CN113423690A - 吡唑衍生物 - Google Patents
吡唑衍生物 Download PDFInfo
- Publication number
- CN113423690A CN113423690A CN202080012471.8A CN202080012471A CN113423690A CN 113423690 A CN113423690 A CN 113423690A CN 202080012471 A CN202080012471 A CN 202080012471A CN 113423690 A CN113423690 A CN 113423690A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- substituted
- ring
- haloalkoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000003217 pyrazoles Chemical class 0.000 title claims description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- -1 nitrovinyl moiety Chemical group 0.000 claims description 8
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 5
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- JKOVQYWMFZTKMX-ONEGZZNKSA-N (e)-n,n-dimethyl-2-nitroethenamine Chemical group CN(C)\C=C\[N+]([O-])=O JKOVQYWMFZTKMX-ONEGZZNKSA-N 0.000 claims description 4
- DBTNVRCCIDISMV-UHFFFAOYSA-L lithium;magnesium;propane;dichloride Chemical compound [Li+].[Mg+2].[Cl-].[Cl-].C[CH-]C DBTNVRCCIDISMV-UHFFFAOYSA-L 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 239000003905 agrochemical Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- UONGHJXSAXBMRD-UHFFFAOYSA-N 5-ethenyl-4-nitro-1H-pyrazole Chemical class [N+](=O)([O-])C=1C=NNC=1C=C UONGHJXSAXBMRD-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 7
- 230000002363 herbicidal effect Effects 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 238000010828 elution Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- COYAJIXIKZYPIE-CLZZGJSISA-N (3R,4R)-4-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]-2-oxopyrrolidine-3-carboxylic acid Chemical compound CN1N=C(C=C1C(F)(F)F)[C@@H]1[C@H](C(NC1)=O)C(=O)O COYAJIXIKZYPIE-CLZZGJSISA-N 0.000 description 3
- BJYIAUXMGMJTEY-OQPBUACISA-N (3S,4R)-N-(2,3-difluorophenyl)-1-methyl-4-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]-2-oxopyrrolidine-3-carboxamide Chemical compound FC1=C(C=CC=C1F)NC(=O)[C@H]1C(N(C[C@@H]1C1=NN(C(=C1)C(F)(F)F)C)C)=O BJYIAUXMGMJTEY-OQPBUACISA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 238000005191 phase separation Methods 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- BXDBSTTVLIADLA-SVGQVSJJSA-N (3R,4R)-1-methyl-4-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]-2-oxopyrrolidine-3-carboxylic acid Chemical compound CN1C([C@@H]([C@H](C1)C1=NN(C(=C1)C(F)(F)F)C)C(=O)O)=O BXDBSTTVLIADLA-SVGQVSJJSA-N 0.000 description 2
- CZRVKCCXKZFTEW-SKDRFNHKSA-N (3S,4S)-N-(2,3-difluorophenyl)-1-methyl-4-[1-methyl-5-(trifluoromethyl)pyrazol-4-yl]-2-oxopyrrolidine-3-carboxamide Chemical compound FC1=C(C=CC=C1F)NC(=O)[C@H]1C(N(C[C@@H]1C=1C=NN(C=1C(F)(F)F)C)C)=O CZRVKCCXKZFTEW-SKDRFNHKSA-N 0.000 description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 2
- GPDZADIAVAAYDR-NSCUHMNNSA-N 1-methyl-3-[(E)-2-nitroethenyl]-5-(trifluoromethyl)pyrazole Chemical compound CN1N=C(C=C1C(F)(F)F)\C=C\[N+](=O)[O-] GPDZADIAVAAYDR-NSCUHMNNSA-N 0.000 description 2
- ICFGFAUMBISMLR-UHFFFAOYSA-N 1h-pyrazole-5-carbaldehyde Chemical compound O=CC=1C=CNN=1 ICFGFAUMBISMLR-UHFFFAOYSA-N 0.000 description 2
