JP7294661B2 - ５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス - Google Patents
５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス Download PDFInfo
- Publication number
- JP7294661B2 JP7294661B2 JP2019534154A JP2019534154A JP7294661B2 JP 7294661 B2 JP7294661 B2 JP 7294661B2 JP 2019534154 A JP2019534154 A JP 2019534154A JP 2019534154 A JP2019534154 A JP 2019534154A JP 7294661 B2 JP7294661 B2 JP 7294661B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- solvent
- reaction mixture
- temperature
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000003839 salts Chemical class 0.000 title claims description 54
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- OXVFDZYQLGRLCD-UHFFFAOYSA-N hydroxypioglitazone Chemical compound N1=CC(C(O)C)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 OXVFDZYQLGRLCD-UHFFFAOYSA-N 0.000 title description 15
- 238000000034 method Methods 0.000 claims description 277
- 150000001875 compounds Chemical class 0.000 claims description 273
- 230000008569 process Effects 0.000 claims description 264
- 239000011541 reaction mixture Substances 0.000 claims description 225
- 239000002904 solvent Substances 0.000 claims description 209
- 239000000203 mixture Substances 0.000 claims description 114
- 238000006243 chemical reaction Methods 0.000 claims description 99
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 70
- 239000000243 solution Substances 0.000 claims description 67
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 61
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 60
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 59
- 125000006239 protecting group Chemical group 0.000 claims description 54
- 239000002841 Lewis acid Substances 0.000 claims description 52
- 150000007517 lewis acids Chemical class 0.000 claims description 52
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical class [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 47
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 46
- -1 alkyl lithium Chemical compound 0.000 claims description 39
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 38
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 37
- 239000003960 organic solvent Substances 0.000 claims description 35
- 239000002585 base Substances 0.000 claims description 29
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 26
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 26
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 25
- 239000003153 chemical reaction reagent Substances 0.000 claims description 19
- SBHOQYCDAHAMDW-UHFFFAOYSA-N 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione;hydrochloride Chemical compound Cl.N1=CC(C(O)C)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 SBHOQYCDAHAMDW-UHFFFAOYSA-N 0.000 claims description 18
- 150000007524 organic acids Chemical class 0.000 claims description 17
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 15
- 239000002244 precipitate Substances 0.000 claims description 15
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 15
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical group OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 14
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 13
- 239000000376 reactant Substances 0.000 claims description 13
- 229910021645 metal ion Inorganic materials 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 10
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 10
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 10
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 239000003638 chemical reducing agent Substances 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 8
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 8
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 8
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 6
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 6
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 5
