CS219280B2 - Method of making the pyrazol derivatives - Google Patents
Method of making the pyrazol derivatives Download PDFInfo
- Publication number
- CS219280B2 CS219280B2 CS803546A CS354680A CS219280B2 CS 219280 B2 CS219280 B2 CS 219280B2 CS 803546 A CS803546 A CS 803546A CS 354680 A CS354680 A CS 354680A CS 219280 B2 CS219280 B2 CS 219280B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- group
- general formula
- pyrazole
- fluorophenyl
- chlorophenyl
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 150000007513 acids Chemical class 0.000 claims abstract description 5
- 150000003217 pyrazoles Chemical class 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 5
- 150000001412 amines Chemical class 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract 2
- 125000001424 substituent group Chemical group 0.000 abstract 2
- 239000005864 Sulphur Substances 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 125000003277 amino group Chemical group 0.000 abstract 1
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical group CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 abstract 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 11
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- -1 dlethylamine Chemical compound 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- GTWSEYQKBWXICU-UHFFFAOYSA-N 2-(4-chlorophenyl)-n,n-dimethylethenamine Chemical compound CN(C)C=CC1=CC=C(Cl)C=C1 GTWSEYQKBWXICU-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- RMCCCVIYWRJQEW-UHFFFAOYSA-N 4-[2-(4-bromophenyl)ethenyl]morpholine Chemical compound C1=CC(Br)=CC=C1C=CN1CCOCC1 RMCCCVIYWRJQEW-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-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
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- SDHFIWNBYPDKTQ-UHFFFAOYSA-N 1-[1,4-bis(4-chlorophenyl)pyrazol-3-yl]ethanone Chemical compound CC(=O)C1=NN(C=2C=CC(Cl)=CC=2)C=C1C1=CC=C(Cl)C=C1 SDHFIWNBYPDKTQ-UHFFFAOYSA-N 0.000 description 1
- VMLSODMFKSZXDR-UHFFFAOYSA-N 1-[4-(4-bromophenyl)-2-(4-fluorophenyl)-3-morpholin-4-yl-3,4-dihydropyrazol-5-yl]ethanone Chemical compound CC(=O)C1=NN(C=2C=CC(F)=CC=2)C(N2CCOCC2)C1C1=CC=C(Br)C=C1 VMLSODMFKSZXDR-UHFFFAOYSA-N 0.000 description 1
- BMMBSROJAOISIS-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]ethanone Chemical compound CC(=O)C1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 BMMBSROJAOISIS-UHFFFAOYSA-N 0.000 description 1
- ZVPZZMHGAOROCC-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-1-(4-methylsulfanylphenyl)pyrazol-3-yl]ethanone Chemical compound C1=CC(SC)=CC=C1N1N=C(C(C)=O)C(C=2C=CC(Cl)=CC=2)=C1 ZVPZZMHGAOROCC-UHFFFAOYSA-N 0.000 description 1
- IRGRRSWKJQLVRB-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)-1-phenylpyrazol-3-yl]ethanone Chemical compound CC(=O)C1=NN(C=2C=CC=CC=2)C=C1C1=CC=C(Cl)C=C1 IRGRRSWKJQLVRB-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- MFHFWRBXPQDZSA-UHFFFAOYSA-N 2-(4-bromophenyl)acetonitrile Chemical compound BrC1=CC=C(CC#N)C=C1 MFHFWRBXPQDZSA-UHFFFAOYSA-N 0.000 description 1
- MWSNYBOKRSGWAN-UHFFFAOYSA-N 2-(4-chlorophenyl)acetaldehyde Chemical compound ClC1=CC=C(CC=O)C=C1 MWSNYBOKRSGWAN-UHFFFAOYSA-N 0.000 description 1
- QDNFDLUXFADBPV-UHFFFAOYSA-N 2-[1,4-bis(4-chlorophenyl)pyrazol-3-yl]-1-morpholin-4-ylethanethione Chemical compound C1=CC(Cl)=CC=C1C1=CN(C=2C=CC(Cl)=CC=2)N=C1CC(=S)N1CCOCC1 QDNFDLUXFADBPV-UHFFFAOYSA-N 0.000 description 1
