AT262274B - Verfahren zur Herstellung neuer Indolderivate - Google Patents
Verfahren zur Herstellung neuer IndolderivateInfo
- Publication number
- AT262274B AT262274B AT693363A AT693363A AT262274B AT 262274 B AT262274 B AT 262274B AT 693363 A AT693363 A AT 693363A AT 693363 A AT693363 A AT 693363A AT 262274 B AT262274 B AT 262274B
- Authority
- AT
- Austria
- Prior art keywords
- sep
- radical
- alkyl
- methyl
- substituted
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 33
- 150000002475 indoles Chemical class 0.000 title claims description 9
- 229940054051 antipsychotic indole derivative Drugs 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- -1 amine salt Chemical class 0.000 claims description 65
- 238000002360 preparation method Methods 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 150000003254 radicals Chemical class 0.000 claims description 16
- 150000002825 nitriles Chemical class 0.000 claims description 15
- 150000008064 anhydrides Chemical class 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000005907 alkyl ester group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 5
- 150000003335 secondary amines Chemical class 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 3
- 239000012433 hydrogen halide Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 150000001768 cations Chemical class 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- QOPBEBWGSGFROG-UHFFFAOYSA-N 2-(1h-indol-2-yl)acetic acid Chemical compound C1=CC=C2NC(CC(=O)O)=CC2=C1 QOPBEBWGSGFROG-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 89
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000002253 acid Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 17
- 125000001424 substituent group Chemical group 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 125000001041 indolyl group Chemical group 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 12
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 150000004075 acetic anhydrides Chemical class 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- PAHPPIKBPFJMQU-UHFFFAOYSA-N 1-[1-[(4-chlorophenyl)methyl]-5-methoxy-2-methylindol-3-yl]-2,2,2-trifluoroethanone Chemical compound CC1=C(C(=O)C(F)(F)F)C2=CC(OC)=CC=C2N1CC1=CC=C(Cl)C=C1 PAHPPIKBPFJMQU-UHFFFAOYSA-N 0.000 description 4
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- YEEXWGCVZCGHDQ-UHFFFAOYSA-N FC(F)(F)C(C(=O)O)C1=C(N(C2=CC=C(C=C12)OC)CC1=CC=C(C=C1)Cl)C Chemical compound FC(F)(F)C(C(=O)O)C1=C(N(C2=CC=C(C=C12)OC)CC1=CC=C(C=C1)Cl)C YEEXWGCVZCGHDQ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 3
- XEMWKJGWVPQCTI-UHFFFAOYSA-N 2,2,2-trifluoro-1-(5-methoxy-2-methyl-1h-indol-3-yl)ethanone Chemical compound COC1=CC=C2NC(C)=C(C(=O)C(F)(F)F)C2=C1 XEMWKJGWVPQCTI-UHFFFAOYSA-N 0.000 description 3
- VSWGLJOQFUMFOQ-UHFFFAOYSA-N 5-methoxy-2-methyl-1h-indole Chemical compound COC1=CC=C2NC(C)=CC2=C1 VSWGLJOQFUMFOQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000003973 alkyl amines Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 150000004982 aromatic amines Chemical class 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 3
- 150000001805 chlorine compounds Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- OTGHWLKHGCENJV-UHFFFAOYSA-N glycidic acid Chemical compound OC(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000002780 morpholines Chemical class 0.000 description 3
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HDOQKRSTAOHSFU-UHFFFAOYSA-N CC1=C(C(C(F)(F)F)C(OC(C(C(F)(F)F)C(C2=C3)=C(C)N(CC(C=C4)=CC=C4Cl)C2=CC=C3OC)=O)=O)C2=CC(OC)=CC=C2N1CC(C=C1)=CC=C1Cl Chemical compound CC1=C(C(C(F)(F)F)C(OC(C(C(F)(F)F)C(C2=C3)=C(C)N(CC(C=C4)=CC=C4Cl)C2=CC=C3OC)=O)=O)C2=CC(OC)=CC=C2N1CC(C=C1)=CC=C1Cl HDOQKRSTAOHSFU-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- GAOFQNVCACBCRO-UHFFFAOYSA-N N-[2-[1-[(4-chlorophenyl)methyl]-5-methoxy-2-methylindol-3-yl]-3,3,3-trifluoropropylidene]hydroxylamine Chemical compound FC(C(C=NO)C1=C(N(C2=CC=C(C=C12)OC)CC1=CC=C(C=C1)Cl)C)(F)F GAOFQNVCACBCRO-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000001931 aliphatic group Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000012435 aralkylating agent Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- KFYKZKISJBGVMR-ZCFIWIBFSA-N (2r)-n-ethylbutan-2-amine Chemical compound CCN[C@H](C)CC KFYKZKISJBGVMR-ZCFIWIBFSA-N 0.000 description 1
