DK2912013T3 - Process for the preparation of bile acid derivatives - Google Patents
Process for the preparation of bile acid derivatives Download PDFInfo
- Publication number
- DK2912013T3 DK2912013T3 DK13849263.2T DK13849263T DK2912013T3 DK 2912013 T3 DK2912013 T3 DK 2912013T3 DK 13849263 T DK13849263 T DK 13849263T DK 2912013 T3 DK2912013 T3 DK 2912013T3
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- formula
- pharmaceutically acceptable
- acceptable salt
- preparing
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims description 11
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical class C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 242
- 150000003839 salts Chemical class 0.000 claims abstract description 96
- 239000012453 solvate Substances 0.000 claims abstract description 28
- 238000004519 manufacturing process Methods 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 239000007789 gas Substances 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 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 9
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical compound O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical group CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 3
- HGBGABMSTHQFNJ-UHFFFAOYSA-N 1,4-dioxane;sulfur trioxide Chemical compound O=S(=O)=O.C1COCCO1 HGBGABMSTHQFNJ-UHFFFAOYSA-N 0.000 claims description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910010084 LiAlH4 Inorganic materials 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 241000546339 Trioxys Species 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 239000012280 lithium aluminium hydride Substances 0.000 claims 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 55
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 40
- 229910001868 water Inorganic materials 0.000 description 38
- 239000000203 mixture Substances 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 239000003880 polar aprotic solvent Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000003586 protic polar solvent Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical group O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 239000012279 sodium borohydride Substances 0.000 description 12
- 229910000033 sodium borohydride Inorganic materials 0.000 description 12
- 239000011734 sodium Substances 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- 239000012267 brine Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical group CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 150000008064 anhydrides Chemical class 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 6
- 150000004678 hydrides Chemical class 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- -1 C23 carboxylic acid Chemical class 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 229940125890 compound Ia Drugs 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000007248 oxidative elimination reaction Methods 0.000 description 3
- 239000000126 substance Chemical group 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- NYENCOMLZDQKNH-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)bismuthanyl trifluoromethanesulfonate Chemical compound [Bi+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F NYENCOMLZDQKNH-UHFFFAOYSA-K 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical compound CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-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
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 2
- 238000006277 sulfonation reaction Methods 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UJJDEOLXODWCGK-UHFFFAOYSA-N tert-butyl carbonochloridate Chemical compound CC(C)(C)OC(Cl)=O UJJDEOLXODWCGK-UHFFFAOYSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 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 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 101100101413 Caenorhabditis elegans ubh-4 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229910019065 NaOH 1 M Inorganic materials 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261718966P | 2012-10-26 | 2012-10-26 | |
| PCT/US2013/066917 WO2014066819A1 (en) | 2012-10-26 | 2013-10-25 | Process for preparing bile acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2912013T3 true DK2912013T3 (en) | 2018-01-15 |
Family
