TWI640500B - 製備曲伏前列腺素之新穎方法 - Google Patents
製備曲伏前列腺素之新穎方法 Download PDFInfo
- Publication number
- TWI640500B TWI640500B TW101148584A TW101148584A TWI640500B TW I640500 B TWI640500 B TW I640500B TW 101148584 A TW101148584 A TW 101148584A TW 101148584 A TW101148584 A TW 101148584A TW I640500 B TWI640500 B TW I640500B
- Authority
- TW
- Taiwan
- Prior art keywords
- formula
- compound
- travoprost
- mixture
- iii
- Prior art date
Links
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 title claims abstract description 39
- 229960002368 travoprost Drugs 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 40
- 238000002425 crystallisation Methods 0.000 claims abstract description 12
- 230000008025 crystallization Effects 0.000 claims abstract description 12
- -1 p -phenyl-benzyl group Chemical group 0.000 claims abstract description 8
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000007239 Wittig reaction Methods 0.000 claims abstract description 5
- 125000006239 protecting group Chemical group 0.000 claims abstract description 4
- 238000011916 stereoselective reduction Methods 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims abstract description 3
- 125000000686 lactone group Chemical group 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 238000006722 reduction reaction Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000005886 esterification reaction Methods 0.000 claims description 9
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 8
- 230000032050 esterification Effects 0.000 claims description 7
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 5
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000000354 decomposition reaction Methods 0.000 claims 1
- 230000005484 gravity Effects 0.000 claims 1
- 238000010898 silica gel chromatography Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 29
- 239000000243 solution Substances 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 238000002329 infrared spectrum Methods 0.000 description 12
- 239000010410 layer Substances 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 235000021317 phosphate Nutrition 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 230000005595 deprotonation Effects 0.000 description 3
- 238000010537 deprotonation reaction Methods 0.000 description 3
- 150000002085 enols Chemical class 0.000 description 3
- 239000012454 non-polar solvent Substances 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 2
- RTLMATDNIKWIIO-UHFFFAOYSA-N 2-n,2-n,6-n,6-n-tetrakis(2-chloroethyl)-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diamine Chemical compound C=12N=C(N(CCCl)CCCl)N=C(N3CCCCC3)C2=NC(N(CCCl)CCCl)=NC=1N1CCCCC1 RTLMATDNIKWIIO-UHFFFAOYSA-N 0.000 description 2
- VSEVUQXKWHTETG-UHFFFAOYSA-N 2h-cyclopenta[b]furan-2,5-diol Chemical compound OC1=CC2=CC(O)OC2=C1 VSEVUQXKWHTETG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- WWSWYXNVCBLWNZ-QIZQQNKQSA-N fluprostenol Chemical compound C([C@H](O)\C=C\[C@@H]1[C@H]([C@@H](O)C[C@H]1O)C\C=C/CCCC(O)=O)OC1=CC=CC(C(F)(F)F)=C1 WWSWYXNVCBLWNZ-QIZQQNKQSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 150000002940 palladium Chemical class 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VMKAFJQFKBASMU-KRWDZBQOSA-N (3as)-1-methyl-3,3-diphenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaborole Chemical compound C([C@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-KRWDZBQOSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- DBUJFULDVAZULB-UHFFFAOYSA-N 1-methoxypentane Chemical compound CCCCCOC DBUJFULDVAZULB-UHFFFAOYSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- VHEYCTCATJSAAI-UHFFFAOYSA-N 4-phenylbenzenecarboximidamide Chemical group C1=CC(C(=N)N)=CC=C1C1=CC=CC=C1 VHEYCTCATJSAAI-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010018307 Glaucoma and ocular hypertension Diseases 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 1
