AU2002228413B8 - Process for producing (3R,5S)-(E)-7-[2-Cyclopropyl-4-(4-Fluorophenyl)-Quinolin-3-yl]-3,5-Dihydroxyhept -6-enic acid esters - Google Patents
Process for producing (3R,5S)-(E)-7-[2-Cyclopropyl-4-(4-Fluorophenyl)-Quinolin-3-yl]-3,5-Dihydroxyhept -6-enic acid esters Download PDFInfo
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- AU2002228413B8 AU2002228413B8 AU2002228413A AU2002228413A AU2002228413B8 AU 2002228413 B8 AU2002228413 B8 AU 2002228413B8 AU 2002228413 A AU2002228413 A AU 2002228413A AU 2002228413 A AU2002228413 A AU 2002228413A AU 2002228413 B8 AU2002228413 B8 AU 2002228413B8
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- 238000000034 method Methods 0.000 title claims description 45
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical class OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 143
- 244000005700 microbiome Species 0.000 claims description 97
- 238000006243 chemical reaction Methods 0.000 claims description 83
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- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 24
- 241001112159 Ogataea Species 0.000 claims description 18
- 241000221207 Filobasidium Species 0.000 claims description 17
- 241000235648 Pichia Species 0.000 claims description 17
- 241000223682 Exophiala Species 0.000 claims description 14
- -1 sulfonyloxy group Chemical group 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 13
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- 241000193624 Wickerhamiella Species 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
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- 241001480014 Trigonopsis Species 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000468 ketone group Chemical group 0.000 claims description 6
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- 241000186321 Cellulomonas Species 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 claims description 5
- JAHBIRPTCXOGLB-UHFFFAOYSA-N 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-carbaldehyde Chemical compound C1=CC(F)=CC=C1C1=C(C=O)C(C2CC2)=NC2=CC=CC=C12 JAHBIRPTCXOGLB-UHFFFAOYSA-N 0.000 claims description 4
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- 239000013543 active substance Substances 0.000 claims description 4
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 239000004576 sand Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
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- 238000004519 manufacturing process Methods 0.000 description 47
- 239000000203 mixture Substances 0.000 description 40
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- MAUQAXOHCVNUMX-BUHFOSPRSA-N ethyl (e)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CCOC(=O)CC(O)CC(O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 MAUQAXOHCVNUMX-BUHFOSPRSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 238000004128 high performance liquid chromatography Methods 0.000 description 26
- 238000004809 thin layer chromatography Methods 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 230000003287 optical effect Effects 0.000 description 20
- 239000001963 growth medium Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000008103 glucose Substances 0.000 description 18
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 238000009630 liquid culture Methods 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- 239000002585 base Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 10
- 238000005119 centrifugation Methods 0.000 description 10
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
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- 239000002253 acid Substances 0.000 description 7
- ZFZZSKJFCXBRLJ-BUHFOSPRSA-N ethyl (e)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dioxohept-6-enoate Chemical compound CCOC(=O)CC(=O)CC(=O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 ZFZZSKJFCXBRLJ-BUHFOSPRSA-N 0.000 description 7
- VYFOPSXXZQZCAJ-UHFFFAOYSA-N ethyl 7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-7-hydroxy-3,5-dioxoheptanoate Chemical compound CCOC(=O)CC(=O)CC(=O)CC(O)C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VYFOPSXXZQZCAJ-UHFFFAOYSA-N 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000186216 Corynebacterium Species 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 241000221418 Piskurozyma capsuligena Species 0.000 description 6
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 6
- 229950006238 nadide Drugs 0.000 description 6