- 150000004791 alkyl magnesium halides Chemical class 0.000 claims description 5
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 4
- 125000005104 aryl silyl group Chemical group 0.000 claims description 4
- 239000008139 complexing agent Substances 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 4
- DVFXLNFDWATPMW-IWOKLKJTSA-N tert-butyldiphenylsilyl Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO[Si](C=2C=CC=CC=2)(C=2C=CC=CC=2)C(C)(C)C)[C@@H](OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](CC(O2)N2C3=NC=NC(N)=C3N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 DVFXLNFDWATPMW-IWOKLKJTSA-N 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 166
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 239000010410 layer Substances 0.000 description 30
- 238000007792 addition Methods 0.000 description 29
- 239000003921 oil Substances 0.000 description 29
- 235000019198 oils Nutrition 0.000 description 29
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 28
- 229910015900 BF3 Inorganic materials 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 26
- 239000000725 suspension Substances 0.000 description 26
- 239000007787 solid Substances 0.000 description 25
- 229910015845 BBr3 Inorganic materials 0.000 description 23
- 229910015844 BCl3 Inorganic materials 0.000 description 23
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 239000012044 organic layer Substances 0.000 description 19
- 239000003880 polar aprotic solvent Substances 0.000 description 19
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
- 239000012279 sodium borohydride Substances 0.000 description 17
- 229910000033 sodium borohydride Inorganic materials 0.000 description 17
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 16
- 239000003495 polar organic solvent Substances 0.000 description 16
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical class N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 15
- OMSAAQUHZXHUGS-JWGURIENSA-N (5Z)-5-[[4-[2-[5-[2-[tert-butyl(dimethyl)silyl]oxyethyl]pyridin-2-yl]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical class CC(C)(C)[Si](C)(C)OCCC1=CN=C(CCOC2=CC=C(\C=C3/SC(=O)NC3=O)C=C2)C=C1 OMSAAQUHZXHUGS-JWGURIENSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
- OUTOIAUNYUCUGG-UHFFFAOYSA-N 4-[2-[5-[2-[tert-butyl(dimethyl)silyl]oxyethyl]pyridin-2-yl]ethoxy]benzaldehyde Chemical compound CC(C)(C)[Si](C)(C)OCCC1=CN=C(CCOC2=CC=C(C=O)C=C2)C=C1 OUTOIAUNYUCUGG-UHFFFAOYSA-N 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 229910052805 deuterium Inorganic materials 0.000 description 11
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- DHNIYCWDTAPKJI-UHFFFAOYSA-N 2-[5-[1-[tert-butyl(dimethyl)silyl]oxyethyl]pyridin-2-yl]ethanol Chemical compound [Si](C)(C)(C(C)(C)C)OC(C)C=1C=CC(=NC=1)CCO DHNIYCWDTAPKJI-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- QOQYGKBTOFYPKJ-UHFFFAOYSA-N 1-(6-bromopyridin-3-yl)ethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC(C)C1=CC=C(Br)N=C1 QOQYGKBTOFYPKJ-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 8
- 229910000085 borane Inorganic materials 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- JGUQDUKBUKFFRO-CIIODKQPSA-N dimethylglyoxime Chemical compound O/N=C(/C)\C(\C)=N\O JGUQDUKBUKFFRO-CIIODKQPSA-N 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 8
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 8
- ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 229940125898 compound 5 Drugs 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 229960005095 pioglitazone Drugs 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 6
- 150000008041 alkali metal carbonates Chemical class 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 6
- 125000003944 tolyl group Chemical group 0.000 description 6
