JP6572891B2 - N−置換スルホンアミド化合物およびその製造方法 - Google Patents
N−置換スルホンアミド化合物およびその製造方法 Download PDFInfo
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- JP6572891B2 JP6572891B2 JP2016527836A JP2016527836A JP6572891B2 JP 6572891 B2 JP6572891 B2 JP 6572891B2 JP 2016527836 A JP2016527836 A JP 2016527836A JP 2016527836 A JP2016527836 A JP 2016527836A JP 6572891 B2 JP6572891 B2 JP 6572891B2
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- carbon atoms
- substituent
- general formula
- sulfonamide compound
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- -1 N-substituted sulfonamide compound Chemical class 0.000 title claims description 220
- 238000000034 method Methods 0.000 title description 15
- 125000001424 substituent group Chemical group 0.000 claims description 133
- 238000006243 chemical reaction Methods 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 238000004519 manufacturing process Methods 0.000 claims description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 33
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 26
- 229940124530 sulfonamide Drugs 0.000 claims description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 239000003960 organic solvent Substances 0.000 claims description 21
- 150000002894 organic compounds Chemical class 0.000 claims description 20
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 19
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 description 143
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 35
- 238000004128 high performance liquid chromatography Methods 0.000 description 25
- 125000003545 alkoxy group Chemical group 0.000 description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 20
- 239000007788 liquid Substances 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 18
- 229940011051 isopropyl acetate Drugs 0.000 description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 16
- 125000006413 ring segment Chemical group 0.000 description 16
- 125000004093 cyano group Chemical group *C#N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 125000001188 haloalkyl group Chemical group 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002994 raw material Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 11
- 125000003277 amino group Chemical group 0.000 description 11
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 11
- 125000004104 aryloxy group Chemical group 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 9
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 6
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- RQMOEJCTBHVAEL-UHFFFAOYSA-N n-[(4-pyrazol-1-ylphenyl)methyl]pyridine-3-sulfonamide Chemical compound C=1C=CN=CC=1S(=O)(=O)NCC(C=C1)=CC=C1N1C=CC=N1 RQMOEJCTBHVAEL-UHFFFAOYSA-N 0.000 description 6
- 230000000704 physical effect Effects 0.000 description 6
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 5
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 0 *c1ccc(CNS(*)(=O)=O)cc1 Chemical compound *c1ccc(CNS(*)(=O)=O)cc1 0.000 description 4
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 208000012839 conversion disease Diseases 0.000 description 4
- 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 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 3
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 2
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 2
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000020169 heat generation Effects 0.000 description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
- 125000006038 hexenyl group Chemical group 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000005980 hexynyl group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 2
