FI64146C - Foerfarande foer framstaellning av farmakologiskt vaerdefull 2-brom-6-fluor-n-2-imidazolidinyliden-bensamin och dess syraadditionssalter - Google Patents
Foerfarande foer framstaellning av farmakologiskt vaerdefull 2-brom-6-fluor-n-2-imidazolidinyliden-bensamin och dess syraadditionssalter Download PDFInfo
- Publication number
- FI64146C FI64146C FI771972A FI771972A FI64146C FI 64146 C FI64146 C FI 64146C FI 771972 A FI771972 A FI 771972A FI 771972 A FI771972 A FI 771972A FI 64146 C FI64146 C FI 64146C
- Authority
- FI
- Finland
- Prior art keywords
- bromo
- formula
- fluoro
- acid
- imidazolidinylidene
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 title description 4
- 230000000144 pharmacologic effect Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 16
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 9
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- -1 aliphatic alcohols Chemical class 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- JMSVCTWVEWCHDZ-UHFFFAOYSA-M syringate Chemical compound COC1=CC(C([O-])=O)=CC(OC)=C1O JMSVCTWVEWCHDZ-UHFFFAOYSA-M 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- ALZFPYUPNVLVQM-UHFFFAOYSA-N 2-bromo-6-fluoroaniline Chemical compound NC1=C(F)C=CC=C1Br ALZFPYUPNVLVQM-UHFFFAOYSA-N 0.000 description 5
- 230000003276 anti-hypertensive effect Effects 0.000 description 5
- BVDYBDSQUWIDGG-UHFFFAOYSA-N 1-[2-(2-bromo-6-fluoroanilino)-4,5-dihydroimidazol-1-yl]ethanone Chemical compound C(C)(=O)N1C(NCC1)=NC1=C(C=CC=C1F)Br BVDYBDSQUWIDGG-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 150000002461 imidazolidines Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012454 non-polar solvent Substances 0.000 description 3
- 239000003880 polar aprotic solvent Substances 0.000 description 3
- 239000003586 protic polar solvent Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- IFOVNLDXKNVXNV-UHFFFAOYSA-N (2-bromo-6-fluorophenyl)thiourea Chemical compound NC(=S)NC1=C(F)C=CC=C1Br IFOVNLDXKNVXNV-UHFFFAOYSA-N 0.000 description 2
- FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RLAROPIDCNCRNR-UHFFFAOYSA-N Cl.Cl.[C-]#N Chemical compound Cl.Cl.[C-]#N RLAROPIDCNCRNR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229960002896 clonidine Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- JCOPITWIWLFFPC-UHFFFAOYSA-N n-phenyl-4,5-dihydro-1h-imidazol-2-amine Chemical compound N1CCN=C1NC1=CC=CC=C1 JCOPITWIWLFFPC-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
- 229940116357 potassium thiocyanate Drugs 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GTTSBSWIYBDWTN-UHFFFAOYSA-N (2-bromo-6-fluorophenyl)cyanamide Chemical compound BrC1=C(C(=CC=C1)F)NC#N GTTSBSWIYBDWTN-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JJWACYUTERPMBM-UHFFFAOYSA-N 1-acetylimidazolidin-2-one Chemical compound CC(=O)N1CCNC1=O JJWACYUTERPMBM-UHFFFAOYSA-N 0.000 description 1
- FKVIYERFOLSTTM-UHFFFAOYSA-N 2-fluoro-n-phenylacetamide Chemical compound FCC(=O)NC1=CC=CC=C1 FKVIYERFOLSTTM-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- YPCONUGFUOVIMF-UHFFFAOYSA-N C(C1=CC=CC=C1)S(=O)(=O)O.C(CN)N Chemical compound C(C1=CC=CC=C1)S(=O)(=O)O.C(CN)N YPCONUGFUOVIMF-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- XCKAEOVJLGBGIY-UHFFFAOYSA-N Cl.BrC1=C(C(=CC=C1)F)NC(=N)N Chemical compound Cl.BrC1=C(C(=CC=C1)F)NC(=N)N XCKAEOVJLGBGIY-UHFFFAOYSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-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