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 241000308595 Buckleyzyma aurantiaca Species 0.000 description 5
- 241001508786 Citeromyces matritensis Species 0.000 description 5
- 241000235036 Debaryomyces hansenii Species 0.000 description 5
- 241001304303 Kuraishia molischiana Species 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
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- 241000222173 Candida parapsilosis Species 0.000 description 4
- 241000512906 Candida solani Species 0.000 description 4
- 241000222178 Candida tropicalis Species 0.000 description 4
- 241000186226 Corynebacterium glutamicum Species 0.000 description 4
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 4
- 241001489172 Ogataea glucozyma Species 0.000 description 4
- 241000222051 Papiliotrema laurentii Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
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- 238000004587 chromatography analysis Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 229910001410 inorganic ion Inorganic materials 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
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- 241000894007 species Species 0.000 description 4
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- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- VGYFMXBACGZSIL-VAWYXSNFSA-N (e)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical class OC(=O)CC(O)CC(O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-VAWYXSNFSA-N 0.000 description 3
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
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- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 2
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- DSTZLNOPNQSCLE-UHFFFAOYSA-N ethanol;hexane;2,2,2-trifluoroacetic acid Chemical compound CCO.CCCCCC.OC(=O)C(F)(F)F DSTZLNOPNQSCLE-UHFFFAOYSA-N 0.000 description 2
- SSOOGSMECVGPOT-UHFFFAOYSA-N ethyl 3,5-dioxohexanoate Chemical compound CCOC(=O)CC(=O)CC(C)=O SSOOGSMECVGPOT-UHFFFAOYSA-N 0.000 description 2
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- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
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- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
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- 235000019270 ammonium chloride Nutrition 0.000 description 1
- CAMXVZOXBADHNJ-UHFFFAOYSA-N ammonium nitrite Chemical compound [NH4+].[O-]N=O CAMXVZOXBADHNJ-UHFFFAOYSA-N 0.000 description 1
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- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
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- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
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- 210000001072 colon Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000011161 development Methods 0.000 description 1
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- 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- DDONWQMFQGSJMF-UHFFFAOYSA-N ethyl 2-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dioxohept-6-enoate Chemical compound C(C)OC(C(C(CC(C=C)=O)=O)C=1C(=NC2=CC=CC=C2C=1C1=CC=C(C=C1)F)C1CC1)=O DDONWQMFQGSJMF-UHFFFAOYSA-N 0.000 description 1
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- 230000002068 genetic effect Effects 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 229940099607 manganese chloride Drugs 0.000 description 1
- 229910001437 manganese ion Inorganic materials 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- RYGIHSLRMNXWCN-UHFFFAOYSA-N quinoline-3-carbaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CN=C21 RYGIHSLRMNXWCN-UHFFFAOYSA-N 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 description 1
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-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
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/10—Nitrogen as only ring hetero atom
- C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001-26316 | 2001-02-02 | ||
| JP2001026316 | 2001-02-02 | ||
| JP2001-331480 | 2001-10-29 | ||
| JP2001331480A JP2003137870A (ja) | 2001-10-29 | 2001-10-29 | ３，５−ジオキソ−６−ヘプテン酸誘導体類の製造方法及びその中間体 |
| PCT/JP2002/000835 WO2002063028A1 (fr) | 2001-02-02 | 2002-02-01 | Procede de production d'esters d'acide (3r,5s)-(e)-7-[2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl]-3,5-dihydroxyhept-6-enique |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2002228413A1 AU2002228413A1 (en) | 2002-08-19 |
| AU2002228413B2 AU2002228413B2 (en) | 2007-02-22 |