- CUNUHKDDCQBLDQ-UHFFFAOYSA-N 2-[4-(4-bromophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]-1-morpholin-4-ylethanethione Chemical compound C1=CC(F)=CC=C1N1N=C(CC(=S)N2CCOCC2)C(C=2C=CC(Br)=CC=2)=C1 CUNUHKDDCQBLDQ-UHFFFAOYSA-N 0.000 description 1
- IPNXVPVVRDCNAB-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-1-phenylpyrazol-3-yl]-1-morpholin-4-ylethanethione Chemical compound C1=CC(Cl)=CC=C1C1=CN(C=2C=CC=CC=2)N=C1CC(=S)N1CCOCC1 IPNXVPVVRDCNAB-UHFFFAOYSA-N 0.000 description 1
- WMJZPMJTHUVWSW-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-1-phenylpyrazol-3-yl]acetic acid Chemical compound OC(=O)CC1=NN(C=2C=CC=CC=2)C=C1C1=CC=C(Cl)C=C1 WMJZPMJTHUVWSW-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 1
- YKFROQCFVXOUPW-UHFFFAOYSA-N 4-(methylthio) aniline Chemical compound CSC1=CC=C(N)C=C1 YKFROQCFVXOUPW-UHFFFAOYSA-N 0.000 description 1
- AOAJHBQTGNMXKH-UHFFFAOYSA-N 4-[2-(4-chlorophenyl)ethenyl]morpholine Chemical compound C1=CC(Cl)=CC=C1C=CN1CCOCC1 AOAJHBQTGNMXKH-UHFFFAOYSA-N 0.000 description 1
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 1
- IVYMIRMKXZAHRV-UHFFFAOYSA-N 4-chlorophenylacetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1 IVYMIRMKXZAHRV-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VIJMMQUAJQEELS-UHFFFAOYSA-N n,n-bis(ethenyl)ethenamine Chemical compound C=CN(C=C)C=C VIJMMQUAJQEELS-UHFFFAOYSA-N 0.000 description 1
- RJHCGGWBOWGPJS-UHFFFAOYSA-N n-(4-chlorophenyl)-2-oxopropanehydrazonoyl chloride Chemical compound CC(=O)C(Cl)=NNC1=CC=C(Cl)C=C1 RJHCGGWBOWGPJS-UHFFFAOYSA-N 0.000 description 1
- GLYDHOZNBVJYBG-UHFFFAOYSA-N n-(4-fluorophenyl)-2-oxopropanehydrazonoyl chloride Chemical compound CC(=O)C(Cl)=NNC1=CC=C(F)C=C1 GLYDHOZNBVJYBG-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000012485 toluene extract Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Vynález se týká způsobu výroby pyrazolových derivátů obecného vzorce IThe invention relates to a process for the preparation of pyrazole derivatives of the general formula I
<l) ve kterém jsou substituenty Ri, Rz, R3 a Ri v poloze ortho-, para- nebo meta- a značí vodíkový atom, atom halogenu, nitroskupinu nebo methylthioskupinu, s tou podmínkou, že alespoň jeden ze substituentů Ri až R4 je různý od vodíku, a jejich solí s fyziologicky neškodnými zásadami.<1) wherein R 1, R 2, R 3 and R 1 are ortho-, para- or meta- and denote a hydrogen atom, a halogen atom, a nitro group or a methylthio group, with the proviso that at least one of R 1 to R 4 is different from hydrogen, and their salts with physiologically harmless bases.
Pyrazolové deriváty obecného vzorce I jsou známé z DOS č. 26 33 992. Jejich příprava podle známého způsobu je však velmi nákladná a dosahované výtěžky jsou často neuspokojivé.The pyrazole derivatives of the formula I are known from DOS 26 33 992. However, their preparation according to the known process is very expensive and the yields obtained are often unsatisfactory.
Úkolem ' vynálezu tedy je nalézt nový způsob výroby pyrazolových derivátů obecného vzorce I, který by byl jednoduchý a při kterém by se dosahovalo uspokojivých výsledků.SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a novel process for the preparation of the pyrazole derivatives of the general formula I which is simple and satisfactory.