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- CCTVAKFPGRUNID-UHFFFAOYSA-N FC1=C([N+]#[C-])C(Br)=CC=C1 Chemical compound FC1=C([N+]#[C-])C(Br)=CC=C1 CCTVAKFPGRUNID-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VSEKTFKBSOLJFR-UHFFFAOYSA-N [amino(methylsulfanyl)methylidene]-(2-bromo-6-fluorophenyl)azanium;iodide Chemical compound [I-].CSC(N)=[NH+]C1=C(F)C=CC=C1Br VSEKTFKBSOLJFR-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N butenedioic acid Chemical compound OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 150000001912 cyanamides Chemical class 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- DYDNPESBYVVLBO-UHFFFAOYSA-N formanilide Chemical compound O=CNC1=CC=CC=C1 DYDNPESBYVVLBO-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229960004198 guanidine Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- GNYKPRZVSYJFIV-UHFFFAOYSA-N imidazolidin-1-ium;chloride Chemical compound Cl.C1CNCN1 GNYKPRZVSYJFIV-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 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
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940005605 valeric acid Drugs 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
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2630060 | 1976-07-03 | ||
| DE2630060A DE2630060C2 (de) | 1976-07-03 | 1976-07-03 | 2-(2-Brom-6-fluor-phenylimino)-imidazolidin, dessen Säureadditionssalze, diese enthaltende Arzneimittel und Verfahren zu deren Herstellung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI771972A7 FI771972A7 (cs) | 1978-01-04 |
| FI64146B FI64146B (fi) | 1983-06-30 |
| FI64146C true FI64146C (fi) | 1983-10-10 |
Family
ID=5982175
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI771972A FI64146C (fi) | 1976-07-03 | 1977-06-23 | Foerfarande foer framstaellning av farmakologiskt vaerdefull 2-brom-6-fluor-n-2-imidazolidinyliden-bensamin och dess syraadditionssalter |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4166859A (cs) |
| JP (1) | JPS6026108B2 (cs) |
| AT (1) | AT354436B (cs) |
| AU (1) | AU507260B2 (cs) |
| BE (1) | BE856395A (cs) |
| BG (1) | BG28049A3 (cs) |
| CA (1) | CA1088550A (cs) |
| CH (2) | CH633273A5 (cs) |
| CS (1) | CS204005B2 (cs) |
| DD (1) | DD132965A5 (cs) |
| DE (1) | DE2630060C2 (cs) |
| DK (1) | DK146281C (cs) |
| ES (4) | ES460351A1 (cs) |
| FI (1) | FI64146C (cs) |
| FR (1) | FR2356642B1 (cs) |
| GB (1) | GB1575147A (cs) |
| GR (1) | GR63636B (cs) |
| HU (1) | HU180429B (cs) |
| IE (1) | IE45109B1 (cs) |
| IL (1) | IL52433A (cs) |
| LU (1) | LU77679A1 (cs) |
| MX (1) | MX4841E (cs) |
| NL (2) | NL188643C (cs) |
| NO (2) | NO145951C (cs) |
| NZ (1) | NZ184539A (cs) |
| PH (1) | PH14572A (cs) |
| PL (1) | PL102918B1 (cs) |
| PT (1) | PT66756B (cs) |
| SE (1) | SE431871B (cs) |
| SU (2) | SU680644A3 (cs) |
| YU (1) | YU161977A (cs) |
| ZA (1) | ZA773979B (cs) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2806811A1 (de) * | 1978-02-17 | 1979-08-23 | Boehringer Sohn Ingelheim | Neue substituierte 2-phenylimino- imidazolidine, deren saeureadditionssalze, diese enthaltene arzneimittel und verfahren zur herstellung derselben |
| DE2806775A1 (de) * | 1978-02-17 | 1979-08-30 | Boehringer Sohn Ingelheim | Neue substituierte 2-phenylimino- imidazolidine deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zur herstellung derselben |
| US4461904A (en) * | 1981-11-20 | 1984-07-24 | Alcon Laboratories, Inc. | 2-(Trisubstituted phenylimino)-imidazolines |
| US4517199A (en) * | 1981-11-20 | 1985-05-14 | Alcon Laboratories, Inc. | Method for lowering intraocular pressure using phenylimino-imidazoles |
| US4644007A (en) * | 1981-11-20 | 1987-02-17 | Alcon Laboratories, Inc. | 3-chloro-4-(4,5-dihydro-1H-imidazo-2-yl)-amino-5-alkylbenzoic acids, esters, salts, compositions and methods |
| US4515800A (en) * | 1981-11-20 | 1985-05-07 | Icilio Cavero | Method of lowering intraocular pressure using phenylimino-imidazoles |
| DE3437694A1 (de) * | 1984-10-15 | 1986-04-17 | Boehringer Ingelheim Vetmedica GmbH, 6507 Ingelheim | Verwendung einer substanz als sedativum |
| US4587257A (en) * | 1984-12-14 | 1986-05-06 | Alcon Laboratories, Inc. | Control of ocular bleeding using clonidine derivatives |
| US5441339A (en) * | 1992-10-22 | 1995-08-15 | Prince Corporation | Vehicle light |