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- SGIUZRHJVBLINW-UHFFFAOYSA-N 5-(2-nitroethenyl)-1H-pyrazole Chemical compound [N+](=O)([O-])C=CC1=NNC=C1 SGIUZRHJVBLINW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OIFIKWIFICPTTR-UHFFFAOYSA-N Cn1nc(I)cc1C(F)(F)F Chemical compound Cn1nc(I)cc1C(F)(F)F OIFIKWIFICPTTR-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
- XIVVMPWSYHAGFP-UHFFFAOYSA-N 1-methyl-5-(trifluoromethyl)pyrazol-3-amine Chemical compound CN1N=C(N)C=C1C(F)(F)F XIVVMPWSYHAGFP-UHFFFAOYSA-N 0.000 description 1
- YCCQGFYAVUTQFK-UHFFFAOYSA-N 2,3-difluoroaniline Chemical compound NC1=CC=CC(F)=C1F YCCQGFYAVUTQFK-UHFFFAOYSA-N 0.000 description 1
- PCHVEBIHYNZHNC-UHFFFAOYSA-N 4,6-dihydro-1h-pyrrolo[3,2-c]pyrazol-5-one Chemical group N1N=CC2=C1CC(=O)N2 PCHVEBIHYNZHNC-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 101000603877 Homo sapiens Nuclear receptor subfamily 1 group I member 2 Proteins 0.000 description 1
- 101001098560 Homo sapiens Proteinase-activated receptor 2 Proteins 0.000 description 1
- 101000713170 Homo sapiens Solute carrier family 52, riboflavin transporter, member 1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102100036863 Solute carrier family 52, riboflavin transporter, member 1 Human genes 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- XZWYPDBOUJUGFL-HZGVNTEJSA-N ethyl (3R,4R)-4-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]-2-oxopyrrolidine-3-carboxylate Chemical compound CN1N=C(C=C1C(F)(F)F)[C@@H]1[C@H](C(NC1)=O)C(=O)OCC XZWYPDBOUJUGFL-HZGVNTEJSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- XNQULTQRGBXLIA-UHFFFAOYSA-O phosphonic anhydride Chemical compound O[P+](O)=O XNQULTQRGBXLIA-UHFFFAOYSA-O 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006476 reductive cyclization reaction Methods 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
-
- 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
- A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
-
- 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
- A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
-
- 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
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
-
- 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
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P13/00—Herbicides; Algicides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Plant Pathology (AREA)
- Environmental Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pest Control & Pesticides (AREA)
- Dentistry (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明涉及具有下式的硝基‑乙烯基‑吡唑化合物,其中环A、RB2和RB3是如权利要求1中所定义的;以及此类化合物的制造及其随后在农用化学品和/或药物的生产中的用途。
Description
本发明涉及如本文所述的具有式(B)和式(C)的吡唑衍生物,其是在农用化学品和药物的生产中的有价值的中间体。本发明扩展到此类吡唑衍生物的制造,及其随后在农用化学品和/或药物的制造中的用途。
在第一方面,提供了一种具有式(B)的化合物
其中环A是二取代的吡唑,在环氮上被RB2取代并在环碳上被RB3取代,其中RB2是C1-C3烷基或C1-C3氟烷基并且RB3是卤素、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、C1-C3卤代烷基、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、或C1-C3烷基。
在第二方面,提供了一种具有式(C)的化合物
其中环A是二取代的吡唑,在环氮上被RB2取代并在环碳上被RB3取代,其中RB2是C1-C3烷基或C1-C3氟烷基,并且RB3是卤素、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、C1-C3卤代烷基、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、或C1-C3烷基。
具有式(B)和(C)的化合物可以用作在包括吡唑并-吡咯烷酮基序的药物和农用化学品的制造中的中间体。例如,US 2007/0123508描述了用作PAR2抑制剂的2-氧代-1-吡咯烷酮衍生物,具有式(B)、(C)、(D)和(E)的化合物可以在其中US 2007/0123508的化合物的R1是取代的吡唑的此类化合物的合成中使用。本文还描述了使用具有式(B)和(C)的化合物制造新颖的除草化合物。
