TW202317514A - 新穎方法 - Google Patents
新穎方法 Download PDFInfo
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- TW202317514A TW202317514A TW111123528A TW111123528A TW202317514A TW 202317514 A TW202317514 A TW 202317514A TW 111123528 A TW111123528 A TW 111123528A TW 111123528 A TW111123528 A TW 111123528A TW 202317514 A TW202317514 A TW 202317514A
- Authority
- TW
- Taiwan
- Prior art keywords
- piperidine
- typically
- solvent
- group
- protected
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 158
- 150000003839 salts Chemical class 0.000 claims abstract description 151
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 250
- 239000002904 solvent Substances 0.000 claims description 210
- 239000000203 mixture Substances 0.000 claims description 145
- 238000006243 chemical reaction Methods 0.000 claims description 137
- -1 N-protected 4-hydroxypiperidine Chemical class 0.000 claims description 126
- 239000003054 catalyst Substances 0.000 claims description 106
- 239000002585 base Substances 0.000 claims description 75
- SMXMELMJCICPJG-UHFFFAOYSA-N piperidine-4-sulfonamide Chemical compound NS(=O)(=O)C1CCNCC1 SMXMELMJCICPJG-UHFFFAOYSA-N 0.000 claims description 71
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
- 229910052757 nitrogen Inorganic materials 0.000 claims description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 62
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 60
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 59
- GPGBNMNANZFYBU-UHFFFAOYSA-N CCN1CCC(CC1)S(N)(=O)=O Chemical compound CCN1CCC(CC1)S(N)(=O)=O GPGBNMNANZFYBU-UHFFFAOYSA-N 0.000 claims description 58
- 239000001257 hydrogen Substances 0.000 claims description 58
- 125000001424 substituent group Chemical group 0.000 claims description 56
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
- 125000005843 halogen group Chemical group 0.000 claims description 50
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 49
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical group CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 47
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 46
- 239000002253 acid Substances 0.000 claims description 43
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 43
- 239000000460 chlorine Substances 0.000 claims description 40
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 32
- 125000004122 cyclic group Chemical group 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 229910052801 chlorine Inorganic materials 0.000 claims description 31
- 229910052794 bromium Inorganic materials 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 19
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 17
- 229910052740 iodine Inorganic materials 0.000 claims description 17
- 125000002950 monocyclic group Chemical group 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000002619 bicyclic group Chemical group 0.000 claims description 16
- 230000003197 catalytic effect Effects 0.000 claims description 16
- 239000003153 chemical reaction reagent Substances 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 150000003461 sulfonyl halides Chemical class 0.000 claims description 13
- 229910021529 ammonia Inorganic materials 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 230000002140 halogenating effect Effects 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
- 125000006660 (C3-C4) halocycloalkyl group Chemical group 0.000 claims description 10
- 238000006467 substitution reaction Methods 0.000 claims description 10
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229940124530 sulfonamide Drugs 0.000 claims description 9
- 239000002243 precursor Substances 0.000 claims description 8
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 6
- 125000006659 (C1-C20) hydrocarbyl group Chemical group 0.000 claims description 4
- 239000003125 aqueous solvent Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000004437 phosphorous atom Chemical group 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 4
- 150000003512 tertiary amines Chemical class 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 229910052698 phosphorus Chemical group 0.000 claims description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- 125000005035 acylthio group Chemical group 0.000 claims 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 102000000874 Pyrin Domain-Containing 3 Protein NLR Family Human genes 0.000 abstract description 7
- 108010001946 Pyrin Domain-Containing 3 Protein NLR Family Proteins 0.000 abstract description 7
- 208000035475 disorder Diseases 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 6
- 230000005764 inhibitory process Effects 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract description 2
- OHIFQOUPTWBQLE-UHFFFAOYSA-N CCN1CCC(CC1)S(=O)(=O)NC(=O)Nc1c2CCCc2cc2CCCc12 Chemical compound CCN1CCC(CC1)S(=O)(=O)NC(=O)Nc1c2CCCc2cc2CCCc12 OHIFQOUPTWBQLE-UHFFFAOYSA-N 0.000 abstract 2
- 239000011541 reaction mixture Substances 0.000 description 168
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 113
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- 239000012044 organic layer Substances 0.000 description 100
