JP2021528405A - ＲＯＲγｔのモジュレータとしてのアミド置換チアゾール - Google Patents

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Publication number

JP2021528405A

JP2021528405A JP2020570426A JP2020570426A JP2021528405A JP 2021528405 A JP2021528405 A JP 2021528405A JP 2020570426 A JP2020570426 A JP 2020570426A JP 2020570426 A JP2020570426 A JP 2020570426A JP 2021528405 A JP2021528405 A JP 2021528405A

Authority

JP

Japan

Prior art keywords

alkyl

ethyl

disease

bromo

nhc

Prior art date

2018-06-18

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.)

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• 108091008778 RORγ2 Proteins 0.000 title claims abstract description 25
• 150000003557 thiazoles Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 417
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 180
• 201000010099 disease Diseases 0.000 claims abstract description 173
• 238000000034 method Methods 0.000 claims abstract description 98
• 208000011580 syndromic disease Diseases 0.000 claims abstract description 82
• 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 15
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims abstract description 11
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims abstract description 11
• 230000001404 mediated effect Effects 0.000 claims abstract description 10
• 239000000203 mixture Substances 0.000 claims description 329
• -1 R 4 is Chemical group 0.000 claims description 273
• 125000000217 alkyl group Chemical group 0.000 claims description 209
• 201000006417 multiple sclerosis Diseases 0.000 claims description 58
• 238000011282 treatment Methods 0.000 claims description 54
• 125000001153 fluoro group Chemical group F* 0.000 claims description 49
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
• 150000003839 salts Chemical class 0.000 claims description 32
• 239000003795 chemical substances by application Substances 0.000 claims description 29
• 201000004681 Psoriasis Diseases 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 14
• 102000013691 Interleukin-17 Human genes 0.000 claims description 14
• 108050003558 Interleukin-17 Proteins 0.000 claims description 14
• 208000006673 asthma Diseases 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 230000002757 inflammatory effect Effects 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 8
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 8
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 8
• 201000002661 Spondylitis Diseases 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 230000001256 tonic effect Effects 0.000 claims description 7
• 208000011231 Crohn disease Diseases 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 210000000440 neutrophil Anatomy 0.000 claims description 6
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 5
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 5
• 238000002648 combination therapy Methods 0.000 claims description 5
• 229940125721 immunosuppressive agent Drugs 0.000 claims description 5
• 239000003018 immunosuppressive agent Substances 0.000 claims description 5
• 150000003431 steroids Chemical class 0.000 claims description 5
• 238000002156 mixing Methods 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 4
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• 230000002401 inhibitory effect Effects 0.000 claims description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 1
• 125000002345 steroid group Chemical group 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 7