具有式(B)的化合物可以由具有式(A)的卤化吡唑其中环A、RB2和RB3是如以上所定义的,并且Hal是选自碘、溴和氯的卤素,通过使具有式(A)的化合物与异丙基氯化镁-氯化锂在合适的溶剂(如四氢呋喃)中在-20℃下反应来制备。两小时后,添加1-二甲基氨基-2-硝基乙烯并在一小时的时间内将反应物缓慢温热至室温。在处理和纯化后,这得到了具有式(B)的所希望的硝基乙烯基吡唑(反应方案1)。具有式(A)的化合物是已知的,或者可以根据本领域熟知的方法制备。
反应方案1
具有式(B)的硝基乙烯基吡唑化合物还可以通过在合适的溶剂中用合适的碱使相应的吡唑醛(x)和硝基甲烷一起反应随后进行脱水步骤来制备,如下面的反应方案1.1所示。此类方法报告于WO 2016/100050和WO 2019/169153中。
反应方案1.1
然后使具有式(B)的硝基乙烯基吡唑化合物在合适的溶剂(如甲苯)中在对映选择性镍催化下与丙二酸酯(如丙二酸二乙酯)反应,如J.Am.Chem.Soc.[美国化学会志]2005,127,9958-9959中所述,以得到为具有式(C)的化合物的对映体富集的丙二酸酯加成产物,如反应方案2所示。
反应方案2
在具有式(A)、(B)和(C)的化合物中,如本文所述,环A是带有两个取代基的吡唑部分,其中所述取代基中的一个(RB2)由环氮携带,并且第二个取代基(RB3)在环碳原子上携带。显然在这种构型下,A是与相应分子的其余部分连接的碳。
当A是二取代的并且RB3在邻近取代的环氮原子的环碳原子上携带时,所述RB3取代基可以定义为RB3SN。为了避免疑问,RB3SN是仅用于表示吡唑部分内的位置布局的RB3的子定义,并且因此RB3SN也选自由以下组成的组:卤素、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基和C1-C3烷基。因此,当A是二取代的时,它可以由基团A1、A2、A3、A4、或A5表示,如下所示,其中RB2、RB3和RB3SN是如以上所定义的,并且锯齿状线表示与相关分子的其余部分的附接点。
基团A1和A2是特别优选的,其中A2是最优选的二取代吡唑。
优选地,RB2选自由以下组成的组:甲基、乙基、正丙基、氟甲基、三氟甲基、氟乙基、二氟乙基和三氟乙基。更优选地,RB2选自由以下组成的组:甲基、乙基、正丙基、三氟甲基和二氟乙基。还更优选地,RB2选自由以下组成的组:甲基、乙基和二氟乙基。
优选地,RB3(以及因此还有RB3SN)选自氯、氟、溴、甲基、乙基、二氟甲基、三氟甲基、C1-C3卤代烷氧基、C1-C3烷氧基、或C1-C3烷基。
下表1和2提供了用于本发明的具有式(B)和(C)的化合物的具体实例。
表1根据本发明的具有式B的化合物
表2根据本发明的具有式C的化合物
如本文所述的具有式(B)和(C)的化合物可以用于合成具有式(D)的吡唑并-内酰胺-甲酸酯,
同样其中环A、RB2和RB3是如本文所定义的。这些新颖的化合物构成本发明的又另外的方面。
使用合适的还原剂(如硼氢化钠),用合适的催化剂(如氯化镍),在合适的溶剂(如乙醇)中,将具有式(C)化合物还原环化得到具有式(D)的吡唑并-内酰胺-甲酸酯(下面的反应方案3)。
反应方案3
具有式(D)的化合物然后可以在水性氢氧化物/乙醇混合物中水解以得到适当的具有式(E)的吡唑并-内酰胺-3-甲酸衍生物,如反应方案4所示。
反应方案4
具有式(D)和式(E)的化合物也是在吡唑并-内酰胺除草剂的生产中的有价值的中间体,特别是因为它们产生优选的除草对映异构体。下表3和4提供了用于本发明的具有式(D)和(E)的化合物的具体实例。
表3根据本发明的具有式(D)的化合物
表4根据本发明的具有式(E)的化合物
由具有式(E)的化合物制造具有式(G)的新颖的吡唑并-内酰胺除草剂的方法在下面在反应方案5和6中进行了概括地描述,并对于实例中的具体的除草化合物进行了描述。
反应方案5
使用过量的碱(如叔丁醇钾),用碘甲烷或替代性甲基化试剂,在合适的溶剂(如四氢呋喃)中将具有式(E)的化合物在内酰胺氮上甲基化(以上反应方案5)。
使用标准酰胺偶联条件,如丙烷膦酸酐在合适的溶剂(如二氯甲烷)中,用合适的碱,将具有式(F)的3-羧基取代的N-甲基内酰胺与具有式R2-NH2(其中R2是如下文所定义的)的苯胺偶联以得到具有式(G)的除草的吡唑并-内酰胺甲酰胺(反应方案6)。
反应方案6
对于具有式R2-NH2的苯胺和具有式(G)的除草化合物,R2取代基包括氢、C1-C6烷基、-Cr烷氧基Cs烷基、C1-C6卤代烷基、-Cr烷氧基Cs卤代烷基、C2-C6烯基、C2-C6炔基、以及-(CR21R22)tR20,其中每个R20独立地是-C(O)OR23、-OC(O)R23、-C3-C6环烷基、或-芳基、-芳氧基、-杂芳基、-杂芳氧基或-杂环基环,其中所述环任选地被1至3个独立的R25取代;r是1、2、3、4、或5的整数,s是1、2、3、4、或5的整数,并且r+s之和小于或等于6;t是0、1、2、3、4、5或6的整数,每个R21独立地是氢或C1-C2烷基;每个R22独立地是氢或C1-C2烷基;R23是氢或C1-C4烷基。
在某些实施例中,其中R2是任选地被1至3个R25取代的芳基或杂芳基环,并且所述芳基或杂芳基环选自由以下组成的组:苯基、吡啶基和噻吩基环***,它可以由以下通用结构表示
在某些实施例中,R2选自由以下组成的组:R2-1、R2-2、R2-3、R2-4、R2-5和R2-6,其中p和锯齿状线是如先前所述的,并且每个R25独立地是卤素、C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6卤代烷氧基、氰基、硝基、C1-C6烷硫基、C1-C6烷基亚磺酰基、或C1-C6烷基磺酰基
更优选地,每个R25独立地是卤素、C1-C4烷基、C1-C3卤代烷基、C1-C3烷氧基、或C1-C3卤代烷氧基;甚至更优选地,氯、氟、溴、C1-C2卤代烷基、C1-C2卤代烷氧基、或C1-C2烷氧基;还更优选地,氟、乙基、三氟甲基、二氟乙基、甲氧基、二氟甲氧基、或三氟甲氧基。如本文所述,p的值是1、2或3。优选地,p是0、1、或2并且每个R25被环碳原子携带。
具有式R2-NH2的苯胺是已知的,或者可以根据本领域熟知的方法制备。
下面所示的反应方案1a、2a、3a、4a和5a例示了如以上对于一组优选的实施例所述的本发明的化合物和方法,其中具有式(A)的化合物中的吡唑环具有上文描述为A2的结构。除非另有说明,否则RB2、RB3、Hal和R2是如上文所定义的。
反应方案1a
反应方案2a
反应方案3a
反应方案4a
反应方案5a
反应方案6a
现在将通过举例更详细地说明本发明的不同方面和实施例。应当理解的是,在不偏离本发明范围的情况下,可以对细节做出修改。
为了避免疑问,在本申请的正文中引用文献参考、专利申请、或专利时,将所述引用的全文通过援引并入本文。
实例
实例1:`除草化合物(3S,4R)-N-(2,3-二氟苯基)-1-甲基-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酰胺的制备
步骤3中使用的镍催化剂,其催化不对称丙二酸酯加成至硝基烯烃,可以如J.Am.Chem.Soc.[美国化学会志]2005,127,9958-9959中制备。
步骤1 3-碘-1-甲基-5-(三氟甲基)吡唑
