DD210907A5 - Verfahren zur herstellung von phenylessigsaeure-derivaten - Google Patents
Verfahren zur herstellung von phenylessigsaeure-derivaten Download PDFInfo
- Publication number
- DD210907A5 DD210907A5 DD83252755A DD25275583A DD210907A5 DD 210907 A5 DD210907 A5 DD 210907A5 DD 83252755 A DD83252755 A DD 83252755A DD 25275583 A DD25275583 A DD 25275583A DD 210907 A5 DD210907 A5 DD 210907A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- group
- general formula
- phenyl
- carbon atoms
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- FWEOQOXTVHGIFQ-UHFFFAOYSA-N 8-anilinonaphthalene-1-sulfonic acid Chemical class C=12C(S(=O)(=O)O)=CC=CC2=CC=CC=1NC1=CC=CC=C1 FWEOQOXTVHGIFQ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 131
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 128
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 59
- 239000000460 chlorine Substances 0.000 claims abstract description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 44
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 22
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 19
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000011737 fluorine Substances 0.000 claims abstract description 11
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 8
- -1 nitro, amino, piperidino Chemical group 0.000 claims description 254
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 167
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 49
- 239000002904 solvent Substances 0.000 claims description 40
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 230000007062 hydrolysis Effects 0.000 claims description 20
- 238000006460 hydrolysis reaction Methods 0.000 claims description 20
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 101000588924 Anthopleura elegantissima Delta-actitoxin-Ael1a Proteins 0.000 claims description 15
- 238000009835 boiling Methods 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 12
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
- 239000011541 reaction mixture Substances 0.000 claims description 11
- 125000001118 alkylidene group Chemical group 0.000 claims description 10
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 238000005984 hydrogenation reaction Methods 0.000 claims description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 150000007530 organic bases Chemical group 0.000 claims description 8
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 7
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 7
- 150000007522 mineralic acids Chemical class 0.000 claims description 7
- 150000007524 organic acids Chemical class 0.000 claims description 7
- 235000005985 organic acids Nutrition 0.000 claims description 7
- 230000003213 activating effect Effects 0.000 claims description 6
- 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 239000012024 dehydrating agents Substances 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 6
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 claims description 6
- 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 claims description 5
- 238000006114 decarboxylation reaction Methods 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 239000012954 diazonium Substances 0.000 claims description 5
- 150000001989 diazonium salts Chemical class 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 5
- 235000010288 sodium nitrite Nutrition 0.000 claims description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 150000005840 aryl radicals Chemical group 0.000 claims description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 4
- 238000005695 dehalogenation reaction Methods 0.000 claims description 4
- 125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 4
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 238000006264 debenzylation reaction Methods 0.000 claims description 3
