TW201323422A - 製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法 - Google Patents
製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法 Download PDFInfo
- Publication number
- TW201323422A TW201323422A TW101131668A TW101131668A TW201323422A TW 201323422 A TW201323422 A TW 201323422A TW 101131668 A TW101131668 A TW 101131668A TW 101131668 A TW101131668 A TW 101131668A TW 201323422 A TW201323422 A TW 201323422A
- Authority
- TW
- Taiwan
- Prior art keywords
- methyl
- chloro
- dimethyl
- ether
- cyanamide
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- HOKKPVIRMVDYPB-UHFFFAOYSA-N thiacloprid Chemical compound C1=NC(Cl)=CC=C1CN1C(=NC#N)SCC1 HOKKPVIRMVDYPB-UHFFFAOYSA-N 0.000 title abstract 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- SKCNYHLTRZIINA-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)pyridine Chemical compound ClCC1=CC=C(Cl)N=C1 SKCNYHLTRZIINA-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 239000011541 reaction mixture Substances 0.000 claims abstract description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 8
- 229960003151 mercaptamine Drugs 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- AKSDINGSUZIIOO-UHFFFAOYSA-N [3-[(6-chloropyridin-3-yl)methyl]-1,3-thiazolidin-2-yl]cyanamide Chemical compound ClC1=CC=C(C=N1)CN1C(SCC1)NC#N AKSDINGSUZIIOO-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- YORYHIGSMSIWMG-UHFFFAOYSA-N C(=S)(OC)OC(=O)OC Chemical compound C(=S)(OC)OC(=O)OC YORYHIGSMSIWMG-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 abstract description 4
- 238000000746 purification Methods 0.000 abstract 1
- -1 cyanodithiocarbamic acid dimethyl carbonate Chemical compound 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- BOOQVRGRSDTZRZ-UHFFFAOYSA-N 1,2-dipropylhydrazine Chemical compound CCCNNCCC BOOQVRGRSDTZRZ-UHFFFAOYSA-N 0.000 description 2
- BGPJLYIFDLICMR-UHFFFAOYSA-N 1,4,2,3-dioxadithiolan-5-one Chemical compound O=C1OSSO1 BGPJLYIFDLICMR-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-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
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- PGHMDPHPIKEYOG-UHFFFAOYSA-N iminomethylidenecyanamide Chemical compound N=C=NC#N PGHMDPHPIKEYOG-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 1
- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
- PKIAPHXIWGFWRY-UHFFFAOYSA-N 1,2-bis(2-methylpropyl)-9H-fluorene Chemical compound C(C(C)C)C1=C(C=2CC3=CC=CC=C3C=2C=C1)CC(C)C PKIAPHXIWGFWRY-UHFFFAOYSA-N 0.000 description 1
- JXNGSBXJYUTFET-UHFFFAOYSA-N 1,2-bis(3-methylbutyl)hydrazine Chemical compound CC(C)CCNNCCC(C)C JXNGSBXJYUTFET-UHFFFAOYSA-N 0.000 description 1
- KRYYEHQQUCXJDI-UHFFFAOYSA-N 1,2-dibutyl-9h-fluorene Chemical compound C1=CC=C2C3=CC=C(CCCC)C(CCCC)=C3CC2=C1 KRYYEHQQUCXJDI-UHFFFAOYSA-N 0.000 description 1
- FEBRIAPYLGMZSR-UHFFFAOYSA-N 1,2-dibutylhydrazine Chemical compound CCCCNNCCCC FEBRIAPYLGMZSR-UHFFFAOYSA-N 0.000 description 1
- ZPKVXYPKROQWOB-UHFFFAOYSA-N 1,2-diethylanthracene Chemical compound C1=CC=CC2=CC3=C(CC)C(CC)=CC=C3C=C21 ZPKVXYPKROQWOB-UHFFFAOYSA-N 0.000 description 1
- MJLIHWWXDNNKON-UHFFFAOYSA-N 1,2-dihexylhydrazine Chemical compound CCCCCCNNCCCCCC MJLIHWWXDNNKON-UHFFFAOYSA-N 0.000 description 1
- YBQZXXMEJHZYMB-UHFFFAOYSA-N 1,2-diphenylhydrazine Chemical compound C=1C=CC=CC=1NNC1=CC=CC=C1 YBQZXXMEJHZYMB-UHFFFAOYSA-N 0.000 description 1
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- FTBYHABJPALDSP-UHFFFAOYSA-N 1-benzyl-1-methylhydrazine Chemical compound CN(N)CC1=CC=CC=C1 FTBYHABJPALDSP-UHFFFAOYSA-N 0.000 description 1
- NVJUHMXYKCUMQA-UHFFFAOYSA-N 1-ethoxypropane Chemical compound CCCOCC NVJUHMXYKCUMQA-UHFFFAOYSA-N 0.000 description 1
- SRPRMXWUMUHGED-UHFFFAOYSA-N 1-ethyl-1-(2-methylpropyl)hydrazine Chemical compound CCN(N)CC(C)C SRPRMXWUMUHGED-UHFFFAOYSA-N 0.000 description 1
- ZFSFKYIBIOKXKI-UHFFFAOYSA-N 1-ethyl-1-methylhydrazine Chemical compound CCN(C)N ZFSFKYIBIOKXKI-UHFFFAOYSA-N 0.000 description 1
- JWEHBOYGKRBMBV-UHFFFAOYSA-N 1-ethyl-1-propylhydrazine Chemical compound CCCN(N)CC JWEHBOYGKRBMBV-UHFFFAOYSA-N 0.000 description 1
- AMOYMEBHYUTMKJ-UHFFFAOYSA-N 2-(2-phenylethoxy)ethylbenzene Chemical compound C=1C=CC=CC=1CCOCCC1=CC=CC=C1 AMOYMEBHYUTMKJ-UHFFFAOYSA-N 0.000 description 1
- QQZOPKMRPOGIEB-UHFFFAOYSA-N 2-Oxohexane Chemical compound CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 1
- COYKQXRRXFAMBX-UHFFFAOYSA-N 2-[(6-chloropyridin-3-yl)methylamino]ethanethiol Chemical compound SCCNCC1=CC=C(Cl)N=C1 COYKQXRRXFAMBX-UHFFFAOYSA-N 0.000 description 1