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 1
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/22—Radicals 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 an aralkyl radical attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/26—Radicals 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 an acyl radical attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
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- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US222179A US3259622A (en) | 1962-09-07 | 1962-09-07 | 1-benzyl-3-indolyl-alpha-haloalkyl and alkylidenyl acetic acids |
US45201865A | 1965-04-29 | 1965-04-29 | |
US452015A US3399198A (en) | 1962-09-07 | 1965-04-29 | 1-pyrimidinoyl-and 1-imidazoloyl-3-haloacetyl indoles |
US452022A US3326930A (en) | 1962-09-07 | 1965-04-29 | alpha-halomethyl-(1-oxazole-carbonylindol-3-yl) acetic acids and certain intermediates therefor |
US452010A US3388127A (en) | 1962-09-07 | 1965-04-29 | Alpha-halomethyl-1-pyrazine carbonyl-3-indolylacetic acids |
Publications (1)
Publication Number | Publication Date |
---|---|
AT262274B true AT262274B (de) | 1968-06-10 |
Family
ID=27539838
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT693363A AT262274B (de) | 1962-09-07 | 1963-08-28 | Verfahren zur Herstellung neuer Indolderivate |
AT481266A AT263765B (de) | 1962-09-07 | 1963-08-28 | Verfahren zur Herstellung neuer Indolderivate |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT481266A AT263765B (de) | 1962-09-07 | 1963-08-28 | Verfahren zur Herstellung neuer Indolderivate |
Country Status (10)
Country | Link |
---|---|
US (5) | US3259622A (en:Method) |
AT (2) | AT262274B (en:Method) |
BE (2) | BE637037A (en:Method) |
CH (1) | CH450416A (en:Method) |
DE (1) | DE1470045A1 (en:Method) |
DK (1) | DK120898B (en:Method) |
FR (3) | FR1535407A (en:Method) |
GB (6) | GB1048347A (en:Method) |
NL (2) | NL297644A (en:Method) |
SE (1) | SE309040B (en:Method) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3929820A (en) * | 1967-09-26 | 1975-12-30 | Bayer Ag | Process for the production of N-tritylimidazoles |
JPS5683472A (en) * | 1979-12-12 | 1981-07-08 | Teijin Ltd | Preparation of 3-acyl-1-substituted indole derivative |
US4499279A (en) * | 1980-04-10 | 1985-02-12 | Sandoz, Inc. | Isoxazolyl indolamines |
JPS57159738A (en) * | 1981-03-30 | 1982-10-01 | Sagami Chem Res Center | 2-halomethylene-arylacetice acid derivative |
US5238938A (en) * | 1989-02-10 | 1993-08-24 | Otsuka Pharmaceutical Co., Ltd. | Indole derivatives |
DE69029231T2 (de) * | 1989-02-10 | 1997-03-20 | Otsuka Pharma Co Ltd | Indolderivate, ihre herstellung und diese enthaltendes arzneimittel zum verhindern und behandeln von nephritis |
US5166170A (en) * | 1989-07-03 | 1992-11-24 | Hoechst-Roussel Pharmaceuticals Incorporated | 2-(aminoaryl) indoles and indolines as topical antiinflammatory agents for the treatment of skin disorders |
US5283251A (en) * | 1990-02-26 | 1994-02-01 | Fujisawa Pharmaceutical Co., Ltd. | Indole derivatives |
GB9004301D0 (en) * | 1990-02-26 | 1990-04-18 | Fujisawa Pharmaceutical Co | Indolebutyric acid derivatives and process for preparation thereof |
FR2658818B1 (fr) * | 1990-02-27 | 1993-12-31 | Adir Cie | Nouveaux derives a structure naphtalenique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
US5064851A (en) * | 1990-07-24 | 1991-11-12 | Pfizer Inc. | 3-(1-substituted-pyrazoyl)-2-oxindole derivatives, compositions and use |
