CN102127003B - 抗流感药物达菲的中间体化合物及其合成方法和用途 - Google Patents
抗流感药物达菲的中间体化合物及其合成方法和用途 Download PDFInfo
- Publication number
- CN102127003B CN102127003B CN2010106132468A CN201010613246A CN102127003B CN 102127003 B CN102127003 B CN 102127003B CN 2010106132468 A CN2010106132468 A CN 2010106132468A CN 201010613246 A CN201010613246 A CN 201010613246A CN 102127003 B CN102127003 B CN 102127003B
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- carbon
- solvent
- nitro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 58
- PGZUMBJQJWIWGJ-ONAKXNSWSA-N oseltamivir phosphate Chemical compound OP(O)(O)=O.CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 PGZUMBJQJWIWGJ-ONAKXNSWSA-N 0.000 title claims abstract description 19
- 229940061367 tamiflu Drugs 0.000 title claims abstract description 16
- 239000003814 drug Substances 0.000 title claims description 15
- 238000001308 synthesis method Methods 0.000 title abstract 2
- -1 amino compound Chemical class 0.000 claims abstract description 91
- 238000000034 method Methods 0.000 claims abstract description 65
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000000543 intermediate Substances 0.000 claims abstract description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 105
- 238000006243 chemical reaction Methods 0.000 claims description 88
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 76
- 239000002904 solvent Substances 0.000 claims description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 44
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 34
- 238000006722 reduction reaction Methods 0.000 claims description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- 239000012467 final product Substances 0.000 claims description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 230000002829 reductive effect Effects 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 18
- 238000001514 detection method Methods 0.000 claims description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000005576 amination reaction Methods 0.000 claims description 12
- 230000009467 reduction Effects 0.000 claims description 11
- 239000011701 zinc Substances 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 239000000654 additive Substances 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 7
- 230000001476 alcoholic effect Effects 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 239000000377 silicon dioxide Substances 0.000 claims description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 6
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 6
- 239000012279 sodium borohydride Substances 0.000 claims description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 6
- 229910004373 HOAc Inorganic materials 0.000 claims description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 4
- 238000010189 synthetic method Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- CXDHJGCWMIOAQP-UHFFFAOYSA-N 2-pyridin-3-yl-1,4,5,6-tetrahydropyrimidine;hydrochloride Chemical compound Cl.C1CCNC(C=2C=NC=CC=2)=N1 CXDHJGCWMIOAQP-UHFFFAOYSA-N 0.000 claims description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- MPCRDALPQLDDFX-UHFFFAOYSA-L Magnesium perchlorate Chemical compound [Mg+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O MPCRDALPQLDDFX-UHFFFAOYSA-L 0.000 claims description 2