ID=50545344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK13849263.2T DK2912013T3 (en) | 2012-10-26 | 2013-10-25 | Process for the preparation of bile acid derivatives |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US9777038B2 (enExample) |
| EP (1) | EP2912013B1 (enExample) |
| JP (1) | JP6272888B2 (enExample) |
| KR (1) | KR102068381B1 (enExample) |
| CN (2) | CN108250264A (enExample) |
| AU (1) | AU2013334122B2 (enExample) |
| BR (1) | BR112015009395A2 (enExample) |
| CA (1) | CA2889592A1 (enExample) |
| CY (1) | CY1119731T1 (enExample) |
| DK (1) | DK2912013T3 (enExample) |
| ES (1) | ES2655034T3 (enExample) |
| HK (1) | HK1253301A1 (enExample) |
| HU (1) | HUE036887T2 (enExample) |
| IL (1) | IL238454B (enExample) |
| MX (1) | MX361653B (enExample) |
| NO (1) | NO2968302T3 (enExample) |
| NZ (2) | NZ745013A (enExample) |
| PL (1) | PL2912013T3 (enExample) |
| PT (1) | PT2912013T (enExample) |
| SG (1) | SG11201503247UA (enExample) |
| SM (1) | SMT201700602T1 (enExample) |
| WO (1) | WO2014066819A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2013334122B2 (en) | 2012-10-26 | 2017-11-02 | Intercept Pharmaceuticals, Inc. | Process for preparing bile acid derivatives |
| US10407462B2 (en) | 2014-05-29 | 2019-09-10 | Bar Pharmaceuticals S.R.L. | Cholane derivatives for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases |
| US10131688B2 (en) | 2014-11-19 | 2018-11-20 | NZP UK Limited | 5.beta.-6-alkyl-7-hydroxy-3-one steroids as intermediates for the production of steroidal FXR modulators |
| US10538550B2 (en) | 2014-11-19 | 2020-01-21 | NZP UK Limited | 6.alpha.-alkyl-3,7-dione steroids as intermediates for the production of steroidal FXR modulators |
| KR102526631B1 (ko) | 2014-11-19 | 2023-04-27 | 엔제트피 유케이 리미티드 | 스테로이드 fxr 조절인자를 제조하기 위한 중간체로서의 6-알킬-7-하이드록시-4-엔-3-온 스테로이드 |
| TWI688571B (zh) | 2014-11-19 | 2020-03-21 | 英商Ｎｚｐ英國有限公司 | 化合物（四） |
| CN104672290B (zh) * | 2015-01-05 | 2017-06-06 | 北京普禄德医药科技有限公司 | 一种用于预防或治疗fxr‑介导的疾病的药物及其制备方法和用途 |
| EA036404B1 (ru) | 2015-02-06 | 2020-11-06 | Интерсепт Фармасьютикалз, Инк. | Фармацевтические композиции для комбинированной терапии |
| EP3353189A4 (en) * | 2015-09-24 | 2019-06-19 | Intercept Pharmaceuticals, Inc. | METHOD AND INTERMEDIATE PRODUCTS FOR THE PREPARATION OF GALLENIC ACID DERIVATIVES |
| MX2018005520A (es) * | 2015-11-06 | 2018-08-01 | Intercept Pharmaceuticals Inc | Metodos para preparacion de acido obeticolico y derivados de los mismos. |
| WO2017142895A1 (en) * | 2016-02-15 | 2017-08-24 | Regents Of The University Of Minnesota | Compositions and methods for treating clostridium associated diseases |
| WO2017180577A1 (en) | 2016-04-13 | 2017-10-19 | Intercept Pharmaceuticals, Inc. | Methods of treating cancer |
| TW201738254A (zh) | 2016-04-19 | 2017-11-01 | 英特賽普醫藥品公司 | 奧貝膽酸及其衍生物之製備方法 |
| GB201608777D0 (en) | 2016-05-18 | 2016-06-29 | Dextra Lab Ltd | Compounds |
| GB201608776D0 (en) | 2016-05-18 | 2016-06-29 | Dextra Lab Ltd | Methods and compounds |
| CA3038534A1 (en) * | 2016-09-30 | 2018-04-05 | Intercept Pharmaceuticals, Inc. | Crystalline forms of a bile acid derivative |
| WO2019023103A1 (en) | 2017-07-24 | 2019-01-31 | Intercept Pharmaceuticals, Inc. | BILIARY ACID DERIVATIVES WITH ISOTOPIC MARKING |
| US11059854B2 (en) * | 2017-07-26 | 2021-07-13 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Method for preparing steroid derivative FXR agonist |
| GB201812382D0 (en) | 2018-07-30 | 2018-09-12 | Nzp Uk Ltd | Compounds |
| SG11202113155XA (en) | 2019-05-30 | 2021-12-30 | Intercept Pharmaceuticals Inc | Pharmaceutical compositions comprising a fxr agonist and a fibrate for use in the treatment of cholestatic liver disease |
| KR20220150270A (ko) | 2019-10-07 | 2022-11-10 | 칼리오페, 인크. | Gpr119 효능제 |
| TW202140440A (zh) | 2020-02-28 | 2021-11-01 | 美商克力歐普股份有限公司 | Gpr40激動劑 |
| WO2021236617A1 (en) | 2020-05-19 | 2021-11-25 | Kallyope, Inc. | Ampk activators |
| CN116390925A (zh) | 2020-06-26 | 2023-07-04 | 卡尔优普公司 | Ampk活化剂 |
| US20230331766A1 (en) | 2020-09-18 | 2023-10-19 | Seoul National University R&Db Foundation | Method for mass-producing sodium taurodeoxycholate |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5216015A (en) * | 1991-02-05 | 1993-06-01 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Compounds having hypocholesterolemic properties |