• 241000124008 Mammalia Species 0.000 abstract description 3
• 230000001105 regulatory effect Effects 0.000 abstract 1
• 239000000543 intermediate Substances 0.000 description 826
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 305
• 239000000243 solution Substances 0.000 description 224
• 230000015572 biosynthetic process Effects 0.000 description 202
• 238000003786 synthesis reaction Methods 0.000 description 202
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 183
• 235000019439 ethyl acetate Nutrition 0.000 description 152
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 141
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 131
• 239000007787 solid Substances 0.000 description 106
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 103
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
• 239000010410 layer Substances 0.000 description 96
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 94
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 75
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 67
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
• 239000012044 organic layer Substances 0.000 description 64
• 238000010898 silica gel chromatography Methods 0.000 description 62
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 58
• 239000000725 suspension Substances 0.000 description 55
• 238000005481 NMR spectroscopy Methods 0.000 description 54
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 50
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 47
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
• 239000012065 filter cake Substances 0.000 description 44
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 44
• 239000000706 filtrate Substances 0.000 description 43
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
• 238000006243 chemical reaction Methods 0.000 description 41
• NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 41
• 239000011734 sodium Substances 0.000 description 40
• 239000011541 reaction mixture Substances 0.000 description 38
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
• 239000002904 solvent Substances 0.000 description 33
• 239000012141 concentrate Substances 0.000 description 32
• 238000003756 stirring Methods 0.000 description 31
• 239000003153 chemical reaction reagent Substances 0.000 description 30
• 229920006395 saturated elastomer Polymers 0.000 description 29
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
• 125000004093 cyano group Chemical group *C#N 0.000 description 27
• 239000012267 brine Substances 0.000 description 26
• UKCNODMPTBZWCH-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)OC UKCNODMPTBZWCH-UHFFFAOYSA-N 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• 239000007864 aqueous solution Substances 0.000 description 25
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 25
• 238000009472 formulation Methods 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
• 239000002585 base Substances 0.000 description 21
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 19
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 18
• 150000001408 amides Chemical class 0.000 description 18
• 150000007942 carboxylates Chemical class 0.000 description 18
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 18
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 18
• KYZHKXMHJFOQPM-UHFFFAOYSA-N 1-(4-bromo-2-methoxyphenyl)ethanone Chemical compound COC1=CC(Br)=CC=C1C(C)=O KYZHKXMHJFOQPM-UHFFFAOYSA-N 0.000 description 16
• SKEHVMZPBBGBAO-UHFFFAOYSA-N ethylhydrazine;hydrochloride Chemical compound Cl.CCNN SKEHVMZPBBGBAO-UHFFFAOYSA-N 0.000 description 16