- 150000001409 amidines Chemical group 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- YPWBYWNNJVSNPQ-UHFFFAOYSA-N borane;n,n-diethylaniline Chemical class B.CCN(CC)C1=CC=CC=C1 YPWBYWNNJVSNPQ-UHFFFAOYSA-N 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- KHYAFFAGZNCWPT-UHFFFAOYSA-N boron;n,n-diethylaniline Chemical compound [B].CCN(CC)C1=CC=CC=C1 KHYAFFAGZNCWPT-UHFFFAOYSA-N 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- UOALEFQKAOQICC-UHFFFAOYSA-N chloroborane Chemical compound ClB UOALEFQKAOQICC-UHFFFAOYSA-N 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- 239000012004 corey–bakshi–shibata catalyst Substances 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 239000010779 crude oil Substances 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
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- HBNBMOGARBJBHS-UHFFFAOYSA-N dimethylarsane Chemical compound C[AsH]C HBNBMOGARBJBHS-UHFFFAOYSA-N 0.000 description 1
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical group CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N o-dihydroxy-benzene Natural products OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- GNWXVOQHLPBSSR-UHFFFAOYSA-N oxolane;toluene Chemical compound C1CCOC1.CC1=CC=CC=C1 GNWXVOQHLPBSSR-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
- C07D307/937—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Furan Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU1100701A HU231203B1 (hu) | 2011-12-21 | 2011-12-21 | Új eljárás travoprost előállítására |
| HUP1100701 | 2011-12-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201336816A TW201336816A (zh) | 2013-09-16 |
| TWI640500B true TWI640500B (zh) | 2018-11-11 |
Family
ID=89990547
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW101148584A TWI640500B (zh) | 2011-12-21 | 2012-12-20 | 製備曲伏前列腺素之新穎方法 |
Country Status (18)
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2837261C (en) * | 2011-06-02 | 2020-12-15 | CHINOIN Zrt. | Novel processes for the preparation of prostaglandin amides |
| US9115109B2 (en) | 2013-08-15 | 2015-08-25 | Chirogate International Inc. | Processes and intermediates for the preparations of isomer free prostaglandins |
| HU231214B1 (hu) * | 2014-03-13 | 2021-11-29 | CHINOIN Gyógyszer és Vegyészeti Termékek Gyára Zrt. | Új eljárás nagytisztaságú prosztaglandinok előállítására |
| US11458041B2 (en) | 2015-10-08 | 2022-10-04 | Ocular Therapeutix, Inc. | Punctal plug and bioadhesives |
| EP3950672A4 (en) * | 2019-03-27 | 2023-01-11 | Kyowa Pharma Chemical Co., Ltd. | PROCESS FOR PRODUCTION OF PROSTAGLANDIN |
| HU231350B1 (hu) * | 2019-12-18 | 2023-01-28 | CHINOIN Gyógyszer és Vegyészeti Termékek Gyára Zrt | Eljárás királis prosztaglandin-enol intermedier előállítására, és az eljárásban hasznos köztitermék vegyületek |
| DK3861985T3 (da) | 2020-02-06 | 2023-07-24 | Ocular Therapeutix Inc | Sammensætninger og fremgangsmåder til behandling af øjensygdomme |
| EP4142664A4 (en) | 2020-04-27 | 2024-05-29 | Ocular Therapeutix, Inc. | METHODS FOR TREATING ALLERGIC CONJUNCTIVITIS |
