UA112344C2 - Спосіб одержання медетомідину - Google Patents

Спосіб одержання медетомідину Download PDF

Info

Publication number: UA112344C2
Authority: UA; Ukraine
Prior art keywords: reaction; reagent; compound; acid; formula
Prior art date: 2012-05-08

Application number

UAA201410217A

Other languages

English (en)

Ukrainian (uk)

Inventor

Дьорвальд Флоренсіо Сарагоса

Анна Кулеша

Штефан Ельцнер

Роберт Буйок

Збігнев Вробель

Кшиштоф Войцеховскі

Original Assignee

Лонза Лтд

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2012-05-08

Filing date

2012-11-15

Publication date

2016-08-25

2012-11-15 Application filed by Лонза Лтд filed Critical Лонза Лтд

2012-11-15 Priority claimed from PCT/EP2012/072796 external-priority patent/WO2013011155A2/fr

2016-08-25 Publication of UA112344C2 publication Critical patent/UA112344C2/uk

Links

HRLIOXLXPOHXTA-UHFFFAOYSA-N medetomidine Chemical compound C=1C=CC(C)=C(C)C=1C(C)C1=CN=C[N]1 HRLIOXLXPOHXTA-UHFFFAOYSA-N 0.000 title claims abstract description 29
229960002140 medetomidine Drugs 0.000 title claims abstract description 27
238000000034 method Methods 0.000 title claims description 26
238000002360 preparation method Methods 0.000 title abstract description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 29
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
239000000460 chlorine Substances 0.000 claims abstract description 3
229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
229910052740 iodine Inorganic materials 0.000 claims abstract 2
238000006243 chemical reaction Methods 0.000 claims description 268
150000001875 compounds Chemical class 0.000 claims description 123
239000003153 chemical reaction reagent Substances 0.000 claims description 101
239000002904 solvent Substances 0.000 claims description 96
239000000203 mixture Substances 0.000 claims description 87
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 69
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 66
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 52
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 46
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 46
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 27
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 27
229910021529 ammonia Inorganic materials 0.000 claims description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 24
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 22
235000011054 acetic acid Nutrition 0.000 claims description 22
239000002253 acid Substances 0.000 claims description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
239000003054 catalyst Substances 0.000 claims description 20
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 18
-1 C1-6 alkanol Substances 0.000 claims description 18
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 16
239000007795 chemical reaction product Substances 0.000 claims description 16
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 16
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 14
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 12
235000019253 formic acid Nutrition 0.000 claims description 12
239000000047 product Substances 0.000 claims description 12
YELGFTGWJGBAQU-UHFFFAOYSA-N mephedrone Chemical compound CNC(C)C(=O)C1=CC=C(C)C=C1 YELGFTGWJGBAQU-UHFFFAOYSA-N 0.000 claims description 11
BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 claims description 11
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 10
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
239000003456 ion exchange resin Substances 0.000 claims description 10
229920003303 ion-exchange polymer Polymers 0.000 claims description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
150000002373 hemiacetals Chemical class 0.000 claims description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 8
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 8
229940098779 methanesulfonic acid Drugs 0.000 claims description 8
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 8
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 8
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 7
108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 7
150000001299 aldehydes Chemical class 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 claims description 7
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
229910003480 inorganic solid Inorganic materials 0.000 claims description 6
IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims description 6
150000007522 mineralic acids Chemical class 0.000 claims description 6
LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims description 6
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 5
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 5
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 5
229940092714 benzenesulfonic acid Drugs 0.000 claims description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 claims description 5
PKOFBDHYTMYVGJ-UHFFFAOYSA-N n-(4-sulfamoylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(S(N)(=O)=O)C=C1 PKOFBDHYTMYVGJ-UHFFFAOYSA-N 0.000 claims description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
239000005708 Sodium hypochlorite Substances 0.000 claims description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 4
239000003570 air Substances 0.000 claims description 4
229910000323 aluminium silicate Inorganic materials 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
239000011575 calcium Substances 0.000 claims description 4
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 4
