JP6082353B2 - イミダゾール誘導体の製造方法 - Google Patents
イミダゾール誘導体の製造方法 Download PDFInfo
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- JP6082353B2 JP6082353B2 JP2013549084A JP2013549084A JP6082353B2 JP 6082353 B2 JP6082353 B2 JP 6082353B2 JP 2013549084 A JP2013549084 A JP 2013549084A JP 2013549084 A JP2013549084 A JP 2013549084A JP 6082353 B2 JP6082353 B2 JP 6082353B2
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- 238000004519 manufacturing process Methods 0.000 title claims description 25
- 150000002460 imidazoles Chemical class 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 167
- 238000006243 chemical reaction Methods 0.000 claims description 149
- -1 N, N-dimethylaminosulfonyl Chemical group 0.000 claims description 58
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 57
- 150000003839 salts Chemical class 0.000 claims description 55
- 239000011541 reaction mixture Substances 0.000 claims description 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 13
- OZPFIJIOIVJZMN-UHFFFAOYSA-N 6-(7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthalenecarboxamide Chemical compound C1=CC2=CC(C(=O)NC)=CC=C2C=C1C1(O)C2=CN=CN2CC1 OZPFIJIOIVJZMN-UHFFFAOYSA-N 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 238000010511 deprotection reaction Methods 0.000 claims description 7
- 238000007363 ring formation reaction Methods 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 238000006722 reduction reaction Methods 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 239000000243 solution Substances 0.000 description 174
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
- 239000013078 crystal Substances 0.000 description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
- 239000000203 mixture Substances 0.000 description 73
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 49
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 23
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- 238000003756 stirring Methods 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 235000015165 citric acid Nutrition 0.000 description 16
- 239000012046 mixed solvent Substances 0.000 description 16
- 239000011701 zinc Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 15
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- 229910052725 zinc Inorganic materials 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- HPUCFMPIKISIIO-UHFFFAOYSA-N 6-bromo-n-methylnaphthalene-2-carboxamide Chemical compound C1=C(Br)C=CC2=CC(C(=O)NC)=CC=C21 HPUCFMPIKISIIO-UHFFFAOYSA-N 0.000 description 9
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 9
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 9
- 229910000033 sodium borohydride Inorganic materials 0.000 description 9
- 239000012279 sodium borohydride Substances 0.000 description 9
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 7
- 150000002170 ethers Chemical class 0.000 description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 7
- 239000002198 insoluble material Substances 0.000 description 7
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- OYOPLDKKDPMONE-UHFFFAOYSA-N 6-[hydroxy-(1-tritylimidazol-4-yl)methyl]-n-methylnaphthalene-2-carboxamide Chemical compound C1=CC2=CC(C(=O)NC)=CC=C2C=C1C(O)C(N=C1)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 OYOPLDKKDPMONE-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 6
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 6
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 6
- 229940117389 dichlorobenzene Drugs 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
- 239000002798 polar solvent Substances 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- IJUSERSRWSAJFA-HNNXBMFYSA-N 6-[(7s)-1-hydroxy-6,7-dihydro-5h-pyrrolo[1,2-c]imidazol-7-yl]-n-methylnaphthalene-2-carboxamide Chemical group C1=CC2=CC(C(=O)NC)=CC=C2C=C1[C@H]1C2=C(O)N=CN2CC1 IJUSERSRWSAJFA-HNNXBMFYSA-N 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- OZQXEOSNFMMMRD-UHFFFAOYSA-M [Cl-].CC(C)[Mg+].C1CCOC1 Chemical compound [Cl-].CC(C)[Mg+].C1CCOC1 OZQXEOSNFMMMRD-UHFFFAOYSA-M 0.000 description 5
- 239000012190 activator Substances 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
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- YQYLLBSWWRWWAY-UHFFFAOYSA-N 1-tritylimidazole-4-carbaldehyde Chemical compound C1=NC(C=O)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 YQYLLBSWWRWWAY-UHFFFAOYSA-N 0.000 description 4