- 125000005981 pentynyl group Chemical group 0.000 description 2
- 239000012450 pharmaceutical intermediate Substances 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
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- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- PESKMXYELUEORL-UHFFFAOYSA-N 1-ethoxy-2-phenylbenzene Chemical group CCOC1=CC=CC=C1C1=CC=CC=C1 PESKMXYELUEORL-UHFFFAOYSA-N 0.000 description 1
- DVVGIUUJYPYENY-UHFFFAOYSA-N 1-methylpyridin-2-one Chemical compound CN1C=CC=CC1=O DVVGIUUJYPYENY-UHFFFAOYSA-N 0.000 description 1
- 125000005978 1-naphthyloxy group Chemical group 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- MJJRDTKNLLMJDJ-UHFFFAOYSA-N 2-methoxy-1,3-thiazole Chemical compound COC1=NC=CS1 MJJRDTKNLLMJDJ-UHFFFAOYSA-N 0.000 description 1
- 125000005979 2-naphthyloxy group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000005977 3-phenylpropyloxy group Chemical group 0.000 description 1
- YSWBFLWKAIRHEI-UHFFFAOYSA-N 4,5-dimethyl-1h-imidazole Chemical compound CC=1N=CNC=1C YSWBFLWKAIRHEI-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 125000005914 C6-C14 aryloxy group Chemical group 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- RIUVLOXDBAJYGF-UHFFFAOYSA-N [1,3]thiazolo[5,4-f]quinoline Chemical group N1=CC=CC2=C(SC=N3)C3=CC=C21 RIUVLOXDBAJYGF-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006612 decyloxy group Chemical group 0.000 description 1
- 125000005070 decynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 125000006301 indolyl methyl group Chemical group 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- BPFQRGOFBYOROO-UHFFFAOYSA-N n-benzylpyridine-3-sulfonamide Chemical compound C=1C=CN=CC=1S(=O)(=O)NCC1=CC=CC=C1 BPFQRGOFBYOROO-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006611 nonyloxy group Chemical group 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 125000005003 perfluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000011425 standardization method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- 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
-
- 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
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)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Description
さらに、その他の方法も収率の点で満足できる方法ではなく、またエステル等の反応性官能基がある場合、使用する塩基との反応により副生成物が生成する可能性もあり、工業的に好ましい方法ではない。
一般式(1):
R1およびR2は、それぞれ独立して、置換基を有していてもよい、アルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基、ヘテロアリール基、アラルキル基またはヘテロアリールアルキル基である)
で示されるスルホンアミド化合物と、一般式(2):
R3は、置換基を有していてもよい、アルキル基、アラルキル基またはヘテロアリールアルキル基であり、Xはハロゲン原子である)
で示されるハロゲン化有機化合物とを、炭酸セシウムまたは炭酸カリウムの存在下、有機溶媒中で反応させる工程を含む、一般式(3):
で示されるN−置換スルホンアミド化合物の製造方法である。
ハロゲン化有機化合物とを、炭酸セシウム(Cs2CO3)または炭酸カリウム(K2CO3)の存在下、有機溶媒中で反応させることにより得ることが出来る(下記、〔反応式1〕参照;ただし、炭酸セシウムを使用した例のみ示す。)。
(式中、
R1aは、R1と同義であり、
R4は、置換基を有していてもよい、アリール基またはヘテロアリール基である)で示されるスルホンアミド化合物である。
R4における「置換基を有していてもよいヘテロアリール基」としては、好ましくは、2−チアゾール基、2−(4−メチル)チアゾール基、2−(5−フルオロ)チアゾール基、1H−1−ピラゾール基、1H−(3−メチル)ピラゾール基または2−メトキシチアゾールである。
(式中、R5は、アルキル基であり、X2は、ハロゲン原子又はヒドロキシ基である)
で示される。一般式(9)において、R5は、アルキル基、例えば、炭素数1〜10のアルキル基であり、好ましくは、炭素数1〜6のアルキル基、例えば、メチル基、エチル基、n−プロピル基、イソプロピル基、t−ブチル基またはn−ヘキシル基であり、X2は、ハロゲン原子、好ましくは塩素原子または臭素原子である。一般式(9)の化合物の具体的態様は、下記の実施例に開示されている。
EI−MS(m/z): 520 [M].
CI−MS(m/z): 521 [M+1].
1H−NMR(CDCl3, δ(ppm)): 1.24 (6H, d, J=6.3Hz), 3.82 (2H, d, J=5.5Hz), 4.31 (2H, s), 4.64 (2H,s), 4.94 (1H, t, J=5.5Hz), 5.07 (1H, sep, J=6.3Hz), 6.26 (1H, d, J=8.3Hz), 6.41 (1H, dd, J=7.2, 0.5Hz), 6.46 (1H, dd, J=2.5, 1.8Hz), 7.25 (1H, dd, J=8.3, 7.2Hz), 7.32 (1H, ddd, J=8.0, 4.9, 0.8Hz), 7.37-7.42(2H, m), 7.62-7.66 (2H, m), 7.71 (1H, dd, J=1.8, 0.6Hz), 7.93 (1H, dd, J=2.6, 0.6Hz), 7.94 (1H, ddd, J=8.0, 2.4, 1.7Hz), 8.69 (1H, dd, J=4.8, 1.6Hz), 8.98 (1H, dd, J=2.4, 0.8Hz).