- 230000018044 dehydration Effects 0.000 claims description 3
- 238000006297 dehydration reaction Methods 0.000 claims description 3
- 238000007323 disproportionation reaction Methods 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 238000001149 thermolysis Methods 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 238000010533 azeotropic distillation Methods 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000002274 desiccant Substances 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 2
- 229910001923 silver oxide Inorganic materials 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- 150000001728 carbonyl compounds Chemical class 0.000 claims 1
- 229940117975 chromium trioxide Drugs 0.000 claims 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-N sodium;hydron;carbonate Chemical compound [Na+].OC(O)=O UIIMBOGNXHQVGW-UHFFFAOYSA-N 0.000 claims 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 abstract description 7
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 2
- 125000000547 substituted alkyl group Chemical group 0.000 abstract description 2
- 230000004531 blood pressure lowering effect Effects 0.000 abstract 1
- 238000007796 conventional method Methods 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 146
- 230000008018 melting Effects 0.000 description 146
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
- 239000005711 Benzoic acid Substances 0.000 description 80
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 79
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 60
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 235000010233 benzoic acid Nutrition 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 238000001704 evaporation Methods 0.000 description 26
- 230000008020 evaporation Effects 0.000 description 26
- 238000004440 column chromatography Methods 0.000 description 25
- 125000005907 alkyl ester group Chemical group 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000000284 extract Substances 0.000 description 11
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- KRIUSKSGYZBPBM-UHFFFAOYSA-N 4-[1-amino-1-oxo-3-(2-piperidin-1-ylphenyl)hexan-2-yl]benzoic acid Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(O)=O)C=C1 KRIUSKSGYZBPBM-UHFFFAOYSA-N 0.000 description 7
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- MEFOPTMOBQDUIL-UHFFFAOYSA-N 4-[2-[[(4-methylphenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]benzoic acid Chemical compound C1=CC(C)=CC=C1C(C=1C(=CC=CC=1)N1CCCCC1)NC(=O)CC1=CC=C(C(O)=O)C=C1 MEFOPTMOBQDUIL-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- 239000007868 Raney catalyst Substances 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- YEXGUCKJHHKPEH-UHFFFAOYSA-N ethyl 4-[1-amino-1-oxo-3-(2-piperidin-1-ylphenyl)hexan-2-yl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 YEXGUCKJHHKPEH-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229940093915 gynecological organic acid Drugs 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- ISDXXLAJBAYROO-UHFFFAOYSA-N 1-(2-piperidin-1-ylphenyl)butan-1-amine Chemical compound CCCC(N)C1=CC=CC=C1N1CCCCC1 ISDXXLAJBAYROO-UHFFFAOYSA-N 0.000 description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- KBEBGUQPQBELIU-CMDGGOBGSA-N Ethyl cinnamate Chemical compound CCOC(=O)\C=C\C1=CC=CC=C1 KBEBGUQPQBELIU-CMDGGOBGSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
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- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- KGKZAFYTMFFVHR-OOAXWGSJSA-N ethyl 4-[(e)-1-amino-1-oxo-5-phenyl-3-(2-piperidin-1-ylphenyl)pent-3-en-2-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C(C(N)=O)C(\C=1C(=CC=CC=1)N1CCCCC1)=C/CC1=CC=CC=C1 KGKZAFYTMFFVHR-OOAXWGSJSA-N 0.000 description 1
- PENUQXVIGZIGSF-UHFFFAOYSA-N ethyl 4-[1-amino-1-oxo-3-(2-piperidin-1-ylphenyl)hept-3-en-2-yl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(=CCCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 PENUQXVIGZIGSF-UHFFFAOYSA-N 0.000 description 1