- XSJVWZAETSBXKU-UHFFFAOYSA-N 2-ethoxypropane Chemical compound CCOC(C)C XSJVWZAETSBXKU-UHFFFAOYSA-N 0.000 description 1
- WBUOVKBZJOIOAE-UHFFFAOYSA-N 3-chlorobenzonitrile Chemical compound ClC1=CC=CC(C#N)=C1 WBUOVKBZJOIOAE-UHFFFAOYSA-N 0.000 description 1
- WTUAWWLVVCGTRG-UHFFFAOYSA-N 4,5-dihydro-1,3-thiazol-2-ylcyanamide Chemical compound N#CNC1=NCCS1 WTUAWWLVVCGTRG-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 description 1
- MQYUFSDHJSQGRU-UHFFFAOYSA-N CN1C(CCCC1)C1=CC=CC=2C3=CC=CC=C3CC12 Chemical compound CN1C(CCCC1)C1=CC=CC=2C3=CC=CC=C3CC12 MQYUFSDHJSQGRU-UHFFFAOYSA-N 0.000 description 1
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N Caprolactam Natural products O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- AQZGPSLYZOOYQP-UHFFFAOYSA-N Diisoamyl ether Chemical compound CC(C)CCOCCC(C)C AQZGPSLYZOOYQP-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- ICBJCVRQDSQPGI-UHFFFAOYSA-N Methyl hexyl ether Chemical compound CCCCCCOC ICBJCVRQDSQPGI-UHFFFAOYSA-N 0.000 description 1
- XFTIKWYXFSNCQF-UHFFFAOYSA-N N,N-dipropylformamide Chemical compound CCCN(C=O)CCC XFTIKWYXFSNCQF-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- ZWXPDGCFMMFNRW-UHFFFAOYSA-N N-methylcaprolactam Chemical compound CN1CCCCCC1=O ZWXPDGCFMMFNRW-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-O Piperidinium(1+) Chemical compound C1CC[NH2+]CC1 NQRYJNQNLNOLGT-UHFFFAOYSA-O 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical group OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- DIOQZVSQGTUSAI-NJFSPNSNSA-N decane Chemical compound CCCCCCCCC[14CH3] DIOQZVSQGTUSAI-NJFSPNSNSA-N 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- NZMAJUHVSZBJHL-UHFFFAOYSA-N n,n-dibutylformamide Chemical compound CCCCN(C=O)CCCC NZMAJUHVSZBJHL-UHFFFAOYSA-N 0.000 description 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- IWOKCMBOJXYDEE-UHFFFAOYSA-N sulfinylmethane Chemical compound C=S=O IWOKCMBOJXYDEE-UHFFFAOYSA-N 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本發明係關於一種用於製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法,其包括下列步驟:(i)使N-氰基碳亞胺基二硫碳酸二甲酯及2-胺基乙硫醇或其鹽在鹼存在下反應;(ii)使反應混合物與5-氯甲基-2-氯吡啶反應,其中氰基亞胺基-1,3-噻唑啶中間物不需要任何純化。
Description
本發明係關於一種用於製備式(IV)的[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法,其係一種農作物保護活性成份。