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 95
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 81
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- 238000004128 high performance liquid chromatography Methods 0.000 description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 43
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- 239000010410 layer Substances 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 26
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 25
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 24
- UWHWFKKNOBFVRC-UHFFFAOYSA-N benzyl 4-sulfamoylpiperidine-1-carboxylate Chemical compound C1CC(S(=O)(=O)N)CCN1C(=O)OCC1=CC=CC=C1 UWHWFKKNOBFVRC-UHFFFAOYSA-N 0.000 description 24
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 239000003880 polar aprotic solvent Substances 0.000 description 23
- 239000008213 purified water Substances 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 229910052763 palladium Inorganic materials 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 16
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 16
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 15
- 238000002425 crystallisation Methods 0.000 description 15
- 230000008025 crystallization Effects 0.000 description 15
- 239000012065 filter cake Substances 0.000 description 15
- 239000003586 protic polar solvent Substances 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 229910052783 alkali metal Inorganic materials 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
- 238000001556 precipitation Methods 0.000 description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 13
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical group ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
- 239000012467 final product Substances 0.000 description 12
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 12
- 229910052759 nickel Inorganic materials 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 230000029936 alkylation Effects 0.000 description 11
- 238000005804 alkylation reaction Methods 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 10
- 150000001340 alkali metals Chemical class 0.000 description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
- 239000012454 non-polar solvent Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- BUCNTISNWFUIBC-UHFFFAOYSA-N 2-benzyl-4-hydroxypiperidine-1-carboxylic acid Chemical compound C1C(O)CCN(C(O)=O)C1CC1=CC=CC=C1 BUCNTISNWFUIBC-UHFFFAOYSA-N 0.000 description 9
- VTEOHCVWRXWJEI-UHFFFAOYSA-N 3-chloro-1-(2,3-dihydro-1h-inden-5-yl)propan-1-one Chemical compound ClCCC(=O)C1=CC=C2CCCC2=C1 VTEOHCVWRXWJEI-UHFFFAOYSA-N 0.000 description 9
- ITNYAUZZLZURCE-UHFFFAOYSA-N 4-acetylsulfanylpiperidine-1-carboxylic acid Chemical compound CC(=O)SC1CCN(C(O)=O)CC1 ITNYAUZZLZURCE-UHFFFAOYSA-N 0.000 description 9
- SGVSTYFVBPJDRH-UHFFFAOYSA-N 4-methylsulfonyloxypiperidine-1-carboxylic acid Chemical compound CS(=O)(=O)OC1CCN(C(O)=O)CC1 SGVSTYFVBPJDRH-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 9
- JNDJNOHSTONCMQ-UHFFFAOYSA-N 4-chlorosulfonylpiperidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(S(Cl)(=O)=O)CC1 JNDJNOHSTONCMQ-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 238000004817 gas chromatography Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 8
- 239000002002 slurry Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 7
- AMBWIRHJLQDRCN-UHFFFAOYSA-N benzyl 4-methylsulfonyloxypiperidine-1-carboxylate Chemical compound C1CC(OS(=O)(=O)C)CCN1C(=O)OCC1=CC=CC=C1 AMBWIRHJLQDRCN-UHFFFAOYSA-N 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 125000001153 fluoro group Chemical group F* 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000010936 aqueous wash Methods 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- 125000001309 chloro group Chemical group Cl* 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 6
- 238000012805 post-processing Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 150000001768 cations Chemical class 0.000 description 5
- 239000003610 charcoal Substances 0.000 description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000004744 fabric Substances 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000012265 solid product Substances 0.000 description 5
- 229910021653 sulphate ion Inorganic materials 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
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- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- DWJMBQYORXLGAE-UHFFFAOYSA-N pyridine-2-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=N1 DWJMBQYORXLGAE-UHFFFAOYSA-N 0.000 description 1
- XFIUZEAHIJGTTB-UHFFFAOYSA-N pyridine-4-sulfonamide Chemical compound NS(=O)(=O)C1=CC=NC=C1 XFIUZEAHIJGTTB-UHFFFAOYSA-N 0.000 description 1
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- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
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- 239000011593 sulfur Substances 0.000 description 1
- TWPVZKPFIMFABN-UHFFFAOYSA-N sulfuryl diiodide Chemical compound IS(I)(=O)=O TWPVZKPFIMFABN-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/40—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