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 16
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
• 239000011701 zinc Substances 0.000 description 16
• 229910002091 carbon monoxide Inorganic materials 0.000 description 15
• 238000006722 reduction reaction Methods 0.000 description 15
• 230000005526 G1 to G0 transition Effects 0.000 description 14
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 14
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 14
• 230000009467 reduction Effects 0.000 description 14
• 229910052725 zinc Inorganic materials 0.000 description 14
• 206010061218 Inflammation Diseases 0.000 description 13
• 150000001412 amines Chemical class 0.000 description 13
• 230000004054 inflammatory process Effects 0.000 description 13
• 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 12
• 210000000068 Th17 cell Anatomy 0.000 description 12
• 125000001309 chloro group Chemical group Cl* 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 239000012230 colorless oil Substances 0.000 description 11
• 239000003208 petroleum Substances 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• XVRFRUNBIBOLPT-UHFFFAOYSA-N 1,1,1-trifluoro-3-iodo-2,2-dimethylpropane Chemical compound C(C)(C(F)(F)F)(C)CI XVRFRUNBIBOLPT-UHFFFAOYSA-N 0.000 description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical compound CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 description 10
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 229940124530 sulfonamide Drugs 0.000 description 10
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 108010065637 Interleukin-23 Proteins 0.000 description 9
• 102000013264 Interleukin-23 Human genes 0.000 description 9
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 9
• HMPFIGZCHPKESX-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)OC(F)F)CC)C(=O)OCC HMPFIGZCHPKESX-UHFFFAOYSA-N 0.000 description 9
• BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• 239000012453 solvate Substances 0.000 description 9
• KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 8
• 108090000695 Cytokines Proteins 0.000 description 8
• 238000003776 cleavage reaction Methods 0.000 description 8
• AAPRWSRRUUHVNL-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CC)C(=O)OCC)OC AAPRWSRRUUHVNL-UHFFFAOYSA-N 0.000 description 8
• IFPVDZDLGKSAMG-UHFFFAOYSA-N ethyl 5-[4-bromo-2-(difluoromethoxy)phenyl]-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)OC(F)F IFPVDZDLGKSAMG-UHFFFAOYSA-N 0.000 description 8
• 238000005984 hydrogenation reaction Methods 0.000 description 8
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
• 238000002953 preparative HPLC Methods 0.000 description 8
• 239000002002 slurry Substances 0.000 description 8
• SCJCDNUXDWFVFI-UHFFFAOYSA-N 4,4,4-trifluorobutanal Chemical compound FC(F)(F)CCC=O SCJCDNUXDWFVFI-UHFFFAOYSA-N 0.000 description 7
• PMWVVXDDEDPHSV-UHFFFAOYSA-N 9-(3,3,3-trifluoropropyl)-9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2CCC(F)(F)F PMWVVXDDEDPHSV-UHFFFAOYSA-N 0.000 description 7
• 102000004127 Cytokines Human genes 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 230000000875 corresponding effect Effects 0.000 description 7
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexyloxide Natural products O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• QMEMCJVHDBMFHH-UHFFFAOYSA-N ethyl 4-[4-bromo-2-(trifluoromethoxy)phenyl]-2,4-dioxobutanoate Chemical compound CCOC(=O)C(=O)CC(=O)C1=CC=C(Br)C=C1OC(F)(F)F QMEMCJVHDBMFHH-UHFFFAOYSA-N 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• 229910052739 hydrogen Inorganic materials 0.000 description 7