Tento úkol byl podle vynálezu vyřešen nalezením nového· způsobu, jehož podstata spočívá v tom, že se nechá reagovat sloučenina obecného· vzorce IIAccording to the invention, this object has been solved by finding a novel process which comprises reacting a compound of the formula II
ve kterém má Ri, Rz, R3 a R4 výše uvedený význam, se sírou a morfolinem a získané sloučeniny obecného vzorce IVwherein R 1, R 2, R 3 and R 4 are as defined above, with sulfur and morpholine and the obtained compounds of formula IV
S IIS II
ve kterých mají Ri, R2 R3 a R4 výše uvedený význam, se potom hydrolyzují pomocí kyselin nebo zásad a získané kyseliny se převedou na své soli.wherein R 1, R 2, R 3 and R 4 are as defined above are then hydrolyzed with acids or bases and the resulting acids are converted into their salts.
Způsob podle vynálezu se provádí za obecně známých podmínek (Org. Reactions, 3, 1946, 83—107; Angew. Chem., 70, 1958, 331— —367 a Synthesis, 1975, 338—373].The method of the invention is carried out under generally known conditions (Org. Reactions, 3, 1946, 83-107; Angew. Chem., 70, 1958, 331-367 and Synthesis, 1975, 338-373).
Způsob podle vynálezu se provádí za přítomnosti primárních nebo sekundárních aminů. Vhodné aminy j'sou například methylamin, ethylamin, dimethylamín, dlethylamin, dibutylamin, anilin, alfa-, beta- nebo gama-pikolin, piperidin nebo obzvláště morfolin a pyrrolidin.The process according to the invention is carried out in the presence of primary or secondary amines. Suitable amines are, for example, methylamine, ethylamine, dimethylamine, dlethylamine, dibutylamine, aniline, alpha-, beta- or gamma-picoline, piperidine or especially morpholine and pyrrolidine.
Následující příklady provedení slouží k bližšímu objasnění způsobu podle vynálezu.The following examples serve to illustrate the process of the invention in more detail.
Příklad 1Example 1
a] 28,9 g 4-fluoranilinu se smísí se 260 ml 13% kyseliny chlorovodíkové a 260 g ledu, směs se ochladí na teplotu —δ °C a diazotuje se 19,7 g dusitanu sodného v 30 ml vody. Za stálého míchání a chlazení se k tomuto reakčnímu roztoku přikapává roztok 38,4 g 3-chlor-2,4-pentadionu, 260 ml ethylalkoholu a 330 g hydrátu octanu sodného. Reakční směs se potom míchá ještě po dobu 3 hodiny při teplotě 0 °C, potom se zředí vodou, přičemž substance vykrystalizuje. Krystalický zbytek se překrystalizuje z ethylalkoholu a získá se 30 g l-chlor-l.-[ 4-fluorfenylhydrazono' j -2-propanonu.a] 28.9 g of 4-fluoroaniline are mixed with 260 ml of 13% hydrochloric acid and 260 g of ice, cooled to -8 DEG C. and diazotized with 19.7 g of sodium nitrite in 30 ml of water. While stirring and cooling, a solution of 38.4 g of 3-chloro-2,4-pentadione, 260 ml of ethanol and 330 g of sodium acetate hydrate is added dropwise to this reaction solution. The reaction mixture is stirred for a further 3 hours at 0 [deg.] C., then diluted with water and the substance crystallizes. The crystalline residue was recrystallized from ethanol to give 30 g of 1-chloro-1- [4-fluorophenylhydrazono] -2-propanone.
