JP2016535081A5 - - Google Patents
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- JP2016535081A5 JP2016535081A5 JP2016548404A JP2016548404A JP2016535081A5 JP 2016535081 A5 JP2016535081 A5 JP 2016535081A5 JP 2016548404 A JP2016548404 A JP 2016548404A JP 2016548404 A JP2016548404 A JP 2016548404A JP 2016535081 A5 JP2016535081 A5 JP 2016535081A5
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- JP
- Japan
- Prior art keywords
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- reaction
- formula
- compound
- acid
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 41
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 24
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 21
- 238000006114 decarboxylation reaction Methods 0.000 claims description 21
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000006239 protecting group Chemical group 0.000 claims description 17
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 14
- -1 t-butoxycarbonyl Chemical group 0.000 claims description 14
- 230000035484 reaction time Effects 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 11
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 10
- GEZOTWYUIKXWOA-UHFFFAOYSA-L copper;carbonate Chemical compound [Cu+2].[O-]C([O-])=O GEZOTWYUIKXWOA-UHFFFAOYSA-L 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 10
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 10
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 10
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 10
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 229940116318 copper carbonate Drugs 0.000 claims description 9
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 8
- 239000005751 Copper oxide Substances 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- 229910000431 copper oxide Inorganic materials 0.000 claims description 8
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 7
- 229940117975 chromium trioxide Drugs 0.000 claims description 7
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims description 7
- 229910052802 copper Inorganic materials 0.000 claims description 7
- 239000010949 copper Substances 0.000 claims description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 7
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims description 7
- 239000007810 chemical reaction solvent Substances 0.000 claims description 6
- JGDFBJMWFLXCLJ-UHFFFAOYSA-N copper chromite Chemical compound [Cu]=O.[Cu]=O.O=[Cr]O[Cr]=O JGDFBJMWFLXCLJ-UHFFFAOYSA-N 0.000 claims description 6
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 5
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- 239000004305 biphenyl Substances 0.000 claims description 5
- 235000010290 biphenyl Nutrition 0.000 claims description 5
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 5
- 239000000920 calcium hydroxide Substances 0.000 claims description 5
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 5
- 229940095643 calcium hydroxide Drugs 0.000 claims description 5
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 5
- 239000000292 calcium oxide Substances 0.000 claims description 5
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 5
- 229940087373 calcium oxide Drugs 0.000 claims description 5
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 5
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 5
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 229910017604 nitric acid Inorganic materials 0.000 claims description 5
- 238000005580 one pot reaction Methods 0.000 claims description 5
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 5
- 229940071536 silver acetate Drugs 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000008096 xylene Substances 0.000 claims description 5
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 4
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 claims description 4
- 230000008030 elimination Effects 0.000 claims description 4