- BDKZHNJTLHOSDW-UHFFFAOYSA-N [Na].CC(O)=O Chemical compound [Na].CC(O)=O BDKZHNJTLHOSDW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 229910000085 borane Inorganic materials 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 claims description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- 239000002994 raw material Substances 0.000 abstract description 22
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000000047 product Substances 0.000 description 61
- 238000005160 1H NMR spectroscopy Methods 0.000 description 48
- 239000011734 sodium Substances 0.000 description 47
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 41
- 238000001819 mass spectrum Methods 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 238000004458 analytical method Methods 0.000 description 39
- 238000004440 column chromatography Methods 0.000 description 33
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- 239000003480 eluent Substances 0.000 description 30
- 150000001299 aldehydes Chemical class 0.000 description 21
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 20
- 230000005311 nuclear magnetism Effects 0.000 description 20
- 238000001228 spectrum Methods 0.000 description 18
- 239000000376 reactant Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000001035 drying Methods 0.000 description 14
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 14
- 238000000605 extraction Methods 0.000 description 13
- 238000005406 washing Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 11
- 235000015320 potassium carbonate Nutrition 0.000 description 11
- 150000003839 salts Chemical class 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 238000006555 catalytic reaction Methods 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000003513 alkali Substances 0.000 description 7
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 0 CCC(CC)O[C@@]([C@@]([C@@](CC1(*)C(OCC)=O)*=C)NC(C)=O)[C@]1O Chemical compound CCC(CC)O[C@@]([C@@]([C@@](CC1(*)C(OCC)=O)*=C)NC(C)=O)[C@]1O 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 238000005815 base catalysis Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 150000002466 imines Chemical class 0.000 description 4
- 206010022000 influenza Diseases 0.000 description 4
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 4
- 239000005051 trimethylchlorosilane Substances 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000007259 addition reaction Methods 0.000 description 3
- 238000005575 aldol reaction Methods 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 238000010523 cascade reaction Methods 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 150000002081 enamines Chemical class 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229960003752 oseltamivir Drugs 0.000 description 3
- 229960002194 oseltamivir phosphate Drugs 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 241000712461 unidentified influenza virus Species 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- OKWJBGYZNFRKEC-UHFFFAOYSA-N benzenethiol toluene Chemical compound C1(=CC=CC=C1)S.CC1=CC=CC=C1 OKWJBGYZNFRKEC-UHFFFAOYSA-N 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000007524 organic acids Chemical group 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- NENPYTRHICXVCS-YNEHKIRRSA-N oseltamivir acid Chemical compound CCC(CC)O[C@@H]1C=C(C(O)=O)C[C@H](N)[C@H]1NC(C)=O NENPYTRHICXVCS-YNEHKIRRSA-N 0.000 description 2