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- CJGLGKMZZCTLTF-RSAXXLAASA-N CNC(=O)C1=CC2=C(C=C1)C=C(C=C2)[C@@H]3CCN4C3=C(N=C4)O.O Chemical compound CNC(=O)C1=CC2=C(C=C1)C=C(C=C2)[C@@H]3CCN4C3=C(N=C4)O.O CJGLGKMZZCTLTF-RSAXXLAASA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 4
- 238000009776 industrial production Methods 0.000 description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 4
- 229910001507 metal halide Inorganic materials 0.000 description 4
- 150000005309 metal halides Chemical class 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- BXIZVEYIKFJEEF-UHFFFAOYSA-N n-methyl-6-(1-tritylimidazole-4-carbonyl)naphthalene-2-carboxamide Chemical compound C1=CC2=CC(C(=O)NC)=CC=C2C=C1C(=O)C(N=C1)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BXIZVEYIKFJEEF-UHFFFAOYSA-N 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
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- 229960005453 strychnine Drugs 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 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 1
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
- PFYUMMPFKUVLHX-UHFFFAOYSA-N tert-butyl 4-[6-(methylcarbamoyl)naphthalene-2-carbonyl]imidazole-1-carboxylate Chemical compound C1=CC2=CC(C(=O)NC)=CC=C2C=C1C(=O)C1=CN(C(=O)OC(C)(C)C)C=N1 PFYUMMPFKUVLHX-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- NZBUCABTIWJWAN-UHFFFAOYSA-N tetrabromomethane;triphenylphosphane Chemical compound BrC(Br)(Br)Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NZBUCABTIWJWAN-UHFFFAOYSA-N 0.000 description 1
- VSWLXYAZJZQIKA-UHFFFAOYSA-N tetrachloromethane;triphenylphosphane Chemical compound ClC(Cl)(Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VSWLXYAZJZQIKA-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical group CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 150000003752 zinc compounds Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/28—Antiandrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2013549084A JP6082353B2 (ja) | 2011-06-15 | 2012-06-14 | イミダゾール誘導体の製造方法 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2011133712 | 2011-06-15 | ||
| JP2011133712 | 2011-06-15 | ||
| JP2013549084A JP6082353B2 (ja) | 2011-06-15 | 2012-06-14 | イミダゾール誘導体の製造方法 |
| PCT/JP2012/065795 WO2012173280A1 (en) | 2011-06-15 | 2012-06-14 | Production method of imidazole derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014520066A JP2014520066A (ja) | 2014-08-21 |
| JP2014520066A5 JP2014520066A5 (OSRAM) | 2015-07-02 |
| JP6082353B2 true JP6082353B2 (ja) | 2017-02-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013549084A Expired - Fee Related JP6082353B2 (ja) | 2011-06-15 | 2012-06-14 | イミダゾール誘導体の製造方法 |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US9278938B2 (OSRAM) |
| EP (1) | EP2721010B1 (OSRAM) |
| JP (1) | JP6082353B2 (OSRAM) |
| KR (1) | KR20140028069A (OSRAM) |
| CN (1) | CN103608334B (OSRAM) |
| AR (1) | AR086926A1 (OSRAM) |
| AU (1) | AU2012270496A1 (OSRAM) |
| BR (1) | BR112013030888A2 (OSRAM) |
| CA (1) | CA2838971C (OSRAM) |
| CL (1) | CL2013003492A1 (OSRAM) |
| CO (1) | CO6852075A2 (OSRAM) |
| CR (1) | CR20130655A (OSRAM) |
| DO (1) | DOP2013000287A (OSRAM) |
| EA (1) | EA201490019A1 (OSRAM) |
| EC (1) | ECSP14013128A (OSRAM) |
| ES (1) | ES2554454T3 (OSRAM) |
| IL (1) | IL229566A0 (OSRAM) |
| MA (1) | MA35809B1 (OSRAM) |
| MX (1) | MX2013014009A (OSRAM) |
| PE (1) | PE20141326A1 (OSRAM) |
| PH (1) | PH12013502567A1 (OSRAM) |
| SG (1) | SG195036A1 (OSRAM) |
| TN (1) | TN2013000481A1 (OSRAM) |
| TW (1) | TW201307295A (OSRAM) |
| UY (1) | UY34130A (OSRAM) |
| WO (1) | WO2012173280A1 (OSRAM) |
| ZA (1) | ZA201308884B (OSRAM) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10864460B2 (en) * | 2014-09-30 | 2020-12-15 | Unm Rainforest Innovations | Graphene-based inorganic-organic hybrid materials and separation of racemic mixtures |
| US20200033307A1 (en) * | 2018-07-25 | 2020-01-30 | Honeywell International Inc. | Method of determining an amount of water in a sample using a derivative of imidazole and a hydrogen halide donor |
| KR102253950B1 (ko) * | 2019-07-24 | 2021-05-20 | (주)에니켐텍 | 신규한 메데토미딘 제조방법 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5832880A (ja) * | 1981-08-24 | 1983-02-25 | Isukura Sangyo Kk | ハリントニンの部分合成方法 |
| US6713632B1 (en) | 1999-06-22 | 2004-03-30 | Takeda Chemical Industries, Ltd. | Process for the preparation of imidazole derivatives |