• 150000002825 nitriles Chemical class 0.000 description 7
• 230000007017 scission Effects 0.000 description 7
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 7
• XOLSMTBBIZDHSG-UHFFFAOYSA-N (2,2-difluorocyclopropyl)methanol Chemical compound OCC1CC1(F)F XOLSMTBBIZDHSG-UHFFFAOYSA-N 0.000 description 6
• IPYFTOJOWXZICS-UHFFFAOYSA-N 1-(aminomethyl)-4-methylsulfonylcyclohexane-1,2-diol hydrochloride Chemical compound Cl.NCC1(C(CC(CC1)S(=O)(=O)C)O)O IPYFTOJOWXZICS-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• 239000007821 HATU Substances 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 6
• 150000004703 alkoxides Chemical class 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 6
• FFZQOFQPTUVDMT-UHFFFAOYSA-N ethyl 5-[4-bromo-2-(difluoromethoxy)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CC)C(=O)OCC)OC(F)F FFZQOFQPTUVDMT-UHFFFAOYSA-N 0.000 description 6
• 239000012458 free base Substances 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 6
• 230000003647 oxidation Effects 0.000 description 6
• 238000007254 oxidation reaction Methods 0.000 description 6
• 229920000728 polyester Polymers 0.000 description 6
• 230000002265 prevention Effects 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
• HZDUWRDWIUHEME-UHFFFAOYSA-N 4-methylsulfonylcyclohexan-1-one Chemical compound CS(=O)(=O)C1CCC(=O)CC1 HZDUWRDWIUHEME-UHFFFAOYSA-N 0.000 description 5
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
• 150000001414 amino alcohols Chemical class 0.000 description 5
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
• 229910000085 borane Inorganic materials 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
• 238000007333 cyanation reaction Methods 0.000 description 5
• AAYHAFZXFMIUSN-UHFFFAOYSA-N cyclohexanesulfonamide Chemical compound NS(=O)(=O)C1CCCCC1 AAYHAFZXFMIUSN-UHFFFAOYSA-N 0.000 description 5
• YSZBWLGHPQKHFV-UHFFFAOYSA-N ethyl 4-(4-bromo-2-methoxyphenyl)-2,4-dioxobutanoate Chemical compound CCOC(=O)C(=O)CC(=O)c1ccc(Br)cc1OC YSZBWLGHPQKHFV-UHFFFAOYSA-N 0.000 description 5
• RLSNEWFIHDBSRO-UHFFFAOYSA-N ethyl 5-[4-bromo-2-(trifluoromethoxy)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CC)C(=O)OCC)OC(F)(F)F RLSNEWFIHDBSRO-UHFFFAOYSA-N 0.000 description 5
• 235000019253 formic acid Nutrition 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
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• PRHJXNYVBUPYCY-UHFFFAOYSA-N ethyl 1-ethyl-5-[2-methoxy-4-(4,4,4-trifluorobutyl)phenyl]-4-methylpyrazole-3-carboxylate Chemical compound C(C)N1N=C(C(=C1C1=C(C=C(C=C1)CCCC(F)(F)F)OC)C)C(=O)OCC PRHJXNYVBUPYCY-UHFFFAOYSA-N 0.000 description 1
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• PXDVWKWUFTZXFB-LLVKDONJSA-N ethyl 4-chloro-1-(2-cyanoethyl)-5-[2-methoxy-4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)N[C@@H](C(F)(F)F)C)OC)CCC#N)C(=O)OCC PXDVWKWUFTZXFB-LLVKDONJSA-N 0.000 description 1
• ACPXOPYTIUGLJI-UHFFFAOYSA-N ethyl 4-chloro-1-(2-hydroxyethyl)-5-[2-methoxy-4-(3,3,3-trifluoro-2-methylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)C)OC)CCO)C(=O)OCC ACPXOPYTIUGLJI-UHFFFAOYSA-N 0.000 description 1
• WDUZTESBOGDMTN-SNVBAGLBSA-N ethyl 4-chloro-1-(2-hydroxyethyl)-5-[2-methoxy-4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)N[C@@H](C(F)(F)F)C)OC)CCO)C(=O)OCC WDUZTESBOGDMTN-SNVBAGLBSA-N 0.000 description 1