| WO2005000818A1 (en) | 2003-06-27 | 2005-01-06 | Warner-Lambert Company Llc | 5-substituted-4-`(substituted phenyl)!amino!-2-pyridone deviatives for use as mek inhibitors |
| CN115784896A (zh) * | 2022-11-24 | 2023-03-14 | 山东诚创蓝海医药科技有限公司 | 一种2-溴-6-氟苯胺的制备方法 |
| CN116063184B (zh) * | 2022-12-28 | 2025-01-28 | 浙江车头制药股份有限公司 | 一种2-溴-6-氟苯胺的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1770874B2 (de) * | 1968-07-12 | 1977-09-15 | Veb Arzneimittelwerk Dresden, Ddr 8122 Radebeul | Verfahren zur herstellung von 2-(2,6- dichlorphenylamino)-imidazolin-2 |
| BE787683A (fr) * | 1971-08-20 | 1973-02-19 | Boehringer Sohn Ingelheim | 2-phenylimino-imidazolidines, leurs sels d'addition avec des acides et procedes pour les fabriquer |
| DE2446758C3 (de) * | 1974-10-01 | 1979-01-04 | C.H. Boehringer Sohn, 6507 Ingelheim | 2-(2-Fluor-6-trifluormethylphenylimino)-imidazolidin, dessen Säureadditionssalze, Verfahren zur Herstellung dieser Verbindungen und deren Verwendung bei der Bekämpfung der Hypertonie |
| DE2542702C2 (de) * | 1975-09-25 | 1983-11-10 | Lentia GmbH Chem. u. pharm. Erzeugnisse - Industriebedarf, 8000 München | Verfahren zur Herstellung von 1-Benzoyl-2-(2,6-dichlorphenylamino)-2-imidazolin |
-
1976
- 1976-07-03 DE DE2630060A patent/DE2630060C2/de not_active Expired
-
1977
- 1977-06-20 US US05/808,409 patent/US4166859A/en not_active Expired - Lifetime
- 1977-06-22 AT AT438777A patent/AT354436B/de not_active IP Right Cessation
- 1977-06-23 FI FI771972A patent/FI64146C/fi not_active IP Right Cessation
- 1977-06-30 YU YU01619/77A patent/YU161977A/xx unknown
- 1977-06-30 CA CA281,884A patent/CA1088550A/en not_active Expired
- 1977-06-30 AU AU26620/77A patent/AU507260B2/en not_active Expired
- 1977-06-30 CH CH807577A patent/CH633273A5/fr not_active IP Right Cessation
- 1977-07-01 IL IL52433A patent/IL52433A/xx unknown
- 1977-07-01 ZA ZA00773979A patent/ZA773979B/xx unknown
- 1977-07-01 DK DK296477A patent/DK146281C/da active
- 1977-07-01 PT PT66756A patent/PT66756B/pt unknown
- 1977-07-01 GR GR53854A patent/GR63636B/el unknown
- 1977-07-01 SE SE7707689A patent/SE431871B/xx not_active IP Right Cessation
- 1977-07-01 CS CS774397A patent/CS204005B2/cs unknown
- 1977-07-01 JP JP52077979A patent/JPS6026108B2/ja not_active Expired
- 1977-07-01 GB GB27655/77A patent/GB1575147A/en not_active Expired
- 1977-07-01 SU SU772498148A patent/SU680644A3/ru active
- 1977-07-01 PL PL1977199298A patent/PL102918B1/pl unknown
- 1977-07-01 LU LU77679A patent/LU77679A1/xx unknown
- 1977-07-01 HU HU77BO1672A patent/HU180429B/hu unknown
- 1977-07-01 NO NO772329A patent/NO145951C/no unknown
- 1977-07-01 BE BE179022A patent/BE856395A/xx not_active IP Right Cessation
- 1977-07-01 MX MX775863U patent/MX4841E/es unknown
- 1977-07-01 NZ NZ184539A patent/NZ184539A/xx unknown
- 1977-07-01 PH PH19947A patent/PH14572A/en unknown
- 1977-07-01 IE IE1371/77A patent/IE45109B1/en not_active IP Right Cessation
- 1977-07-01 BG BG036775A patent/BG28049A3/xx unknown
- 1977-07-01 NL NLAANVRAGE7707308,A patent/NL188643C/xx not_active IP Right Cessation
- 1977-07-01 FR FR7720343A patent/FR2356642B1/fr not_active Expired
- 1977-07-01 DD DD7700199844A patent/DD132965A5/xx unknown
- 1977-07-02 ES ES460351A patent/ES460351A1/es not_active Expired
-
1978
- 1978-02-10 ES ES466852A patent/ES466852A1/es not_active Expired
- 1978-02-10 ES ES466851A patent/ES466851A1/es not_active Expired
- 1978-02-10 ES ES466850A patent/ES466850A1/es not_active Expired
- 1978-03-07 SU SU782589253A patent/SU665800A3/ru active
-
1981
- 1981-09-02 CH CH566381A patent/CH633275A5/de not_active IP Right Cessation
-
1993
- 1993-06-29 NL NL930111C patent/NL930111I2/nl unknown
-
1994
- 1994-11-25 NO NO1994024C patent/NO1994024I1/no unknown
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired | ||
| MA | Patent expired |
Owner name: C.H. BOEHRINGER SOHN |