JP6514722B2 - ケチミン類のアシル化を介した3,5−ビス(ハロアルキル)ピラゾール類の製造方法 - Google Patents
ケチミン類のアシル化を介した3,5−ビス(ハロアルキル)ピラゾール類の製造方法 Download PDFInfo
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- JP6514722B2 JP6514722B2 JP2016572234A JP2016572234A JP6514722B2 JP 6514722 B2 JP6514722 B2 JP 6514722B2 JP 2016572234 A JP2016572234 A JP 2016572234A JP 2016572234 A JP2016572234 A JP 2016572234A JP 6514722 B2 JP6514722 B2 JP 6514722B2
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- 238000000034 method Methods 0.000 title claims description 16
- 150000003217 pyrazoles Chemical class 0.000 title claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 title claims description 8
- 150000004658 ketimines Chemical class 0.000 title description 3
- 238000002360 preparation method Methods 0.000 title description 3
- 230000010933 acylation Effects 0.000 title 1
- 238000005917 acylation reaction Methods 0.000 title 1
- -1 2-difluoroethyl Chemical group 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000007363 ring formation reaction Methods 0.000 claims description 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 claims description 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 125000004781 2,2-dichloro-2-fluoroethyl group Chemical group [H]C([H])(*)C(F)(Cl)Cl 0.000 claims description 3
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 3
- 125000004779 2-chloro-2-fluoroethyl group Chemical group [H]C([H])(*)C([H])(F)Cl 0.000 claims description 3
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 claims description 3
- 125000004773 chlorofluoromethyl group Chemical group [H]C(F)(Cl)* 0.000 claims description 3
- 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 claims description 3
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000006337 tetrafluoro ethyl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 12
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000008096 xylene Substances 0.000 description 7
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 6
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 3
- NICRTVVFOCBIKC-UHFFFAOYSA-N CC(C)N=C(C)C(F)F Chemical compound CC(C)N=C(C)C(F)F NICRTVVFOCBIKC-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 125000002723 alicyclic group Chemical group 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 3
- 229950005499 carbon tetrachloride Drugs 0.000 description 3
- 229940117389 dichlorobenzene Drugs 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- 150000003457 sulfones Chemical class 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- HVZJRWJGKQPSFL-UHFFFAOYSA-N tert-Amyl methyl ether Chemical compound CCC(C)(C)OC HVZJRWJGKQPSFL-UHFFFAOYSA-N 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XHILZHAQBOLGFD-UHFFFAOYSA-N 1,1-difluoropropan-2-one Chemical compound CC(=O)C(F)F XHILZHAQBOLGFD-UHFFFAOYSA-N 0.000 description 2