OHUDHPKMAJDBPI-UHFFFAOYSA-N isocyanomethylsulfonylbenzene Chemical compound [C-]#[N+]CS(=O)(=O)C1=CC=CC=C1 OHUDHPKMAJDBPI-UHFFFAOYSA-N 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 4
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 3
ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 claims description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
238000007259 addition reaction Methods 0.000 claims description 3
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
229910052782 aluminium Inorganic materials 0.000 claims description 3
230000003993 interaction Effects 0.000 claims description 3
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
229910052744 lithium Inorganic materials 0.000 claims description 3
239000011777 magnesium Substances 0.000 claims description 3
229910052749 magnesium Inorganic materials 0.000 claims description 3
LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 claims description 3
235000006408 oxalic acid Nutrition 0.000 claims description 3
235000019260 propionic acid Nutrition 0.000 claims description 3
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 claims description 3
XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 claims description 2
GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 claims description 2
FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 claims description 2
YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 claims description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 2
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
241000202943 Hernandia sonora Species 0.000 claims description 2
101100237844 Mus musculus Mmp19 gene Proteins 0.000 claims description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 2
HXWOCVNAFNNHPI-UHFFFAOYSA-N N-[4-(isocyanomethylsulfonyl)phenyl]acetamide Chemical compound CC(=O)Nc1ccc(cc1)S(=O)(=O)C[N+]#[C-] HXWOCVNAFNNHPI-UHFFFAOYSA-N 0.000 claims description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
235000019400 benzoyl peroxide Nutrition 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
229910052791 calcium Inorganic materials 0.000 claims description 2
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
239000000920 calcium hydroxide Substances 0.000 claims description 2
229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
239000004202 carbamide Substances 0.000 claims description 2
FFHWGQQFANVOHV-UHFFFAOYSA-N dimethyldioxirane Chemical compound CC1(C)OO1 FFHWGQQFANVOHV-UHFFFAOYSA-N 0.000 claims description 2
235000010299 hexamethylene tetramine Nutrition 0.000 claims description 2
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 claims description 2
VYUZAWHIOAWCTR-UHFFFAOYSA-N isocyano(methylsulfonyl)methane Chemical compound CS(=O)(=O)C[N+]#[C-] VYUZAWHIOAWCTR-UHFFFAOYSA-N 0.000 claims description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 2
CSELYUIIXLJXHS-UHFFFAOYSA-N trifluoro(isocyanomethylsulfonyl)methane Chemical compound FC(F)(F)S(=O)(=O)C[N+]#[C-] CSELYUIIXLJXHS-UHFFFAOYSA-N 0.000 claims description 2
239000011701 zinc Substances 0.000 claims description 2
229910052725 zinc Inorganic materials 0.000 claims description 2
YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims 1
SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 claims 1
229950001870 spizofurone Drugs 0.000 claims 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 abstract description 8
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 abstract 1
239000011630 iodine Substances 0.000 abstract 1
239000000243 solution Substances 0.000 description 32
235000019439 ethyl acetate Nutrition 0.000 description 15
239000002585 base Substances 0.000 description 14
238000000605 extraction Methods 0.000 description 14
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 12
238000004821 distillation Methods 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
230000002378 acidificating effect Effects 0.000 description 10
238000002425 crystallisation Methods 0.000 description 10
230000008025 crystallization Effects 0.000 description 10
238000005481 NMR spectroscopy Methods 0.000 description 9
239000000872 buffer Substances 0.000 description 9
238000005406 washing Methods 0.000 description 9
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
GGZZISOUXJHYOY-UHFFFAOYSA-N 8-amino-4-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C(N)=CC=CC2=C1O GGZZISOUXJHYOY-UHFFFAOYSA-N 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
238000009835 boiling Methods 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
238000010561 standard procedure Methods 0.000 description 7
239000000126 substance Substances 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
150000001335 aliphatic alkanes Chemical class 0.000 description 6
238000001035 drying Methods 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
WLPXNBYWDDYJTN-UHFFFAOYSA-N 1-bromo-2,3-dimethylbenzene Chemical compound CC1=CC=CC(Br)=C1C WLPXNBYWDDYJTN-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 5
229940011051 isopropyl acetate Drugs 0.000 description 5
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
230000035484 reaction time Effects 0.000 description 5
239000008096 xylene Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
239000004698 Polyethylene Substances 0.000 description 4
125000005907 alkyl ester group Chemical group 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
229920001577 copolymer Polymers 0.000 description 4
229920000573 polyethylene Polymers 0.000 description 4
229920000642 polymer Polymers 0.000 description 4
SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
GNEYVIZQCGXVEV-UHFFFAOYSA-N 2-(2,3-dimethylphenyl)propanal Chemical compound O=CC(C)C1=CC=CC(C)=C1C GNEYVIZQCGXVEV-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
239000003513 alkali Substances 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
239000011260 aqueous acid Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000011261 inert gas Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 2
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
DNKFKCVLEKYHQL-UHFFFAOYSA-N 1,2-dimethyl-3-prop-2-enylbenzene Chemical compound CC1=CC=CC(CC=C)=C1C DNKFKCVLEKYHQL-UHFFFAOYSA-N 0.000 description 2
HBBGAESXDKCELE-UHFFFAOYSA-N 2-[(2,3-dimethylphenyl)methyl]oxirane Chemical compound CC1=CC=CC(CC2OC2)=C1C HBBGAESXDKCELE-UHFFFAOYSA-N 0.000 description 2
VEUMANXWQDHAJV-UHFFFAOYSA-N 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VEUMANXWQDHAJV-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
238000004566 IR spectroscopy Methods 0.000 description 2
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical compound CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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 2
150000003973 alkyl amines Chemical class 0.000 description 2
239000003708 ampul Substances 0.000 description 2
230000000202 analgesic effect Effects 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
238000010574 gas phase reaction Methods 0.000 description 2
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
238000002955 isolation Methods 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical compound CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
238000002156 mixing Methods 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
229910052756 noble gas Inorganic materials 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
239000002699 waste material Substances 0.000 description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 1
UIFVCPMLQXKEEU-UHFFFAOYSA-N 2,3-dimethylbenzaldehyde Chemical compound CC1=CC=CC(C=O)=C1C UIFVCPMLQXKEEU-UHFFFAOYSA-N 0.000 description 1
LYAYPVCAAQCSGB-UHFFFAOYSA-N 2-(2,3-dimethylphenyl)propan-2-ol Chemical compound CC1=CC=CC(C(C)(C)O)=C1C LYAYPVCAAQCSGB-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
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
101150051213 MAOA gene Proteins 0.000 description 1
FWJKNZONDWOGMI-UHFFFAOYSA-N Metharbital Chemical compound CCC1(CC)C(=O)NC(=O)N(C)C1=O FWJKNZONDWOGMI-UHFFFAOYSA-N 0.000 description 1
239000012425 OXONE® Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000012267 brine Substances 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
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
238000011161 development Methods 0.000 description 1
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Substances CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
JZBWUTVDIDNCMW-UHFFFAOYSA-L dipotassium;oxido sulfate Chemical compound [K+].[K+].[O-]OS([O-])(=O)=O JZBWUTVDIDNCMW-UHFFFAOYSA-L 0.000 description 1
239000003814 drug Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
MJEMIOXXNCZZFK-UHFFFAOYSA-N ethylone Chemical compound CCNC(C)C(=O)C1=CC=C2OCOC2=C1 MJEMIOXXNCZZFK-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000003446 ligand Substances 0.000 description 1
WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
PJYPCKZZTIAODG-UHFFFAOYSA-M magnesium;1,2-dimethylbenzene-6-ide;bromide Chemical compound [Mg+2].[Br-].CC1=CC=C[C-]=C1C PJYPCKZZTIAODG-UHFFFAOYSA-M 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
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
125000001979 organolithium group Chemical group 0.000 description 1
125000002734 organomagnesium group Chemical group 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
230000037361 pathway Effects 0.000 description 1
HJKYXKSLRZKNSI-UHFFFAOYSA-I pentapotassium;hydrogen sulfate;oxido sulfate;sulfuric acid Chemical compound [K+].[K+].[K+].[K+].[K+].OS([O-])(=O)=O.[O-]S([O-])(=O)=O.OS(=O)(=O)O[O-].OS(=O)(=O)O[O-] HJKYXKSLRZKNSI-UHFFFAOYSA-I 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000001294 propane Substances 0.000 description 1
239000002994 raw material Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- C07D233/58—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 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
- C07C1/24—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms by elimination of water
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
- C07C29/40—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones with compounds containing carbon-to-metal bonds
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/18—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
- C07C33/20—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part monocyclic
- 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
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/58—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in three-membered rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/228—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing six-membered aromatic rings, e.g. phenylacetaldehyde
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/04—Compounds containing oxirane rings containing only hydrogen and carbon atoms in addition to the ring oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2531/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- C07C2531/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- C07C2531/025—Sulfonic acids

