CN101880227A - 一种用于制备适合于制备他汀类衍生物的中间体化合物的方法及其中间体 - Google Patents
一种用于制备适合于制备他汀类衍生物的中间体化合物的方法及其中间体 Download PDFInfo
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- CN101880227A CN101880227A CN201010004468XA CN201010004468A CN101880227A CN 101880227 A CN101880227 A CN 101880227A CN 201010004468X A CN201010004468X A CN 201010004468XA CN 201010004468 A CN201010004468 A CN 201010004468A CN 101880227 A CN101880227 A CN 101880227A
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- 238000000034 method Methods 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title claims abstract description 20
- 230000008569 process Effects 0.000 title claims description 7
- 239000000543 intermediate Substances 0.000 title abstract description 20
- 238000003786 synthesis reaction Methods 0.000 title description 5
- 230000015572 biosynthetic process Effects 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 26
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract 2
- -1 methoxyl group Chemical group 0.000 claims description 172
- 238000006243 chemical reaction Methods 0.000 claims description 72
- 125000006239 protecting group Chemical group 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 30
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- 150000002367 halogens Chemical class 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
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- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- 125000004494 ethyl ester group Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
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- OUWSNHWQZPEFEX-UHFFFAOYSA-N diethyl glutarate Chemical compound CCOC(=O)CCCC(=O)OCC OUWSNHWQZPEFEX-UHFFFAOYSA-N 0.000 claims description 8
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- 125000003545 alkoxy group Chemical group 0.000 claims description 6
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- 238000001308 synthesis method Methods 0.000 abstract description 2
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- 125000005843 halogen group Chemical group 0.000 abstract 1
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
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- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
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- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
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- OKJPEAGHQZHRQV-UHFFFAOYSA-N iodoform Chemical compound IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 7
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- 239000003638 chemical reducing agent Substances 0.000 description 1
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- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
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- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 239000013078 crystal Substances 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
- FNIATMYXUPOJRW-UHFFFAOYSA-N cyclohexylidene Chemical group [C]1CCCCC1 FNIATMYXUPOJRW-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- PWAPCRSSMCLZHG-UHFFFAOYSA-N cyclopentylidene Chemical group [C]1CCCC1 PWAPCRSSMCLZHG-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- MNNMTFSPSVOWSF-UHFFFAOYSA-N dicyclohexylazanium;chloride Chemical compound Cl.C1CCCCC1NC1CCCCC1 MNNMTFSPSVOWSF-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002195 fatty ethers Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- SYKWLIJQEHRDNH-KRPIADGTSA-N glutaryl-coa Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSC(=O)CCCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SYKWLIJQEHRDNH-KRPIADGTSA-N 0.000 description 1
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- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical group IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([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
- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
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- 159000000003 magnesium salts Chemical group 0.000 description 1