- 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 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- LDGYVEPFXQIYTH-UHFFFAOYSA-N 5-[[4-[2-[5-[2-[tert-butyl(dimethyl)silyl]oxyethyl]pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC(C)(C)[Si](OCCC=1C=CC(=NC=1)CCOC1=CC=C(C=C1)CC1C(NC(S1)=O)=O)(C)C LDGYVEPFXQIYTH-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 4
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 235000015320 potassium carbonate Nutrition 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 239000013557 residual solvent Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 125000005270 trialkylamine group Chemical group 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- 239000011592 zinc chloride Substances 0.000 description 4
- 235000005074 zinc chloride Nutrition 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- QDOJZKXYIAXLDB-UHFFFAOYSA-N 1-(6-bromopyridin-3-yl)ethanol Chemical compound CC(O)C1=CC=C(Br)N=C1 QDOJZKXYIAXLDB-UHFFFAOYSA-N 0.000 description 3
- DCYLRSYWXFRFOX-UHFFFAOYSA-N 2-[5-[1-(methoxymethoxy)ethyl]pyridin-2-yl]ethanol Chemical compound COCOC(C)C1=CC=C(CCO)N=C1 DCYLRSYWXFRFOX-UHFFFAOYSA-N 0.000 description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 229940123464 Thiazolidinedione Drugs 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 2
- LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 2
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 2
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 2
- LYMOQGXOROSRPJ-UHFFFAOYSA-N 1-(6-methylpyridin-3-yl)ethanol Chemical compound CC(O)C1=CC=C(C)N=C1 LYMOQGXOROSRPJ-UHFFFAOYSA-N 0.000 description 2
- PVRYOKQFLBSILA-UHFFFAOYSA-N 1-(6-methylpyridin-3-yl)ethanone Chemical compound CC(=O)C1=CC=C(C)N=C1 PVRYOKQFLBSILA-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- VBIBXVPTBBPIOC-UHFFFAOYSA-N 2-[5-[2-[tert-butyl(dimethyl)silyl]oxyethyl]pyridin-2-yl]ethanol Chemical compound CC(C)(C)[Si](OCCC=1C=CC(=NC=1)CCO)(C)C VBIBXVPTBBPIOC-UHFFFAOYSA-N 0.000 description 2
- WFIFHOWQEJADPH-UHFFFAOYSA-N 2-chloro-4-(2-oxo-4-phenylpyrrolidin-1-yl)benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC=C1N1C(=O)CC(C=2C=CC=CC=2)C1 WFIFHOWQEJADPH-UHFFFAOYSA-N 0.000 description 2
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 2
- PPCLBBXZDXYYQR-UHFFFAOYSA-N 4-[2-[5-[1-(methoxymethoxy)ethyl]pyridin-2-yl]ethoxy]benzaldehyde Chemical compound N1=CC(C(C)OCOC)=CC=C1CCOC1=CC=C(C=O)C=C1 PPCLBBXZDXYYQR-UHFFFAOYSA-N 0.000 description 2
- AOHSDRCYABCFTI-UHFFFAOYSA-N 5-[1-(methoxymethoxy)ethyl]-2-methylpyridine Chemical compound COCOC(C)C1=CC=C(C)N=C1 AOHSDRCYABCFTI-UHFFFAOYSA-N 0.000 description 2
- NPAXFQZLUHJHMA-UHFFFAOYSA-N 5-[[4-[2-[5-[1-(methoxymethoxy)ethyl]pyridin-2-yl]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound N1=CC(C(C)OCOC)=CC=C1CCOC(C=C1)=CC=C1C=C1C(=O)NC(=O)S1 NPAXFQZLUHJHMA-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- VKYXHVFPMYEGSY-UHFFFAOYSA-N CS(=O)(=O)OCCC1=NC=C(C=C1)C(C)OCOC Chemical compound CS(=O)(=O)OCCC1=NC=C(C=C1)C(C)OCOC VKYXHVFPMYEGSY-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910021576 Iron(III) bromide Inorganic materials 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- 108010016731 PPAR gamma Proteins 0.000 description 2
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910003074 TiCl4 Inorganic materials 0.000 description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-M hydrosulfide Chemical compound [SH-] RWSOTUBLDIXVET-UHFFFAOYSA-M 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
- CETVQRFGPOGIQJ-UHFFFAOYSA-N lithium;hexane Chemical compound [Li+].CCCCC[CH2-] CETVQRFGPOGIQJ-UHFFFAOYSA-N 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 2
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 2
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- IDCLTMRSSAXUNY-UHFFFAOYSA-N 5-hydroxylansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC(O)=CC=C2N1 IDCLTMRSSAXUNY-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 229910021581 Cobalt(III) chloride Inorganic materials 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- NDZQGDAWPCKDCD-UHFFFAOYSA-N OC(C)C=1C=CC(=NC1)CCOC1=CC=C(C=C1)CC1NCSC1 Chemical compound OC(C)C=1C=CC(=NC1)CCOC1=CC=C(C=C1)CC1NCSC1 NDZQGDAWPCKDCD-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011281 clinical therapy Methods 0.000 description 1