| JP7686673B2 (ja) * | 2020-12-23 | 2025-06-02 | 協和ファーマケミカル株式会社 | 幾何異性体の分離方法 |
| CN114671906B (zh) * | 2020-12-24 | 2024-03-15 | 武汉武药制药有限公司 | 制备曲伏前列素中间体的方法 |
| CN116947725A (zh) * | 2022-04-14 | 2023-10-27 | 广州楷石医药有限公司 | 曲伏前列素的合成方法 |
| CN115806517A (zh) * | 2022-12-21 | 2023-03-17 | 上海彩迩文生化科技有限公司 | 一种高纯度地诺前列腺素的制备方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2143712A1 (en) * | 2008-07-10 | 2010-01-13 | Sandoz AG | Improved Process for the Production of Prostaglandins and Prostaglandin Analogs |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2328131C3 (de) * | 1973-05-30 | 1986-11-13 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neues Verfahren zur Herstellung von Prostaglandin-F↓2↓↓α↓ und seinen Analogen |
| HU184948B (en) * | 1981-04-14 | 1984-11-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing 5-substituted 4-oxo-pgi down 1 derivatives |
| HU190007B (en) | 1982-05-06 | 1986-08-28 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt,Hu | Process for producing new aromatic prostacylin analogues |
| CS239696B1 (cs) * | 1984-05-03 | 1986-01-16 | Jiri Hajek | Způsob dělení 15S-a 15R-isomerů 4-/4-/substituovaných X-fenoxy/-3-hydroxy-1butenyí/hexahydro-5-hydroxy- -2H-cyklopenta[b]furan-2-onů |
| HU212570B (en) * | 1991-06-24 | 1996-08-29 | Chinoin Gyogyszer Es Vegyeszet | Process for producing 13,14-dihydro-15(r)-17-phenyl-18,19,20-trinor-pgf2alfa-isopropylester |
| US5510383A (en) * | 1993-08-03 | 1996-04-23 | Alcon Laboratories, Inc. | Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension |
| US7166730B2 (en) * | 2000-01-27 | 2007-01-23 | Fine Tech Laboratories, Ltd | Process for the preparation of prostaglandin derivatives |
| GB0112699D0 (en) * | 2001-05-24 | 2001-07-18 | Resolution Chemicals Ltd | Process for the preparation of prostglandins and analogues thereof |
| GB0329379D0 (en) * | 2003-12-19 | 2004-01-21 | Johnson Matthey Plc | Prostaglandin synthesis |
| PL1704141T3 (pl) * | 2004-01-05 | 2016-08-31 | Nicox Sa | Nitrooksypochodne prostaglandyn |
| IT1393112B1 (it) * | 2009-02-27 | 2012-04-11 | Sifavitor S R L | Procedimento per la preparazione di derivati di prostaglandine |
| EP2488508A4 (en) | 2009-10-16 | 2013-04-24 | Cayman Chemical Co Inc | PROCESS FOR THE PREPARATION OF PROSTAGLANDINS OF THE F-SERIES |
| RU2012122367A (ru) * | 2009-11-05 | 2013-12-10 | Биокон Лимитед | Способ получения простагландинов и промежуточные соединения для их получения |
| EP2495235B1 (en) | 2011-03-04 | 2015-08-05 | Newchem S.p.A. | Process for the synthesis of prostaglandins and intermediates thereof |
| CA2837261C (en) | 2011-06-02 | 2020-12-15 | CHINOIN Zrt. | Novel processes for the preparation of prostaglandin amides |
-
2011
- 2011-12-21 HU HU1100701A patent/HU231203B1/hu unknown
-
2012
- 2012-12-10 JP JP2014548213A patent/JP6174040B2/ja active Active
- 2012-12-10 TR TR2019/05687T patent/TR201905687T4/tr unknown
- 2012-12-10 KR KR1020147020311A patent/KR102027889B1/ko active Active
- 2012-12-10 EP EP12816098.3A patent/EP2802562B1/en active Active
- 2012-12-10 BR BR112014014060A patent/BR112014014060A2/pt not_active Application Discontinuation
- 2012-12-10 RU RU2014129492A patent/RU2631316C2/ru active
- 2012-12-10 IN IN3482CHN2014 patent/IN2014CN03482A/en unknown
- 2012-12-10 WO PCT/HU2012/000132 patent/WO2013093528A1/en not_active Ceased
- 2012-12-10 CN CN201280063528.2A patent/CN103998423B/zh active Active
- 2012-12-10 CA CA2859923A patent/CA2859923C/en active Active
- 2012-12-10 MX MX2014007684A patent/MX2014007684A/es unknown