| AU2002308295B2 (en) | 2001-03-12 | 2007-08-23 | Intercept Pharmaceuticals, Inc. | Steroids as agonists for FXR |
| EP1568706A1 (en) | 2004-02-26 | 2005-08-31 | Intercept Pharmaceuticals, Inc. | Novel steroid agonist for FXR |
| PT2040713E (pt) * | 2006-06-27 | 2014-10-13 | Intercept Pharmaceuticals Inc | Para a prevenção ou o tratamento de doenças ou estados clínicos mediados por fxr |
| US9943614B2 (en) * | 2008-06-17 | 2018-04-17 | Brigham Young University | Cationic steroid antimicrobial diagnostic, detection, screening and imaging methods |
| EA020310B1 (ru) * | 2008-07-30 | 2014-10-30 | Интерсепт Фармасьютикалз, Инк. | Модуляторы рецептора tgr5 и их применение |
| CN102282157B (zh) * | 2008-11-19 | 2017-02-22 | 英特塞普特医药品公司 | G蛋白偶联受体5(tgr5)调节剂及其使用方法 |
| AU2013334122B2 (en) | 2012-10-26 | 2017-11-02 | Intercept Pharmaceuticals, Inc. | Process for preparing bile acid derivatives |
-
2013
- 2013-10-25 AU AU2013334122A patent/AU2013334122B2/en not_active Ceased
- 2013-10-25 KR KR1020157012805A patent/KR102068381B1/ko not_active Expired - Fee Related
- 2013-10-25 PT PT138492632T patent/PT2912013T/pt unknown
- 2013-10-25 US US14/438,323 patent/US9777038B2/en active Active
- 2013-10-25 NZ NZ745013A patent/NZ745013A/en not_active IP Right Cessation
- 2013-10-25 NZ NZ707389A patent/NZ707389A/en not_active IP Right Cessation
- 2013-10-25 SM SM20170602T patent/SMT201700602T1/it unknown
- 2013-10-25 BR BR112015009395A patent/BR112015009395A2/pt not_active Application Discontinuation
- 2013-10-25 WO PCT/US2013/066917 patent/WO2014066819A1/en not_active Ceased
- 2013-10-25 SG SG11201503247UA patent/SG11201503247UA/en unknown
- 2013-10-25 CA CA2889592A patent/CA2889592A1/en not_active Abandoned
- 2013-10-25 ES ES13849263.2T patent/ES2655034T3/es active Active
- 2013-10-25 CN CN201810282054.XA patent/CN108250264A/zh active Pending
- 2013-10-25 JP JP2015539862A patent/JP6272888B2/ja not_active Expired - Fee Related
- 2013-10-25 HU HUE13849263A patent/HUE036887T2/hu unknown
- 2013-10-25 DK DK13849263.2T patent/DK2912013T3/en active
- 2013-10-25 EP EP13849263.2A patent/EP2912013B1/en not_active Not-in-force
- 2013-10-25 PL PL13849263T patent/PL2912013T3/pl unknown
- 2013-10-25 MX MX2015005286A patent/MX361653B/es active IP Right Grant
- 2013-10-25 CN CN201380068062.XA patent/CN105102425B/zh not_active Expired - Fee Related
-
2014
- 2014-03-14 NO NO14725812A patent/NO2968302T3/no unknown
-
2015
- 2015-04-26 IL IL238454A patent/IL238454B/en active IP Right Grant
-
2016
- 2016-02-24 HK HK18112593.6A patent/HK1253301A1/zh unknown
-
2017
- 2017-08-21 US US15/681,609 patent/US10202414B2/en not_active Expired - Fee Related
-
2018
- 2018-01-03 CY CY20181100003T patent/CY1119731T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2912013T3 (en) | Process for the preparation of bile acid derivatives | |
| KR100555970B1 (ko) | 2-아미노-1,3-프로판디올유도체의 제조방법 | |
| JP5202635B2 (ja) | インテグラーゼ阻害剤の調製のためのプロセスおよび中間体 | |
| US8273889B2 (en) | Method for producing 2-azaadamantane | |
| ITMI20100284A1 (it) | Nuovo procedimento per la preparazione del dronedarone | |
| CA2339250C (en) | Synthesis of acyclic nucleoside derivatives | |
| EP3498695B1 (en) | Method for synthesizing 3-(difluoromethyl)-1-methyl-1h-pyrazole-4-carboxylic acid | |
| JP7678153B2 (ja) | ハイブチミブ中間体およびその調製法 | |
| CN112939814B (zh) | 一种氘代达卡他韦中间体的制备方法 | |
| EP4269387A1 (en) | Pyrrolinone compound and synthesis method therefor | |
| HK1214239B (en) | Process for preparing bile acid derivatives | |
| EP1791808B1 (en) | Process for the preparation of 4,5-diamino shikimicacid | |
| EA049355B1 (ru) | Промежуточное соединение гибутимиба и способ его получения | |
| Ye et al. | Expedient Construction of the Ziegler Intermediate Useful for the Synthesis of Forskolin via Consecutive Rearrangements | |
| JP4864328B2 (ja) | α−ケトエステル化合物の製造方法 | |
| US5196608A (en) | Use of an allylchloride for preparing an aldehyde | |
| CN107098868B (zh) | 一种帕立骨化醇中间体的制备方法 | |
| IT202000019897A1 (it) | Procedimento per la preparazione di un intermedio chiave del siponimod | |
| KR19980065189A (ko) | 무스콘의 신규합성중간체 및 그의 제조방법 | |
| JP2019131510A (ja) | ルビプロストンの製造方法 | |
| KR19980065188A (ko) | 무스콘의 신규합성중간체 및 그의 제조방법 | |
| JP2019108304A (ja) | デスモシンおよびイソデスモシンの製造方法 | |
| PL197215B1 (pl) | Nowy chiralny bromospirolakton karanu i sposób jego wytwarzania | |
| JPH01100195A (ja) | １α，２４―ジヒドロキシコレステロール類の製造法 |