- 229910001429 cobalt ion Inorganic materials 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 150000004699 copper complex Chemical class 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([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
- 230000001419 dependent effect Effects 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Inorganic materials [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 1
- UKZCGMDMXDLAGZ-UHFFFAOYSA-M magnesium;2-methylpropane;bromide Chemical compound [Mg+2].[Br-].C[C-](C)C UKZCGMDMXDLAGZ-UHFFFAOYSA-M 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
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/127—Preparation from compounds containing pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023016009A JP2023052918A (ja) | 2016-12-23 | 2023-02-06 | ５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16382648 | 2016-12-23 | ||
| EP16382648.0 | 2016-12-23 | ||
| PCT/IB2017/058374 WO2018116281A1 (en) | 2016-12-23 | 2017-12-22 | Process for preparing 5-[[4-[2-[5-(1-hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione and salts thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023016009A Division JP2023052918A (ja) | 2016-12-23 | 2023-02-06 | ５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020502228A JP2020502228A (ja) | 2020-01-23 |
| JP2020502228A5 JP2020502228A5 (https=) | 2021-02-12 |
| JP7294661B2 true JP7294661B2 (ja) | 2023-06-20 |
Family
ID=57799523
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019534154A Active JP7294661B2 (ja) | 2016-12-23 | 2017-12-22 | ５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス |
| JP2023016009A Withdrawn JP2023052918A (ja) | 2016-12-23 | 2023-02-06 | ５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023016009A Withdrawn JP2023052918A (ja) | 2016-12-23 | 2023-02-06 | ５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US11124505B2 (https=) |
| EP (1) | EP3559010B1 (https=) |
| JP (2) | JP7294661B2 (https=) |
| KR (1) | KR102609373B1 (https=) |
| CN (1) | CN110198945B (https=) |
| BR (1) | BR112019012972B1 (https=) |
| CA (1) | CA3046744A1 (https=) |
| CY (1) | CY1125531T1 (https=) |
| DK (1) | DK3559010T3 (https=) |
| ES (1) | ES2926580T3 (https=) |
| HR (1) | HRP20221067T1 (https=) |
| HU (1) | HUE059604T2 (https=) |
| IL (1) | IL267557B (https=) |
| LT (1) | LT3559010T (https=) |
| MX (1) | MX379709B (https=) |
| PL (1) | PL3559010T3 (https=) |
| PT (1) | PT3559010T (https=) |
| SI (1) | SI3559010T1 (https=) |
| WO (1) | WO2018116281A1 (https=) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2926580T3 (es) | 2016-12-23 | 2022-10-27 | Minoryx Therapeutics S L | Proceso para preparar 5-[[4-[2-[5-(1-hidroxietil)-2-piridinil]etoxi]fenil]metil]-2,4-tiazolidindiona y sales de la misma |
| CN112823004A (zh) | 2018-06-06 | 2021-05-18 | 米尼奥尔克斯治疗有限公司 | 5-[[4-[2-[5-乙酰基吡啶-2-基]乙氧基]苄基]-1,3-噻唑烷-2,4-二酮及其盐的用途 |
| EP3801515B1 (en) | 2018-06-06 | 2025-04-09 | Minoryx Therapeutics S.L. | 5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione and its salts for use in the treatment of mitochondrial diseases |
| CN112512524A (zh) | 2018-06-06 | 2021-03-16 | 米尼奥尔克斯治疗有限公司 | 给予治疗有效量的5-[[4-[2-[5-(1-羟基乙基)吡啶-2-基]乙氧基]苯基]甲基]-1,3-噻唑烷-2,4-二酮的方法 |
| EP4642456A1 (en) | 2022-12-28 | 2025-11-05 | Minoryx Therapeutics S.L. | Optimized dosing of leriglitazone |
| WO2024231881A2 (en) | 2023-05-09 | 2024-11-14 | Minoryx Therapeutics S.L. | Polymorphic forms and formulations of leriglitazone |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008038692A1 (en) | 2006-09-28 | 2008-04-03 | Banyu Pharmaceutical Co., Ltd. | Diaryl ketimine derivative |
| WO2008136428A1 (ja) | 2007-04-27 | 2008-11-13 | Takeda Pharmaceutical Company Limited | 含窒素５員複素環化合物 |