13C−NMR(CDCl3, δ(ppm)): 21.8, 43.7, 51.0, 51.1, 68.9, 107.4, 107.7, 112.6, 119.2, 123.3, 126.7, 129.9, 133.8, 134.6, 137.3, 137.6, 139.8, 141.1, 148.0, 152.6, 153.2, 157.3, 170.5.
IR(KBr cm-1): 764(C-H), 1161(S=O), 1525(C=N), 1737(C=O), (2981, 2933)(C-H), 3437(N-H).
元素分析;Calcd:C, 59.80%; H, 5.31%; N, 16.07%
Found:C, 59.98%; H, 5.42%; N, 16.14%.
EI−MS(m/z): 454 [M].
CI−MS(m/z): 455 [M+1].
1H−NMR(CDCl3, δ(ppm)): 1.27 (6H, d, J=6.3Hz), 3.82 (2H, d, J=5.4Hz), 4.31 (2H, s), 4.62 (2H, s), 4.73 (1H, t, J=5.2Hz), 5.09 (1H, sep, J=6.3Hz), 6.26 (1H, d, J=8.1Hz), 6.43 (1H, d, J=6.9Hz), 7.26-7.33 (7H, m), 7.90-7.93 (1H, m), 8.69 (1H, dd, J=4.8, 1.6Hz), 8.95 (1H, dd, J=2.3, 0.7Hz).
13C−NMR(CDCl3, δ(ppm)): 21.8, 43.8, 51.1, 51.6, 69.0, 107.2, 112.6, 123.2, 127.9, 128.6, 128.8, 134.7, 135.6, 137.6, 137.7, 148.2, 152.5, 153.6, 157.3, 170.5.
IR(KBr cm-1): 1169(S=O), 1724(C=O), (2936, 2984)(C-H), 3428(N-H).
元素分析;Calcd: C, 60.77%; H, 5.77%; N, 12.33%
Found: C, 61.03%; H, 5.85%;N, 12.15%.
2−{[6−({N−[4−(1H−ピラゾール−1−イル)ベンジル]ピリジン−3−スルホンアミド}メチル)ピリジン−2−イル]アミノ}酢酸イソプロピルの合成
EI−MS(m/z): 520 [M].
CI−MS(m/z): 521 [M+1].
1H−NMR(CDCl3, δ(ppm)): 1.24 (6H, d, J=6.3Hz), 3.82 (2H, d, J=5.5Hz), 4.31 (2H, s), 4.64 (2H, s), 4.94 (1H, t, J=5.5Hz), 5.07 (1H, sep, J=6.3Hz), 6.26 (1H, d, J=8.3Hz), 6.41 (1H, dd, J=7.2, 0.5Hz), 6.46 (1H, dd, J=2.5, 1.8Hz), 7.25 (1H, dd, J=8.3, 7.2Hz), 7.32 (1H, ddd, J=8.0, 4.9, 0.8Hz), 7.37-7.42 (2H, m), 7.62-7.66 (2H, m), 7.71 (1H, dd, J=1.8, 0.6Hz), 7.93 (1H, dd, J=2.6, 0.6Hz), 7.94 (1H, ddd, J=8.0, 2.4, 1.7Hz), 8.69 (1H, dd, J=4.8, 1.6Hz), 8.98 (1H, dd, J=2.4, 0.8Hz).
13C−NMR(CDCl3, δ(ppm)): 21.8, 43.7, 51.0, 51.1, 68.9, 107.4, 107.7, 112.6, 119.2, 123.3, 126.7, 129.9, 133.8, 134.6, 137.3, 137.6, 139.8, 141.1, 148.0, 152.6, 153.2, 157.3, 170.5.
IR(KBr cm-1): 764(C-H), 1161(S=O), 1525(C=N), 1737(C=O), (2981, 2933)(C-H), 3437(N-H).
元素分析;Calcd:C, 59.80%; H, 5.31%; N, 16.07%
Found:C, 59.98%; H, 5.42%; N, 16.14%.