| PE20010781A1 (es) | 1999-10-22 | 2001-08-08 | Takeda Chemical Industries Ltd | Compuestos 1-(1h-imidazol-4-il)-1-(naftil-2-sustituido)etanol, su produccion y utilizacion |
| DE10031604A1 (de) * | 2000-06-29 | 2002-01-17 | Consortium Elektrochem Ind | Verfahren zur Herstellung von beta-Hydroxy- und beta-Aminocarbonylverbindungen |
| EP1681290B9 (en) | 2000-11-17 | 2013-06-19 | Takeda Pharmaceutical Company Limited | Imidazole derivatives, production method thereof and use thereof |
| WO2003059839A1 (en) | 2002-01-04 | 2003-07-24 | Koninklijke Philips Electronics N.V. | Sintered body and electric lamp |
| JP3959033B2 (ja) | 2002-01-10 | 2007-08-15 | 武田薬品工業株式会社 | 縮合イミダゾール化合物の製造方法、ならびに安定な形態のリフォルマツキー試薬およびその製造方法 |
| EP1394140A1 (de) * | 2002-08-14 | 2004-03-03 | Consortium für elektrochemische Industrie GmbH | Enantioselektives Reformatsky-Verfahren zur Herstellung von optisch aktiven Alkoholen, Aminen und deren Derivaten |
| EP2164409B1 (en) | 2007-06-29 | 2018-08-08 | Atheromed, Inc. | Atherectomy system |
-
2012
- 2012-06-14 WO PCT/JP2012/065795 patent/WO2012173280A1/en not_active Ceased
- 2012-06-14 KR KR1020137032819A patent/KR20140028069A/ko not_active Withdrawn
- 2012-06-14 AR ARP120102106A patent/AR086926A1/es unknown
- 2012-06-14 BR BR112013030888A patent/BR112013030888A2/pt not_active IP Right Cessation
- 2012-06-14 AU AU2012270496A patent/AU2012270496A1/en not_active Abandoned
- 2012-06-14 UY UY0001034130A patent/UY34130A/es not_active Application Discontinuation
- 2012-06-14 US US14/123,381 patent/US9278938B2/en not_active Expired - Fee Related
- 2012-06-14 EA EA201490019A patent/EA201490019A1/ru unknown
- 2012-06-14 SG SG2013085345A patent/SG195036A1/en unknown
- 2012-06-14 PE PE2013002711A patent/PE20141326A1/es not_active Application Discontinuation
- 2012-06-14 PH PH1/2013/502567A patent/PH12013502567A1/en unknown
- 2012-06-14 CN CN201280029606.7A patent/CN103608334B/zh not_active Expired - Fee Related
- 2012-06-14 TW TW101121273A patent/TW201307295A/zh unknown
- 2012-06-14 MX MX2013014009A patent/MX2013014009A/es unknown
- 2012-06-14 CA CA2838971A patent/CA2838971C/en not_active Expired - Fee Related
- 2012-06-14 ES ES12732719.5T patent/ES2554454T3/es active Active
- 2012-06-14 JP JP2013549084A patent/JP6082353B2/ja not_active Expired - Fee Related
- 2012-06-14 EP EP12732719.5A patent/EP2721010B1/en active Active
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2013
- 2013-11-19 TN TNP2013000481A patent/TN2013000481A1/fr unknown
- 2013-11-21 IL IL229566A patent/IL229566A0/en unknown
- 2013-11-26 ZA ZA2013/08884A patent/ZA201308884B/en unknown
- 2013-12-05 CL CL2013003492A patent/CL2013003492A1/es unknown
- 2013-12-06 DO DO2013000287A patent/DOP2013000287A/es unknown
- 2013-12-13 CR CR20130655A patent/CR20130655A/es not_active Application Discontinuation
-
2014
- 2014-01-08 EC ECSP14013128 patent/ECSP14013128A/es unknown
- 2014-01-10 MA MA36668A patent/MA35809B1/fr unknown
- 2014-01-14 CO CO14006049A patent/CO6852075A2/es not_active Application Discontinuation
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2016
- 2016-01-21 US US15/002,692 patent/US10005780B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2838971A1 (en) | 2012-12-20 |
| TW201307295A (zh) | 2013-02-16 |
| MA35809B1 (fr) | 2014-12-01 |
| CL2013003492A1 (es) | 2014-07-18 |
| CR20130655A (es) | 2014-03-03 |
| CA2838971C (en) | 2019-07-30 |
| CN103608334A (zh) | 2014-02-26 |
| MX2013014009A (es) | 2014-03-12 |
| IL229566A0 (en) | 2014-01-30 |
| ECSP14013128A (es) | 2014-02-28 |
| TN2013000481A1 (en) | 2015-03-30 |
| ES2554454T3 (es) | 2015-12-21 |
| SG195036A1 (en) | 2013-12-30 |
| CO6852075A2 (es) | 2014-01-30 |
| UY34130A (es) | 2013-01-31 |
| CN103608334B (zh) | 2015-12-23 |
| US9278938B2 (en) | 2016-03-08 |
| BR112013030888A2 (pt) | 2017-03-21 |
| PE20141326A1 (es) | 2014-10-16 |
| JP2014520066A (ja) | 2014-08-21 |
| PH12013502567A1 (en) | 2014-01-27 |
| AU2012270496A1 (en) | 2013-12-19 |
| US10005780B2 (en) | 2018-06-26 |
| EP2721010B1 (en) | 2015-09-09 |
| EP2721010A1 (en) | 2014-04-23 |
| US20140100373A1 (en) | 2014-04-10 |
| EA201490019A1 (ru) | 2014-04-30 |
| DOP2013000287A (es) | 2014-02-16 |
| US20160244454A1 (en) | 2016-08-25 |
| WO2012173280A1 (en) | 2012-12-20 |
| AR086926A1 (es) | 2014-01-29 |
| ZA201308884B (en) | 2015-02-25 |
| KR20140028069A (ko) | 2014-03-07 |
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