- 229940093916 potassium phosphate Drugs 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- JXOHGGNKMLTUBP-HSUXUTPPSA-N shikimic acid Chemical compound O[C@@H]1CC(C(O)=O)=C[C@@H](O)[C@H]1O JXOHGGNKMLTUBP-HSUXUTPPSA-N 0.000 description 2
- JXOHGGNKMLTUBP-JKUQZMGJSA-N shikimic acid Natural products O[C@@H]1CC(C(O)=O)=C[C@H](O)[C@@H]1O JXOHGGNKMLTUBP-JKUQZMGJSA-N 0.000 description 2
- 238000010572 single replacement reaction Methods 0.000 description 2
- 229960004249 sodium acetate Drugs 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- OSNIIMCBVLBNGS-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-2-(dimethylamino)propan-1-one Chemical compound CN(C)C(C)C(=O)C1=CC=C2OCOC2=C1 OSNIIMCBVLBNGS-UHFFFAOYSA-N 0.000 description 1
- UPLPHRJJTCUQAY-WIRWPRASSA-N 2,3-thioepoxy madol Chemical compound C([C@@H]1CC2)[C@@H]3S[C@@H]3C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C)(O)[C@@]2(C)CC1 UPLPHRJJTCUQAY-WIRWPRASSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- UPHFPDKGGXRIFF-VMPITWQZSA-N CC(C)=C/C(/C(F)(F)F)=C\C(C(F)(F)F)=C Chemical compound CC(C)=C/C(/C(F)(F)F)=C\C(C(F)(F)F)=C UPHFPDKGGXRIFF-VMPITWQZSA-N 0.000 description 1
- DYBLKVUTYDRVHQ-MIHQHQCYSA-N CC(C)=C[C@H](CNC1)[C@@H]1N(C(c1c2cccc1)O)C2=O Chemical compound CC(C)=C[C@H](CNC1)[C@@H]1N(C(c1c2cccc1)O)C2=O DYBLKVUTYDRVHQ-MIHQHQCYSA-N 0.000 description 1
- KDWZHVIBLSSKCK-VVLHAWIVSA-N CCC(CC)O[C@@H]([C@@H]([C@H](CC1(C(OCC)=O)C(OCC)=O)N=C)NC(C)=O)[C@H]1O Chemical compound CCC(CC)O[C@@H]([C@@H]([C@H](CC1(C(OCC)=O)C(OCC)=O)N=C)NC(C)=O)[C@H]1O KDWZHVIBLSSKCK-VVLHAWIVSA-N 0.000 description 1
- BNTIRBLEZWBVSR-XUWVNRHRSA-N CCC(CC)O[C@@H]([C@@H]([C@H](CC1(C(OCC)=O)C(OCC)=O)[N+]([O-])=O)NC(C)=O)[C@H]1O Chemical compound CCC(CC)O[C@@H]([C@@H]([C@H](CC1(C(OCC)=O)C(OCC)=O)[N+]([O-])=O)NC(C)=O)[C@H]1O BNTIRBLEZWBVSR-XUWVNRHRSA-N 0.000 description 1
- BSOHBLMETSDNAU-LURJTMIESA-N CC[C@@H](CC[N+]([O-])=O)C=O Chemical compound CC[C@@H](CC[N+]([O-])=O)C=O BSOHBLMETSDNAU-LURJTMIESA-N 0.000 description 1
- GWNSSQSAAYXCIV-JTZLXEIQSA-N CC[C@H](CNC1)C1N(C(C1=C2C=CCC1)O)C2=O Chemical compound CC[C@H](CNC1)C1N(C(C1=C2C=CCC1)O)C2=O GWNSSQSAAYXCIV-JTZLXEIQSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical group [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 206010064097 avian influenza Diseases 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 238000006362 organocatalysis Methods 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229940000673 orphan drug Drugs 0.000 description 1
- 239000002859 orphan drug Substances 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- XZAFZXJXZHRNAQ-STQMWFEESA-N vosaroxin Chemical compound C1[C@H](OC)[C@@H](NC)CN1C1=CC=C2C(=O)C(C(O)=O)=CN(C=3SC=CN=3)C2=N1 XZAFZXJXZHRNAQ-STQMWFEESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
- C07C319/12—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols by reactions not involving the formation of mercapto groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/66—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by doubly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/30—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
- C07C233/31—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/18—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/61—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
- C07D213/73—Unsubstituted amino or imino radicals
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2010106132468A CN102127003B (zh) | 2009-12-23 | 2010-12-17 | 抗流感药物达菲的中间体化合物及其合成方法和用途 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200910200558A CN101735140A (zh) | 2009-12-23 | 2009-12-23 | 手性胺基化合物、合成方法及其抗流感药物达菲中间体的用途 |