該製備是在數個分離的步驟生效,從氰基亞胺基-1,3-噻唑啶及5-氯甲基-2-氯吡啶(EP 1 024 140)、N-(2-氯-5-吡啶甲基)半胱胺及氰基二硫亞胺基碳酸二甲酯(EP 0 235 725)開始進行。在這些情形中,氰基亞胺基-1,3-噻唑啶或N-(2-氯-5-吡啶甲基)半胱胺首先必須製備並純化,且最終產物也必須純化。另外,從N-氰基碳亞胺基二硫碳酸二甲酯及半胱胺開始的全部階段之整體產量並不滿意。
針對上列的缺點及問題,有需要提供一種方法,其從N-氰基碳亞胺基二硫碳酸二甲酯開始,不需要分離中間物而得到[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺,並具有高產量及高選擇性。
此目的藉由下列方法達成:使半胱胺或其鹽(式(I))
及式(II)之N-氰基碳亞胺基二硫碳酸二甲酯
在水存在下反應並隨意地添加溶劑及鹼,且沒有分離中間物氰基亞胺基-1,3-噻唑啶,用式(III)之2-氯-5-氯甲基吡啶烷基化
X在此是酸基,例如鹵基、醋酸根、硫酸根或硫酸氫根。
該反應根據圖示1進行:
訝異地,沒有分離中間物氰基亞胺基-1,3-噻唑啶所達到的產量高於當有分離中間物時,標的產物非常良好
的品質沒有任何惡化。
本申請案據此係關於一種用於製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法,其包括下列步驟:(i)使N-氰基碳亞胺基二硫碳酸二甲酯及2-胺基乙硫醇或其鹽在鹼存在下反應;(ii)使反應混合物與5-氯甲基-2-氯吡啶反應。
根據本發明之方法較宜使用式(I)化合物進行,其中X是酸基,例如鹵基、醋酸根、硫酸根或硫酸氫根。
X較宜是氯、硫酸根或硫酸氫根。
根據本發明之方法,使用的鹼是鹼金屬及鹼土金屬氫氧化物、鹼金屬碳酸鹽或鹼金屬碳酸氫鹽。較宜是使用氫氧化鈉、氫氧化鉀、碳酸氫鈉、碳酸氫鉀、碳酸鈉及碳酸鉀。
在根據本發明之方法中作為起始物質使用的式(I)之半胱胺是可得自商業化供應且是有機化學中普遍已知的化合物。
根據本發明之方法是在水存在下進行。也可能使用含水的溶劑混合物。除了水以外,這些也包含其他溶劑。實例包括醇類例如甲醇、乙醇、異丙醇、正丁醇、異丁醇;醚類例如乙基丙基醚、甲基第三丁基醚、正丁基醚、茴香醚、苯乙醚、環己基甲基醚、二甲基醚、乙醚、二甲基乙二醇、二苯基醚、二丙基醚、二異丙基醚、二正丁基醚、二異丁基醚、二異戊基醚、乙二醇二甲醚、
異丙基乙基醚、四氫呋喃、二烷、二氯二乙基醚及環氧乙烷及/或環氧丙烷之聚醚類;胺類例如三甲胺、三乙胺、三丙胺、三丁胺、N-甲基嗎福啉、吡啶及烷基化的吡啶;腈類例如乙腈、丙腈、丁腈、異丁腈、苄腈、苯基腈、間-氯苄腈及化合物例如四氫噻吩二氧化物及二甲亞碸、四亞甲基亞碸、二丙基亞碸、苄基甲基亞碸、二異丁基亞碸、二丁基亞碸、二異戊基亞碸;碸類例如二甲基碸、二乙基碸、二丙基碸、二丁基碸、二苯基碸、二己基碸、甲基乙基碸、乙基丙基碸、乙基異丁基碸及五亞甲基碸;脂族、環脂族或芳族烴類例如戊烷、己烷、庚烷、辛烷、壬烷;例如含有沸點範圍例如從40℃至250℃的成份之石油溶劑、異丙基苯、沸點範圍從70℃至190℃的揮發油餾份、環己烷、甲基環己烷、石油醚、粗汽油、辛烷、苯、甲苯、氯苯、溴苯、硝基苯、二甲苯;酯類例如醋酸甲酯、乙酯、丁酯及異丁酯,及碳酸二甲酯、二丁酯及亞乙酯;醯胺類例如六亞甲基磷酸醯胺、甲醯胺、N-甲基甲醯胺、N,N-二甲基甲醯胺、N,N-二丙基甲醯胺、N,N-二丁基甲醯胺、N-甲基吡咯烷酮、N-甲基己內醯胺、1,3-二甲基-3,4,5,6-四氫-2(1 H)-嘧啶、辛基吡咯烷酮、辛基己內醯胺、1,3-二甲基-2-咪唑啉二酮、N-甲醯基六氫吡啶、N,N’-1,4-二甲醯基六氫吡;酮類例如丙酮、苯乙酮、甲基乙基酮、甲基丁基酮。
較佳的共溶劑是:甲醇、乙醇、THF、正丁醇。
在一個特別較佳的具體實施例中,反應是在水及正丁醇的混合物中進行。
使用的觸媒可以是相轉移觸媒,例如四級銨鹽。
此外,根據本發明之方法可以在水性二相系統中進行。在此情形中,使用零或只有非常有限的水混溶性之其他溶劑。
在步驟(i)中,將半胱胺鹽酸鹽或半胱胺溶解在鹼金屬氫氧化物、鹼金屬碳酸鹽或鹼金屬碳酸氫鹽的溶液中。使用的溶劑可以是水或含水之混合物。此操作可以在室溫進行。隨後,將溶液冷卻至溫度5至40℃,較宜是10至20℃。計量加入N-氰基碳亞胺基二硫碳酸二甲酯(隨意地以熔化物)。
半胱胺鹽酸鹽對N-氰基碳亞胺基二硫碳酸二甲酯的莫耳比例可以從1:0.7至1:1.5,較宜是1:0.95至1:1.05。
計量加入已結束後,將混合物在10至25℃的溫度攪拌另外0.5至10小時,較宜是1至4小時。較長的反應時間是無區分性的。
反應合適在大氣壓力下進行,但是也可能在減壓或加壓下進行。
在步驟(ii)中,可以加入鹼金屬氫氧化物、鹼金屬碳酸鹽或鹼金屬碳酸氫鹽形式之其他鹼。2-氯-5-氯甲基吡啶是以溶解的形式加入,例如在正丁醇中,或以熔化物的形式加入。在步驟(ii)中的方法可以在廣大的溫度
範圍內進行,例如從30℃及100℃之間,較宜在50℃及80℃之間。
反應合適在大氣壓力下進行,但是也可能在減壓或加壓下進行。
在方法的實際表現中,例如1莫耳的化合物(I)是與1莫耳的化合物(II)及與1.05莫耳的化合物(III)反應。
根據本發明之方法可以批次或連續進行。該方法也可以在標準壓力、減壓或加壓下進行。
處理可以藉由過濾或萃取而進行。
根據本發明用於製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法是在下面的實例中說明,其進一步說明上面的敘述。但是,這些實例不能以限制性的方式解釋。