- 239000000463 material Substances 0.000 description 1
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- 239000002184 metal Substances 0.000 description 1
- 150000001457 metallic cations Chemical class 0.000 description 1
- VCRYGHPVKURQMM-UHFFFAOYSA-N methane;platinum Chemical compound C.[Pt] VCRYGHPVKURQMM-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000000199 molecular distillation Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- PHVXTQIROLEEDB-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-n-pyrrolidin-3-ylbenzamide Chemical compound CC1=CC=CC=C1C1CN(CC=2C=CC(=CC=2)C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CNCC2)CCC1 PHVXTQIROLEEDB-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 235000012736 patent blue V Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000003408 phase transfer catalysis Methods 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- RHGYHLPFVJEAOC-FFNUKLMVSA-L pitavastatin calcium Chemical compound [Ca+2].[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1.[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 RHGYHLPFVJEAOC-FFNUKLMVSA-L 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 239000001327 prunus amygdalus amara l. extract Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000005554 pyridyloxy group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 108010031354 thermitase Proteins 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- 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
- C07C227/30—Preparation of optical isomers
- C07C227/32—Preparation of optical isomers by stereospecific synthesis
-
- 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
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/716—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- 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
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/62—Carboxylic acid esters
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01810670 | 2001-07-06 | ||
| EP01810670.8 | 2001-07-06 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA028135342A Division CN1610657A (zh) | 2001-07-06 | 2002-07-02 | 制备用于合成他汀类衍生物、特别是7－氨基3,5－二羟基庚酸衍生物的中间体的方法,及其中间体 |
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| CNA028135342A Pending CN1610657A (zh) | 2001-07-06 | 2002-07-02 | 制备用于合成他汀类衍生物、特别是7－氨基3,5－二羟基庚酸衍生物的中间体的方法,及其中间体 |
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| CNA028135342A Pending CN1610657A (zh) | 2001-07-06 | 2002-07-02 | 制备用于合成他汀类衍生物、特别是7－氨基3,5－二羟基庚酸衍生物的中间体的方法,及其中间体 |
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| EP (2) | EP2161250A1 (https=) |
| JP (1) | JP2004533479A (https=) |
| KR (2) | KR20040017278A (https=) |
| CN (2) | CN101880227A (https=) |
| AR (3) | AR034735A1 (https=) |
| AU (1) | AU2002354701B2 (https=) |
| BR (1) | BR0210842A (https=) |
| CA (1) | CA2448917A1 (https=) |
| CZ (1) | CZ2004150A3 (https=) |
| ES (1) | ES2340260T3 (https=) |
| HR (1) | HRPK20040119B3 (https=) |
| HU (1) | HUP0401145A3 (https=) |
| IL (3) | IL159050A0 (https=) |
| PL (1) | PL366392A1 (https=) |
| PT (1) | PT1404642E (https=) |
| WO (1) | WO2003004450A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997324A (zh) * | 2018-08-21 | 2018-12-14 | 南京欧信医药技术有限公司 | 瑞舒伐他汀钙中间体的制备方法 |
| CN118772052A (zh) * | 2024-09-10 | 2024-10-15 | 湖南九维生物医药有限公司 | 一种医药中间体及其制备方法 |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6101484A (en) | 1999-03-31 | 2000-08-08 | Mercata, Inc. | Dynamic market equilibrium management system, process and article of manufacture |
| WO2002057229A1 (en) | 2001-01-19 | 2002-07-25 | Biocon India Limited | FORM V CRYSTALLINE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1- HEPTANOIC ACID HEMI CALCIUM SALT. (ATORVASTATIN) |
| HUP0401145A3 (en) * | 2001-07-06 | 2008-08-28 | Ciba Sc Holding Ag | Process for the preparation of intermediates useful in the synthesis of statin derivatives especially 7-amino 3,5-dihydroxy heptanoic acid derivatives, and intermediates thereof |
| MXPA04000322A (es) | 2001-07-13 | 2005-09-08 | Astrazeneca Uk Ltd | Preparacion de compuestos de aminopirimidina. |