将化合物1-甲基-5-(三氟甲基)吡唑-3-胺(5.00g,30.3mmol)在9M硫酸(818mmol,91mL)中在500mL烧杯中,使用顶置式搅拌器在0℃(冰浴)下搅拌,直到产生均匀的混合物。然后在5分钟内逐滴添加在10mL水中的亚硝酸钠(60.6mmol,4.18g),得到无色溶液并将反应物在0℃下再搅拌20分钟。将在20mL水中的碘化钾(75.7mmol,12.6g)逐滴添加到反应物中,并且然后将混合物再搅拌4小时。将反应物用饱和硫代硫酸钠淬灭,直到混合物变得澄清。然后将混合物用二氯甲烷稀释并且分离相。将水溶液进一步用二氯甲烷萃取,并将合并的有机萃取物用水洗涤、干燥(MgSO4)、过滤并在真空下浓缩,以得到淡黄色油状物。通过柱色谱法(EtOAc/己烷梯度洗脱)纯化粗产物,以得到呈无色油状物的3-碘-1-甲基-5-(三氟甲基)吡唑,3.9g,(47%)。
1H NMR(400MHz,CDCl3)δ=6.76(s,1H)4.01(d,J=0.61Hz,3H)。
步骤2 1-甲基-3-[(E)-2-硝基乙烯基]-5-(三氟甲基)吡唑
在-20℃下将THF中的异丙基氯化镁-氯化锂(23.55mmol,1.3mol/L)逐滴添加到THF(90mL)中的3-碘-1-甲基-5-(三氟甲基)吡唑(5.0g,18.12mmol)中并将混合物搅拌2小时。添加1-二甲基氨基-2-硝基乙烯(27.17mmol,3.321g)并在1小时内将反应物缓慢温热至室温。然后将反应混合物小心地用2M HCl淬灭,并用乙酸乙酯萃取。将有机萃取物用盐水洗涤、干燥(MgSO4)、过滤、浓缩并通过色谱法(EtOAc/环己烷梯度洗脱)纯化,以得到呈黄色油状物的1-甲基-3-[(E)-2-硝基乙烯基]-5-(三氟甲基)吡唑(74.6%),2.99g(74.6%)。
1H NMR(400MHz,CDCl3)δ=7.89(d,J=13.7Hz,1H),7.63(d,J=13.7Hz,1H),6.88(s,1H),4.05(d,J=0.6Hz,3H)。
步骤3 2-[(1S)-1-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-硝基-乙基]丙二酸二乙酯
向甲苯(19.5mL)中的1-甲基-3-[(E)-2-硝基乙烯基]-5-(三氟甲基)吡唑(0.650g,2.94mmol)溶液中添加丙二酸二乙酯(0.676mL,4.41mmol),然后添加镍(II)双[(1R,2R)-N1,N2-双(苯基甲基)-1,2-环己烷二胺-N1,N2]二溴化物(0.0588mmol,0.0472g),并将混合物在环境温度下搅拌20小时。
将反应混合物用水(2x10mL)洗涤并将有机相分离、浓缩并通过色谱法(EtOAc/环己烷梯度洗脱)纯化,以得到呈淡黄色油状物的2-[(1S)-1-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-硝基-乙基]丙二酸二乙酯,1.07g(95%)。
1H NMR(400MHz,CDCl3)δ=6.53(s,1H),5.01(dd,1H),4.88(dd,J=4.3,13.9Hz,1H),4.35(ddd,J=4.4,7.7,9.0Hz,1H),4.22(q,2H),4.16(q,J=7.1Hz,2H),3.90(s,3H),3.89(d,1H),1.26(t,3H),1.20(t,J=7.2Hz,3H)。
步骤4(3R,4R)-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酸乙酯
向在氮气下的冷却至0℃-5℃(冰浴)的乙醇(42.1mL)中的2-[(1R)-1-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-硝基-乙基]丙二酸二乙酯(1.07g,2.81mmol)溶液中添加二氯化镍六水合物(2.95mmol,0.700g)。然后将硼氢化钠(8.42mmol,0.325g)分批添加到淡绿蓝色的溶液中。30分钟后,除去冷却,并使反应混合物温热至环境温度。搅拌5小时后,在环境温度下,将反应混合物在冰-水浴中冷却到5℃-10℃,并缓慢地用氯化铵溶液淬灭,并将混合物再搅拌20分钟。然后将混合物用EtOAc(20mL)稀释,并通过硅藻土床过滤,用分批的水和EtOAc洗涤。将收集的两相混合物浓缩以除去大部分溶剂,并将残余物转移到分液漏斗中、用EtOAc(20mL)稀释并将有机相分离。将水相进一步用EtOAc(2x 25mL)萃取,并将所有的有机萃取物合并,通过相分离浓缩并通过色谱法(EtOAc/己烷梯度洗脱)纯化,以得到淡黄色油状物,0.61g(77%),其在静置后结晶。
1H NMR(400MHz,CDCl3)δ=6.91(br s,1H),6.47(s,1H),4.28(q,J=7.2Hz,2H),4.14(q,1H),3.94(d,3H),3.80(dt,J=1.0,9.0Hz,1H),3.63(d,J=9.3Hz,1H),3.52(dd,J=8.2,9.5Hz,1H),1.32(t,J=7.2Hz,3H)。
步骤5(3R,4R)-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酸
在0℃(冰浴)下向乙醇(6.0mL)和水(2.0mL)中的(3R,4R)-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酸乙酯(0.61g,2.0mmol)溶液中添加2M氢氧化钠(3mL,6.0mmol)。将反应混合物在0℃下搅拌30分钟并且然后用水(15mL)稀释并用EtOAc(25mL)萃取。将有机萃取物用水(10mL)洗涤,并将水性萃取物合并并且用稀HCl酸化至pH2。然后将酸化的水性萃取物用EtOAc(3x 20mL)再萃取,并将这些有机萃取物穿过相分离筒并浓缩,得到淡黄色油状物,0.54g(定量),其在静置后结晶。
1H NMR(400MHz,CDCl3)δ=6.59(s,1H),4.09(q,1H),3.94(s,3H),3.85-3.77(m,1H),3.72(d,J=10.0Hz,1H),3.66-3.58(m,1H)。
步骤6(3R,4R)-1-甲基-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酸
在氮气氛下,在室温下,向四氢呋喃(16mL)中的(3R,4R)-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酸(0.57g,2.1mmol,0.57g)搅拌溶液中添加叔丁醇钾(1.0M在THF中)(4.5mL,4.5mmol),得到淡黄色精细悬浮液。向此悬浮液中添加碘甲烷(0.19mL,3.1mmol),并在室温下继续搅拌20h。将搅拌的反应混合物用稀HCl酸化至pH 2,并将混合物用水(10mL)稀释并用EtOAc(3x 30mL)萃取。将合并的有机萃取物用盐水(15mL)洗涤、经硫酸镁干燥、过滤并将滤液浓缩,得到透明的琥珀色胶状物,0.63g(定量)。
1H NMR:(400MHz,CDCl3)δ=6.68(s,1H),3.97(q,1H),3.94(s,3H),3.76-3.68(m,3H),2.99(s,3H)。
步骤7(3S,4R)-N-(2,3-二氟苯基)-1-甲基-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酰胺