CN200910200558.3 | 2009-12-23 | ||
CN2010106132468A CN102127003B (zh) | 2009-12-23 | 2010-12-17 | 抗流感药物达菲的中间体化合物及其合成方法和用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102127003A CN102127003A (zh) | 2011-07-20 |
CN102127003B true CN102127003B (zh) | 2013-09-11 |
Family
ID=42459222
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200910200558A Pending CN101735140A (zh) | 2009-12-23 | 2009-12-23 | 手性胺基化合物、合成方法及其抗流感药物达菲中间体的用途 |
CN2010106132468A Active CN102127003B (zh) | 2009-12-23 | 2010-12-17 | 抗流感药物达菲的中间体化合物及其合成方法和用途 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200910200558A Pending CN101735140A (zh) | 2009-12-23 | 2009-12-23 | 手性胺基化合物、合成方法及其抗流感药物达菲中间体的用途 |
Country Status (3)
Country | Link |
---|---|
US (1) | US9040738B2 (zh) |
CN (2) | CN101735140A (zh) |
WO (1) | WO2011076086A1 (zh) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101735140A (zh) * | 2009-12-23 | 2010-06-16 | 中国科学院上海有机化学研究所 | 手性胺基化合物、合成方法及其抗流感药物达菲中间体的用途 |
SK288218B6 (sk) * | 2010-05-05 | 2014-08-05 | Synkola, S.R.O. | Spôsob prípravy 1-nitro-4-oxobutanylamidov a ich opačných enantiomérov |
WO2012109996A1 (zh) | 2011-02-18 | 2012-08-23 | 上海璎黎科技有限公司 | 一种芳基糖苷类化合物及其制备方法和应用 |
JP5784336B2 (ja) * | 2011-03-08 | 2015-09-24 | 公益財団法人微生物化学研究会 | 化合物、及びその製造方法、並びにリン酸オセルタミビルの製造方法 |
CN102180821A (zh) * | 2011-03-10 | 2011-09-14 | 杭州师范大学 | 一种达菲中间体及其合成方法 |
CN111116567B (zh) * | 2013-09-09 | 2023-10-10 | 中国科学院上海有机化学研究所 | 扎那米韦和拉那米韦的中间体及其合成方法 |
CN107121506B (zh) * | 2017-04-13 | 2019-06-07 | 杭州华东医药集团新药研究院有限公司 | 奥泽沙星杂质及其用途 |
CN107304171A (zh) * | 2017-05-05 | 2017-10-31 | 杭州师范大学 | 一种奥司他韦的合成方法 |
CN111763157B (zh) * | 2020-04-26 | 2021-10-26 | 中山大学 | 一种手性氨基化合物及其制备方法和应用、及由其制备依度沙班中间体的制备方法 |
CN114634471B (zh) * | 2022-04-14 | 2023-05-19 | 河南师范大学 | 一种合成γ-羟基-γ-全氟甲基环外双键丁内酯类化合物的方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011076086A1 (zh) * | 2009-12-23 | 2011-06-30 | 中国科学院上海有机化学研究所 | 达菲的中间体化合物及其合成方法和用途 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080009639A1 (en) * | 2006-07-10 | 2008-01-10 | Apotex Pharmachem Inc. | Preparation of oseltamivir phosphate (Tamiflu) and intermediates starting from D-glucose or D-xylose |
US8304553B2 (en) * | 2007-12-19 | 2012-11-06 | Nanyang Technological University | Method of forming oseltamivir and derivatives thereof |
CN103288696B (zh) * | 2008-05-30 | 2015-08-19 | 住友化学株式会社 | 磷酸奥司他韦的中间体化合物 |
-
2009
- 2009-12-23 CN CN200910200558A patent/CN101735140A/zh active Pending
-
2010
- 2010-12-17 CN CN2010106132468A patent/CN102127003B/zh active Active
- 2010-12-17 US US14/123,870 patent/US9040738B2/en not_active Expired - Fee Related
- 2010-12-17 WO PCT/CN2010/079936 patent/WO2011076086A1/zh active Application Filing
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011076086A1 (zh) * | 2009-12-23 | 2011-06-30 | 中国科学院上海有机化学研究所 | 达菲的中间体化合物及其合成方法和用途 |
Non-Patent Citations (2)
Title |
---|
Hayato Ishikawa, Takaki Suzuki, Yujiro Hayashi.High-Yielding Synthesis of the Anti-Influenza Neuramidase Inhibitor (-)-Oseltamivir by Three "One-Pot"Operations.《Angewandte Chemie International Edition》.2009,第48卷(第7期),1304-1307. |
Zhu Shaolin,Yu Shouyun,Wang You,Ma Dawei.Organocatalytic Michael Addition of Aldehydes to Protected 2-Amino-1-Nitroethenes: The Practical Syntheses of Oseltamivir (Tamiflu) and Substituted 3-Aminopyrrolidines.《Angewandte Chemie International Edition》.2010,第49卷(第27期), * |