- RSKBWJYKCORKFV-UHFFFAOYSA-N ethyl 4-[1-amino-1-oxo-3-(2-piperidin-1-ylphenyl)heptan-2-yl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 RSKBWJYKCORKFV-UHFFFAOYSA-N 0.000 description 1
- LNCGRTRTEGPAMM-UHFFFAOYSA-N ethyl 4-[1-amino-1-oxo-3-(2-piperidin-1-ylphenyl)hexan-2-yl]-3-chlorobenzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1Cl LNCGRTRTEGPAMM-UHFFFAOYSA-N 0.000 description 1
- BRPSNRLWPWHGHQ-UHFFFAOYSA-N ethyl 4-[1-amino-1-oxo-3-(2-pyrrolidin-1-ylphenyl)hexan-2-yl]benzoate Chemical compound C=1C=CC=C(N2CCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 BRPSNRLWPWHGHQ-UHFFFAOYSA-N 0.000 description 1
- IOSVKLMDNSGBLK-UHFFFAOYSA-N ethyl 4-[1-amino-3-(2-chloro-6-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound ClC=1C=CC=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 IOSVKLMDNSGBLK-UHFFFAOYSA-N 0.000 description 1
- ZGKMJGVBTHZCDA-UHFFFAOYSA-N ethyl 4-[1-amino-3-(3-chloro-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C=CC(Cl)=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 ZGKMJGVBTHZCDA-UHFFFAOYSA-N 0.000 description 1
- HJOXFVUJQABZSH-UHFFFAOYSA-N ethyl 4-[1-amino-3-(3-methyl-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C=CC(C)=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 HJOXFVUJQABZSH-UHFFFAOYSA-N 0.000 description 1
- AQGJJYQHXIFAPF-UHFFFAOYSA-N ethyl 4-[1-amino-3-(4-bromo-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C=C(Br)C=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 AQGJJYQHXIFAPF-UHFFFAOYSA-N 0.000 description 1
- JTBBZGJZPNOXKS-UHFFFAOYSA-N ethyl 4-[1-amino-3-(4-hydroxy-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C=C(O)C=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 JTBBZGJZPNOXKS-UHFFFAOYSA-N 0.000 description 1
- CFACTFSQUXYCIZ-UHFFFAOYSA-N ethyl 4-[1-amino-3-(4-methoxy-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C=C(OC)C=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 CFACTFSQUXYCIZ-UHFFFAOYSA-N 0.000 description 1
- JZZLBLYGGHPAJG-UHFFFAOYSA-N ethyl 4-[1-amino-3-(4-methyl-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C=C(C)C=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 JZZLBLYGGHPAJG-UHFFFAOYSA-N 0.000 description 1
- BWYFRJSMXIUDCH-UHFFFAOYSA-N ethyl 4-[1-amino-3-(5-amino-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C(N)=CC=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 BWYFRJSMXIUDCH-UHFFFAOYSA-N 0.000 description 1
- ULVWIGDSKOAIHX-UHFFFAOYSA-N ethyl 4-[1-amino-3-(5-fluoro-2-piperidin-1-ylphenyl)-1-oxohexan-2-yl]benzoate Chemical compound C=1C(F)=CC=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 ULVWIGDSKOAIHX-UHFFFAOYSA-N 0.000 description 1
- VKIRRQQMKQEGLP-UHFFFAOYSA-N ethyl 4-[1-amino-3-[2-(4-methylpiperidin-1-yl)phenyl]-1-oxohexan-2-yl]benzoate Chemical compound C=1C=CC=C(N2CCC(C)CC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OCC)C=C1 VKIRRQQMKQEGLP-UHFFFAOYSA-N 0.000 description 1
- SMMWDMPBRUPNMN-UHFFFAOYSA-N ethyl 4-[2-[1-(4-hydroxy-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound C=1C=C(O)C=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C=C1 SMMWDMPBRUPNMN-UHFFFAOYSA-N 0.000 description 1
- YKJOHDCWMYFCLV-UHFFFAOYSA-N ethyl 4-[2-[1-(4-nitro-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound C=1C=C([N+]([O-])=O)C=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C=C1 YKJOHDCWMYFCLV-UHFFFAOYSA-N 0.000 description 1
- VAPHUTCRGPSGBC-UHFFFAOYSA-N ethyl 4-[2-[1-(5-hydroxy-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound C=1C(O)=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C=C1 VAPHUTCRGPSGBC-UHFFFAOYSA-N 0.000 description 1
- AKMNJDULCXPGCS-UHFFFAOYSA-N ethyl 4-[2-[1-(5-methyl-2-piperidin-1-ylphenyl)butylamino]-2-oxoethyl]benzoate Chemical compound C=1C(C)=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C=C1 AKMNJDULCXPGCS-UHFFFAOYSA-N 0.000 description 1