- 238000003379 elimination reaction Methods 0.000 claims description 4
- 229940071870 hydroiodic acid Drugs 0.000 claims description 4
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 4
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 3
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- 229940090181 propyl acetate Drugs 0.000 claims description 3
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 17
- 150000003839 salts Chemical class 0.000 claims 11
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 10
- 238000006460 hydrolysis reaction Methods 0.000 claims 10
- 238000000034 method Methods 0.000 claims 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 4
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 4
- 230000002378 acidificating effect Effects 0.000 claims 4
- 150000001298 alcohols Chemical class 0.000 claims 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 4
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 claims 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 3
- DEFLNOSTNCSZRB-IDTAVKCVSA-N 9-[(2r,3r,4r,5r)-3,4-dimethoxy-5-(methoxymethyl)oxolan-2-yl]-n-methoxypurin-6-amine Chemical compound CO[C@@H]1[C@H](OC)[C@@H](COC)O[C@H]1N1C2=NC=NC(NOC)=C2N=C1 DEFLNOSTNCSZRB-IDTAVKCVSA-N 0.000 claims 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims 3
- 125000002252 acyl group Chemical group 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 3
- 229910052794 bromium Inorganic materials 0.000 claims 3
- 229910052801 chlorine Inorganic materials 0.000 claims 3
- 239000000460 chlorine Chemical group 0.000 claims 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims 3
- 229910052731 fluorine Inorganic materials 0.000 claims 3
- 239000011737 fluorine Substances 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- 229910052740 iodine Chemical group 0.000 claims 3
- 239000011630 iodine Chemical group 0.000 claims 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims 3
- 229940066528 trichloroacetate Drugs 0.000 claims 3
- SSUJUUNLZQVZMO-UHFFFAOYSA-N 1,2,3,4,8,9,10,10a-octahydropyrimido[1,2-a]azepine Chemical compound C1CCC=CN2CCCNC21 SSUJUUNLZQVZMO-UHFFFAOYSA-N 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 2
- 229910002651 NO3 Inorganic materials 0.000 claims 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 2
- 229910019142 PO4 Inorganic materials 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims 2
- 230000009615 deamination Effects 0.000 claims 2
- 238000006481 deamination reaction Methods 0.000 claims 2
- 235000011187 glycerol Nutrition 0.000 claims 2
- 125000005179 haloacetyl group Chemical group 0.000 claims 2
- 230000007062 hydrolysis Effects 0.000 claims 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims 2
- 229940035429 isobutyl alcohol Drugs 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 2
- 239000010452 phosphate Substances 0.000 claims 2
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims 1
- XEUCQOBUZPQUMQ-UHFFFAOYSA-N Glycolone Chemical compound COC1=C(CC=C(C)C)C(=O)NC2=C1C=CC=C2OC XEUCQOBUZPQUMQ-UHFFFAOYSA-N 0.000 claims 1
- 229910021577 Iron(II) chloride Inorganic materials 0.000 claims 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims 1
- 229910000009 copper(II) carbonate Inorganic materials 0.000 claims 1
- 239000011646 cupric carbonate Substances 0.000 claims 1
- 235000019854 cupric carbonate Nutrition 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 230000014509 gene expression Effects 0.000 claims 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- ZLQNJKNOTXUHIP-UHFFFAOYSA-N C(C)OC(=O)C1=CC2=C(S1)C=CC=C2N1CCN(CC1)C(=O)OC(C)(C)C Chemical compound C(C)OC(=O)C1=CC2=C(S1)C=CC=C2N1CCN(CC1)C(=O)OC(C)(C)C ZLQNJKNOTXUHIP-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- PWGQHOJABIQOOS-UHFFFAOYSA-N copper;dioxido(dioxo)chromium Chemical compound [Cu+2].[O-][Cr]([O-])(=O)=O PWGQHOJABIQOOS-UHFFFAOYSA-N 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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| PCT/CN2014/000921 WO2015054976A1 (zh) | 2013-10-18 | 2014-10-20 | 布瑞哌唑、其关键中间体及其盐的制备方法 |