Teplota tání: 148 °C-,Melting point: 148 ° C,
b] Roztok 19,6 g 4-brombenzyIkyanidu ve 100 ml toluenu se při teplotě —10 °C a pod ochrannou atmosférou dusíku po kapkách smísí se 108 ml 20% roztoku diisobutylaluminiumbydridu v toulenu a potom se reakční směs míchá ještě po dobu 16 minut. Po opatrném přídavku 33 ml ethylalkoholu se tato směs smísí s 230 ml vody a asi 20 ml koncentrované kyseliny sírové (do pH 2) a reakční směs se míchá po dobu 13 minut při teplotě 0 °C.b] A solution of 19.6 g of 4-bromobenzyl cyanide in 100 ml of toluene was treated dropwise with 10 ml of a 20% solution of diisobutylaluminum hydride in toluene at -10 DEG C. under nitrogen and then stirred for 16 minutes. After careful addition of 33 ml of ethanol, this mixture was mixed with 230 ml of water and about 20 ml of concentrated sulfuric acid (until pH 2) and the reaction mixture was stirred for 13 minutes at 0 ° C.
Potom se toluenová fáze oddělí, vodná fáze se ještě jednou extrahuje toluenem, spojené toluenové extrakty se promyjí vodou a vysuší se síranem hořečnatým. Po filtraci se toluenový roztok 4-chlorfenylacetaldehydu smísí s 87 g morfolinu a pomalu se ve vakuu zkoncentruje na polovinu a reakční směs se nechá stát přes noc. Po zahuštění roztoku na polovinu se zbytek rozmíchá s cyklohexanem, přičemž nastane krystalizace. Krystalizát se potom překrystaluje z diisopropyletheru a získá se 12 g 4-(4-bromstyrylj-morfolinu s teplotou tání 142 °C.The toluene phase is separated, the aqueous phase is extracted once more with toluene, the combined toluene extracts are washed with water and dried over magnesium sulphate. After filtration, the toluene solution of 4-chlorophenylacetaldehyde was treated with 87 g of morpholine and slowly concentrated in half in vacuo and the reaction mixture was allowed to stand overnight. After concentrating the solution in half, the residue is stirred with cyclohexane to crystallize. The crystallizate is then recrystallized from diisopropyl ether to give 12 g of 4- (4-bromostyryl) -morpholine, m.p. 142 ° C.
c] Roztok 7,2 g 4-(4-bromstyryl)-morfolinu ve 30 ml chloroformu se smísí postupně s 2,7 g triethylenaminu a s roztokem 3,3 g 1-chlor-l- (4-fluorfenylhydrazono )-2-propa5c] A solution of 7.2 g of 4- (4-bromostyryl) morpholine in 30 ml of chloroform is treated successively with 2.7 g of triethyleneamine and a solution of 3.3 g of 1-chloro-1- (4-fluorophenylhydrazono) -2-propa5.
219 2Š O nonu ve 30 ml chloroformu. Tato reakční směs -se míchá pres noc při teplotě místnosti (alternativně se může vařit po dobu 4 hodin pod zpětným chladičem]. Po promytí 2N kyselinou chlorovodíkovou, roztokem kyselého uhličitanu sodného a vodou se chloroformová fáze vysuší síranem hořečnatým a zahustí. Z hexanu (cyklohexanu) krystalizující zbytek (10,5 g] se může dále zpracovávat, nebo se může překrystalizovát z ethylalkoholu. Získá se 3-acetyl-4-(4-bromfenyl ] -1- (4-f luorfenyl) -5-morf olino-4,5-dihydropyrazol s teplotou tání 148 °C.219 NONO in 30 ml chloroform. The reaction mixture is stirred overnight at room temperature (alternatively, it can be refluxed for 4 hours.) After washing with 2N hydrochloric acid, sodium bicarbonate solution and water, the chloroform phase is dried over magnesium sulfate and concentrated from hexane (cyclohexane). ) the crystallizing residue (10.5 g] can be further processed or recrystallized from ethanol to give 3-acetyl-4- (4-bromophenyl) -1- (4-fluorophenyl) -5-morpholino-4 5-dihydropyrazole, m.p. 148 ° C.