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical class OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 2
- YYPFZXBEOCAFDL-UHFFFAOYSA-N 3,5-bis(difluoromethyl)-1h-pyrazole Chemical compound FC(F)C=1C=C(C(F)F)NN=1 YYPFZXBEOCAFDL-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical class O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000005594 diketone group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000003541 multi-stage reaction Methods 0.000 description 2
- MYVITOFBNPFGNU-UHFFFAOYSA-N n-benzyl-1,1,1-trifluoropropan-2-imine Chemical compound FC(F)(F)C(C)=NCC1=CC=CC=C1 MYVITOFBNPFGNU-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- YTBBOHJDGLEWEF-UHFFFAOYSA-N 1,1,1-trifluoro-n-propan-2-ylpropan-2-imine Chemical compound CC(C)N=C(C)C(F)(F)F YTBBOHJDGLEWEF-UHFFFAOYSA-N 0.000 description 1
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 1
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 1
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 1
- 125000004515 1,2,4-thiadiazol-3-yl group Chemical group S1N=C(N=C1)* 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 description 1
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 1
- 125000004317 1,3,5-triazin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=N1 0.000 description 1
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 1
- SXOREXSEUSTNNQ-UHFFFAOYSA-N 16-bromo-1,1,1-trifluorohexadecane Chemical compound FC(F)(F)CCCCCCCCCCCCCCCBr SXOREXSEUSTNNQ-UHFFFAOYSA-N 0.000 description 1
- DCEPGADSNJKOJK-UHFFFAOYSA-N 2,2,2-trifluoroacetyl fluoride Chemical compound FC(=O)C(F)(F)F DCEPGADSNJKOJK-UHFFFAOYSA-N 0.000 description 1
- KURKJXZWCPWPFX-UHFFFAOYSA-N 2,2-difluoroacetyl chloride Chemical compound FC(F)C(Cl)=O KURKJXZWCPWPFX-UHFFFAOYSA-N 0.000 description 1
- CRLSHTZUJTXOEL-UHFFFAOYSA-N 2,2-difluoroacetyl fluoride Chemical compound FC(F)C(F)=O CRLSHTZUJTXOEL-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- JNZMCMSGSKHZQW-UHFFFAOYSA-N 5-(difluoromethyl)-3-(trifluoromethyl)-1h-pyrazole Chemical compound FC(F)C1=CC(C(F)(F)F)=NN1 JNZMCMSGSKHZQW-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- AJZKCZBXGUUREN-UHFFFAOYSA-N N-benzyl-1,1-difluoropropan-2-imine Chemical compound FC(C(C)=NCC1=CC=CC=C1)F AJZKCZBXGUUREN-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- PBWZKZYHONABLN-UHFFFAOYSA-N difluoroacetic acid Chemical compound OC(=O)C(F)F PBWZKZYHONABLN-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- QAMFBRUWYYMMGJ-UHFFFAOYSA-N hexafluoroacetylacetone Chemical compound FC(F)(F)C(=O)CC(=O)C(F)(F)F QAMFBRUWYYMMGJ-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 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
- C07D231/10—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
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Environmental Sciences (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Agronomy & Crop Science (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