| AU2002228413B8 true AU2002228413B8 (en) | 2007-03-22 |
Family
ID=26608822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002228413A Ceased AU2002228413B8 (en) | 2001-02-02 | 2002-02-01 | Process for producing (3R,5S)-(E)-7-[2-Cyclopropyl-4-(4-Fluorophenyl)-Quinolin-3-yl]-3,5-Dihydroxyhept -6-enic acid esters |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6965031B2 (enExample) |
| EP (1) | EP1365029A4 (enExample) |
| KR (1) | KR100883874B1 (enExample) |
| CN (1) | CN1329520C (enExample) |
| AU (1) | AU2002228413B8 (enExample) |
| CA (1) | CA2437312C (enExample) |
| TW (1) | TWI322829B (enExample) |
| WO (1) | WO2002063028A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI322829B (enExample) * | 2001-02-02 | 2010-04-01 | Mitsubishi Chem Corp | |
| UA76984C2 (en) * | 2001-04-05 | 2006-10-16 | Nissan Chemical Ind Ltd | A method for preparing a 7-qunolinyl-3,5-dihydroxyhept-6-enoate |
| ATE426594T1 (de) * | 2002-01-31 | 2009-04-15 | Novartis Pharma Gmbh | Verfahren zur herstellung von inhibitoren der hmg-coa-reduktase |
| EP1491633B1 (en) * | 2002-03-19 | 2008-08-27 | Mitsubishi Chemical Corporation | Novel carbonyl reductase, gene encoding it and process for producing optically active alcohols using the same |
| ITMI20100753A1 (it) * | 2010-04-30 | 2011-10-31 | Dipharma Francis Srl | Procedimento per la preparazione di statine |
| EP2383260A3 (en) * | 2010-04-30 | 2011-12-28 | Dipharma Francis S.r.l. | Process for the preparation of statins |
| CN103848784B (zh) * | 2012-12-05 | 2016-12-21 | 安徽省庆云医药化工有限公司 | 匹伐他汀酯的晶型及其制备方法 |
| JP6150703B2 (ja) * | 2013-10-08 | 2017-06-21 | ダイト株式会社 | ピタバスタチンカルシウム塩の分解抑制方法 |
| CN106029895B (zh) * | 2014-02-06 | 2021-07-16 | 株式会社Api | 瑞舒伐他汀钙及其中间体的生产方法 |
| JP6649263B2 (ja) * | 2014-10-10 | 2020-02-19 | 株式会社エーピーアイ コーポレーション | スタチン系化合物の精製方法 |
| CN107949556B (zh) * | 2015-08-05 | 2021-12-07 | 株式会社Api | 生产匹伐他汀钙的方法 |
| CN105481838A (zh) * | 2015-11-18 | 2016-04-13 | 北京万全德众医药生物技术有限公司 | 一种制备匹伐他汀内酯杂质的方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6965031B2 (en) * | 2001-02-02 | 2005-11-15 | Mitsubishi Chemical Corporation | Process for producing (3R,5S)-(E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-quinolin- 3-yl]-3,5-dihydroxyhept-6-enic acid esters |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1336714C (en) * | 1987-08-20 | 1995-08-15 | Yoshihiro Fujikawa | Quinoline type mevalonolactone inhibitors of cholesterol biosynthesis |
| JP2648897B2 (ja) | 1991-07-01 | 1997-09-03 | 塩野義製薬株式会社 | ピリミジン誘導体 |
| JP3149265B2 (ja) | 1992-05-12 | 2001-03-26 | 鐘淵化学工業株式会社 | 光学活性な３，５−ジヒドロキシ脂肪酸エステル誘導体の製造法 |
| US5324662A (en) * | 1992-05-15 | 1994-06-28 | E. R. Squibb & Sons, Inc. | Stereoselective microbial or enzymatic reduction of 3,5-dioxo esters to 3-hydroxy-5-oxo, 3-oxo-5-hydroxy, and 3,5-dihydroxy esters |
| JP3554036B2 (ja) * | 1994-09-06 | 2004-08-11 | 宇部興産株式会社 | 光学活性な７−置換キノリル−３，５−ジヒドロキシ−ヘプト−６−エン酸エステル誘導体の製造方法 |
| JP3481325B2 (ja) * | 1994-09-06 | 2003-12-22 | 宇部興産株式会社 | 光学活性な３−オキシ−５−オキソ−６−ヘプテン酸誘導体の製法 |
| GB9512837D0 (en) | 1995-06-23 | 1995-08-23 | Zeneca Ltd | reduction of ketone groups |
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2002
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- 2002-02-01 CN CNB028078527A patent/CN1329520C/zh not_active Expired - Lifetime
- 2002-02-01 AU AU2002228413A patent/AU2002228413B8/en not_active Ceased
- 2002-02-01 KR KR1020037010128A patent/KR100883874B1/ko not_active Expired - Fee Related
- 2002-02-01 EP EP02710461A patent/EP1365029A4/en not_active Withdrawn
- 2002-02-01 CA CA2437312A patent/CA2437312C/en not_active Expired - Fee Related
- 2002-02-01 WO PCT/JP2002/000835 patent/WO2002063028A1/ja not_active Ceased
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6965031B2 (en) * | 2001-02-02 | 2005-11-15 | Mitsubishi Chemical Corporation | Process for producing (3R,5S)-(E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-quinolin- 3-yl]-3,5-dihydroxyhept-6-enic acid esters |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1329520C (zh) | 2007-08-01 |
| EP1365029A4 (en) | 2009-07-29 |
| EP1365029A1 (en) | 2003-11-26 |
| AU2002228413A1 (en) | 2002-08-19 |
| US6965031B2 (en) | 2005-11-15 |
| AU2002228413B2 (en) | 2007-02-22 |
| WO2002063028A1 (fr) | 2002-08-15 |
| CA2437312A1 (en) | 2002-08-15 |
| TWI322829B (enExample) | 2010-04-01 |
| CA2437312C (en) | 2010-03-23 |
| KR100883874B1 (ko) | 2009-02-17 |
| US20040030139A1 (en) | 2004-02-12 |
| KR20030072618A (ko) | 2003-09-15 |
| CN1633502A (zh) | 2005-06-29 |
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