- 2012-12-10 ES ES12816098T patent/ES2721662T3/es active Active
- 2012-12-10 US US14/367,317 patent/US9212125B2/en active Active
- 2012-12-10 PL PL12816098T patent/PL2802562T3/pl unknown
- 2012-12-20 TW TW101148584A patent/TWI640500B/zh active
-
2014
- 2014-05-14 IL IL232625A patent/IL232625B/en active IP Right Grant
- 2014-06-17 ZA ZA2014/04440A patent/ZA201404440B/en unknown
-
2015
- 2015-10-30 US US14/928,629 patent/US20160137621A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2143712A1 (en) * | 2008-07-10 | 2010-01-13 | Sandoz AG | Improved Process for the Production of Prostaglandins and Prostaglandin Analogs |
Non-Patent Citations (4)
| Title |
|---|
| Aswathanarayanappa, C. et al., Org. Process Res. Dev., 2011, 15: 1085-1087 * |
| Cho, B. C., Tetrahedron, 2006, 62: 7621-7643 * |
| SYLVIANE GIORGI-RENAULT et. al., "Heterocyclic Quinones. XIII. Dimerization in the Series of 5,8-Quinazolinediones: Synthesis and Antitumor Effect of Bis(4-amino-5,8-quinazolinediones)", Chem. Pharm. Bull., 1988, Vol. 36, No. 10, page 3933-3947 * |
| SYLVIANE GIORGI-RENAULT et. al., "Heterocyclic Quinones. XIII. Dimerization in the Series of 5,8-Quinazolinediones: Synthesis and Antitumor Effect of Bis(4-amino-5,8-quinazolinediones)", Chem. Pharm. Bull., 1988, Vol. 36, No. 10, page 3933-3947。 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20140343299A1 (en) | 2014-11-20 |
| RU2014129492A (ru) | 2016-02-10 |
| EP2802562A1 (en) | 2014-11-19 |
| WO2013093528A1 (en) | 2013-06-27 |
| CN103998423B (zh) | 2018-04-27 |
| ZA201404440B (en) | 2015-12-23 |
| JP6174040B2 (ja) | 2017-08-02 |
| MX2014007684A (es) | 2014-07-28 |
| TW201336816A (zh) | 2013-09-16 |
| IN2014CN03482A (cg-RX-API-DMAC7.html) | 2015-07-03 |
| ES2721662T3 (es) | 2019-08-02 |
| US9212125B2 (en) | 2015-12-15 |
| HUP1100701A2 (en) | 2013-07-29 |
| IL232625B (en) | 2019-03-31 |
| RU2631316C2 (ru) | 2017-09-21 |
| CN103998423A (zh) | 2014-08-20 |
| CA2859923C (en) | 2020-11-24 |
| CA2859923A1 (en) | 2013-06-27 |
| BR112014014060A2 (pt) | 2017-06-13 |
| TR201905687T4 (tr) | 2019-05-21 |
| HK1198584A1 (en) | 2015-04-30 |
| JP2015506343A (ja) | 2015-03-02 |
| IL232625A0 (en) | 2014-06-30 |
| HU231203B1 (hu) | 2021-10-28 |
| EP2802562B1 (en) | 2019-01-23 |
| US20160137621A1 (en) | 2016-05-19 |
| KR102027889B1 (ko) | 2019-10-04 |
| KR20140107541A (ko) | 2014-09-04 |
| PL2802562T3 (pl) | 2019-08-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI640500B (zh) | 製備曲伏前列腺素之新穎方法 | |
| JP5485980B2 (ja) | プロスタグランジン類似物の製造方法及びその中間体 | |
| JP3989377B2 (ja) | プロスタグランジン誘導体の製造方法及びその立体特異的出発物質 | |
| JP4580758B2 (ja) | プロスタグランジン誘導体の製造方法及びその出発物質 | |
| CN111777538A (zh) | 贝美前列素的制备方法 | |
| KR102436114B1 (ko) | 신규한 이노토디올의 제조방법 | |
| JP2667135B2 (ja) | ジイソピノカンフェイルクロロボランのインシトゥー製造 | |
| JP7302918B2 (ja) | マキサカルシトールの製造方法及びそのための中間体 | |
| WO2014094511A1 (zh) | 一种制备曲前列尼尔的中间体、其制备方法以及通过其制备曲前列尼尔的方法 | |
| US20030004368A1 (en) | Novel intermediate for the synthesis of prostaglandins | |
| TWI792440B (zh) | 製備拉坦前列烯布諾德（ｌａｔａｎｏｐｒｏｓｔｅｎｅ ｂｕｎｏｄ）之方法及其中間物與包含其之組合物 | |
| JP2008037782A (ja) | プロスタグランジン誘導体の製造方法 | |
| KR102418153B1 (ko) | 신규한 이노토디올의 제조방법 | |
| KR20190016820A (ko) | 라타노프로스틴 부노드의 제조 방법 및 그를 위한 중간체 | |
| CN105985370B (zh) | 制备利马前列腺素的关键中间体及其应用 | |
| HK1198584B (en) | Process for the preparation of travoprost | |
| CN117843599A (zh) | 一种含有1-烷基-1-烯基乙醇结构的前列腺素中间体的制备方法 | |
| EP1169325B1 (en) | Novel intermediate for the synthesis of prostaglandins | |
| JPH0649669B2 (ja) | 光学活性アルコールの製法 |