向二氯甲烷(15mL)中的(3R,4R)-1-甲基-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酸(0.61g,2.1mmol)溶液中添加2,3-二氟苯胺(0.21mL,2.1mmol)。然后添加乙酸乙酯中的丙基膦酸酐(50质量%)(2.3g,3.6mmol,2.1mL),并且然后将反应混合物浸入室温的水浴中。逐滴添加N,N-二异丙基乙胺(1.1mL,6.3mmol),并将反应物在室温下搅拌2.5小时。将反应混合物通过添加水(15mL)淬灭并转移到相分离筒中。将水溶液进一步用DCM(2x 10mL)萃取并将合并的有机萃取物浓缩并通过色谱法(EtOAc/己烷梯度洗脱)纯化,以得到粉色油状物。用异己烷研磨得到淡粉色固体398mg(47%)。
1H NMR:(400MHz,CDCl3)δ=10.16(br s,1H),8.08-8.01(m,1H),7.02(ddt,J=2.1,5.9,8.3Hz,1H),6.93-6.84(m,1H),6.69(s,1H),4.09(q,1H),3.94(s,3H),3.78(d,J=9.5Hz,1H),3.76-3.65(m,2H),2.98(s,3H)。
通过上述方法进行的手性HPLC分析确认对映异构体比率为97:3。
实例2(3S,4S)-N-(2,3-二氟苯基)-1-甲基-4-[1-甲基-5-(三氟甲基)吡唑-4-基]-2-氧代-吡咯烷-3-甲酰胺的制备
除草化合物(3S,4S)-N-(2,3-二氟苯基)-1-甲基-4-[1-甲基-5-(三氟甲基)吡唑-4-基]-2-氧代-吡咯烷-3-甲酰胺以与以上对于以上实例1中的(3S,4R)-N-(2,3-二氟苯基)-1-甲基-4-[1-甲基-5-(三氟甲基)吡唑-3-基]-2-氧代-吡咯烷-3-甲酰胺所述的完全类似的方式制造。单一对映异构体的NMR数据如下:
1HNMR(CDCl3)δ=10.05(br s,1H),8.04-7.97(m,1H),7.46(s,1H),7.01(ddt,J=2.1,5.9,8.3Hz,1H),6.93-6.84(m,1H),4.21(q,J=8.8Hz,1H),4.00(s,3H),3.75(t,J=9.5Hz,1H),3.64(d,J=9.4Hz,1H),3.27(dd,J=8.1,9.9Hz,1H),2.97(s,3H)。
Claims (7)
4.如权利要求1至3中任一项所述的化合物,其中,RB2选自由以下组成的组:甲基、乙基、正丙基、氟甲基、三氟甲基、氟乙基、二氟乙基和三氟乙基。
5.如前述权利要求中任一项所述的化合物,其中,RB3选自由以下组成的组:氯、氟、溴、甲基、乙基、二氟甲基、三氟甲基、C1-C3卤代烷氧基、C1-C3烷氧基和C1-C3烷基。
6.一种用于制造具有式(D)的化合物的对映选择性方法
其中环A是二取代的吡唑,在环氮上被RB2取代并在环碳上被RB3取代,其中RB2是C1-C3烷基或C1-C3氟烷基并且每个RB3是卤素、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、C1-C3卤代烷基、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、或C1-C3烷基,
所述对映选择性方法包括:
(i)使具有式(A)的卤化吡唑,
与异丙基氯化镁-氯化锂在合适的溶剂中反应并且随后添加1-二甲基氨基-2-硝基乙烯以得到具有式(B)的化合物
(ii)使来自步骤(i)的所述具有式(B)的化合物与丙二酸酯在溶剂中在对映选择性镍催化下反应以得到具有式(C)的化合物
以及
(iii)使来自步骤2的所述具有式(C)的化合物与还原剂在溶剂中在催化剂存在下反应以得到所述具有式(D)的化合物
7.一种用于制造具有式(E)的化合物的对映选择性方法
其中环A是二取代的吡唑,在环氮上被RB2取代并在环碳上被RB3取代,其中RB2是C1-C3烷基或C1-C3氟烷基并且每个RB3是卤素、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、C1-C3卤代烷基、C1-C3氟烷基、C1-C3卤代烷氧基、C1-C3烷氧基、或C1-C3烷基,
(i)所述对映选择性方法包括:使具有式(A)的卤化吡唑,
与异丙基氯化镁-氯化锂在合适的溶剂中反应并且随后添加1-二甲基氨基-2-硝基乙烯以得到具有式(B)的化合物
(ii)使来自步骤(i)的所述具有式(B)的化合物与丙二酸酯在溶剂中在对映选择性镍催化下反应以得到具有式(C)的化合物
(iii)使来自步骤2的所述具有式(C)的化合物与还原剂在溶剂中在催化剂存在下反应以得到具有式(D)的化合物
(iv)在水性氢氧化物/乙醇混合物中水解来自步骤(iii)的所述具有式(D)的化合物以得到所述具有式(E)的化合物
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1901559.3A GB201901559D0 (en) | 2019-02-05 | 2019-02-05 | Herbicidal compositions |
GB1901559.3 | 2019-02-05 | ||
PCT/EP2020/052892 WO2020161199A1 (en) | 2019-02-05 | 2020-02-05 | Pyrazole derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113423690A true CN113423690A (zh) | 2021-09-21 |
CN113423690B CN113423690B (zh) | 2023-12-22 |
Family
ID=65997122
Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202080012473.7A Pending CN113412254A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
CN202311588225.9A Pending CN117683024A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
CN202311588227.8A Pending CN117700363A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
CN202080012476.0A Active CN113423270B (zh) | 2019-02-05 | 2020-02-04 | 除草混合物 |
CN202311588226.3A Pending CN117658988A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
CN202080012471.8A Active CN113423690B (zh) | 2019-02-05 | 2020-02-05 | 吡唑衍生物 |
Family Applications Before (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202080012473.7A Pending CN113412254A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
