DD205682A5 - Verfahren zur herstellung von (-)-2-(1-(2,6-dichlorphenoxy)-ethyl)-1,3-diazacyclopent-2-en und seinen salzen - Google Patents
Verfahren zur herstellung von (-)-2-(1-(2,6-dichlorphenoxy)-ethyl)-1,3-diazacyclopent-2-en und seinen salzen Download PDFInfo
- Publication number
- DD205682A5 DD205682A5 DD82245653A DD24565382A DD205682A5 DD 205682 A5 DD205682 A5 DD 205682A5 DD 82245653 A DD82245653 A DD 82245653A DD 24565382 A DD24565382 A DD 24565382A DD 205682 A5 DD205682 A5 DD 205682A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- acid
- diazacyclopent
- converted
- ene
- ethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- KSMAGQUYOIHWFS-UHFFFAOYSA-N lofexidine Chemical compound N=1CCNC=1C(C)OC1=C(Cl)C=CC=C1Cl KSMAGQUYOIHWFS-UHFFFAOYSA-N 0.000 title abstract 2
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 12
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 7
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- HOLHYSJJBXSLMV-UHFFFAOYSA-N 2,6-dichlorophenol Chemical compound OC1=C(Cl)C=CC=C1Cl HOLHYSJJBXSLMV-UHFFFAOYSA-N 0.000 claims description 3
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims 2
- 101100127888 Schizosaccharomyces pombe (strain 972 / ATCC 24843) les1 gene Proteins 0.000 claims 1
- 150000008043 acidic salts Chemical class 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 239000002585 base Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- -1 thiamides Chemical class 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- NTBIYBAYFBNTCD-UHFFFAOYSA-N dibenzoyl 2,3-dihydroxybutanedioate Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C(O)C(O)C(=O)OC(=O)C1=CC=CC=C1 NTBIYBAYFBNTCD-UHFFFAOYSA-N 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- GAWAYYRQGQZKCR-UWTATZPHSA-N (2r)-2-chloropropanoic acid Chemical compound C[C@@H](Cl)C(O)=O GAWAYYRQGQZKCR-UWTATZPHSA-N 0.000 description 2
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 2
- OCQAXYHNMWVLRH-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 OCQAXYHNMWVLRH-UHFFFAOYSA-N 0.000 description 2
- JTSKVVDMNKQPAO-UHFFFAOYSA-N 2-(2,6-dichlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=C(Cl)C=CC=C1Cl JTSKVVDMNKQPAO-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-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
- 150000001408 amides Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- PKKDWPSOOQBWFB-UHFFFAOYSA-N 2,4-dichloro-6-[(3,5-dichloro-2-hydroxyphenyl)methyl]phenol Chemical compound OC1=C(Cl)C=C(Cl)C=C1CC1=CC(Cl)=CC(Cl)=C1O PKKDWPSOOQBWFB-UHFFFAOYSA-N 0.000 description 1
- KVCQWFJJUHDPLB-UHFFFAOYSA-N 2-(2,6-dichlorophenoxy)propanamide Chemical compound NC(=O)C(C)OC1=C(Cl)C=CC=C1Cl KVCQWFJJUHDPLB-UHFFFAOYSA-N 0.000 description 1
- IDAFCZRTKFHCGS-UHFFFAOYSA-N 2-(2,6-dichlorophenoxy)propanenitrile Chemical compound N#CC(C)OC1=C(Cl)C=CC=C1Cl IDAFCZRTKFHCGS-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 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
- 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 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 101100371861 Caenorhabditis elegans unc-7 gene Proteins 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
- 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
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- DINOPBPYOCMGGD-VEDJBHDQSA-N Man(a1-2)Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-3)[Man(a1-2)Man(a1-6)]Man(a1-6)]Man(b1-4)GlcNAc(b1-4)GlcNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO[C@@H]3[C@H]([C@@H](O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)O3)O)O2)O)[C@@H](CO)O1 DINOPBPYOCMGGD-VEDJBHDQSA-N 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- DGIDDDIFEQSDJB-UHFFFAOYSA-J [Cl-].[Cl-].[Cl-].[Cl-].[Li+].[Li+].[Li+].[Li+] Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Li+].[Li+].[Li+].[Li+] DGIDDDIFEQSDJB-UHFFFAOYSA-J 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 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
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- 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
-
- 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
- C07D233/20—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 substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/22—Radicals substituted by oxygen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Photoreceptors In Electrophotography (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813149009 DE3149009A1 (de) | 1981-12-10 | 1981-12-10 | (-)-2-(1-(2,6-dichlorphenoxy)-ethyl)-1,3-diazacyclopent-2-en, dessen herstellung und seine verwendung in pharmazeutischen praeparaten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD205682A5 true DD205682A5 (de) | 1984-01-04 |
Family