• PCFRFDWSFZLEHX-LLVKDONJSA-N ethyl 4-chloro-1-(2-methoxyethyl)-5-[2-methoxy-4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)N[C@@H](C(F)(F)F)C)OC)CCOC)C(=O)OCC PCFRFDWSFZLEHX-LLVKDONJSA-N 0.000 description 1
• ZKDCZENLBKLTGI-UHFFFAOYSA-N ethyl 4-chloro-1-(3-cyanopropyl)-5-[2-(difluoromethoxy)-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)OC(F)F)CCCC#N)C(=O)OCC ZKDCZENLBKLTGI-UHFFFAOYSA-N 0.000 description 1
• FQNVYMREUQCHDN-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-(trifluoromethoxy)-4-(3,3,3-trifluoro-2-methylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)C)OC(F)(F)F)CC)C(=O)OCC FQNVYMREUQCHDN-UHFFFAOYSA-N 0.000 description 1
• XWDACZNGZVLNIN-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-(trifluoromethoxy)-4-(3,3,3-trifluoropropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CCC(F)(F)F)OC(F)(F)F)CC)C(=O)OCC XWDACZNGZVLNIN-UHFFFAOYSA-N 0.000 description 1
• SDPJOOQCMJOMJV-SECBINFHSA-N ethyl 4-chloro-1-ethyl-5-[2-(trifluoromethoxy)-4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)N[C@@H](C(F)(F)F)C)OC(F)(F)F)CC)C(=O)OCC SDPJOOQCMJOMJV-SECBINFHSA-N 0.000 description 1
• CTKMOCUCGTUAAR-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-(trifluoromethyl)-4-(3,3,3-trifluoropropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CCC(F)(F)F)C(F)(F)F)CC)C(=O)OCC CTKMOCUCGTUAAR-UHFFFAOYSA-N 0.000 description 1
• FAHXBKKLEVOWQH-SECBINFHSA-N ethyl 4-chloro-1-ethyl-5-[2-(trifluoromethyl)-4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)N[C@@H](C(F)(F)F)C)C(F)(F)F)CC)C(=O)OCC FAHXBKKLEVOWQH-SECBINFHSA-N 0.000 description 1
• ZHPXPGUUMIAEDB-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-fluoro-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)F)CC)C(=O)OCC ZHPXPGUUMIAEDB-UHFFFAOYSA-N 0.000 description 1
• QNNGCCPTDUGAJN-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-fluoro-4-(3,3,3-trifluoropropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CCC(F)(F)F)F)CC)C(=O)OCC QNNGCCPTDUGAJN-UHFFFAOYSA-N 0.000 description 1
• DMAJZNQPWRJOIB-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-methoxy-4-(2-methylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound N1(CC)C(C2=C(C=C(C=C2)CC(C)C)OC)=C(C(=N1)C(=O)OCC)Cl DMAJZNQPWRJOIB-UHFFFAOYSA-N 0.000 description 1
• UFCAHLFLXQBJMP-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-methoxy-4-(3,3,3-trifluoro-2-methylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)C)OC)CC)C(=O)OCC UFCAHLFLXQBJMP-UHFFFAOYSA-N 0.000 description 1
• HYLZJCGHKPGKOJ-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-methoxy-4-(3,3,3-trifluoropropoxy)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)OCCC(F)(F)F)OC)CC)C(=O)OCC HYLZJCGHKPGKOJ-UHFFFAOYSA-N 0.000 description 1
• IZZOJOSOXWTRRL-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-methoxy-4-(3-methylbutyl)phenyl]pyrazole-3-carboxylate Chemical compound N1(CC)C(C2=CC=C(CCC(C)C)C=C2OC)=C(C(=N1)C(=O)OCC)Cl IZZOJOSOXWTRRL-UHFFFAOYSA-N 0.000 description 1
• HQTLLAMTGMPVPL-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-methoxy-4-[(1-methylcyclopropyl)methoxy]phenyl]pyrazole-3-carboxylate Chemical compound N1(CC)C(C2=C(C=C(C=C2)OCC2(C)CC2)OC)=C(C(=N1)C(=O)OCC)Cl HQTLLAMTGMPVPL-UHFFFAOYSA-N 0.000 description 1
• YISWHSITTKNRSH-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[2-methyl-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)C)CC)C(=O)OCC YISWHSITTKNRSH-UHFFFAOYSA-N 0.000 description 1
• RVMQNSNBAWZZON-UHFFFAOYSA-N ethyl 4-chloro-1-ethyl-5-[4-(3,3,3-trifluoro-2,2-dimethylpropyl)-2-(trifluoromethyl)phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)C(F)(F)F)CC)C(=O)OCC RVMQNSNBAWZZON-UHFFFAOYSA-N 0.000 description 1