CN202311588225.9A Pending CN117683024A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
CN202311588227.8A Pending CN117700363A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
CN202080012476.0A Active CN113423270B (zh) | 2019-02-05 | 2020-02-04 | 除草混合物 |
CN202311588226.3A Pending CN117658988A (zh) | 2019-02-05 | 2020-02-04 | 吡唑衍生物 |
Country Status (15)
Country | Link |
---|---|
US (11) | US11059806B2 (zh) |
EP (3) | EP3921306A2 (zh) |
JP (3) | JP2022519657A (zh) |
KR (1) | KR20210125022A (zh) |
CN (6) | CN113412254A (zh) |
AU (3) | AU2020218608A1 (zh) |
BR (2) | BR112021015296A2 (zh) |
CA (3) | CA3128447A1 (zh) |
CL (1) | CL2021001983A1 (zh) |
CO (1) | CO2021010365A2 (zh) |
EA (1) | EA202192135A1 (zh) |
GB (1) | GB201901559D0 (zh) |
IL (1) | IL284977A (zh) |
MX (1) | MX2021009422A (zh) |
WO (3) | WO2020161148A2 (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11589583B2 (en) | 2013-12-03 | 2023-02-28 | Fmc Corporation | Pyrrolidinones herbicides |
GB201901559D0 (en) * | 2019-02-05 | 2019-03-27 | Syngenta Crop Protection Ag | Herbicidal compositions |
PE20221411A1 (es) * | 2019-05-24 | 2022-09-20 | Fmc Corp | Pirrolidinonas sustituidas con pirazol como herbicidas |
GB202012143D0 (en) * | 2020-08-05 | 2020-09-16 | Syngenta Crop Protection Ag | Herbicidal compounds |
GB202012651D0 (en) * | 2020-08-13 | 2020-09-30 | Syngenta Crop Protection Ag | Herbicidal compositions |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006127396A1 (en) * | 2005-05-27 | 2006-11-30 | Acadia Pharmaceuticals Inc. | Par2-modulating compounds and their use |
CN112236423A (zh) * | 2018-03-01 | 2021-01-15 | 武田药品工业株式会社 | 哌啶基-3-(芳氧基)丙酰胺和丙酸酯 |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4302239A (en) | 1980-02-19 | 1981-11-24 | Ppg Industries, Inc. | 3-(5- or 3-Substituted-5- or 3-isoxazolyl)-1-allyl or alkyl-4-substituted-5-substituted or unsubstituted-2-imidazolidinones for controlling weeds |
CA1205077A (en) | 1983-03-28 | 1986-05-27 | Jay K. Rinehart | Herbicidally active 3-isoxazolyl-2-imidazolidinone derivatives |
US4600430A (en) | 1985-02-22 | 1986-07-15 | Eli Lilly And Company | Pyridinylimidazolidinone compounds |
US4874422A (en) | 1988-12-27 | 1989-10-17 | Ici Americas Inc. | 1-Phenyl-3-carboxyamidopyrrolidones and their use as herbicides |
US5763470A (en) | 1995-06-07 | 1998-06-09 | Sugen Inc. | Benzopyran compounds and methods for their use |
AR031027A1 (es) | 2000-10-23 | 2003-09-03 | Syngenta Participations Ag | Composiciones agroquimicas |
DE60218193T2 (de) | 2001-10-08 | 2007-11-22 | Ucb S.A. | Verwendung von 2-oxo-1-pyrrolidin-derivaten zur herstellung eines arzneimittels zur behandlung von dyskinesia |
AR041867A1 (es) * | 2002-11-01 | 2005-06-01 | Takeda Pharmaceutical | Agente para prevenir o tratar neuropatia |
DE10300124A1 (de) * | 2003-01-07 | 2004-07-15 | Bayer Ag | Verfahren zur Herstellung von Arylalkinen |
CH697574B1 (de) * | 2003-01-07 | 2008-12-15 | Lanxess Deutschland Gmbh | Pyrazolylarylalkine. |
ATE482973T1 (de) | 2003-03-14 | 2010-10-15 | Oriental Yeast Co Ltd | Peptidfragment von lyve-1 und gegen dieses gerichteter antikörper |
PT2680694T (pt) * | 2011-02-28 | 2019-03-14 | Biomarin Pharm Inc | Inibidores de histona deacetilase |