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

UAA201410217A 2012-05-08 2012-11-15 Спосіб одержання медетомідину UA112344C2 (uk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP12167134		2012-05-08
PCT/EP2012/072796 WO2013011155A2 (fr)	2012-05-08	2012-11-15	Procédé de préparation de médétomidine

Publications (1)

Publication Number	Publication Date
UA112344C2 true UA112344C2 (uk)	2016-08-25

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UA (1)	UA112344C2 (fr)
WO (1)	WO2012172119A2 (fr)

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US9045433B2 (en) *	2012-05-08	2015-06-02	Lonza Ltd.	Method for preparation of medetomidine
KR101537204B1 (ko) *	2012-05-08	2015-07-22	론자 아게 (론자 엘티디.)	2-(2,3-디메틸페닐)-1-프로파날의 제조 방법
CA2866441C (fr) *	2012-06-28	2017-01-17	Lonza Ltd.	Procede de preparation de 2-(2,3-dimethylphenyl)-1-propanal avec du chloro-acetone
WO2013011157A1 (fr) *	2012-06-28	2013-01-24	Lonza Ltd	Procédé de préparation de médétomidine à partir de chloro-acétone
GB201501593D0 (en) *	2015-01-30	2015-03-18	Cambrex Karlskoga Ab	New compounds and processes
US11198063B2 (en)	2016-09-14	2021-12-14	Square Enix Co., Ltd.	Video display system, video display method, and video display program
CN111903674B (zh) *	2020-08-05	2022-07-12	马保臣	一种质量均一稳定的过硫酸氢钾复合粉及其制备工艺
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Publication number	Publication date
WO2012172119A3 (fr)	2013-04-04
WO2012172119A2 (fr)	2012-12-20

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EP2867195B1 (fr)	2015-12-30	Procédé de préparation de 2-(2,3-diméthylphényl)-1-propanal avec du chloro-acétone
UA112344C2 (uk)	2016-08-25	Спосіб одержання медетомідину
WO2012172120A2 (fr)	2012-12-20	2-(2,3-diméthylphényl)-1-propanal et son utilisation comme parfum
EP2847173B1 (fr)	2015-12-30	Procédé de préparation de médétomidine
EP2847157B1 (fr)	2015-10-28	Procédé de préparation de 2-(2,3-diméthylphényl)-1-propanal
JP5777841B2 (ja)	2015-09-09	クロロアセトンを用いてメデトミジンを調製するための方法
WO2012172122A2 (fr)	2012-12-20	Procédé de préparation de 2-(2,3-diméthylphényl)-1-propanal
AU2012285676A1 (en)	2014-10-02	Method for preparation of 2-(2,3-dimethylphenyl)-1-propanal
UA110746C2 (uk)	2016-02-10	Спосіб одержання 2-(2,3-диметилфеніл)-1-пропаналю
NZ700640B2 (en)	2016-07-01	Method for preparation of medetomidine
HK1201060B (en)	2016-11-04	Method for preparation of 2-(2,3-dimethylphenyl)-1-propanal