將13.7克碳酸鈉(0.129莫耳)溶解在78克水中。在室溫,加入15.0克98%半胱胺鹽酸鹽(0.129莫耳)。將懸浮液冷卻至10℃並逐部份與21.0克90%氰基亞胺基二硫碳酸二甲酯(0.129莫耳)混合。立即明顯地溫和釋出氣體。然後在2小時內使混合物溫度上升至20℃。HPLC監視顯示完全轉化。
加入130毫升正丁醇。在減壓及最高50℃下,在
水分離器上將懸浮液去除水。隨後,將通風後的懸浮液與39.3克碳酸鉀(0.285莫耳)混合並加熱至75℃。將混合物再攪拌1小時。
在2小時內,逐滴加入22.1克(0.136莫耳)的2-氯-5-氯甲基吡啶在44.1克正丁醇中的溶液。然後將混合物加熱至80℃並在此溫度下攪拌2小時。冷卻至70℃後,加入在70℃的130毫升水並在70℃將液層分離。將水層在70℃各次用20毫升正丁醇萃取兩次。將合併的丁醇層冷卻至25℃。將沈澱的固體吸氣過濾。將母液冷卻至-5℃。將沈澱的固體經由先前的固體吸氣過濾並用20毫升在-10℃的正丁醇清洗。將所得的固體在40℃的真空乾燥箱內乾燥。
如此得到26.5克純度是98.2%的白色固體(相當於79.6%的理論值)。
1H NMR,DMSO,298 K:3.50 ppm(t)2H;3.91 ppm(t)2H;4.64 ppm(s)2H;7.54 ppm(d)1H;7.79 ppm(dd)1H;8.38 ppm(d)1H.
Claims (4)
- 一種用於製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法,其包括下列步驟:(i)使N-氰基碳亞胺基二硫碳酸二甲酯與半胱胺或其鹽在鹼存在下反應;(ii)使反應混合物與5-氯甲基-2-氯吡啶反應。
- 根據申請專利範圍第1項之方法,其中半胱胺是以式(I)的鹽使用
- 根據申請專利範圍第1或2項中任一項之方法,其中存在下列鹼之一:氫氧化鈉、氫氧化鉀、碳酸氫鈉、碳酸氫鉀、碳酸鈉及碳酸鉀。
- 根據申請專利範圍第1至3項中任一項之方法,其中該反應是在水與正丁醇的混合物中進行。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11179883 | 2011-09-02 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201323422A true TW201323422A (zh) | 2013-06-16 |
TWI527812B TWI527812B (zh) | 2016-04-01 |
Family
ID=46785401
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW101131668A TWI527812B (zh) | 2011-09-02 | 2012-08-31 | 製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法 |
Country Status (12)
Country | Link |
---|---|
US (1) | US20150005502A1 (zh) |
EP (1) | EP2751100B1 (zh) |
JP (1) | JP2014525422A (zh) |
KR (1) | KR20140059206A (zh) |
CN (1) | CN103797008B (zh) |
BR (1) | BR112014004852A2 (zh) |
DK (1) | DK2751100T3 (zh) |
ES (1) | ES2556470T3 (zh) |
IL (1) | IL231022A (zh) |
MX (1) | MX357595B (zh) |
TW (1) | TWI527812B (zh) |
WO (1) | WO2013030152A1 (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107629045A (zh) * | 2017-11-10 | 2018-01-26 | 上海生农生化制品股份有限公司 | 一种噻虫啉的水相合成方法 |
CN109354590B (zh) * | 2018-12-18 | 2020-06-23 | 山东省联合农药工业有限公司 | 一种噻虫啉的合成方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU188852B (en) * | 1983-03-16 | 1986-05-28 | Richter Gedeon Vegyeszeti Gyar Rt,Hu | Process for producing thiazolidine derivatives active against gastric ulcer and intestinal ulcer |
JPH0717621B2 (ja) * | 1986-03-07 | 1995-03-01 | 日本バイエルアグロケム株式会社 | 新規ヘテロ環式化合物 |