US8957066B2 (en) * | 2011-02-28 | 2015-02-17 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
UA118035C2 (uk) | 2013-10-07 | 2018-11-12 | Сінгента Партісіпейшнс Аг | Гербіцидні сполуки |
GB201318863D0 (en) | 2013-10-25 | 2013-12-11 | Syngenta Ltd | Herbicidal compounds |
ES2786927T3 (es) | 2013-12-03 | 2020-10-14 | Fmc Corp | Pirrolidinonas como herbicidas |
US9751865B2 (en) | 2013-12-23 | 2017-09-05 | Syngenta Limited | Dihydro-hydantoin derivatives with herbicidal activity |
TWI659019B (zh) | 2014-02-28 | 2019-05-11 | 日商帝人製藥股份有限公司 | 吡唑醯胺衍生物 |
AR100776A1 (es) | 2014-06-16 | 2016-11-02 | Syngenta Participations Ag | Compuestos herbicidas |
US10208008B2 (en) | 2014-11-26 | 2019-02-19 | Visolis, Inc. | Processes for conversion of biologically derived mevalonic acid |
WO2016095089A1 (en) | 2014-12-15 | 2016-06-23 | Merck Sharp & Dohme Corp. | Erk inhibitors |
CN104844519A (zh) * | 2015-06-09 | 2015-08-19 | 浙江华海药业股份有限公司 | 一种制备依普罗沙坦杂质ep12a的方法 |
GB201617050D0 (en) | 2016-10-07 | 2016-11-23 | Syngenta Participations Ag | Herbicidal mixtures |
WO2018177837A1 (de) * | 2017-03-30 | 2018-10-04 | Bayer Aktiengesellschaft | 4-cyclopentyl- und 4-cyclopropyl-2-oxopyrrolidin-3-carboxami d-derivate und verwandte verbindungen als herbizide pflanzenschutzmittel |
WO2018177836A1 (de) * | 2017-03-30 | 2018-10-04 | Bayer Aktiengesellschaft | N-cyclopropyl-2-oxopyrrolidin-3-carboxamid-derivate und verwandte verbindungen als herbizide pflanzenschutzmittel |
WO2019025156A1 (de) * | 2017-08-03 | 2019-02-07 | Bayer Aktiengesellschaft | Substituierte pyrrolidinone sowie deren salze und ihre verwendung als herbizide wirkstoffe |
GB201901559D0 (en) * | 2019-02-05 | 2019-03-27 | Syngenta Crop Protection Ag | Herbicidal compositions |
-
2019
- 2019-02-05 GB GBGB1901559.3A patent/GB201901559D0/en not_active Ceased
-
2020
- 2020-02-04 EA EA202192135A patent/EA202192135A1/ru unknown
- 2020-02-04 EP EP20703984.3A patent/EP3921306A2/en active Pending
- 2020-02-04 WO PCT/EP2020/052782 patent/WO2020161148A2/en active Application Filing
- 2020-02-04 CA CA3128447A patent/CA3128447A1/en active Pending
- 2020-02-04 WO PCT/EP2020/052780 patent/WO2020161147A1/en unknown
- 2020-02-04 CN CN202080012473.7A patent/CN113412254A/zh active Pending
- 2020-02-04 AU AU2020218608A patent/AU2020218608A1/en active Pending
- 2020-02-04 KR KR1020217027433A patent/KR20210125022A/ko unknown
- 2020-02-04 AU AU2020219393A patent/AU2020219393A1/en active Pending
- 2020-02-04 CN CN202311588225.9A patent/CN117683024A/zh active Pending
- 2020-02-04 BR BR112021015296-2A patent/BR112021015296A2/pt unknown
- 2020-02-04 EP EP20703983.5A patent/EP3920700A1/en active Pending
- 2020-02-04 JP JP2021545858A patent/JP2022519657A/ja active Pending
- 2020-02-04 CN CN202311588227.8A patent/CN117700363A/zh active Pending
- 2020-02-04 MX MX2021009422A patent/MX2021009422A/es unknown
- 2020-02-04 CA CA3128444A patent/CA3128444A1/en active Pending
- 2020-02-04 CN CN202080012476.0A patent/CN113423270B/zh active Active
- 2020-02-04 JP JP2021545787A patent/JP2022519857A/ja active Pending
- 2020-02-04 CN CN202311588226.3A patent/CN117658988A/zh active Pending
- 2020-02-05 CA CA3128449A patent/CA3128449A1/en active Pending