| US7361772B2 (en) | 2001-08-16 | 2008-04-22 | Biocon Limited | Process for the production of atorvastatin calcium |
| HUP0500074A3 (en) | 2002-03-18 | 2005-07-28 | Biocon Ltd Bangalore | Amorphous hmg-coa reductase inhibitors of desired particle size and process for producing them |
| US7179942B2 (en) | 2002-07-05 | 2007-02-20 | Bicon Limited | Halo-substituted active methylene compounds |
| AU2003295684A1 (en) * | 2002-11-15 | 2004-06-15 | Teva Pharmaceutical Industries Ltd. | Synthesis of 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids |
| ES2323366T3 (es) | 2003-04-22 | 2009-07-14 | Biocon Limited | Procedimiento novedoso para la reduccion estereoselectiva de beta-cetoesteres. |
| AU2003272080A1 (en) | 2003-09-18 | 2005-04-06 | Biocon Limited | Novel process for the preparation of tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate |
| GB0428328D0 (en) | 2004-12-24 | 2005-02-02 | Astrazeneca Uk Ltd | Chemical process |
| WO2007034909A1 (ja) * | 2005-09-22 | 2007-03-29 | Kaneka Corporation | （３ｒ，５ｒ）－７－アミノ－３，５－ジヒドロキシヘプタン酸誘導体の製造法 |
| KR20100080432A (ko) * | 2008-12-29 | 2010-07-08 | 한미약품 주식회사 | 스타틴 화합물의 신규 제조방법 및 이에 사용되는 벤조티아졸릴 술폰 화합물 |
| EP2616454B1 (en) * | 2010-09-16 | 2015-04-15 | DSM Sinochem Pharmaceuticals Netherlands B.V. | Esters of hexanoic acids as intermediates for the preparation of atorvastatin |
| JP6073292B2 (ja) | 2011-05-06 | 2017-02-01 | ビーエーエスエフ ソシエタス・ヨーロピアＢａｓｆ Ｓｅ | 吸水性ポリマー粒子の製造法 |
| US8420773B2 (en) | 2011-05-06 | 2013-04-16 | Basf Se | Process for producing water-absorbing polymer particles |
| AU2012345473B2 (en) * | 2011-11-28 | 2017-05-25 | Mylan Laboratories Ltd | Process for producing chiral statin side chain intermediates employing candida|antarctica lipase B |
| US10149720B2 (en) | 2013-03-08 | 2018-12-11 | Auris Health, Inc. | Method, apparatus, and a system for facilitating bending of an instrument in a surgical or medical robotic environment |
| EP2778229A1 (de) * | 2013-03-11 | 2014-09-17 | Sandoz Ag | Verfahren zur enantioselektiven Herstellung von 3-Hydroxyglutarsäuremonoestern und deren Verwendung |
| US10376672B2 (en) | 2013-03-15 | 2019-08-13 | Auris Health, Inc. | Catheter insertion system and method of fabrication |
| US9499621B2 (en) | 2013-04-08 | 2016-11-22 | Cytodyn, Inc. | Felinized antibodies and methods of treating retroviral infections in felines |
| CN104230879B (zh) * | 2014-08-15 | 2016-08-24 | 新发药业有限公司 | 一种2-((4r, 6s)-6-甲酰基-2,2-二取代基-1,3-二氧六环-4-基)乙酸酯制备方法 |
| CN108033899B (zh) * | 2017-12-06 | 2020-04-10 | 浙江科技学院 | 一种(r)-6-氰基-5-羟基-3-羰基己酸叔丁酯的制备方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4677211A (en) | 1984-06-29 | 1987-06-30 | Sandoz Pharmaceuticals Corp. | Preparation of lactones |
| US4950775A (en) | 1985-10-11 | 1990-08-21 | University Of California | Antihypercholesterolemic compounds and synthesis thereof |
| US5003080A (en) | 1988-02-22 | 1991-03-26 | Warner-Lambert Company | Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis |
| IT1226726B (it) * | 1988-07-29 | 1991-02-05 | Zambon Spa | Composti attivi come inibitori della biosintesi del colesterolo. |
| US5196440A (en) * | 1988-07-29 | 1993-03-23 | Zambon Group S.P.A. | Compounds active as inhibitors of the cholesterol biosynthesis |
| IT1224795B (it) * | 1988-12-01 | 1990-10-24 | Sigma Tau Ind Farmaceuti | Uso dell'acetil d-carnitina nel trattamento terapeutico del glaucoma e composizioni farmaceutiche utili in tale trattamento |
| IT1237792B (it) | 1989-12-21 | 1993-06-17 | Zambon Spa | Composti attivi come inibitori dell'enzima hmg-coa reduttasi |
| US5155251A (en) | 1991-10-11 | 1992-10-13 | Warner-Lambert Company | Process for the synthesis of (5R)-1,1-dimethylethyl-6-cyano-5-hydroxy-3-oxo-hexanoate |
| JP3652394B2 (ja) | 1995-01-27 | 2005-05-25 | 高砂香料工業株式会社 | Ｎ−置換−７−アミノ−５−ヒドロキシ−３−オキソヘプタン酸誘導体およびその製造法 |
| CN1217930C (zh) | 2000-05-26 | 2005-09-07 | 西巴特殊化学品控股有限公司 | 吲哚衍生物的制备方法和该方法的中间体 |
| MXPA03012045A (es) | 2001-07-06 | 2004-03-29 | Teva Pharma | Proceso para preparar derivados del acido 7-amino sin 3,5-dihidroxi heptanoico a traves de derivados del acido 6-ciano sin 3,5-dihidroxi hexanoico. |