2−{[6−({N−[4−(1H−ピラゾール−1−イル)ベンジル]ピリジン−3−スルホンアミド}メチル)ピリジン−2−イル]アミノ}酢酸イソプロピルの合成
EI−MS(m/z): 520 [M].
CI−MS(m/z): 521 [M+1].
1H−NMR(CDCl3, δ(ppm)): 1.24 (6H, d, J=6.3Hz), 3.82 (2H, d, J=5.5Hz), 4.31 (2H, s), 4.64 (2H, s), 4.94 (1H, t, J=5.5Hz), 5.07 (1H, sep, J=6.3Hz), 6.26 (1H, d, J=8.3Hz), 6.41 (1H, dd, J=7.2, 0.5Hz), 6.46 (1H, dd, J=2.5, 1.8Hz), 7.25 (1H, dd, J=8.3, 7.2Hz), 7.32 (1H, ddd, J=8.0, 4.9, 0.8Hz), 7.37-7.42 (2H, m), 7.62-7.66 (2H, m), 7.71 (1H, dd, J=1.8, 0.6Hz), 7.93 (1H, dd, J=2.6, 0.6Hz), 7.94 (1H, ddd, J=8.0, 2.4, 1.7Hz), 8.69 (1H, dd, J=4.8, 1.6Hz), 8.98 (1H, dd, J=2.4, 0.8Hz).
13C−NMR(CDCl3, δ(ppm)): 21.8, 43.7, 51.0, 51.1, 68.9, 107.4, 107.7, 112.6, 119.2, 123.3, 126.7, 129.9, 133.8, 134.6, 137.3, 137.6, 139.8, 141.1, 148.0, 152.6, 153.2, 157.3, 170.5.
IR(KBr cm-1): 764(C-H), 1161(S=O), 1525(C=N), 1737(C=O), (2981, 2933)(C-H), 3437(N-H).
2−{[6−(ヒドロキシメチル)ピリジン−2−イル]アミノ}酢酸イソプロピルの合成
EI−MS(m/z): 224 [M].
CI−MS(m/z): 225 [M+1].
1H−NMR(CDCl3, δ(ppm)): 1.27 (6H, d, J=6.3Hz), 3.76 (1H, s), 4.10 (2H, d, J=5.5Hz), 4.59 (2H, s), 5.00 (1H, s), 5.10 (1H, m), 6.36 (1H, dd, J=8.2, 0.6Hz), 6.51 (1H, dd, J=7.3, 0.7Hz), 7.41 (1H, ddd, J=5.74, 3.88Hz).
13C−NMR(CDCl3, δ(ppm)): 21.8, 44.1, 63.5, 69.0, 106.6, 109.5, 138.0, 156.8, 156.9, 170.7.
IR(KBr cm-1):416, 469, 531, 559, 731, 785, 826, 862, 903, 916, 941, 980, 1014, 1052, 1082, 1106, 1131, 1147, 1182, 1217, 1256, 1276, 1347, 1378, 1402, 1471, 1526(C=N), 1582, 1607, 1687, 1724(C=O), 2878, 2935(C-H), 2983(C-H), 3381(N-H).
元素分析;Calcd:C, 58.91%; H, 7.19%; N, 12.49%
Found:C, 58.99%; H, 7.17%; N, 12.48%.
2−{[6−(クロロメチル)ピリジン−2−イル]アミノ}酢酸イソプロピルの合成
EI−MS(m/z): 242 [M].
CI−MS(m/z): 243 [M+1].
1H−NMR(CDCl3, δ(ppm)): 1.24 (6H, m), 4.10 (2H, d, J=5.4Hz), 4.48 (2H, s), 5.03 (1H, s), 5.10 (1H, m), 6.39 (1H, d, J=8.3Hz), 6.76 (1H, d, J=7.3Hz), 7.43 (1H, dd, J=7.8, 7.8Hz).
13C−NMR(CDCl3, δ(ppm)):21.8, 44.0, 44.7, 68.9, 107.7, 112.2, 138.1, 154.6, 157.3, 170.7.