US5219868A (en) * | 1990-12-10 | 1993-06-15 | Mitsui Toatsu Chemicals, Inc. | Imidazolidine derivatives, preparation thereof, insecticides containing same as an effective ingredient and intermediates therefor |
DE4427569A1 (de) * | 1994-08-04 | 1996-02-08 | Bayer Ag | Verfahren zur Herstellung von Cyanimino-1,3-thiazolidin |
DE19904310A1 (de) | 1999-01-28 | 2000-08-03 | Bayer Ag | Verfahren zur Herstellung heterocyclischer Verbindungen |
KR100676222B1 (ko) * | 1999-08-18 | 2007-01-30 | 바이엘 악티엔게젤샤프트 | 4,6-디클로로-5-플루오로피리미딘의 제조방법 |
MXPA02007060A (es) * | 2000-01-19 | 2003-01-28 | Bayer Ag | Procedimiento para la obtencion de compuestos heterociclicos. |
JP2005119992A (ja) * | 2003-10-15 | 2005-05-12 | Fuji Photo Film Co Ltd | ピリジンカルボン酸誘導体及びインドリルアザフタリド化合物の製造方法 |
CN100567274C (zh) * | 2007-09-04 | 2009-12-09 | 中国农业大学 | [反]-β-法尼烯类似物及其制备方法与应用 |
EP2042493A1 (de) * | 2007-09-14 | 2009-04-01 | Bayer CropScience AG | Verfahren zum Herstellen von Cyanimino-1,3-thiazolidinen |
KR101348304B1 (ko) * | 2011-03-22 | 2014-01-20 | 동부팜한농 주식회사 | ((2Z)-3-[(6-메틸피리딘-3-일)메틸-1,3-티아졸리딘-2-이리덴]시아나미드, 티아클로프리드(Thiacloprid))의 제조방법 |
-
2012
- 2012-08-27 MX MX2014002274A patent/MX357595B/es active IP Right Grant
- 2012-08-27 JP JP2014527614A patent/JP2014525422A/ja active Pending
- 2012-08-27 ES ES12753705.8T patent/ES2556470T3/es active Active
- 2012-08-27 CN CN201280042379.1A patent/CN103797008B/zh active Active
- 2012-08-27 US US14/241,538 patent/US20150005502A1/en not_active Abandoned
- 2012-08-27 BR BR112014004852A patent/BR112014004852A2/pt not_active Application Discontinuation
- 2012-08-27 WO PCT/EP2012/066602 patent/WO2013030152A1/de active Application Filing
- 2012-08-27 EP EP12753705.8A patent/EP2751100B1/de active Active
- 2012-08-27 DK DK12753705.8T patent/DK2751100T3/en active
- 2012-08-27 KR KR1020147005004A patent/KR20140059206A/ko not_active Application Discontinuation
- 2012-08-31 TW TW101131668A patent/TWI527812B/zh not_active IP Right Cessation
-
2014
- 2014-02-18 IL IL231022A patent/IL231022A/en active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
IL231022A (en) | 2016-04-21 |
BR112014004852A2 (pt) | 2017-04-04 |
MX2014002274A (es) | 2014-03-31 |
TWI527812B (zh) | 2016-04-01 |
IL231022A0 (en) | 2014-03-31 |
WO2013030152A1 (de) | 2013-03-07 |
CN103797008A (zh) | 2014-05-14 |
JP2014525422A (ja) | 2014-09-29 |