- 2020-02-05 US US16/782,796 patent/US11059806B2/en active Active
- 2020-02-05 BR BR112021015362-4A patent/BR112021015362A2/pt unknown
- 2020-02-05 US US16/782,866 patent/US10882846B2/en active Active
- 2020-02-05 AU AU2020217580A patent/AU2020217580A1/en active Pending
- 2020-02-05 US US16/782,530 patent/US11472792B2/en active Active
- 2020-02-05 JP JP2021545830A patent/JP2022519864A/ja active Pending
- 2020-02-05 WO PCT/EP2020/052892 patent/WO2020161199A1/en active Application Filing
- 2020-02-05 EP EP20704804.2A patent/EP3921307B1/en active Active
- 2020-02-05 CN CN202080012471.8A patent/CN113423690B/zh active Active
- 2020-05-14 US US16/874,165 patent/US10947219B2/en active Active
- 2020-05-14 US US16/874,136 patent/US10851085B2/en active Active
- 2020-05-15 US US16/874,715 patent/US10865197B2/en active Active
- 2020-12-01 US US17/108,110 patent/US11548873B2/en active Active
-
2021
- 2021-01-29 US US17/161,788 patent/US11680057B2/en active Active
- 2021-07-19 IL IL284977A patent/IL284977A/en unknown
- 2021-07-28 CL CL2021001983A patent/CL2021001983A1/es unknown
- 2021-08-06 CO CONC2021/0010365A patent/CO2021010365A2/es unknown
-
2022
- 2022-09-15 US US17/945,221 patent/US20230286952A1/en active Pending
- 2022-12-07 US US18/062,744 patent/US11851420B2/en active Active
-
2023
- 2023-05-17 US US18/319,066 patent/US20230286954A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006127396A1 (en) * | 2005-05-27 | 2006-11-30 | Acadia Pharmaceuticals Inc. | Par2-modulating compounds and their use |
CN112236423A (zh) * | 2018-03-01 | 2021-01-15 | 武田药品工业株式会社 | 哌啶基-3-(芳氧基)丙酰胺和丙酸酯 |
Non-Patent Citations (2)
Title |
---|
BARNES, DAVID M.,等: "Development of a Catalytic Enantioselective Conjugate Addition of 1,3-Dicarbonyl Compounds to Nitroalkenes for the Synthesis of Endothelin-A Antagonist ABT-546. Scope, Mechanism, and Further Application to the Synthesis of the Antidepressant Rolipram.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 124, no. 44, pages 13097 * |
DAVID A. EVANS,等: "Ni(II)-Bis[(R,R)- N,N′-dibenzylcyclohexane-1,2-diamine]Br 2 Catalyzed Enantioselective Michael Additions of 1,3-Dicarbonyl Compounds to Conjugated Nitroalkenes", JACS, vol. 127, no. 28, pages 9958, XP002543743, DOI: 10.1021/JA052935R * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113423690B (zh) | 吡唑衍生物 | |
KR100953251B1 (ko) | 치환된 디히드로 3-할로-1h-피라졸-5-카르복실레이트, 그의 제조 방법 및 용도 | |
AU2016346207B2 (en) | Intermediates to prepare pyridazinone herbicides, and a process to prepare them | |
JPWO2006090778A1 (ja) | 1−置換−3−フルオロアルキルピラゾール−4−カルボン酸エステルの製造方法 | |
JP2007326784A (ja) | 1−置換−5−フルオロアルキルピラゾール−4−カルボン酸エステルの製造方法 | |
EP2114884B1 (en) | Process for the preparation of 2-substituted-5-(1-alkylthio) alkylpyridines | |
EP0990647B1 (en) | Process for producing quinolone derivatives | |
JP2023538572A (ja) | キノロン化合物及びその製造方法 | |
EP2866562B1 (en) | Pyridine n-oxides and processes for their preparation | |
Hegde et al. | Aromatization reactions of 2-cyclohexenones and 1, 3-cyclohexadien-1-amines with iodine/sodium alkoxide | |
AU2017258668A1 (en) | Process for the preparation of herbicidal pyridinylimidazolone compounds | |
KR20000056672A (ko) | 광학활성 퀴놀론카르복실산 유도체의 제조방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |