JP5533654B2 - ３，５−ジヒドロキシ−６−ヘプテン酸アミン塩類の製造方法 - Google Patents
３，５−ジヒドロキシ−６−ヘプテン酸アミン塩類の製造方法 Download PDFInfo
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- JP5533654B2 JP5533654B2 JP2010527837A JP2010527837A JP5533654B2 JP 5533654 B2 JP5533654 B2 JP 5533654B2 JP 2010527837 A JP2010527837 A JP 2010527837A JP 2010527837 A JP2010527837 A JP 2010527837A JP 5533654 B2 JP5533654 B2 JP 5533654B2
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- dihydroxy
- cyclopropyl
- fluorophenyl
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- -1 3,5-dihydroxy-6-heptenoic acid amine salt Chemical class 0.000 title claims description 96
- 238000004519 manufacturing process Methods 0.000 title claims description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 102
- VGYFMXBACGZSIL-RTBURBONSA-N (3r,5s)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)C=CC1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-RTBURBONSA-N 0.000 claims description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 150000001412 amines Chemical class 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 25
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 21
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 19
- 239000013078 crystal Substances 0.000 claims description 17
- 239000012046 mixed solvent Substances 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 12
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- STVVMTBJNDTZBF-UHFFFAOYSA-N -2-Amino-3-phenyl-1-propanol Natural products OCC(N)CC1=CC=CC=C1 STVVMTBJNDTZBF-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- NWYYWIJOWOLJNR-YFKPBYRVSA-N (2r)-2-amino-3-methylbutan-1-ol Chemical group CC(C)[C@@H](N)CO NWYYWIJOWOLJNR-YFKPBYRVSA-N 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- RTCUCQWIICFPOD-SECBINFHSA-N (1r)-1-naphthalen-1-ylethanamine Chemical group C1=CC=C2C([C@H](N)C)=CC=CC2=C1 RTCUCQWIICFPOD-SECBINFHSA-N 0.000 claims description 4
- AQFLVLHRZFLDDV-SECBINFHSA-N (1r)-1-phenylpropan-1-amine Chemical group CC[C@@H](N)C1=CC=CC=C1 AQFLVLHRZFLDDV-SECBINFHSA-N 0.000 claims description 4
- STVVMTBJNDTZBF-SECBINFHSA-N (2r)-2-amino-3-phenylpropan-1-ol Chemical group OC[C@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-SECBINFHSA-N 0.000 claims description 4
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical group OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 claims description 4
- MMTXSCWTVRMIIY-UHFFFAOYSA-N 3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)CC(O)CC(O)C=C MMTXSCWTVRMIIY-UHFFFAOYSA-N 0.000 claims description 2
- BHFLUDRTVIDDOR-QMMMGPOBSA-N methyl (2s)-2-amino-2-phenylacetate Chemical group COC(=O)[C@@H](N)C1=CC=CC=C1 BHFLUDRTVIDDOR-QMMMGPOBSA-N 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 41
- 239000007787 solid Substances 0.000 description 20
- 239000000243 solution Substances 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- 125000000217 alkyl group Chemical group 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 0 *CC(CC(C=C[C@](C1c(cc2)ccc2F)C(C2CC2)=Nc2c1cccc2)=O)=O Chemical compound *CC(CC(C=C[C@](C1c(cc2)ccc2F)C(C2CC2)=Nc2c1cccc2)=O)=O 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 description 4
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000011914 asymmetric synthesis Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 3
- VGYFMXBACGZSIL-MCBHFWOFSA-N O[C@H](C[C@@H](/C=C/c1c(-c(cc2)ccc2F)c(cccc2)c2nc1C1CC1)O)CC(O)=O Chemical compound O[C@H](C[C@@H](/C=C/c1c(-c(cc2)ccc2F)c(cccc2)c2nc1C1CC1)O)CC(O)=O VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000005157 alkyl carboxy group Chemical group 0.000 description 3
- 125000005427 anthranyl group Chemical group 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000006267 biphenyl group Chemical group 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- VGYFMXBACGZSIL-RBUKOAKNSA-N (3R,5R)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@@H](O)C=CC1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-RBUKOAKNSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical class CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 2
- JFVAZAQELKYEFZ-UHFFFAOYSA-N 2-cyclopropyl-4-(4-fluorophenyl)quinoline Chemical compound C1=CC(F)=CC=C1C1=CC(C2CC2)=NC2=CC=CC=C12 JFVAZAQELKYEFZ-UHFFFAOYSA-N 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011403 purification operation Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- WKPZUCBZSGJGMI-WOJBJXKFSA-N (3S,5R)-1-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]hept-1-ene-3,5-diol Chemical compound CC[C@@H](O)C[C@H](O)C=CC1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 WKPZUCBZSGJGMI-WOJBJXKFSA-N 0.000 description 1
- VGYFMXBACGZSIL-MOPGFXCFSA-N (3S,5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@@H](O)C[C@H](O)C=CC1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MOPGFXCFSA-N 0.000 description 1
- MNQDQKPGBOCXNP-GOSISDBHSA-N (5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-5-hydroxy-3-oxohept-6-enoic acid Chemical compound O[C@@H](CC(=O)CC(O)=O)C=Cc1c(nc2ccccc2c1-c1ccc(F)cc1)C1CC1 MNQDQKPGBOCXNP-GOSISDBHSA-N 0.000 description 1
- RWZYEKXHAQMRIO-UHFFFAOYSA-N 2,2-dihydroxyhept-6-enoic acid Chemical class OC(=O)C(O)(O)CCCC=C RWZYEKXHAQMRIO-UHFFFAOYSA-N 0.000 description 1
- FLYIRERUSAMCDQ-UHFFFAOYSA-N 2-azaniumyl-2-(2-methylphenyl)acetate Chemical compound CC1=CC=CC=C1C(N)C(O)=O FLYIRERUSAMCDQ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- NCUNSUMNJBVBKV-WEIRHIGXSA-N C1(=CC=CC2=CC=CC=C12)[C@@H](C)N.C1(CC1)C1=NC2=CC=CC=C2C(=C1C=C[C@H](C[C@H](CC(=O)O)O)O)C1=CC=C(C=C1)F Chemical compound C1(=CC=CC2=CC=CC=C12)[C@@H](C)N.C1(CC1)C1=NC2=CC=CC=C2C(=C1C=C[C@H](C[C@H](CC(=O)O)O)O)C1=CC=C(C=C1)F NCUNSUMNJBVBKV-WEIRHIGXSA-N 0.000 description 1
- JFALZICZKQXRGA-STYNFMPRSA-N C1(CC1)C1=NC2=CC=CC=C2C(=C1C=C[C@H](C[C@H](CC(=O)O)O)O)C1=CC=C(C=C1)F.C(C)N Chemical compound C1(CC1)C1=NC2=CC=CC=C2C(=C1C=C[C@H](C[C@H](CC(=O)O)O)O)C1=CC=C(C=C1)F.C(C)N JFALZICZKQXRGA-STYNFMPRSA-N 0.000 description 1
- NWJUCTSWJKMGJX-HVMKRBRFSA-N C[C@@H](N)c1ccccc1.O[C@H](C[C@H](O)C=Cc1c(nc2ccccc2c1-c1ccc(F)cc1)C1CC1)CC(O)=O Chemical compound C[C@@H](N)c1ccccc1.O[C@H](C[C@H](O)C=Cc1c(nc2ccccc2c1-c1ccc(F)cc1)C1CC1)CC(O)=O NWJUCTSWJKMGJX-HVMKRBRFSA-N 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- UVRKEKLLNCVEAX-YTWASRRYSA-N N[C@@H](CO)C(C)C.C1(CC1)C1=NC2=CC=CC=C2C(=C1C=C[C@H](C[C@H](CC(=O)O)O)O)C1=CC=C(C=C1)F Chemical compound N[C@@H](CO)C(C)C.C1(CC1)C1=NC2=CC=CC=C2C(=C1C=C[C@H](C[C@H](CC(=O)O)O)O)C1=CC=C(C=C1)F UVRKEKLLNCVEAX-YTWASRRYSA-N 0.000 description 1
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- JBNHLBWRVBDKPJ-FVGYRXGTSA-N N[C@H](CO)CC1=CC=CC=C1.C(CCCCC=C)(=O)O Chemical compound N[C@H](CO)CC1=CC=CC=C1.C(CCCCC=C)(=O)O JBNHLBWRVBDKPJ-FVGYRXGTSA-N 0.000 description 1