Also Published As
Publication number | Publication date |
---|---|
US9040738B2 (en) | 2015-05-26 |
CN102127003A (zh) | 2011-07-20 |
US20140221662A1 (en) | 2014-08-07 |
CN101735140A (zh) | 2010-06-16 |
WO2011076086A1 (zh) | 2011-06-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102127003B (zh) | 抗流感药物达菲的中间体化合物及其合成方法和用途 | |
Juaristi | Recent developments in next generation (S)-proline-derived chiral organocatalysts | |
TW201100412A (en) | Methods and intermediates for preparing pharmaceutical agents | |
RU2730006C1 (ru) | Способ получения 5r-[(бензилокси)амино]пиперидин-2s-карбоновой кислоты или её производного | |
CN102757431B (zh) | 一种合成西他列汀的新方法 | |
CN103080088B (zh) | 用于合成药物的中间体化合物的制备方法 | |
US20100022795A1 (en) | Process for producing optically active beta-hydroxy-alpha-aminocarboxylic acid ester | |
JP2023534965A (ja) | C-ヌクレオシド化合物の合成方法 | |
CA3230199A1 (en) | Process for synthesizing naphthyridine derivatives and intermediates thereof | |
TWI397380B (zh) | 含磷之α胺基酸之製造方法及其製造中間體 | |
WO2013114173A1 (en) | A novel process for the preparation of sitagliptin | |
Tang et al. | Rhodium (iii)-catalyzed C4-amidation of indole-oximes with dioxazolones via C–H activation | |
BRPI1014070B1 (pt) | processos para a produção de inibidor de dipeptidil peptidase-iv e intermediário | |
CN101977890B (zh) | 光学活性氟胺类的制造方法 | |
CN106111190A (zh) | 一种手性联芳骨架吡哆胺类催化剂及其合成方法与应用 | |
EP1995250A1 (en) | Ligand, method for producing the same, and catalyst using the ligand | |
CN100422138C (zh) | 生产旋光活性1-烷基-取代的2,2,2-三氟乙基胺的方法 | |
CN107602454B (zh) | 磺酰胺类化合物及其制备方法和用途 | |
CN105111134A (zh) | 一种制备(r)-或(s)-3-氨基哌啶双盐酸盐的方法 | |
CN109293631A (zh) | 3-氨基-n-(2,6-二氧代-3-哌啶基)-邻苯二甲酰亚胺化合物的制备方法 | |
EP1926709A1 (en) | Process for the preparation of chiral 3-hydroxy pyrrolidine compound and derivatives thereof having high optical purity | |
CN110483369B (zh) | 合成(7s)-5-氮杂螺[2.4]庚烷-7-基氨基甲酸叔丁酯的方法 | |
CN114315773B (zh) | 一种哌嗪化合物及其制备方法 | |
WO2004103990A1 (ja) | 光学活性n-モノアルキル-3-ヒドロキシ-3-アリールプロピルアミン類の製造方法および中間体 | |
KR100298145B1 (ko) | 올레핀 화합물의 비균일계 비대칭 아미노히드록시화 반응용 신코나알칼로이드 촉매 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: LIANHE CHEMICAL TECHNOLOGY CO., LTD. LIANHE TECHNO Free format text: FORMER OWNER: LIANHE CHEMICAL TECHNOLOGY CO., LTD. Effective date: 20150121 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20150121 Address after: 200032 Shanghai city Xuhui District Fenglin Road No. 354 Patentee after: SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES Patentee after: LIANHE CHEMICAL TECHNOLOGY Co.,Ltd. Patentee after: LIANHE CHEMICAL TECHNOLOGY (TAIZHOU) Co.,Ltd. Address before: 200032 Shanghai city Xuhui District Fenglin Road No. 354 Patentee before: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences Patentee before: LIANHE CHEMICAL TECHNOLOGY Co.,Ltd. |
|
CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: 200032 Shanghai city Xuhui District Fenglin Road No. 354 Patentee after: SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES Country or region after: China Patentee after: LIANHE CHEMICAL TECHNOLOGY Co.,Ltd. Patentee after: Lianhua Angjian (Zhejiang) Pharmaceutical Co.,Ltd. Address before: 200032 Shanghai city Xuhui District Fenglin Road No. 354 Patentee before: SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES Country or region before: China Patentee before: LIANHE CHEMICAL TECHNOLOGY Co.,Ltd. Patentee before: LIANHE CHEMICAL TECHNOLOGY (TAIZHOU) Co.,Ltd. |