d) Roztok 10 g 3-acetyl-4-(4-bromfenylj-1- (4-fluorfenyl) -5-morf olino-4,5-dihydropyrazolu ve 110 ml dioxanu se vaří pod zpětným chladičem se 30 ml 2 N kyseliny chlorovodíkové po dobu 60 až 90 minut. Potom se reakční směs zahustí ve vakuu, zbytek se vyjme do ethylacetátu, promyje se vodou, vysuší se síranem hořečnatým a ve vakuu se zahustí. Tento- zbytek se krystalizuje z methylalkoholu a získá se 7,5 g 3-acetyl-4- (4-br omfenyl ] -1- {4-fluorfenyl ] -pyrazolu.(d) A solution of 10 g of 3-acetyl-4- (4-bromophenyl) -1- (4-fluorophenyl) -5-morpholino-4,5-dihydropyrazole in 110 ml of dioxane is refluxed with 30 ml of 2 N hydrochloric acid. The reaction mixture is concentrated in vacuo, the residue is taken up in ethyl acetate, washed with water, dried over magnesium sulphate and concentrated in vacuo, and the residue is crystallized from methanol and 7.5 g of 3 are obtained. -acetyl-4- (4-bromophenyl) -1- (4-fluorophenyl) -pyrazole.
Teplota tání: 185 °C.Melting point: 185 ° C.
e) Směs 7,2 g S-jacetyl-^^-řď-^i^jroi^í^f^i^^l ]-l^-(4-fluorfenyl]-pyrazolu a 0,84 g síry v 9 ml morfolinu se zahřívá po dobu 3 až 4 hodin na teplotu 135 °C, potom se vlije do 150 ml ledové vody a dobře se tato· směs promíchá. Vzniklá sraženina se odsaje, krystalizuje se ze směsí -ethylacetátu a dioxanu a získá se 7,8 g 4-[4-(4-bromfenyl)-l-(4-fluorfenyl)-3-pyrazolyl-thioacetyl ] -morfolinu.e) A mixture of 7.2 g of S-acetyl-4- (4-fluorophenyl) -1- (4-fluorophenyl) pyrazole and 0.84 g of sulfur in 9 ml. The morpholine is heated for 3 to 4 hours at 135 ° C, then poured into 150 ml of ice-water and mixed well, the precipitate formed is filtered off with suction, crystallized from a mixture of ethyl acetate and dioxane and 7.8 is obtained. g of 4- [4- (4-bromophenyl) -1- (4-fluorophenyl) -3-pyrazolyl-thioacetyl] morpholine.
Teplota tání: 211 °C.Melting point: 211 ° C.
f) - Směs 7,4 g 4-[4- orfenyl ] -3-pyrazolyl-thioacetyl ] -morfolinu ve 20 ml dimethylsulfoxidu se smísí se 6,4 g hydroxidu sodného ve 30 ml vody a reakční směs se vaří pod zpětným chladičem po dobu 5 hodin. Po nalití do ledové vody vykrystalizuje sodná sůl; tato sůl se odsaje, promyje methylenchloridem a suspenduje se ve 2 N kyselině chlorovodíkové. Získá se 5 g 4-(4-bromfenyl)-l-(4-fluorfenyl )-3-pyrazoloctová kyselina.f) - A mixture of 7.4 g of 4- [4-orphenyl] -3-pyrazolyl-thioacetyl] morpholine in 20 ml of dimethylsulfoxide is mixed with 6.4 g of sodium hydroxide in 30 ml of water and the reaction mixture is refluxed for for 5 hours. After pouring into ice water, the sodium salt crystallizes; the salt is filtered off with suction, washed with methylene chloride and suspended in 2 N hydrochloric acid. 5 g of 4- (4-bromophenyl) -1- (4-fluorophenyl) -3-pyrazoloacetic acid are obtained.
Teplota tání: 175- °C.Melting point: 175 ° C.
Příklad 2Example 2
Analogicky j-eko v příkladě 1 se získá kyselina 4- (4-chlorf-enyl ] -1- (4-fluorfenyl ] -3-pyrazol-octová s teplotou tání 148 °C (ethylalkohol/vodá).Analogously to Example 1, 4- (4-chlorophenyl) -1- (4-fluorophenyl) -3-pyrazole acetic acid, m.p. 148 DEG C. (ethanol / water), is obtained.