- IDHSILKTPOBIST-XICOBVEKSA-N O[C@H](C[C@@H](/C=C/c1c(-c(cc2)ccc2F)c(cccc2)c2nc1CC1CC1)O)CC(O)=O Chemical compound O[C@H](C[C@@H](/C=C/c1c(-c(cc2)ccc2F)c(cccc2)c2nc1CC1CC1)O)CC(O)=O IDHSILKTPOBIST-XICOBVEKSA-N 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DTHMTBUWTGVEFG-QRPNPIFTSA-N [(1s)-2-methoxy-2-oxo-1-phenylethyl]azanium;chloride Chemical compound Cl.COC(=O)[C@@H](N)C1=CC=CC=C1 DTHMTBUWTGVEFG-QRPNPIFTSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- MAUQAXOHCVNUMX-NHCUHLMSSA-N ethyl (3r,5s)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CCOC(=O)C[C@H](O)C[C@H](O)C=CC1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 MAUQAXOHCVNUMX-NHCUHLMSSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 125000000686 lactone group Chemical group 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 239000000126 substance Substances 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Quinoline Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010527837A JP5533654B2 (ja) | 2008-09-05 | 2009-09-04 | ３，５−ジヒドロキシ−６−ヘプテン酸アミン塩類の製造方法 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008228750 | 2008-09-05 | ||
| JP2008228750 | 2008-09-05 | ||
| PCT/JP2009/065527 WO2010027060A1 (fr) | 2008-09-05 | 2009-09-04 | Procédé pour la fabrication de sel d'amine d'acide 3,5-dihydroxy-6-hepténoïque |
| JP2010527837A JP5533654B2 (ja) | 2008-09-05 | 2009-09-04 | ３，５−ジヒドロキシ−６−ヘプテン酸アミン塩類の製造方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPWO2010027060A1 JPWO2010027060A1 (ja) | 2012-02-02 |
| JP5533654B2 true JP5533654B2 (ja) | 2014-06-25 |
Family
ID=41797224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010527837A Expired - Fee Related JP5533654B2 (ja) | 2008-09-05 | 2009-09-04 | ３，５−ジヒドロキシ−６−ヘプテン酸アミン塩類の製造方法 |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP5533654B2 (fr) |
| WO (1) | WO2010027060A1 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105189458A (zh) * | 2013-03-29 | 2015-12-23 | 中化帝斯曼制药有限公司荷兰公司 | 匹伐他汀和罗素伐他汀的胺盐 |
| EP2978744A1 (fr) | 2013-03-29 | 2016-02-03 | DSM Sinochem Pharmaceuticals Netherlands B.V. | Sels d'amine de pitavastatine et de rosuvastatine |
| 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 (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05148237A (ja) * | 1991-06-24 | 1993-06-15 | Nissan Chem Ind Ltd | 光学活性キノリンメバロン酸のジアステレオマー塩 |
| JP2005047803A (ja) * | 2001-05-15 | 2005-02-24 | Ube Ind Ltd | （３ｒ，５ｓ）−７−置換−３，５−ジヒドロキシヘプト−６−エン酸の製法 |
-
2009
- 2009-09-04 JP JP2010527837A patent/JP5533654B2/ja not_active Expired - Fee Related
- 2009-09-04 WO PCT/JP2009/065527 patent/WO2010027060A1/fr active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05148237A (ja) * | 1991-06-24 | 1993-06-15 | Nissan Chem Ind Ltd | 光学活性キノリンメバロン酸のジアステレオマー塩 |
| JP2005047803A (ja) * | 2001-05-15 | 2005-02-24 | Ube Ind Ltd | （３ｒ，５ｓ）−７−置換−３，５−ジヒドロキシヘプト−６−エン酸の製法 |
Non-Patent Citations (3)
| Title |
|---|
| JPN6013063936; 季刊 化学総説 Ｎｏ．６ 「光学異性体の分離」 , 19990610, ｐｐ．４５-５４（４．ジアステレオマー）, 学会出版センター * |
| JPN7013004782; Ｔｅｔｒａｈｅｄｒｏｎ Ａｓｙｍｍｅｔｒｙ １９, 2008, ｐｐ．５１９-５３６ * |
| JPN7013004784; 東京化成工業，「ＴＣＩプロダクトノート『光学分割』」 , 200703 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2010027060A1 (ja) | 2012-02-02 |
| WO2010027060A1 (fr) | 2010-03-11 |
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