| WO2015150476A1 (en) | 2014-04-02 | 2015-10-08 | Minoryx Therapeutics S.L. | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69231886T2 (de) * | 1991-04-11 | 2002-03-28 | Pharmacia & Upjohn Co., Kalamazoo | Thiazolidindionderivate, herstellung und anwendung |
| US5952509A (en) | 1996-06-27 | 1999-09-14 | Takeda Chemical Industries, Ltd. | Production of benzaldehyde compounds |
| US6067749A (en) | 1996-07-11 | 2000-05-30 | Tasmanian Alkaloids Pty. Ltd. | Papaver somniferum strain with high concentration of thebaine and oripavine |
| US5869669A (en) | 1996-07-26 | 1999-02-09 | Penick Corporation | Preparation of 14-hydroxynormorphinones from normorphinone dienol acylates |
| HUP0304096A2 (hu) | 2003-12-19 | 2005-08-29 | Richter Gedeon Vegyészeti Gyár Rt. | Eljárás pioglitazon hidrogénklorid előállítására és intermedierjei |
| GB0421687D0 (en) | 2004-09-30 | 2004-11-03 | Johnson Matthey Plc | Preparation of opiate analgesics |
| CA2594666A1 (en) | 2005-02-16 | 2006-08-24 | Micromet Ag | Use of activated polymers for separation of protein and polypeptide multimers |
| EP2855489B1 (en) * | 2012-04-26 | 2017-01-04 | Bristol-Myers Squibb Company | Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation |
| WO2014152843A1 (en) | 2013-03-14 | 2014-09-25 | Deuterx, Llc | Deuterium-enriched 2,4-thiazolidinediones and methods of treatment |
| ES2926580T3 (es) | 2016-12-23 | 2022-10-27 | Minoryx Therapeutics S L | Proceso para preparar 5-[[4-[2-[5-(1-hidroxietil)-2-piridinil]etoxi]fenil]metil]-2,4-tiazolidindiona y sales de la misma |
-
2017
- 2017-12-22 ES ES17829042T patent/ES2926580T3/es active Active
- 2017-12-22 SI SI201731203T patent/SI3559010T1/sl unknown
- 2017-12-22 HR HRP20221067TT patent/HRP20221067T1/hr unknown
- 2017-12-22 BR BR112019012972-3A patent/BR112019012972B1/pt active IP Right Grant
- 2017-12-22 EP EP17829042.5A patent/EP3559010B1/en active Active
- 2017-12-22 HU HUE17829042A patent/HUE059604T2/hu unknown
- 2017-12-22 US US16/470,866 patent/US11124505B2/en active Active
- 2017-12-22 KR KR1020197021529A patent/KR102609373B1/ko active Active
- 2017-12-22 WO PCT/IB2017/058374 patent/WO2018116281A1/en not_active Ceased
- 2017-12-22 PL PL17829042.5T patent/PL3559010T3/pl unknown
- 2017-12-22 JP JP2019534154A patent/JP7294661B2/ja active Active
- 2017-12-22 DK DK17829042.5T patent/DK3559010T3/da active
- 2017-12-22 LT LTEPPCT/IB2017/058374T patent/LT3559010T/lt unknown
- 2017-12-22 MX MX2019007327A patent/MX379709B/es unknown
- 2017-12-22 PT PT178290425T patent/PT3559010T/pt unknown
- 2017-12-22 CN CN201780084302.3A patent/CN110198945B/zh active Active
- 2017-12-22 CA CA3046744A patent/CA3046744A1/en active Pending
-
2019
- 2019-06-20 IL IL267557A patent/IL267557B/en unknown
-
2021
- 2021-09-20 US US17/479,838 patent/US11731963B2/en active Active
-
2022
- 2022-09-06 CY CY20221100593T patent/CY1125531T1/el unknown
-
2023
- 2023-02-06 JP JP2023016009A patent/JP2023052918A/ja not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008038692A1 (en) | 2006-09-28 | 2008-04-03 | Banyu Pharmaceutical Co., Ltd. | Diaryl ketimine derivative |
| WO2008136428A1 (ja) | 2007-04-27 | 2008-11-13 | Takeda Pharmaceutical Company Limited | 含窒素５員複素環化合物 |
| WO2015150476A1 (en) | 2014-04-02 | 2015-10-08 | Minoryx Therapeutics S.L. | 2,4-thiazolidinedione derivatives in the treatment of central nervous system disorders |
Non-Patent Citations (2)
| Title |
|---|
| SOHDA T; ET AL，STUDIES ON ANTIDIABETIC AGENTS. XII. SYNTHESIS AND ACTIVITY OF THE METABOLITES OF (PLUS OR 以下備考，CHEMICAL AND PHARMACEUTICAL BULLETIN，日本，PHARMACEUTICAL SOCIETY OF JAPAN，1995年，VOL:43, NR:12，PAGE(S):2168 - 2172，https://pubmed.ncbi.nlm.nih.gov/8582019/，MINUS)-5-[P-[2-(5-ETHYL-2-PYRIDYL)ETHOXY]BENZYL]-2,4-THIAZOLIDINEDIONE (PIOGLITAZONE) |
| TANIS S P; ET AL，SYNTHESIS AND BIOLOGICAL ACTIVITY OF METABOLITES OF THE ANTIDIABETIC ANTIHYPERGLYCEMIC 以下備考，JOURNAL OF MEDICINAL CHEMISTRY，米国，AMERICAN CHEMICAL SOCIETY，1996年，VOL:39, NR:26，PAGE(S):5053 - 5063，http://dx.doi.org/10.1021/jm9605694，AGENT PIOGLITAZONE |