• WXFMRFUUICASGH-SNVBAGLBSA-N ethyl 4-chloro-1-ethyl-5-[4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=CC=C(C=C1)N[C@@H](C(F)(F)F)C)CC)C(=O)OCC WXFMRFUUICASGH-SNVBAGLBSA-N 0.000 description 1
• IXTTWWZKPJNNOU-UHFFFAOYSA-N ethyl 4-chloro-5-[2,6-difluoro-4-(3,3,3-trifluoro-2-methylpropyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1F)CC(C(F)(F)F)C)F)CC)C(=O)OCC IXTTWWZKPJNNOU-UHFFFAOYSA-N 0.000 description 1
• PQNRJGKBMKYLSR-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)C(C(F)(F)F)(C(F)(F)F)O)OC(F)F)CC)C(=O)OCC PQNRJGKBMKYLSR-UHFFFAOYSA-N 0.000 description 1
• PYOWGEPOGDNAAD-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(2,2,2-trifluoroacetyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)C(C(F)(F)F)=O)OC(F)F)CC)C(=O)OCC PYOWGEPOGDNAAD-UHFFFAOYSA-N 0.000 description 1
• IVZKQHVLFVZQKH-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]-1-(2-methoxyethyl)pyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)OC(F)F)CCOC)C(=O)OCC IVZKQHVLFVZQKH-UHFFFAOYSA-N 0.000 description 1
• XLAAKVSCPZYORV-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]-1-methylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)OC(F)F)C)C(=O)OCC XLAAKVSCPZYORV-UHFFFAOYSA-N 0.000 description 1
• AIAGVFPITPDHTM-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(3,3,3-trifluoropropyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CCC(F)(F)F)OC(F)F)CC)C(=O)OCC AIAGVFPITPDHTM-UHFFFAOYSA-N 0.000 description 1
• KWVGSBODFUOWND-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(4,4,4-trifluoro-1-hydroxybutyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)C(CCC(F)(F)F)O)OC(F)F)CC)C(=O)OCC KWVGSBODFUOWND-UHFFFAOYSA-N 0.000 description 1
• LIEJPNVXERQLEE-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(4,4,4-trifluoro-2,2-dimethylbutyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(CC(F)(F)F)(C)C)OC(F)F)CC)C(=O)OCC LIEJPNVXERQLEE-UHFFFAOYSA-N 0.000 description 1
• KGOGHKMVDVAESU-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(4,4,4-trifluoro-2-hydroxybutan-2-yl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)C(C)(CC(F)(F)F)O)OC(F)F)CC)C(=O)OCC KGOGHKMVDVAESU-UHFFFAOYSA-N 0.000 description 1
• QMYAPFVTNGPCSB-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(4,4,4-trifluorobutyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CCCC(F)(F)F)OC(F)F)CC)C(=O)OCC QMYAPFVTNGPCSB-UHFFFAOYSA-N 0.000 description 1
• XRJAHKLABRKDAH-UHFFFAOYSA-N ethyl 4-chloro-5-[2-(difluoromethoxy)-4-(4,4,4-trifluorobutyl)phenyl]-1-methylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CCCC(F)(F)F)OC(F)F)C)C(=O)OCC XRJAHKLABRKDAH-UHFFFAOYSA-N 0.000 description 1
• DPGSSOVWAXIPON-UHFFFAOYSA-N ethyl 4-chloro-5-[2-chloro-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)(C)C)Cl)CC)C(=O)OCC DPGSSOVWAXIPON-UHFFFAOYSA-N 0.000 description 1
• NIYITQWGJSRYDG-UHFFFAOYSA-N ethyl 4-chloro-5-[2-chloro-4-(3,3,3-trifluoropropyl)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CCC(F)(F)F)Cl)CC)C(=O)OCC NIYITQWGJSRYDG-UHFFFAOYSA-N 0.000 description 1
• BYAIWFPRBVAOMO-SECBINFHSA-N ethyl 4-chloro-5-[2-chloro-4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)N[C@@H](C(F)(F)F)C)Cl)CC)C(=O)OCC BYAIWFPRBVAOMO-SECBINFHSA-N 0.000 description 1
• KPISOTRYKHXLFC-LLVKDONJSA-N ethyl 4-chloro-5-[2-ethoxy-4-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)N[C@@H](C(F)(F)F)C)OCC)CC)C(=O)OCC KPISOTRYKHXLFC-LLVKDONJSA-N 0.000 description 1