ID=6148418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD82245653A DD205682A5 (de) | 1981-12-10 | 1982-12-07 | Verfahren zur herstellung von (-)-2-(1-(2,6-dichlorphenoxy)-ethyl)-1,3-diazacyclopent-2-en und seinen salzen |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4518783A (cs) |
| EP (1) | EP0081748B1 (cs) |
| JP (1) | JPS58105968A (cs) |
| AR (1) | AR242192A1 (cs) |
| AT (1) | ATE25520T1 (cs) |
| AU (1) | AU553892B2 (cs) |
| CA (1) | CA1176641A (cs) |
| DD (1) | DD205682A5 (cs) |
| DE (2) | DE3149009A1 (cs) |
| DK (1) | DK548182A (cs) |
| ES (1) | ES518033A0 (cs) |
| FI (1) | FI73980C (cs) |
| GR (1) | GR77767B (cs) |
| IE (1) | IE54222B1 (cs) |
| NO (1) | NO158016C (cs) |
| PT (1) | PT75961B (cs) |
| SU (1) | SU1241989A3 (cs) |
| YU (1) | YU273682A (cs) |
| ZA (1) | ZA828743B (cs) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3407509A1 (de) * | 1984-03-01 | 1985-09-05 | A. Nattermann & Cie GmbH, 5000 Köln | Neue arzneimittelkombination zur behandlung von bluthochdruck und thromboembolischen erkrankungen |
| US4801617A (en) * | 1987-04-06 | 1989-01-31 | Leclerc Gerard | Iminoimidazolidines useful in lowering intraocular pressure |
| FR2642422A1 (fr) * | 1988-12-22 | 1990-08-03 | Roussel Uclaf | Nouvelles polyamines acylees, leur procede de preparation et leur application comme fongicides |
| JP2011530504A (ja) * | 2008-08-08 | 2011-12-22 | アジーン リミテッド ライアビリティー カンパニー | Ｃｎｓ疾患及び病理の治療に用いるロフェキシジンエナンチオマー、並びにそのキラル合成法 |
| US8101779B2 (en) * | 2008-10-06 | 2012-01-24 | University Of Kentucky Research Foundation | Enantioselective synthesis of (+) and (–)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene |
| IT201900009777A1 (it) | 2019-06-21 | 2020-12-21 | Procos Spa | Processo per la sintesi di lofexidina |
| WO2021209617A1 (en) | 2020-04-17 | 2021-10-21 | Medichem, S.A. | Process for the synthesis of lofexidine |
| CN111393369B (zh) * | 2020-05-13 | 2022-12-16 | 宁夏大学 | 一种2-己基咪唑的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1695555A1 (de) * | 1967-02-23 | 1970-07-16 | Nordmark Werke Gmbh | Neue Aryloxy-isoalkyl-delta2-imidazoline und deren Saeureadditionssalze sowie Verfahren zu ihrer Herstellung |
| US3966757A (en) * | 1967-02-23 | 1976-06-29 | A. Nattermann & Cie Gmbh | Imidazoline derivatives and processes for the production thereof |
| US4025639A (en) * | 1967-02-23 | 1977-05-24 | A. Nattermann & Cie Gmbh | Blood pressure lowering in human mammals |
| AU3546478A (en) * | 1977-04-29 | 1979-11-01 | Ciba Geigy Ag | Ectoparasiticides |
-
1981
- 1981-12-10 DE DE19813149009 patent/DE3149009A1/de not_active Withdrawn
-
1982
- 1982-11-25 IE IE2812/82A patent/IE54222B1/en unknown
- 1982-11-26 ZA ZA828743A patent/ZA828743B/xx unknown
- 1982-12-01 DE DE8282111098T patent/DE3275466D1/de not_active Expired
- 1982-12-01 AT AT82111098T patent/ATE25520T1/de not_active IP Right Cessation
- 1982-12-01 EP EP82111098A patent/EP0081748B1/de not_active Expired
- 1982-12-02 AU AU91059/82A patent/AU553892B2/en not_active Ceased
- 1982-12-02 GR GR69957A patent/GR77767B/el unknown
- 1982-12-07 DD DD82245653A patent/DD205682A5/de unknown
- 1982-12-08 FI FI824216A patent/FI73980C/fi not_active IP Right Cessation
- 1982-12-09 PT PT75961A patent/PT75961B/pt unknown
- 1982-12-09 ES ES518033A patent/ES518033A0/es active Granted
- 1982-12-09 CA CA000417366A patent/CA1176641A/en not_active Expired
- 1982-12-09 SU SU823521885A patent/SU1241989A3/ru active
- 1982-12-09 AR AR82291532A patent/AR242192A1/es active
- 1982-12-09 DK DK548182A patent/DK548182A/da not_active Application Discontinuation
- 1982-12-09 JP JP57214751A patent/JPS58105968A/ja active Pending
- 1982-12-09 NO NO824148A patent/NO158016C/no unknown
- 1982-12-10 YU YU02736/82A patent/YU273682A/xx unknown
-
1983
- 1983-05-27 US US06/498,786 patent/US4518783A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE3275466D1 (en) | 1987-04-02 |
| ZA828743B (en) | 1983-09-28 |
| FI73980C (fi) | 1987-12-10 |
| AU553892B2 (en) | 1986-07-31 |
| NO158016C (no) | 1988-06-29 |
| EP0081748A2 (de) | 1983-06-22 |
| DK548182A (da) | 1983-06-11 |
| ATE25520T1 (de) | 1987-03-15 |
| FI73980B (fi) | 1987-08-31 |
| AR242192A1 (es) | 1993-03-31 |
| SU1241989A3 (ru) | 1986-06-30 |
| ES8401947A1 (es) | 1984-01-01 |
| PT75961A (en) | 1983-01-01 |
| NO158016B (no) | 1988-03-21 |
| IE54222B1 (en) | 1989-07-19 |
| CA1176641A (en) | 1984-10-23 |
| GR77767B (cs) | 1984-09-25 |
| PT75961B (en) | 1985-10-04 |
| DE3149009A1 (de) | 1983-06-23 |
| AU9105982A (en) | 1983-06-16 |
| EP0081748B1 (de) | 1987-02-25 |
| NO824148L (no) | 1983-06-13 |
| US4518783A (en) | 1985-05-21 |
| EP0081748A3 (en) | 1984-03-07 |
| ES518033A0 (es) | 1984-01-01 |
| YU273682A (en) | 1985-04-30 |
| IE822812L (en) | 1983-06-10 |
| FI824216L (fi) | 1983-06-11 |
| JPS58105968A (ja) | 1983-06-24 |
| FI824216A0 (fi) | 1982-12-08 |
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