IR(KBr cm-1):415, 446, 530, 560, 627, 735, 804, 827, 874, 903, 939, 952, 982, 1042, 1088, 1108, 1128, 1144, 1167, 1180, 1219, 1269, 1281, 1350, 1378, 1400, 1420, 1434, 1470, 1525(C=N), 1580, 1613, 1690, 1728(C=O), 2878, 2934(C-H), 2981(C-H), 3379(N-H).
元素分析;Calcd:C, 54.44%; H, 6.23%; N, 11.54%
Found:C, 54.46%; H, 6.23%; N, 11.56%.
Claims (14)
- 一般式(1):
(式中、
R1およびR2は、それぞれ独立して、置換基を有していてもよい、アルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基、ヘテロアリール基、アラルキル基またはヘテロアリールアルキル基である)
で示されるスルホンアミド化合物と、一般式(2):
(式中、
R3は、置換基を有していてもよい、アラルキル基またはヘテロアリールアルキル基であり、Xは、ハロゲン原子である)
で示されるハロゲン化有機化合物とを、炭酸セシウムまたは炭酸カリウムの存在下、有機溶媒中で反応させる工程を含む、一般式(3):
(式中、R1、R2およびR3は前記と同義である)
で示されるN−置換スルホンアミド化合物の製造方法であって、一般式(2)で示されるハロゲン化有機化合物が、一般式(5):
(式中、R 5 は、アルキル基であり、X 1 は、Xと同義である)
で示されるハロゲン化有機化合物である、製造方法。 - R1が、置換基を有していてもよい、アリール基またはヘテロアリール基である、請求項1に記載のN−置換スルホンアミド化合物の製造方法。
- R1が、置換基を有していてもよい、フェニル基またはピリジル基である、請求項1または2に記載のN−置換スルホンアミド化合物の製造方法。
- R2が、置換基を有していてもよい、アラルキル基またはヘテロアリールアルキル基である、請求項1に記載のN−置換スルホンアミド化合物の製造方法。
- R2が、置換基を有していてもよい、ベンジル基またはベンゾフラニルメチル基である、請求項1または4に記載のN−置換スルホンアミド化合物の製造方法。
- Xが、塩素原子、臭素原子またはヨウ素原子である、請求項1に記載のN−置換スルホンアミド化合物の製造方法。
- Xが、塩素原子または臭素原子である、請求項1または6に記載のN−置換スルホンアミド化合物の製造方法。
- 反応温度が、0〜90℃である、請求項1乃至9のいずれかに記載のN−置換スルホンアミド化合物の製造方法。
- 有機溶媒が、ジメチルスルホキシド、ジメチルホルムアミドおよびアセトニトリルよりなる群から選ばれる1種以上の有機溶媒である、請求項1乃至10のいずれかに記載のN−置換スルホンアミド化合物の製造方法。
- 有機溶媒が、アセトニトリルである、請求項1乃至11のいずれかに記載のN−置換スルホンアミド化合物の製造方法。
- 一般式(1):
(式中、
R 1 およびR 2 は、それぞれ独立して、置換基を有していてもよい、アルキル基、アルケニル基、アルキニル基、シクロアルキル基、アリール基、ヘテロアリール基、アラルキル基またはヘテロアリールアルキル基である)
で示されるスルホンアミド化合物と、一般式(2):
(式中、
R 3 は、置換基を有していてもよい、アラルキル基またはヘテロアリールアルキル基であり、Xは、ハロゲン原子である)
で示されるハロゲン化有機化合物とを、炭酸セシウムの存在下、有機溶媒中で反応させる工程を含む、一般式(3):
(式中、R1、R2およびR3は前記と同義である)
で示されるN−置換スルホンアミド化合物の製造方法であって、一般式(2)で示されるハロゲン化有機化合物が、一般式(5):
(式中、R 5 は、アルキル基であり、X 1 は、Xと同義である)
で示されるハロゲン化有機化合物である、製造方法。 - 反応温度が、30〜90℃である、請求項13に記載のN−置換スルホンアミド化合物の製造方法。
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