- C07C271/56—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/54—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/98—Nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| TW202317514A true TW202317514A (zh) | 2023-05-01 |
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| US (1) | US20240150291A1 (enExample) |
| EP (1) | EP4359385A2 (enExample) |
| JP (1) | JP2024524215A (enExample) |
| KR (1) | KR20240024842A (enExample) |
| CN (1) | CN118019727A (enExample) |
| AR (1) | AR126215A1 (enExample) |
| AU (1) | AU2022300325A1 (enExample) |
| CA (1) | CA3219597A1 (enExample) |
| IL (1) | IL308071A (enExample) |
| MX (1) | MX2023014547A (enExample) |
| TW (1) | TW202317514A (enExample) |
| WO (1) | WO2022268935A2 (enExample) |
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| WO2024133610A1 (en) * | 2022-12-23 | 2024-06-27 | F. Hoffmann-La Roche Ag | Proccesses for the preparation of an nlrp3 inhibitor |
| WO2025036914A1 (en) | 2023-08-16 | 2025-02-20 | F. Hoffmann-La Roche Ag | Process for the preparation of preparing 1-ethyl-n-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)piperidine-4-sulfonamide |
| WO2025153532A1 (en) | 2024-01-16 | 2025-07-24 | NodThera Limited | Nlrp3 inhibitors and glp-1 agonists combination therapies |
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| ZA917435B (en) * | 1990-09-26 | 1992-05-27 | Takeda Chemical Industries Ltd | Herbicides |
| CA2059450A1 (en) * | 1991-01-24 | 1992-07-25 | Nobuyuki Sakashita | Subsituted pyridinesulfonamide compound or its salt, process for preparing the same, and herbicide containing the same |
| JP2001518069A (ja) * | 1997-05-02 | 2001-10-09 | ドクター・レディーズ・リサーチ・ファウンデーション | 低脂質性、抗高血圧性特性を有する新規な抗糖尿病化合物、それらの製造方法及びそれらを含有する薬学的組成物 |
| ATE342266T1 (de) * | 2000-11-16 | 2006-11-15 | Sankyo Co | 1-methylcarbapenemderivate |
| US7199147B2 (en) * | 2001-06-12 | 2007-04-03 | Dainippon Sumitomo Pharma Co., Ltd. | Rho kinase inhibitors |
| MXPA04010172A (es) * | 2002-04-18 | 2005-02-03 | Schering Corp | 1-(4-piperidinil)benzimidazolonas como antagonistas de histamina h3). |
| US7759387B2 (en) * | 2003-10-08 | 2010-07-20 | Piramal Life Sciences Limited | Fibrinogen receptor antagonists and their use |
| DOP2006000009A (es) * | 2005-01-13 | 2006-08-15 | Arena Pharm Inc | Procedimiento para preparar eteres de pirazolo [3,4-d] pirimidina |
| US8614215B2 (en) * | 2007-02-22 | 2013-12-24 | Merck Serono Sa | Quinoxaline inhibitors of phosphoinositide-3-kinases (PI3Ks) |
| US20120196889A1 (en) * | 2009-02-25 | 2012-08-02 | H. Lundbeck A/S | Catecholamine derivatives and prodrugs thereof |
| JP5898962B2 (ja) * | 2012-01-11 | 2016-04-06 | 東京応化工業株式会社 | レジスト組成物及びレジストパターン形成方法 |
| EP3383853B1 (en) * | 2015-12-01 | 2020-11-04 | Merck Sharp & Dohme Corp. | Homobispiperidinyl derivatives as liver x receptor (lxr) beta agonists for treating e.g. alzheimer's disease |
| KR102669722B1 (ko) * | 2017-07-07 | 2024-05-29 | 인플라좀 리미티드 | 신규한 설폰아마이드 카복스아마이드 화합물 |
| GB201712282D0 (en) * | 2017-07-31 | 2017-09-13 | Nodthera Ltd | Selective inhibitors of NLRP3 inflammasome |
| SG11202001164SA (en) * | 2017-08-15 | 2020-03-30 | Inflazome Ltd | Novel sulfonamide carboxamide compounds |
| KR20210018199A (ko) * | 2018-03-26 | 2021-02-17 | 씨4 테라퓨틱스, 인코포레이티드 | 이카로스의 분해를 위한 세레블론 결합제 |
| MA52489A (fr) * | 2018-05-04 | 2021-03-10 | Inflazome Ltd | Nouveaux composés |
| CA3113573A1 (en) * | 2018-09-21 | 2020-03-26 | Novartis Ag | Isoxazole carboxamide compounds and uses thereof |
| GB201817038D0 (en) | 2018-10-19 | 2018-12-05 | Inflazome Ltd | Novel processes |
| GB201819083D0 (en) * | 2018-11-23 | 2019-01-09 | Inflazome Ltd | Novel compounds |
| WO2020157069A1 (en) * | 2019-01-28 | 2020-08-06 | NodThera Limited | Amino heterocyclic compounds and uses thereof |
| CN111393415B (zh) * | 2020-04-30 | 2020-11-20 | 苏州信诺维医药科技有限公司 | 一种杂芳腈类化合物及其应用 |
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2022
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- 2022-06-23 TW TW111123528A patent/TW202317514A/zh unknown
- 2022-06-23 EP EP22738569.7A patent/EP4359385A2/en active Pending
- 2022-06-23 JP JP2023578919A patent/JP2024524215A/ja active Pending
- 2022-06-23 KR KR1020237044161A patent/KR20240024842A/ko active Pending
- 2022-06-23 WO PCT/EP2022/067126 patent/WO2022268935A2/en not_active Ceased
- 2022-06-23 AR ARP220101651A patent/AR126215A1/es unknown
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2023
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI876271B (zh) * | 2022-02-15 | 2025-03-11 | 瑞士商赫孚孟拉羅股份公司 | 新穎方法 |
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| AR126215A1 (es) | 2023-09-27 |
| US20240150291A1 (en) | 2024-05-09 |
| CN118019727A (zh) | 2024-05-10 |
| AU2022300325A8 (en) | 2023-11-16 |
| MX2023014547A (es) | 2024-04-29 |
| AU2022300325A1 (en) | 2023-11-02 |
| JP2024524215A (ja) | 2024-07-05 |
| WO2022268935A3 (en) | 2023-02-02 |
| KR20240024842A (ko) | 2024-02-26 |
| IL308071A (en) | 2023-12-01 |
| EP4359385A2 (en) | 2024-05-01 |
| CA3219597A1 (en) | 2022-12-29 |
| WO2022268935A2 (en) | 2022-12-29 |
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