• HAEDYWWYLZWXAA-UHFFFAOYSA-N ethyl 4-chloro-5-[2-methoxy-4-(3,3,3-trifluoro-2-methylpropyl)phenyl]-1-propylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)C)OC)CCC)C(=O)OCC HAEDYWWYLZWXAA-UHFFFAOYSA-N 0.000 description 1
• LRKAQNYJTIABAY-UHFFFAOYSA-N ethyl 4-chloro-5-[4-(2,2-difluoropropoxy)-2-methoxyphenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)OCC(C)(F)F)OC)CC)C(=O)OCC LRKAQNYJTIABAY-UHFFFAOYSA-N 0.000 description 1
• VWJLJMUTUSAIAF-UHFFFAOYSA-N ethyl 4-chloro-5-[4-(4,4-difluoro-1-hydroxycyclohexyl)-2-(difluoromethoxy)phenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)C1(CCC(CC1)(F)F)O)OC(F)F)CC)C(=O)OCC VWJLJMUTUSAIAF-UHFFFAOYSA-N 0.000 description 1
• YOJNHMNPQNXFKS-UHFFFAOYSA-N ethyl 4-chloro-5-[4-(4,4-difluorocyclohexyl)oxy-2-methoxyphenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)OC1CCC(CC1)(F)F)OC)CC)C(=O)OCC YOJNHMNPQNXFKS-UHFFFAOYSA-N 0.000 description 1
• UJLNRLOWVSTCPE-UHFFFAOYSA-N ethyl 4-chloro-5-[4-[(2,2-difluorocyclopropyl)methoxy]-2-methoxyphenyl]-1-ethylpyrazole-3-carboxylate Chemical compound ClC=1C(=NN(C=1C1=C(C=C(C=C1)OCC1C(C1)(F)F)OC)CC)C(=O)OCC UJLNRLOWVSTCPE-UHFFFAOYSA-N 0.000 description 1
• HWVHNKBPOSLPMX-UHFFFAOYSA-N ethyl 4-cyano-1-ethyl-5-[2-methoxy-4-(3,3,3-trifluoro-2-methylpropyl)phenyl]pyrazole-3-carboxylate Chemical compound C(#N)C=1C(=NN(C=1C1=C(C=C(C=C1)CC(C(F)(F)F)C)OC)CC)C(=O)OCC HWVHNKBPOSLPMX-UHFFFAOYSA-N 0.000 description 1
• HGLVFEIUPZQTNW-UHFFFAOYSA-N ethyl 4-cyano-1-ethyl-5-[2-methoxy-4-(3,3,3-trifluoropropyl)phenyl]pyrazole-3-carboxylate Chemical compound C(#N)C=1C(=NN(C=1C1=C(C=C(C=C1)CCC(F)(F)F)OC)CC)C(=O)OCC HGLVFEIUPZQTNW-UHFFFAOYSA-N 0.000 description 1
• VLPQNGMJDSRLSB-UHFFFAOYSA-N ethyl 5-(4-bromo-2-chlorophenyl)-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CC)C(=O)OCC)Cl VLPQNGMJDSRLSB-UHFFFAOYSA-N 0.000 description 1
• MZLUQSZYKFWOPW-UHFFFAOYSA-N ethyl 5-(4-bromo-2-chlorophenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)Cl MZLUQSZYKFWOPW-UHFFFAOYSA-N 0.000 description 1
• QWHLISICGMTSRP-UHFFFAOYSA-N ethyl 5-(4-bromo-2-ethoxyphenyl)-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CC)C(=O)OCC)OCC QWHLISICGMTSRP-UHFFFAOYSA-N 0.000 description 1
• BDWPVGAOHMQGEE-UHFFFAOYSA-N ethyl 5-(4-bromo-2-ethoxyphenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)OCC BDWPVGAOHMQGEE-UHFFFAOYSA-N 0.000 description 1
• BFMGWRHSUYKIHE-UHFFFAOYSA-N ethyl 5-(4-bromo-2-ethylphenyl)-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CC)C(=O)OCC)CC BFMGWRHSUYKIHE-UHFFFAOYSA-N 0.000 description 1
• POFZKWQZJSZFFU-UHFFFAOYSA-N ethyl 5-(4-bromo-2-ethylphenyl)-2,3,5-trioxopentanoate Chemical compound BrC1=CC(=C(C=C1)C(CC(C(C(=O)OCC)=O)=O)=O)CC POFZKWQZJSZFFU-UHFFFAOYSA-N 0.000 description 1
• LMQJPSPXQUYXLI-UHFFFAOYSA-N ethyl 5-(4-bromo-2-ethylphenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)CC LMQJPSPXQUYXLI-UHFFFAOYSA-N 0.000 description 1
• JMWBTGQUHWCSOC-UHFFFAOYSA-N ethyl 5-(4-bromo-2-fluorophenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)F JMWBTGQUHWCSOC-UHFFFAOYSA-N 0.000 description 1
• ZFHRRUUHJFBTHH-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1,4-diethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)CC)OC ZFHRRUUHJFBTHH-UHFFFAOYSA-N 0.000 description 1
• REFBWURWFDPVJQ-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-(2-hydroxyethyl)pyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CCO)C(=O)OCC)OC REFBWURWFDPVJQ-UHFFFAOYSA-N 0.000 description 1
• LVYNPBZUJXKPLB-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-(2-methoxyethyl)pyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CCOC)C(=O)OCC)OC LVYNPBZUJXKPLB-UHFFFAOYSA-N 0.000 description 1