R1およびR3はそれぞれ独立に、C1−C6−ハロアルキルから選択され;
R2は、H、ハロゲン、COOH、(C=O)OR5、CNおよび(C=O)NR6R7から選択され;
R4は、H、C1−C8アルキル、アリール、ピリジルから選択され;
R5は、C1−12−アルキル、C3−8−シクロアルキル、C6−18−アリール、C7−19−アリールアルキルおよびC7−19−アルキルアリールから選択され;
R6およびR7はそれぞれ独立に、C1−12−アルキル、C3−8−シクロアルキル、C6−18−アリール、C7−19−アリールアルキルおよびC7−19−アルキルアリールから選択され、または
R6およびR7が、それらが結合している窒素原子とともに、4員、5員もしくは6員環を形成していても良い。]の製造方法において、
段階(A)で、下記式(II)の酸誘導体:
R8はC1−12−アルキル、C3−8−シクロアルキル、C6−18−アリール、C7−19−アリールアルキルおよびC7−19−アルキルアリール、OR9から選択され;
R9は、C1−12−アルキル、C3−8−シクロアルキル、C6−18−アリール、C7−19−アリールアルキル、C7−19−アルキルアリールから選択され;
R2およびR3は上記で定義の通りである。]と反応させて、下記式(IV)の化合物:
R1、R2、R3、R5、R6、R7、R8、R9は上記で定義の通りである。]を生成し、
段階(B)で、(V)NH2NHR4(R4は上記で定義の通りである。)の存在下での(IV)の環化を行って、(Ia)および(Ib)を生成することを特徴とする方法によって達成された。
R2はH、F、Cl、Br、COOCH3、COOC2H5、COOC3H7、CNおよびCON(CH3)2、CON(C2H5)2から選択され;
R4はH、C1−C8アルキル、アリール、ピリジルから選択され;
R8はそれぞれ独立に、メチル、エチル、n−、イソ−プロピル、n−、イソ−、sec−およびt−ブチル、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、フェニル、ベンジル、フェニルエチル、トリル、2,3−、2,4−、2,5−、2,6−、3,4−または3,5−ジメチルフェニルから選択され;
XはF、Clまたは−O(CO)R1から選択される。
R2はH、Cl、CN、COO(C2H5)2から選択され;
R4はH、メチル、エチル、n−、イソプロピル、n−、イソ−、sec−およびt−ブチル、n−ペンチル、n−ヘキシル、1,3−ジメチルブチル、3,3−ジメチルブチル、アリールから選択され;
R8はメチル、エチル、n−、イソ−プロピル、n−、イソ−、sec−およびt−ブチル、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、ベンジルから選択され;
XはF、Clまたは−OC(O)R1から選択される。
R2はHまたはCOOC2H5から選択され;
R4はH、メチル、エチル、フェニルから選択され;
R8はエチル、n−、イソ−プロピル、n−、シクロペンチル、シクロヘキシル、ベンジルから選択され;
XはClまたはFである。
R2はHであり;
R4はH、メチル、フェニルから選択され;
R8はイソ−プロピル、ベンジルから選択され;
XはClまたはFである。
本発明の文脈において、「ハロゲン」(Hal)という用語は、異なって定義されていない限り、フッ素、塩素、臭素およびヨウ素、好ましくはフッ素、塩素および臭素、より好ましくはフッ素および塩素を含む群から選択される要素を含む。
その方法を図式1で説明している。
段階Aにおいて、式(II)の酸誘導体を、塩基の存在下に、式(III)の化合物と反応させる。
段階Bは、式(V)の化合物の存在下での式(IV)の化合物の環化反応である。
N−(1,1−ジフルオロプロパン−2−イリデン)プロパン−2−アミン、(III−1)
ジフルオロアセトン(94g、1mol)のメチルtert−ブチルエーテル(500mL)中混合物に、イソプロピルアミン(88g、1.5mol)を10℃で加えた。1時間後、BF3・Et2O(70g、0.5mol)を加え、混合物をさらに1時間撹拌した。有機溶液を底部シロップから分離し、溶媒を大気圧で留去した。残った液体を減圧下に蒸留して、沸点70から72℃/400mbarのケチミン139gを得た。
N−1,1−ジフルオロプロパン−2−イリデン−1−フェニルメタンアミン、(III−2)
ジフルオロアセトン(94g、1mol)のトルエン(500mL)中混合物に、ベンジルアミン(107g、1mol)を10℃でゆっくり加えた。20℃で6時間後、トルエンを減圧下に留去し、残留液体を精製せずに用いた。170g。
N−(1,1,1−トリフルオロプロパン−2−イリデン)プロパン−2−アミン、(III−3)
製造については、実施例2を参照する。沸点80−82℃。
N−1,1,1−トリフルオロプロパン−2−イリデン−1−フェニルメタンアミン(III−4)
製造については、実施例2を参照する。沸点90−91℃、1.5mbar。
3,5−ビス(ジフルオロメチル)ピラゾール、(I−1)
N−(1,1−ジフルオロプロパン−2−イリデン)プロパン−2−アミン10.4(75mmol)およびピリジン12gのジクロロメタン(100mL)中溶液を冷却して0℃とした。無水ジフルオロ酢酸19.5gを、高撹拌下にこの温度で少量ずつ加え、混合物を最後に10℃で6時間撹拌した。HCl 50mL(5%水溶液として)およびヒドラジン水和物20gを、温度を40℃以下に維持するように反応溶液にゆっくり加え、混合物を40℃で5時間撹拌した。水100mLおよびジクロロメタン100mLを加え、有機層を分離し、水で洗浄し、MgSO4で脱水し、減圧下に濃縮して、油状生成物を得た。92から95℃/1mbarでの真空蒸留によって、純粋な3,5−ビス(ジフルオロメチル)−1H−ピラゾールb)8.8g(70%)を融点70−71℃の白色固体として得た。
3−(ジフルオロメチル)−5−(トリフルオロメチル)−1H−ピラゾール、(I−2)
同様にして、N−(1,1−ジフルオロプロパン−2−イリデン)プロパン−2−アミンおよび無水トリフルオロ酢酸から得た。
Claims (5)
- 下記式(Ia)および(Ib)の3,5−ビス(ハロアルキル)ピラゾール:
R1およびR3はそれぞれ独立に、C1−C6−ハロアルキルから選択され;
R2は、H、ハロゲン、COOH、(C=O)OR5、CNおよび(C=O)NR6R
7から選択され;
R4は、H、C1−C8アルキル、アリール、ピリジルから選択され;
R5は、C1−12−アルキル、C3−8−シクロアルキル、C6−18−アリール、
C7−19−アリールアルキルおよびC7−19−アルキルアリールから選択され;
R6およびR7はそれぞれ独立に、C1−12−アルキル、C3−8−シクロアルキル
、C6−18−アリール、C7−19−アリールアルキルおよびC7−19−アルキルア
リールから選択され、または
R6およびR7が、それらが結合している窒素原子とともに、4員、5員もしくは6員
環を形成していても良い。]の製造方法において、
段階(A)で、下記式(II)の酸誘導体:
R1は上記で定義の通りであり;
XはF、Cl、Brまたは−OC(O)R1である。]を、下記式(III)の化合物
:
R8はC1−12−アルキル、C3−8−シクロアルキル、C6−18−アリール、C
7−19−アリールアルキルおよびC7−19−アルキルアリール、OR9から選択され
;
R9は、C1−12−アルキル、C3−8−シクロアルキル、C6−18−アリール、
C7−19−アリールアルキル、C7−19−アルキルアリールから選択され;
R2およびR3は上記で定義の通りである。]と反応させて、下記式(IV)の化合物
:
R1、R2、R3、R5、R6、R7、R8、R9は上記で定義の通りである。]を生
成し、
段階(B)で、(V)NH2NHR4(R4は上記で定義の通りである。)の存在下で
の(IV)の環化を行って、(Ia)および(Ib)を生成することを特徴とする方法。 - R1およびR3がそれぞれ独立に、ジフルオロメチル、トリフルオロメチル、クロロフ
ルオロメチル、ジクロロフルオロメチル、クロロジフルオロメチル、1−フルオロエチル
、2−フルオロエチル、2,2−ジフルオロエチル、2,2,2−トリフルオロエチル、
2−クロロ−2−フルオロエチル、2−ジフルオロエチル、2,2−ジクロロ−2−フル
オロエチル、2,2,2−トリクロロエチル、テトラフルオロエチル(CF3CFH)、
ペンタフルオロエチルおよび1,1,1−トリフルオロプロパ−2−イルから選択され;
R2がH、F、Cl、Br、COOCH3、COOC2H5、COOC3H7、CNお
よびCON(CH3)2、CON(C2H5)2から選択され;
R4がH、C1−C8アルキル、アリール、ピリジルから選択され;
R8がそれぞれ独立に、メチル、エチル、n−、イソ−プロピル、n−、イソ−、se
c−およびt−ブチル、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシ
ル、フェニル、ベンジル、フェニルエチル、トリル、2,3−、2,4−、2,5−、2
,6−、3,4−または3,5−ジメチルフェニルから選択され;
XがF、Clまたは−O(CO)R1から選択される、請求項1に記載の方法。 - R1およびR3がそれぞれ独立に、トリフルオロメチル、ジフルオロメチル、ジフルオ
ロクロロメチル、ペンタフルオロエチルから選択され;
R2がH、Cl、CN、COO(C2H5)2から選択され;
R4がH、メチル、エチル、n−、イソプロピル、n−、イソ−、sec−およびt−
ブチル、n−ペンチル、n−ヘキシル、1,3−ジメチルブチル、3,3−ジメチルブチ
ル、アリールから選択され;
R8が、メチル、エチル、n−、イソ−プロピル、n−、イソ−、sec−およびt−
ブチル、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、ベンジルか
ら選択され;
XがF、Clまたは−OC(O)R1から選択される、請求項1に記載の方法。 - R1およびR3がそれぞれ独立に、CF2H、CF3から選択され;
R2がHまたはCOOC2H5から選択され;
R4がH、メチル、エチル、フェニルから選択され;
R8が、エチル、n−、イソ−プロピル、n−、シクロペンチル、シクロヘキシル、ベ
ンジルから選択され;
XがClまたはFである、請求項1に記載の方法。 - R1およびR3がそれぞれ独立に、CF2H、CF3から選択され;
R2がHであり;
R4がH、メチル、フェニルから選択され;
R8がイソ−プロピル、ベンジルから選択され;
XがClまたはFである、請求項1に記載の方法。
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PCT/EP2015/062685 WO2015189138A1 (en) | 2014-06-11 | 2015-06-08 | Process for preparing 3,5-bis(haloalkyl)pyrazoles via acylation of ketimines |
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DK (1) | DK3154947T3 (ja) |
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IL (1) | IL249282B (ja) |
MX (1) | MX2016016399A (ja) |
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DE10161978A1 (de) * | 2001-12-17 | 2003-06-26 | Bayer Ag | Verfahren zur Herstellung von 2-Halogenacyl-3-amino-acrylsäure-derivate |
DE10215292A1 (de) | 2002-02-19 | 2003-08-28 | Bayer Cropscience Ag | Disubstitutierte Pyrazolylcarbocanilide |
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EP2133341A1 (de) | 2008-02-25 | 2009-12-16 | Bayer CropScience AG | Verfahren zur regioselektiven Synthese von 1-Alkyl-3-haloalkyl-pyrazol-4-carbonsäure-Derivaten |
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