BR112020009606A2 - compostos heteroaril sulfona piridina alquil de amidasubstituídos - Google Patents

Info

Publication number

BR112020009606A2

BR112020009606A2 BR112020009606-7A BR112020009606A BR112020009606A2 BR 112020009606 A2 BR112020009606 A2 BR 112020009606A2 BR 112020009606 A BR112020009606 A BR 112020009606A BR 112020009606 A2 BR112020009606 A2 BR 112020009606A2

Authority

BR

Brazil

Prior art keywords

mmol

amino

substituted

carboxamide

pyridin

Prior art date

2017-11-21

Links

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• -1 heteroaryl sulfone pyridine alkyl amides Chemical class 0.000 title description 314
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 abstract description 160
• 150000003839 salts Chemical class 0.000 abstract description 47
• 108010065637 Interleukin-23 Proteins 0.000 abstract description 45
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 179
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 153
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 113
• 239000000203 mixture Substances 0.000 description 107
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 101
• DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 description 95
• 238000000034 method Methods 0.000 description 93
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• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
• 229910052739 hydrogen Inorganic materials 0.000 description 86
• 239000001257 hydrogen Substances 0.000 description 86
• 150000002431 hydrogen Chemical class 0.000 description 83
• 239000007787 solid Substances 0.000 description 81
• 239000000243 solution Substances 0.000 description 81
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 78
• 230000014759 maintenance of location Effects 0.000 description 78
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• 125000005842 heteroatom Chemical group 0.000 description 73
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• 229910052760 oxygen Inorganic materials 0.000 description 71
• 229910052717 sulfur Inorganic materials 0.000 description 69
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 60
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 55
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 53
• 238000005160 1H NMR spectroscopy Methods 0.000 description 48
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 48
• 201000010099 disease Diseases 0.000 description 47
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 42
• 125000000623 heterocyclic group Chemical group 0.000 description 41
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 36
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 34
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 32
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
• 239000012043 crude product Substances 0.000 description 31
• 125000005843 halogen group Chemical group 0.000 description 31
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• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 30
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 29
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• QWMFKVNJIYNWII-UHFFFAOYSA-N 5-bromo-2-(2,5-dimethylpyrrol-1-yl)pyridine Chemical compound CC1=CC=C(C)N1C1=CC=C(Br)C=N1 QWMFKVNJIYNWII-UHFFFAOYSA-N 0.000 description 27
• 229910052757 nitrogen Inorganic materials 0.000 description 27
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• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
• 239000000543 intermediate Substances 0.000 description 23
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 22
• 239000000460 chlorine Substances 0.000 description 22
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• 125000001188 haloalkyl group Chemical group 0.000 description 21
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• 235000017550 sodium carbonate Nutrition 0.000 description 17
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• 125000003118 aryl group Chemical group 0.000 description 16
• 229910000024 caesium carbonate Inorganic materials 0.000 description 16
• 238000003818 flash chromatography Methods 0.000 description 16
• 239000007858 starting material Substances 0.000 description 16
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 15
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 239000002904 solvent Substances 0.000 description 15
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 14
• 208000023275 Autoimmune disease Diseases 0.000 description 14
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 14
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• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
• 125000000217 alkyl group Chemical group 0.000 description 13
• 125000004429 atom Chemical group 0.000 description 13
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• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 12
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• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 8
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• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
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• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 7
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