| EP1404642B1 (en) | 2001-07-06 | 2010-02-17 | Basf Se | Process for the preparatiom of 7-amino syn 3,5-dihydroxy heptanoic acid derivatives, intermediates thereof and methods for their preparation |
| HUP0401145A3 (en) | 2001-07-06 | 2008-08-28 | Ciba Sc Holding Ag | Process for the preparation of intermediates useful in the synthesis of statin derivatives especially 7-amino 3,5-dihydroxy heptanoic acid derivatives, and intermediates thereof |
-
2002
- 2002-07-02 HU HU0401145A patent/HUP0401145A3/hu unknown
- 2002-07-02 EP EP09176993A patent/EP2161250A1/en not_active Withdrawn
- 2002-07-02 IL IL15905002A patent/IL159050A0/xx not_active IP Right Cessation
- 2002-07-02 JP JP2003510418A patent/JP2004533479A/ja active Pending
- 2002-07-02 US US10/482,463 patent/US7420078B2/en not_active Expired - Fee Related
- 2002-07-02 PT PT02764615T patent/PT1404642E/pt unknown
- 2002-07-02 AU AU2002354701A patent/AU2002354701B2/en not_active Ceased
- 2002-07-02 EP EP02782448A patent/EP1404639A1/en not_active Withdrawn
- 2002-07-02 CN CN201010004468XA patent/CN101880227A/zh active Pending
- 2002-07-02 CZ CZ2004150A patent/CZ2004150A3/cs unknown
- 2002-07-02 WO PCT/EP2002/007307 patent/WO2003004450A1/en not_active Ceased
- 2002-07-02 ES ES02764615T patent/ES2340260T3/es not_active Expired - Lifetime
- 2002-07-02 BR BR0210842-9A patent/BR0210842A/pt not_active IP Right Cessation
- 2002-07-02 HR HR20040119A patent/HRPK20040119B3/xx not_active IP Right Cessation
- 2002-07-02 KR KR20047000163A patent/KR20040017278A/ko not_active Withdrawn
- 2002-07-02 KR KR20047000160A patent/KR20040017277A/ko not_active Withdrawn
- 2002-07-02 CN CNA028135342A patent/CN1610657A/zh active Pending
- 2002-07-02 PL PL02366392A patent/PL366392A1/xx not_active Application Discontinuation
- 2002-07-02 CA CA002448917A patent/CA2448917A1/en not_active Abandoned
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2008
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-
2010
- 2010-11-04 US US12/939,401 patent/US8026383B2/en not_active Expired - Fee Related
-
2011
- 2011-07-19 IL IL214164A patent/IL214164A0/en unknown
- 2011-07-19 IL IL214165A patent/IL214165A0/en unknown
Non-Patent Citations (4)
| Title |
|---|
| CHRISTOPHER M. BLACKWELL: "An Improved Procedure for the Introduction of the &Lactone Portion of HMG-CoA Reductase Inhibitors", 《J. ORG. CHEM.》 * |
| CLAYTON H. HEATHCOCK ET AL.: "Total Synthesis and Biological Evaluation of Structural Analogues of Compactin and Dihydromevinolin", 《J. MED. CHEM.》 * |
| DEE W. BROOKS*: "REMOTE SUBSTITUENT EFFECTS IN MICROBIAL REDUCTIONS OF 3-RETOGLUTARATE AND 3-KETOADIPATE ESTERS", 《TETRAHEDRON LETTERS》 * |
| PETER D. THEISEN: "Improved Procedure for Preparation of Optically Active 3-Hydroxyglutarate Monoesters and 3-Hydroxy-5-oxoalkanoic Acids", 《J. ORG. CHEM.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108997324A (zh) * | 2018-08-21 | 2018-12-14 | 南京欧信医药技术有限公司 | 瑞舒伐他汀钙中间体的制备方法 |
| CN118772052A (zh) * | 2024-09-10 | 2024-10-15 | 湖南九维生物医药有限公司 | 一种医药中间体及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| PT1404642E (pt) | 2010-03-29 |
| IL159050A0 (en) | 2004-05-12 |
| EP2161250A1 (en) | 2010-03-10 |
| US8026383B2 (en) | 2011-09-27 |
| BR0210842A (pt) | 2004-07-13 |
| HRP20040119A2 (en) | 2005-04-30 |
| CZ2004150A3 (cs) | 2004-09-15 |
| US7420078B2 (en) | 2008-09-02 |
| IL214165A0 (en) | 2011-08-31 |
| AR034733A1 (es) | 2004-03-17 |
| ES2340260T3 (es) | 2010-06-01 |
| IL214164A0 (en) | 2011-08-31 |
| AR034734A1 (es) | 2004-03-17 |
| US20080312466A1 (en) | 2008-12-18 |
| PL366392A1 (en) | 2005-01-24 |
| US20110046411A1 (en) | 2011-02-24 |
| HUP0401145A2 (hu) | 2004-09-28 |
| AU2002354701B2 (en) | 2007-11-22 |
| EP1404639A1 (en) | 2004-04-07 |
| CN1610657A (zh) | 2005-04-27 |
| KR20040017278A (ko) | 2004-02-26 |
| HRPK20040119B3 (en) | 2006-07-31 |
| HUP0401145A3 (en) | 2008-08-28 |
| CA2448917A1 (en) | 2003-01-16 |
| US7855302B2 (en) | 2010-12-21 |
| US20040186313A1 (en) | 2004-09-23 |
| AR034735A1 (es) | 2004-03-17 |
| WO2003004450A1 (en) | 2003-01-16 |
| JP2004533479A (ja) | 2004-11-04 |
| KR20040017277A (ko) | 2004-02-26 |
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