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| JP2016535081A JP2016535081A (ja) | 2016-11-10 |
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| CN105732572A (zh) * | 2014-12-10 | 2016-07-06 | 苏州鹏旭医药科技有限公司 | 一种Brexpiprazole中间体的制备方法及Brexpiprazole中间体 |
| CN105985314A (zh) * | 2015-02-05 | 2016-10-05 | 苏州旺山旺水生物医药有限公司 | 布瑞哌唑类似物的制备方法 |
| CN104844586A (zh) * | 2015-04-16 | 2015-08-19 | 重庆医药工业研究院有限责任公司 | 一种依匹哌唑无定型物及其制备方法 |
| CN104829588B (zh) * | 2015-04-30 | 2017-03-29 | 苏州苏旺森生物医药科技有限公司 | 一种苯并[b]噻吩的制备方法及其中间体 |
| CN105061414B (zh) * | 2015-07-21 | 2019-01-01 | 杭州新博思生物医药有限公司 | 一锅法制备Brexpiprazole |
| WO2017025987A1 (en) * | 2015-08-11 | 2017-02-16 | Mylan Laboratories Limited | Process for the preparation of brexpiprazole |
| EP3150591A1 (en) | 2015-10-02 | 2017-04-05 | Crystal Pharma S.A.U | Process and intermediates for the preparation of benzo[b]thiophene compounds |
| WO2017078621A1 (en) * | 2015-11-03 | 2017-05-11 | Scinopharm Taiwan, Ltd. | Processes for preparing brexpiprazole |
| CN105461704A (zh) * | 2015-12-15 | 2016-04-06 | 南京艾德凯腾生物医药有限责任公司 | 一种依匹哌唑的制备方法 |
| WO2017115287A1 (en) | 2015-12-28 | 2017-07-06 | Honour (R&D) | Process for the preparation of quinoline-2(1h)-one derivatives |
| CN106938982A (zh) * | 2016-01-05 | 2017-07-11 | 连云港皓海医药科技有限公司 | 布瑞哌唑的制备方法及用于制备布瑞哌唑的化合物 |
| CN105399736B (zh) * | 2016-01-07 | 2018-10-19 | 安徽省逸欣铭医药科技有限公司 | 一种依匹哌唑新的制备方法 |
| US20170320862A1 (en) | 2016-05-03 | 2017-11-09 | Cadila Healthcare Limited | Process for the preparation of brexpiprazole and intermediates thereof |
| CN106645494B (zh) * | 2016-12-29 | 2019-09-06 | 成都百裕制药股份有限公司 | 依匹哌唑起始物料有关物质的检测方法 |
| WO2020087031A1 (en) | 2018-10-26 | 2020-04-30 | The Research Foundation For The State University Of New York | Combination serotonin specific reuptake inhibitor and serotonin 1a receptor partial agonist for reducing l-dopa-induced dyskinesia |
| CN109694343B (zh) * | 2018-12-19 | 2020-07-28 | 帕潘纳(北京)科技有限公司 | 一种杂环羧酸类化合物的脱羧方法 |
| CN110483475B (zh) * | 2019-08-15 | 2020-11-27 | 绍兴文理学院 | 一种氧化银催化法制备苯并噻吩类化合物的方法 |
| CN110483476B (zh) * | 2019-08-15 | 2020-11-27 | 绍兴文理学院 | 一种催化法制备苯并硒吩类化合物的工艺 |
| CN111423452B (zh) * | 2020-03-26 | 2023-08-22 | 江西青峰药业有限公司 | 瑞卢戈利的中间体及其制备方法和应用 |
| CN115894435B (zh) * | 2022-11-14 | 2024-11-22 | 山东厚德精诚药业有限公司 | 一种1-(苯并[b]噻吩-4-基)哌嗪盐酸盐的合成方法 |
| CN116969960A (zh) * | 2023-07-25 | 2023-10-31 | 乳源东阳光药业有限公司 | 酪氨酸激酶抑制剂的中间体的制备方法 |
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| US4977154A (en) * | 1985-12-12 | 1990-12-11 | Warner-Lambert Company | 5-amino and 5-hydroxy-6-fluoroquinolones as antibacterial agents |
| US5436246A (en) | 1992-09-17 | 1995-07-25 | Merrell Dow Pharmaceuticals Inc. | Serotonin receptor agents |
| JP2008508221A (ja) * | 2004-07-28 | 2008-03-21 | グラクソ グループ リミテッド | 消化器疾患の治療に有用なピペラジン誘導体 |
| TWI320783B (en) * | 2005-04-14 | 2010-02-21 | Otsuka Pharma Co Ltd | Heterocyclic compound |
| JP4315393B2 (ja) * | 2005-04-14 | 2009-08-19 | 大塚製薬株式会社 | 複素環化合物 |
| JP4540700B2 (ja) * | 2006-10-13 | 2010-09-08 | 大塚製薬株式会社 | 医薬 |
| JP2011136906A (ja) * | 2008-04-18 | 2011-07-14 | Otsuka Pharmaceut Co Ltd | 複素環化合物 |
| JP5832558B2 (ja) * | 2011-07-28 | 2015-12-16 | 大塚製薬株式会社 | ベンゾ［ｂ］チオフェン化合物の製造方法 |
| CN104892589A (zh) * | 2014-03-07 | 2015-09-09 | 中国科学院上海药物研究所 | 一类杂环化合物、其制备方法和用途 |
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2013
- 2013-10-18 CN CN201310493206.8A patent/CN104557896A/zh active Pending
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2014
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- 2014-10-20 JP JP2016548404A patent/JP6188960B2/ja active Active
- 2014-10-20 WO PCT/CN2014/000921 patent/WO2015054976A1/zh not_active Ceased
- 2014-10-20 US US15/030,331 patent/US10100044B2/en not_active Expired - Fee Related
- 2014-10-20 EP EP14854084.2A patent/EP3059237A4/en not_active Withdrawn
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