Použité meziprodukty jsou následující:The intermediates used are as follows:
4-(4-chlorstyryl]-morfolin, teplota tání 102 stupňů Celsia (diisopropylettΊeг) (získáno analogicky jako v příkladě 1b z 4-chlorbenzylkyanidu);4- (4-chlorostyryl) -morpholine, m.p. 102 DEG C. (from diisopropylethyl) (obtained analogously to Example 1b from 4-chlorobenzyl cyanide);
3-acetyl-4- (4-chlorf eny 1) -1- (4-fluorfenyl ] -5-morfolmo-415-dihydropyi’azol, teplota tání 137 °C (ethylalkohol);3-acetyl-4- (4-chlorophenyl 1) -1- (4-fluorophenyl] -5-morpholino-4-one 5 dihydropyi'azol, mp 137 DEG C. (ethanol);
3- acétyl-4- (4-chlorf enyl) -1- (4-fluorfenyl) -pyrazol, teplota tání 181 °C (ísopropylalkohol);3-Acetyl-4- (4-chlorophenyl) -1- (4-fluorophenyl) pyrazole, m.p. 181 ° C (isopropyl alcohol);
4- [ 4- (4-chlorfenyl )-1-( 4-fluorfenyl) -3-pyrazolyl-thioacetyl]-molfolin, teplota tání 213 stupňů Celsia (dioxan);4- [4- (4-chlorophenyl) -1- (4-fluorophenyl) -3-pyrazolyl-thioacetyl] -molfoline, m.p. 213 DEG C. (dioxane);
4- (4-chlorf enyl) -1- (4-fluorfenyl) -3-pyrazol-octová kyselina, sodná sůl, teplota tání 299 °C (voda'j.4- (4-chlorophenyl) -1- (4-fluorophenyl) -3-pyrazole acetic acid, sodium salt, m.p. 299 DEG C. (water).
Získávání 3-acety 1-4- (4-chlorf enyl) -1- (4-fluolfenyl)-pylazolu může probíhat analogicky jako v příkladě lc z alfa-dimethylamino-4-chlorstyrolu a 1-chlor-l-(4-fluolfenylhydrazo]^o)-propan^-2-onu.The recovery of 3-acetyl-4- (4-chlorophenyl) -1- (4-fluorophenyl) -pylazole can proceed analogously to Example 1c from alpha-dimethylamino-4-chlorostyrol and 1-chloro-1- (4-fluorophenylhydrazo). 1'-Propan-2-one.
Výchozí materiál alfa-dimethylamino-4-chlorstyrol se může získat následujícím způsobem:The alpha-dimethylamino-4-chlorostyrol starting material can be obtained as follows:
Roztok 8 g 4-chlorbenzylchlorídu v 50 ml ethyletheru se pod ochrannou atmosférou argonu přidává po kapkách k 1,5 g hořčíkových hoblin a směs se míchá po dobu 30 minut. Potom se získaný roztok ochladí na teplotu —15 °C a po kapkách se smísí se 30 mililitry tetrahydrofuranu a 11 g čistého dimethylformamidu. Reakční směs se míchá po dobu 3 hodin při teplotě —15 °C, potom se ve vakuu opatrně zahustí a smísí se s 50 mililitry 2 N roztoku chloridu amonného a s ethylacetátem. Organický zbytek se krystalizuje z methylalkoholu a získá se 5 g alfa-dim-eΐhylammo-4-chlorstylolu.A solution of 8 g of 4-chlorobenzyl chloride in 50 ml of ethyl ether is added dropwise to 1.5 g of magnesium shavings under argon and the mixture is stirred for 30 minutes. The solution was cooled to -15 ° C and treated dropwise with 30 mL of tetrahydrofuran and 11 g of pure dimethylformamide. The reaction mixture is stirred for 3 hours at -15 ° C, then concentrated carefully in vacuo and treated with 50 ml of 2 N ammonium chloride solution and ethyl acetate. The organic residue was crystallized from methanol to give 5 g of alpha-dimethylamino-4-chlorostylol.
Teplota tání: 77 fC.Melting point: 77 ° C.