• CQDZNYYGSJZKOI-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-ethyl-4-(trifluoromethyl)pyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)C(F)(F)F)OC CQDZNYYGSJZKOI-UHFFFAOYSA-N 0.000 description 1
• UGPORJGZMMOUQZ-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-ethyl-4-fluoropyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)F)OC UGPORJGZMMOUQZ-UHFFFAOYSA-N 0.000 description 1
• RDSSHVOXAYCVQU-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-ethyl-4-iodopyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)I)OC RDSSHVOXAYCVQU-UHFFFAOYSA-N 0.000 description 1
• BNTLGPVQIRMFIF-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-ethyl-4-methylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)C)OC BNTLGPVQIRMFIF-UHFFFAOYSA-N 0.000 description 1
• QPGSPBYQBDLYTF-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-1-ethyl-4-propan-2-ylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)C(C)C)OC QPGSPBYQBDLYTF-UHFFFAOYSA-N 0.000 description 1
• VCZNQVFVZIBJKF-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-4-chloro-1-(2-cyanoethyl)pyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CCC#N)C(=O)OCC)Cl)OC VCZNQVFVZIBJKF-UHFFFAOYSA-N 0.000 description 1
• SFMUHNUPLMFPOX-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methoxyphenyl)-4-chloro-1-(2-methoxyethyl)pyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CCOC)C(=O)OCC)Cl)OC SFMUHNUPLMFPOX-UHFFFAOYSA-N 0.000 description 1
• ALVKAYKTWGLSGJ-UHFFFAOYSA-N ethyl 5-(4-bromo-2-methylphenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)C ALVKAYKTWGLSGJ-UHFFFAOYSA-N 0.000 description 1
• RRLNPPIPJKQEBW-UHFFFAOYSA-N ethyl 5-(4-bromo-2-propan-2-yloxyphenyl)-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=CC(=NN1CC)C(=O)OCC)OC(C)C RRLNPPIPJKQEBW-UHFFFAOYSA-N 0.000 description 1
• MBXICUICWVVQCM-UHFFFAOYSA-N ethyl 5-(4-bromo-2-propan-2-yloxyphenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)OC(C)C MBXICUICWVVQCM-UHFFFAOYSA-N 0.000 description 1
• BILBJSVYFUWBBN-UHFFFAOYSA-N ethyl 5-(4-bromo-2-propan-2-ylphenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC(=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl)C(C)C BILBJSVYFUWBBN-UHFFFAOYSA-N 0.000 description 1
• USDINWGUKQFPKJ-UHFFFAOYSA-N ethyl 5-(4-bromophenyl)-2,3,5-trioxopentanoate Chemical compound BrC1=CC=C(C=C1)C(CC(C(C(=O)OCC)=O)=O)=O USDINWGUKQFPKJ-UHFFFAOYSA-N 0.000 description 1
• LAUHCSVZLJCFNE-UHFFFAOYSA-N ethyl 5-(4-bromophenyl)-4-chloro-1-ethylpyrazole-3-carboxylate Chemical compound BrC1=CC=C(C=C1)C1=C(C(=NN1CC)C(=O)OCC)Cl LAUHCSVZLJCFNE-UHFFFAOYSA-N 0.000 description 1
• GSIGOGDNAOUVKK-UHFFFAOYSA-N ethyl 5-[2-(difluoromethoxy)-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]-1-(2-hydroxy-2-methylpropyl)-4-methylpyrazole-3-carboxylate Chemical compound FC(OC1=C(C=CC(=C1)CC(C(F)(F)F)(C)C)C1=C(C(=NN1CC(C)(C)O)C(=O)OCC)C)F GSIGOGDNAOUVKK-UHFFFAOYSA-N 0.000 description 1
• XBXJKKAKCLWFIF-UHFFFAOYSA-N ethyl 5-[2-(difluoromethoxy)-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]-1-(2-methoxyethyl)-4-methylpyrazole-3-carboxylate Chemical compound FC(OC1=C(C=CC(=C1)CC(C(F)(F)F)(C)C)C1=C(C(=NN1CCOC)C(=O)OCC)C)F XBXJKKAKCLWFIF-UHFFFAOYSA-N 0.000 description 1
• BXTYTKVLBBISBE-UHFFFAOYSA-N ethyl 5-[2-(difluoromethoxy)-4-(3,3,3-trifluoro-2,2-dimethylpropyl)phenyl]-1-ethyl-4-methylpyrazole-3-carboxylate Chemical compound FC(OC1=C(C=CC(=C1)CC(C(F)(F)F)(C)C)C1=C(C(=NN1CC)C(=O)OCC)C)F BXTYTKVLBBISBE-UHFFFAOYSA-N 0.000 description 1
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