CA2067663A1 (en) * | 1991-05-01 | 1992-11-02 | Hitoshi Tone | Pyrazine derivatives |
IL109311A0 (en) * | 1993-04-16 | 1994-07-31 | Lilly Co Eli | 1H-indole-3-acetamide sPla2 inhibitors |
JP3109974B2 (ja) | 1994-04-01 | 2000-11-20 | イーライ・リリー・アンド・カンパニー | 1H−インドール−3−グリオキシルアミドsPLA2阻害剤 |
US5641800A (en) * | 1994-07-21 | 1997-06-24 | Eli Lilly And Company | 1H-indole-1-functional sPLA2 inhibitors |
US6214876B1 (en) | 1994-07-21 | 2001-04-10 | Eli Lilly And Company | Indene-1-acetamide sPLA2 inhibitors |
US5604253A (en) * | 1995-05-22 | 1997-02-18 | Merck Frosst Canada, Inc. | N-benzylindol-3-yl propanoic acid derivatives as cyclooxygenase inhibitors |
CN1234705C (zh) * | 1998-04-28 | 2006-01-04 | 埃尔比昂股份公司 | 新的羟基吲哚、其作为磷酸二酯酶4抑制剂的应用及其制备方法 |
EP0980863B1 (en) * | 1998-08-17 | 2005-02-02 | Givaudan SA | Oxime carboxylic acid derivatives |
ATE288418T1 (de) | 1998-08-17 | 2005-02-15 | Givaudan Sa | Oximcarbonsäure derivate |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB869775A (en) * | 1958-09-24 | 1961-06-07 | Upjohn Co | 3-indolyl ketones |
US2978459A (en) * | 1959-08-05 | 1961-04-04 | Upjohn Co | Ketals of (3-indolyl)-aminoalkanones |
US3201414A (en) * | 1963-07-22 | 1965-08-17 | Merck & Co Inc | New 1-heteroacyl-3-indolyl aliphatic acids |
AT290523B (de) * | 1962-01-05 | 1971-06-11 | Merck & Co Inc | Verfahren zur Herstellung neuer α-(3-Indolyl)-carbonsäuren |
US3242192A (en) * | 1962-09-07 | 1966-03-22 | Merck & Co Inc | Alpha-haloalkyl (3-indolyl) acetic acid derivatives |
-
1962
- 1962-09-07 US US222179A patent/US3259622A/en not_active Expired - Lifetime
-
1963
- 1963-08-26 GB GB5705/66A patent/GB1048347A/en not_active Expired
- 1963-08-26 GB GB5704/66A patent/GB1049840A/en not_active Expired
- 1963-08-26 GB GB33705/63A patent/GB1048346A/en not_active Expired
- 1963-08-26 GB GB33704/63A patent/GB1063383A/en not_active Expired
- 1963-08-26 GB GB43065/65A patent/GB1063384A/en not_active Expired
- 1963-08-26 DE DE19631470045 patent/DE1470045A1/de active Pending
- 1963-08-26 GB GB43066/65A patent/GB1063385A/en not_active Expired
- 1963-08-28 AT AT693363A patent/AT262274B/de active
- 1963-08-28 AT AT481266A patent/AT263765B/de active
- 1963-08-30 CH CH1075363A patent/CH450416A/de unknown
- 1963-09-05 BE BE637037D patent/BE637037A/xx unknown
- 1963-09-05 BE BE637036D patent/BE637036A/xx unknown
- 1963-09-06 FR FR946855A patent/FR1535407A/fr not_active Expired
- 1963-09-07 DK DK423863AA patent/DK120898B/da unknown
- 1963-09-09 NL NL297644D patent/NL297644A/xx unknown
- 1963-09-09 NL NL297645D patent/NL297645A/xx unknown
- 1963-12-05 FR FR956207A patent/FR3556M/fr not_active Expired
- 1963-12-05 FR FR956206A patent/FR3555M/fr not_active Expired
-
1965
- 1965-04-29 US US452022A patent/US3326930A/en not_active Expired - Lifetime
- 1965-04-29 US US452015A patent/US3399198A/en not_active Expired - Lifetime
- 1965-04-29 US US452010A patent/US3388127A/en not_active Expired - Lifetime
- 1965-04-29 US US452018A patent/US3426038A/en not_active Expired - Lifetime
- 1965-07-15 SE SE9365/65A patent/SE309040B/xx unknown
Also Published As
Publication number | Publication date |
---|---|
FR3556M (en:Method) | 1965-10-22 |
NL297644A (en:Method) | 1965-11-10 |
SE309040B (en:Method) | 1969-03-10 |
GB1048347A (en) | 1966-11-16 |
GB1049840A (en) | 1966-11-30 |
BE637037A (en:Method) | 1964-03-05 |
GB1048346A (en) | 1966-11-16 |
GB1063384A (en) | 1967-03-30 |
FR3555M (en:Method) | 1965-10-22 |
FR1535407A (fr) | 1968-08-09 |
GB1063383A (en) | 1967-03-30 |
US3388127A (en) | 1968-06-11 |
US3326930A (en) | 1967-06-20 |
CH450416A (de) | 1968-01-31 |
US3259622A (en) | 1966-07-05 |
NL297645A (en:Method) | 1965-11-10 |
AT263765B (de) | 1968-08-12 |
DE1470045A1 (de) | 1969-05-29 |
GB1063385A (en) | 1967-03-30 |
US3399198A (en) | 1968-08-27 |
DK120898B (da) | 1971-08-02 |
BE637036A (en:Method) | 1964-03-05 |
US3426038A (en) | 1969-02-04 |
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