Příklad 3Example 3
Analogicky jako v příkladě 1 -se získá- kyselina 1,4-bis (4-chlo-rfenyl) -3-pyrazol-octová s teplotou tání 184 °C (toluen).Analogously to Example 1, 1,4-bis (4-chlorophenyl) -3-pyrazole acetic acid with a melting point of 184 ° C (toluene) is obtained.
Používané meziprodukty jsou následující:The intermediates used are as follows:
1-chlor-l- (4-chlorfenylhydrazono) -2-propanon; teplota tání 175 °C; (ethylalkohol); (získá se analogicky jako v příkladě la z Achloraniimu);1-chloro-1- (4-chlorophenylhydrazono) -2-propanone; mp 175 ° C; (ethyl alcohol); (obtained analogously to Example 1a from Achloraniim);
3- acetyl-l,4-bis (4-chlorfenyl) -pyrazol; teplota tání 190 °C (dioxarí) 1 ;3-Acetyl-1,4-bis (4-chlorophenyl) pyrazole; mp 190 ° C (dioxar) 1 ;
4- [ 1,4-bis (4-chlorfenyl) -3-pyrazolyl-thio- cetylj-morfolin; teplota tání 204 °C (dioxan). ..........4- [1,4-bis (4-chlorophenyl) -3-pyrazolyl-thioacetyl] morpholine; mp 204 ° C (dioxane). ..........
P-ř í k 1 a d 4Example 1 a d 4
Analogicky jako v příkladě 1 se získá kyselina 4- (4-chlo-rfenyl )-1-( 4-methylthiofenyi)-3-pyrazoi-octová s teplotou tání 169 °C (methylalkohol).Analogously to Example 1, 4- (4-chlorophenyl) -1- (4-methylthiophenyl) -3-pyrazole acetic acid is obtained, m.p. 169 DEG C. (methanol).
Používané meziprodukty jsou následující:The intermediates used are as follows:
1-chlor-l- (4-^^^^hylthiof enylhydrazonoj -2-propan; teplota tání 110 °C (tetrachlormet-han); (získá -se analogicky jako v příkladě la z 4-methylthioanilinu);1-chloro-1- (4-methyl-thiophenylhydrazone) -2-propane, m.p. 110 DEG C. (carbon tetrachloride) (obtained analogously to Example 1a from 4-methylthioaniline);
3- acetyl-4- (4-chlorf enyl)-1- (4-methylthiofenylj-pyrazol; teplota tání 85 °C (methylalkohol);3-acetyl-4- (4-chlorophenyl) -1- (4-methylthiophenyl) pyrazole, m.p. 85 DEG C. (methanol);
4- (4-( 4-chlorf enyl-1- (4-methylthiofenyl-3-pyrazolyl-thioacetylj-morfolin; teplota tání 248 °C (ethylacetát).4- (4- (4-chlorophenyl-1- (4-methylthiophenyl-3-pyrazolyl-thioacetyl) morpholine) m.p. 248 ° C (ethyl acetate).
Příklad 5Example 5
Analogicky jako v příkladě 1 se získá kyselina 4- (4-chlorfenyl-l-fenyl-3-pyrazol-octová s teplotou · tání 169 °C · (toluen).Analogously to Example 1, 4- (4-chlorophenyl-1-phenyl-3-pyrazole-acetic acid) with a melting point of 169 ° C (toluene) is obtained.
Použité meziprodukty jsou následující:The intermediates used are as follows:
l-chlor-l-fenylhydrazono-2-propan; teplota tání 136 °C (ethylalkohol);1-chloro-1-phenylhydrazono-2-propane; mp 136 ° C (ethyl alcohol);
3- acetyl-4-(4-chlorfenyl)-l-fenyl-pyrazol; teplota tání 101 °C (methylalkohol);3-Acetyl-4- (4-chlorophenyl) -1-phenyl-pyrazole; mp 101 ° C (methanol);
4- (4-( 4-chlorfenyl) -l-fenyl-3-pyrazolylthioacetylj-morfolin; teplota tání 205 °C (dioxan).4- (4- (4-chlorophenyl) -1-phenyl-3-pyrazolylthioacetyl) morpholine, m.p. 205 ° C (dioxane).
