーポレイティド | 安定化エフィナコナゾール組成物 |
| CA2931144C (en) * | 2013-11-22 | 2020-02-04 | Dow Pharmaceutical Sciences, Inc. | Anti-infective methods, compositions, and devices |
| CN104292214B (zh) * | 2014-09-24 | 2017-04-05 | 南京华威医药科技开发有限公司 | 艾氟康唑及其中间体的合成方法 |
| CN104327047B (zh) * | 2014-10-17 | 2016-04-06 | 苏州明锐医药科技有限公司 | 艾菲康唑的制备方法 |
| CA2910990C (en) * | 2014-11-23 | 2022-03-22 | Mapi Pharma Ltd. | Intermediate compounds and process for the preparation of efinaconazole |
| CA2974180A1 (en) * | 2015-01-20 | 2016-07-28 | Itai Adin | Crystalline forms of efinaconazole |
| ITUB20150417A1 (it) * | 2015-05-08 | 2016-11-08 | Dipharma Francis Srl | Procedimento per la preparazione di composti piperidinici |
| WO2016181306A1 (en) | 2015-05-12 | 2016-11-17 | Lupin Limited | Process for the preparation of efinaconazole |
| WO2016193917A1 (en) * | 2015-06-04 | 2016-12-08 | Glenmark Pharmaceuticals Limited | Process for the preparation of efinaconazole |
| EP3112360A1 (en) | 2015-06-29 | 2017-01-04 | Dipharma Francis S.r.l. | Process for the preparation of efinaconazole |
| CN106565672A (zh) * | 2015-10-08 | 2017-04-19 | 中美华世通生物医药科技（武汉）有限公司 | 制备艾氟康唑的方法 |
| US20170129874A1 (en) * | 2015-11-10 | 2017-05-11 | Virupaksha Organics Limited | Novel improved process for preparing a triazole antifungal agent |
| CN106810534A (zh) * | 2015-11-30 | 2017-06-09 | 中美华世通生物医药科技（武汉）有限公司 | 艾氟康唑晶型及其制备方法 |
| CN106918672B (zh) * | 2015-12-28 | 2021-02-09 | 中美华世通生物医药科技（武汉）有限公司 | 利用hplc测定艾氟康唑原料药及其制剂中有关物质的方法 |
| CN106928186A (zh) * | 2015-12-29 | 2017-07-07 | 中美华世通生物医药科技（武汉）有限公司 | 化合物及其制备方法和用途 |
| ITUB20159795A1 (it) * | 2015-12-30 | 2017-06-30 | Procos Spa | Processo per la sintesi di efinaconazolo |
| CN106995434A (zh) * | 2016-01-25 | 2017-08-01 | 广东东阳光药业有限公司 | 一种三唑类抗真菌药的晶型及其制备方法 |
| ITUA20162545A1 (it) * | 2016-04-13 | 2017-10-13 | Laboratorio Chimico Int S P A | Procedimento per la preparazione di intermedi utili nella sintesi di farmaci |
| CN107759565B (zh) * | 2016-08-15 | 2020-10-23 | 苏州旺山旺水生物医药有限公司 | 一种1-三唑-2-丁醇衍生物的制备方法 |
| WO2018036416A1 (zh) * | 2016-08-26 | 2018-03-01 | 山东特珐曼药业有限公司 | 一种艾氟康唑的制备方法和其晶型m |
| CN107778283A (zh) * | 2016-08-26 | 2018-03-09 | 山东特珐曼药业有限公司 | 一种艾氟康唑的制备方法和其晶型m |
| CN108276381A (zh) * | 2017-01-06 | 2018-07-13 | 上海和博药物研究有限公司 | 一种艾氟康唑的合成方法 |
| IT201700048270A1 (it) | 2017-05-04 | 2018-11-04 | Seegpharm Sa | Procedimento per la preparazione di un derivato azolico. |
| PL3628668T3 (pl) * | 2017-05-19 | 2023-04-24 | Kaken Pharmaceutical Co., Ltd. | Sposoby wytwarzania i oczyszczania efinakonazolu |
| CN108440390A (zh) * | 2018-03-13 | 2018-08-24 | 上药康丽（常州）药业有限公司 | 一种4-亚甲基哌啶盐的制备方法 |
| KR102622061B1 (ko) | 2018-12-29 | 2024-01-08 | 비위트 파마슈티컬 컴퍼니 리미티드 | 에피나코나졸의 제조 방법 |
| CN113929660B (zh) * | 2021-10-18 | 2022-10-04 | 深圳市海滨制药有限公司 | 一种环氧乙烷衍生物开环方法 |
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| JPH02191262A (ja) | 1988-03-04 | 1990-07-27 | Sankyo Co Ltd | トリアゾール誘導体 |
| CN1046278C (zh) * | 1993-05-10 | 1999-11-10 | 科研制药株式会社 | 吡咯胺衍生物 |
| WO1997011939A1 (fr) | 1995-09-28 | 1997-04-03 | Kaken Pharmaceutical Co., Ltd. | Procede d'elaboration de 4-methylenepiperidines |
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| JPWO2012029836A1 (ja) | 2013-10-31 |
| CY1116997T1 (el) | 2017-04-05 |
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| JP5852573B2 (ja) | 2016-02-03 |
| CN106045970B (zh) | 2019-11-08 |
| BR112013004827B1 (pt) | 2020-03-31 |
| TWI518081B (zh) | 2016-01-21 |
| BR112013004827A2 (pt) | 2016-05-31 |
| TW201215601A (en) | 2012-04-16 |
| CN106045970A (zh) | 2016-10-26 |
| CN103080100A (zh) | 2013-05-01 |
| EP2612859A1 (en) | 2013-07-10 |
| RS54330B1 (en) | 2016-02-29 |
| US8871942B2 (en) | 2014-10-28 |
| ES2556782T3 (es) | 2016-01-20 |
| CN103080100B (zh) | 2016-04-27 |
| DK2612859T3 (en) | 2015-10-19 |
| CA2808230C (en) | 2017-02-28 |
| WO2012029836A1 (ja) | 2012-03-08 |
| US20130150586A1 (en) | 2013-06-13 |
| EP2966071B1 (en) | 2017-01-25 |
| PT2612859E (pt) | 2015-11-30 |
| EP2966071A1 (en) | 2016-01-13 |
| CA2808230A1 (en) | 2012-03-08 |
| PL2612859T3 (pl) | 2016-01-29 |
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