- TVLQIBABVHZKKC-UHFFFAOYSA-N ethyl 4-[2-[[(2-chlorophenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1Cl TVLQIBABVHZKKC-UHFFFAOYSA-N 0.000 description 1
- GFHFYQCQLNHAFI-UHFFFAOYSA-N ethyl 4-[2-[[(2-chlorophenyl)-(5-nitro-2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=C(C=1)[N+]([O-])=O)N1CCCCC1)C1=CC=CC=C1Cl GFHFYQCQLNHAFI-UHFFFAOYSA-N 0.000 description 1
- AANHAECNMHHSDC-UHFFFAOYSA-N ethyl 4-[2-[[(2-methylphenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC=C1C AANHAECNMHHSDC-UHFFFAOYSA-N 0.000 description 1
- LEROWZUPEQBRDF-UHFFFAOYSA-N ethyl 4-[2-[[(3-methylphenyl)-(2-piperidin-1-ylphenyl)methyl]amino]-2-oxoethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C1=CC=CC(C)=C1 LEROWZUPEQBRDF-UHFFFAOYSA-N 0.000 description 1
- GFQTTXSBCQHVOW-UHFFFAOYSA-N ethyl 4-[2-[[2-amino-2-oxo-1-(2-piperidin-1-ylphenyl)ethyl]amino]-2-oxoethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C(N)=O)C1=CC=CC=C1N1CCCCC1 GFQTTXSBCQHVOW-UHFFFAOYSA-N 0.000 description 1
- PFXLUVNXXALLKV-UHFFFAOYSA-N ethyl 4-[2-[[[2-(3,3-dimethylpiperidin-1-yl)phenyl]-phenylmethyl]amino]-2-oxoethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CC(C)(C)CCC1)C1=CC=CC=C1 PFXLUVNXXALLKV-UHFFFAOYSA-N 0.000 description 1
- SXKXHUGYRNGIAM-UHFFFAOYSA-N ethyl 4-[2-[[[2-(dimethylamino)phenyl]-phenylmethyl]amino]-2-oxoethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N(C)C)C1=CC=CC=C1 SXKXHUGYRNGIAM-UHFFFAOYSA-N 0.000 description 1
- XGTLOPHTSMQKAW-UHFFFAOYSA-N ethyl 4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)butylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)NC(=O)CC1=CC=C(C(=O)OCC)C=C1 XGTLOPHTSMQKAW-UHFFFAOYSA-N 0.000 description 1
- ZBCOZNDSPRZJNZ-UHFFFAOYSA-N ethyl 4-[2-oxo-2-[1-(2-piperidin-1-ylphenyl)hexylamino]ethyl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCCCC)NC(=O)CC1=CC=C(C(=O)OCC)C=C1 ZBCOZNDSPRZJNZ-UHFFFAOYSA-N 0.000 description 1
- CVZIUQPUTOSDDU-UHFFFAOYSA-N ethyl 4-[2-oxo-2-[[(4-phenylmethoxyphenyl)-(2-piperidin-1-ylphenyl)methyl]amino]ethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)C(C=C1)=CC=C1OCC1=CC=CC=C1 CVZIUQPUTOSDDU-UHFFFAOYSA-N 0.000 description 1
- XUVFYUXHDIHTFS-UHFFFAOYSA-N ethyl 4-[2-oxo-2-[[2-phenyl-1-(2-piperidin-1-ylphenyl)ethyl]amino]ethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CC(=O)NC(C=1C(=CC=CC=1)N1CCCCC1)CC1=CC=CC=C1 XUVFYUXHDIHTFS-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
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- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
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- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
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- KTFPHBUUGPEKBP-UHFFFAOYSA-N methyl 4-[1-amino-1-oxo-3-(2-piperidin-1-ylphenyl)hexan-2-yl]benzoate Chemical compound C=1C=CC=C(N2CCCCC2)C=1C(CCC)C(C(N)=O)C1=CC=C(C(=O)OC)C=C1 KTFPHBUUGPEKBP-UHFFFAOYSA-N 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
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- 125000002524 organometallic group Chemical group 0.000 description 1
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- 229940031826 phenolate Drugs 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- SWWHCQCMVCPLEQ-UHFFFAOYSA-N propan-2-yl methanesulfonate Chemical compound CC(C)OS(C)(=O)=O SWWHCQCMVCPLEQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 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
- 229910001388 sodium aluminate Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 238000010972 statistical evaluation Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Fertilizers (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19823225188 DE3225188A1 (de) | 1982-07-06 | 1982-07-06 | Neue phenylessigsaeurederivate, ihre herstellung und diese verbindungen enthaltende arzneimittel |