Příklad 6Example 6
Roztok 2 g kyseliny 4-(4-chlorfenyl)-1- (4-f luorfenyl) -3-pyrazol-octové (získané podle příkladu 2')' ve 30 ml dimethylformamidu se smísí s roztokem 600 mg octanu měďnatého ve 35 ml dimethylformamidu a reakční směs se míchá po dobu 8 hodin při teplotě místnosti. Po oddestilování rozpouštědla ve vakuu se olejovitý zbytek rozpustí v acetonu a od ostatních zbytků se odfiltruje. Po· odpaření acetonu se zbytek soli krystalizuje z acetonu. Získá se 1,7 g monohydrátu měďnaté soli kyseliny 4-(4-chlorfenyl)-1- (4-f luorfenyy) -3-pyrazol-octové.A solution of 2 g of 4- (4-chlorophenyl) -1- (4-fluorophenyl) -3-pyrazole acetic acid (obtained according to Example 2 ') in 30 ml of dimethylformamide is mixed with a solution of 600 mg of copper acetate in 35 ml of dimethylformamide. and the reaction mixture is stirred for 8 hours at room temperature. After distilling off the solvent in vacuo, the oily residue was dissolved in acetone and filtered off from the other residues. After evaporation of the acetone, the residual salt is crystallized from acetone. 1.7 g of copper (4-chlorophenyl) -1- (4-fluorophenyl) -3-pyrazole acetic acid monohydrate are obtained.
Teplota tání: 171 °C.Melting point: 171 ° C.
Příklad 7Example 7
Analogicky jako v příkladě 1 se vyrobí kyselina 1,4-bis () -3-pyr azol-octová; teplota tání: 116 °C (tetrachlormethan).Analogously to Example 1, 1,4-bis () -3-pyrazole-acetic acid was prepared; 116 ° C (carbon tetrachloride).
Příklad 8Example 8
Analogicky jako . v příkladě 1 se vyrobí kyselina 4- (.2,4-dichlorfenyl) -1- (4-f luorfenyl)-3-pyrazol-octová; teplota tání: 133 °C (toluen).Analogous to. in Example 1, 4- (2,4-dichlorophenyl) -1- (4-fluorophenyl) -3-pyrazole acetic acid was prepared; melting point: 133 ° C (toluene).
Příklad 9Example 9
Analogicky jako v příkladě 1 se vyrobí kyselina 1- (2-f luorf enyl )-4-( 4-nitr of enyl) -3-pyrazol-octová; teplota tání: 208 °C (octan ethylnatý).Analogously to Example 1, 1- (2-fluorophenyl) -4- (4-nitro-phenyl) -3-pyrazole acetic acid was prepared; mp: 208 ° C (ethyl acetate).
Příklad 10Example 10
Analogicky jako v příkladě 1 se vyrobí kyselina 4- (4-chlorfenyl) -1- (2-f luorfenyl) -3-pyrazol-octová; teplota tání: 187 °C (octan· ethylnatý).Analogously to Example 1, 4- (4-chlorophenyl) -1- (2-fluorophenyl) -3-pyrazole acetic acid was prepared; mp: 187 ° C (ethyl acetate).
P říklad 11Example 11
Analogicky jako v příkladě 1 se vyrobí kyselina 1- (4--^]^ι^ι^ι^1^(^ι^·^1 ) -4- (4-nitrofenyl) -3-pyrazol-octová; teplota tání: 254 °C (acetonitrilj.Analogously to Example 1, 1- (4- (4-nitrophenyl) -3- (4-nitrophenyl) -3-pyrazole acetic acid) was prepared; 254 ° C (acetonitrile).
Příklad 12Example 12
Analogicky jako · v příkladě 1 se vyrobí kyselina 4- (3,4-dichlorf enyl) -1- (4-f luorfenyl)-3-pyrazol-octová; teplota tání: 178 °C (toluen).Analogously to Example 1, 4- (3,4-dichlorophenyl) -1- (4-fluorophenyl) -3-pyrazole acetic acid was prepared; melting point: 178 ° C (toluene).
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