MX357595B (es) | 2018-07-16 |
ES2556470T3 (es) | 2016-01-18 |
EP2751100A1 (de) | 2014-07-09 |
DK2751100T3 (en) | 2016-01-18 |
EP2751100B1 (de) | 2015-10-14 |
CN103797008B (zh) | 2016-08-17 |
US20150005502A1 (en) | 2015-01-01 |
KR20140059206A (ko) | 2014-05-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HUE026821T2 (en) | Process 4- {4 - [({[4-Chloro-3- (trifluoromethyl) phenyl] amino} carbonyl) amino] -3-fluorophenoxy} -n-methylpyridine-2-carboxamide, salts and monohydrate preparation of | |
JP2010528071A (ja) | ピラゾールを生産するプロセス | |
AU2006234523B2 (en) | Process for producing an aminomethyl thiazole compound | |
TWI527812B (zh) | 製備[3-[(6-氯-3-吡啶基)甲基]-2-噻唑啶亞基]氰胺之方法 | |
AU2005254863B2 (en) | Compound for preparing thiazole by aminomethylation | |
KR101595140B1 (ko) | 피리미딘계 화합물의 제조 방법 | |
US8884024B1 (en) | Process for preparing benzisothiazolinones | |
US9932321B2 (en) | Process for the preparation of piperidine compounds | |
KR20190055481A (ko) | 고순도 일라프라졸 결정형 b의 제조방법 | |
TWI450892B (zh) | 製備氰亞胺基-1,3-四氫噻唑之方法 | |
US10752600B2 (en) | Procedure for the preparation of 2-cyanoimino-1,3-thiazolidine | |
US20150183742A1 (en) | Process for the preparation of atazanavir bisulfate | |
WO2019150383A1 (en) | A process for preparation of luliconazole | |
TWI535703B (zh) | 用於製備1-烷基-3-二氟甲基-5-羥基吡唑類之方法 | |
US20110071302A1 (en) | Process for preparing intermediate compound for synthesizing an antiulcerant | |
JP6943560B2 (ja) | 2−アミノ−6−メチルニコチン酸エステル又はそのプロトン酸塩の製造方法 | |
US20110098482A1 (en) | Methods of preparing 1-(4-((1r,2s,3r)-1,2,3,4-tetrahydroxybutyl)-1h-imidazol-2-yl)ethanone | |
JP4308667B2 (ja) | 1−(メルカプトメチル)−シクロプロパン酢酸の調製方法 | |
US9212152B2 (en) | Process for the preparation of N-hydroxy-1-(1-alkyl-1H-tetrazol-5-yl)-1-phenylmethanimine derivatives | |
JP6336166B2 (ja) | イミダフェナシンの新規中間体、その製造方法及びそれを用いたイミダフェナシンの製造方法 | |
US10150731B2 (en) | Method for preparing 4-cyanopiperidine hydrochloride | |
CN110461819A (zh) | 制备4-氨基-3-氯-5-氟-6-(4-氯-2-氟-3-甲氧基苯基)吡啶甲酸苄酯的方法 | |
JP2010510258A (ja) | アミノグリコールの製造方法 | |
US20120226049A1 (en) | Method for producing 5-(aminomethyl)-2-chlorothiazole | |
EP3523278A1 (en) | Method for the preparation of h-arg (mis) -oh |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM4A | Annulment or lapse of patent due to non-payment of fees |