| DE19823225155 DE3225155A1 (de) | 1982-07-06 | 1982-07-06 | Neue n-benzylamide und deren salze, ihre herstellung und diese verbindungen enthaltende arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD210907A5 true DD210907A5 (de) | 1984-06-27 |
Family
ID=25802849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD83252755A DD210907A5 (de) | 1982-07-06 | 1983-07-04 | Verfahren zur herstellung von phenylessigsaeure-derivaten |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0099017B1 (cs) |
| KR (1) | KR900004925B1 (cs) |
| AU (1) | AU561274B2 (cs) |
| CA (1) | CA1214773A (cs) |
| CS (1) | CS240970B2 (cs) |
| DD (1) | DD210907A5 (cs) |
| DE (1) | DE3375783D1 (cs) |
| DK (1) | DK159850C (cs) |
| ES (4) | ES8501382A1 (cs) |
| FI (1) | FI78477C (cs) |
| GB (1) | GB2124220B (cs) |
| GR (1) | GR78661B (cs) |
| HU (1) | HU195651B (cs) |
| IE (1) | IE56171B1 (cs) |
| IL (1) | IL69172A (cs) |
| NO (1) | NO159590C (cs) |
| NZ (1) | NZ204814A (cs) |
| PL (1) | PL143992B1 (cs) |
| PT (1) | PT76986B (cs) |
| SU (1) | SU1170969A3 (cs) |
| YU (1) | YU146883A (cs) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5312924A (en) * | 1983-12-30 | 1994-05-17 | Dr. Karl Thomae Gmbh | Phenylacetic acid benzylamides |
| DE3347565A1 (de) * | 1983-12-30 | 1985-07-11 | Thomae Gmbh Dr K | Neue phenylessigsaeurederivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| GB8903592D0 (en) * | 1989-02-16 | 1989-04-05 | Boots Co Plc | Therapeutic agents |
| FR2763590B1 (fr) * | 1997-05-22 | 2000-03-24 | Synthelabo | Derives d'acides[[[(arylmethyl)amino]carbonyl] alkyl]- aromatiques, leur preparation et leur application en therapeutique |
| PE20050630A1 (es) * | 2003-06-09 | 2005-09-22 | Boehringer Ingelheim Int | Compuestos heterociclicos como inhibidores del papiloma virus |
| EP2364977A1 (en) | 2010-01-26 | 2011-09-14 | Reuter Chemische Apparatebau KG | Process for the enantiomeric enrichment of 3-methyl-1-(2-piperidinophenyl)-1-butylamine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE764238A (fr) * | 1971-03-17 | 1971-09-13 | Lilly Industries Ltd | Derives de phenylalkylamine |
| NL7305171A (cs) * | 1973-04-13 | 1974-10-15 | ||
| DE3100575A1 (de) * | 1981-01-10 | 1982-09-02 | Dr. Karl Thomae Gmbh, 7950 Biberach | "neue benzoesaeuren, ihre herstellung und ihre verwendung als arzneimittel" |
-
1983
- 1983-06-27 EP EP83106233A patent/EP0099017B1/de not_active Expired
- 1983-06-27 SU SU833608901A patent/SU1170969A3/ru active
- 1983-06-27 DE DE8383106233T patent/DE3375783D1/de not_active Expired
- 1983-06-29 FI FI832374A patent/FI78477C/fi not_active IP Right Cessation
- 1983-07-04 GR GR71859A patent/GR78661B/el unknown
- 1983-07-04 NO NO832430A patent/NO159590C/no unknown
- 1983-07-04 DD DD83252755A patent/DD210907A5/de unknown
- 1983-07-04 KR KR1019830003043A patent/KR900004925B1/ko not_active Expired
- 1983-07-05 PT PT76986A patent/PT76986B/pt not_active IP Right Cessation
- 1983-07-05 PL PL1983242873A patent/PL143992B1/pl unknown
- 1983-07-05 YU YU01468/83A patent/YU146883A/xx unknown
- 1983-07-05 CS CS835089A patent/CS240970B2/cs unknown
- 1983-07-05 HU HU832420A patent/HU195651B/hu unknown
- 1983-07-05 ES ES523869A patent/ES8501382A1/es not_active Expired
- 1983-07-05 DK DK310883A patent/DK159850C/da not_active IP Right Cessation
- 1983-07-05 CA CA000431796A patent/CA1214773A/en not_active Expired
- 1983-07-05 AU AU16576/83A patent/AU561274B2/en not_active Ceased
- 1983-07-05 IE IE1573/83A patent/IE56171B1/en not_active IP Right Cessation
- 1983-07-05 NZ NZ204814A patent/NZ204814A/en unknown
- 1983-07-06 GB GB08318250A patent/GB2124220B/en not_active Expired
- 1983-07-06 IL IL69172A patent/IL69172A/xx unknown
-
1984
- 1984-02-17 ES ES529808A patent/ES529808A0/es active Granted
- 1984-02-17 ES ES529807A patent/ES8500924A1/es not_active Expired
- 1984-02-17 ES ES529806A patent/ES8500923A1/es not_active Expired
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