Also Published As
| Publication number | Publication date |
|---|---|
| US20190389852A1 (en) | 2019-12-26 |
| CN110198945A (zh) | 2019-09-03 |
| HRP20221067T1 (hr) | 2022-11-25 |
| IL267557B (en) | 2021-10-31 |
| EP3559010A1 (en) | 2019-10-30 |
| IL267557A (en) | 2019-08-29 |
| PL3559010T3 (pl) | 2022-11-21 |
| BR112019012972B1 (pt) | 2023-04-18 |
| SI3559010T1 (sl) | 2022-10-28 |
| PT3559010T (pt) | 2022-09-01 |
| CY1125531T1 (el) | 2026-02-25 |
| MX379709B (es) | 2025-03-11 |
| HUE059604T2 (hu) | 2022-11-28 |
| ES2926580T3 (es) | 2022-10-27 |
| KR20190100300A (ko) | 2019-08-28 |
| BR112019012972A2 (pt) | 2019-12-31 |
| US20220204496A1 (en) | 2022-06-30 |
| DK3559010T3 (da) | 2022-08-15 |
| US11731963B2 (en) | 2023-08-22 |
| JP2023052918A (ja) | 2023-04-12 |
| JP2020502228A (ja) | 2020-01-23 |
| CN110198945B (zh) | 2023-06-27 |
| LT3559010T (lt) | 2022-10-10 |
| EP3559010B1 (en) | 2022-06-08 |
| CA3046744A1 (en) | 2018-06-28 |
| KR102609373B1 (ko) | 2023-12-01 |
| MX2019007327A (es) | 2019-09-02 |
| WO2018116281A1 (en) | 2018-06-28 |
| US11124505B2 (en) | 2021-09-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7294661B2 (ja) | ５－［［４－［２－［５－（１－ヒドロキシエチル）－２－ピリジニル］エトキシ］フェニル］メチル］－２，４－チアゾリジンジオンおよびその塩を調製するためのプロセス | |
| US8198444B2 (en) | Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates | |
| US12145901B1 (en) | Process for preparing tetralin compounds | |
| WO2003042180A9 (en) | Process for producing optically active oxoheptenoic acid ester | |
| KR100474202B1 (ko) | 티아졸 유도체의 제조방법 및 이를 제조하기 위한 중간체 | |
| US9434740B2 (en) | Taxane compounds, compositions and methods | |
| HK40013289A (en) | Process for preparing thiazolidinedione compounds and salts thereof | |
| HK40014767A (en) | Process for preparing 5-[[4-[2-[5-(1-hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione and salts thereof | |
| HK40014767B (en) | Process for preparing 5-[[4-[2-[5-(1-hydroxyethyl)-2-pyridinyl]ethoxy]phenyl]methyl]-2,4-thiazolidinedione and salts thereof | |
| US20080287663A1 (en) | Process For Production Of 4-Biphenylyazetidin-2-Ones | |
| HK40013289B (zh) | 用於制备噻唑烷二酮化合物及其盐的方法 | |
| US9309259B2 (en) | Process for ixabepilone, and intermediates thereof | |
| US7705155B2 (en) | Processes for the production of useful intermediates | |
| JP3565587B2 (ja) | １５−ヒドロキシミルベマイシン誘導体の新規合成法 | |
| TW202608905A (zh) | 手性胺基膦配體、包含該等配體的銥催化劑以及該等催化劑在不對稱氫化中之用途 | |
| US20200308105A1 (en) | Novel method for producing hydroxamic acid derivative, and intermediate therefor | |
| CN106588565A (zh) | 一种羟基邻位为卤原子取代的手性仲烯丙醇的合成方法 | |
| JPH10168057A (ja) | シクロヘキシルアゼチジノン誘導体の製造法 | |
| JP2011020944A (ja) | ポジトロン放出源化合物の製造方法 | |
| JPH11255762A (ja) | 光学活性γ−ピロン化合物、その中間体およびそれらの製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201222 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20201222 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20211125 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20211208 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220302 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220506 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220608 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20221004 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230206 |
|
| C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20230206 |
|
| C11 | Written invitation by the commissioner to file amendments |
Free format text: JAPANESE INTERMEDIATE CODE: C11 Effective date: 20230217 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20230314 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20230403 |
|
| C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20230404 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230508 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230601 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7294661 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |