CA2848377A1 - Improved process for preparing an intermediate of the macrocyclic protease inhibitor tmc 435 - Google Patents
Improved process for preparing an intermediate of the macrocyclic protease inhibitor tmc 435 Download PDFInfo
- Publication number
- CA2848377A1 CA2848377A1 CA2848377A CA2848377A CA2848377A1 CA 2848377 A1 CA2848377 A1 CA 2848377A1 CA 2848377 A CA2848377 A CA 2848377A CA 2848377 A CA2848377 A CA 2848377A CA 2848377 A1 CA2848377 A1 CA 2848377A1
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- Prior art keywords
- compound
- reaction
- ruthenium
- dichloro
- bis
- Prior art date
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- Abandoned
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- JTZZSQYMACOLNN-VDWJNHBNSA-N simeprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCN(C)C(=O)[C@H]1[C@H](C(N2)=O)C[C@H](C1)OC=1C2=CC=C(C(=C2N=C(C=1)C=1SC=C(N=1)C(C)C)C)OC)NS(=O)(=O)C1CC1 JTZZSQYMACOLNN-VDWJNHBNSA-N 0.000 title abstract description 14
- 229960002091 simeprevir Drugs 0.000 title abstract description 14
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 5
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 108
- 239000003054 catalyst Substances 0.000 claims description 49
- -1 diene compound Chemical class 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 29
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 26
- 229910052707 ruthenium Inorganic materials 0.000 claims description 26
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 25
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 24
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 24
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- UQFSVBXCNGCBBW-UHFFFAOYSA-M tetraethylammonium iodide Chemical compound [I-].CC[N+](CC)(CC)CC UQFSVBXCNGCBBW-UHFFFAOYSA-M 0.000 claims description 16
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- RXMRGBVLCSYIBO-UHFFFAOYSA-M tetramethylazanium;iodide Chemical compound [I-].C[N+](C)(C)C RXMRGBVLCSYIBO-UHFFFAOYSA-M 0.000 claims description 7
- 150000003855 acyl compounds Chemical class 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- GKXDJYKZFZVASJ-UHFFFAOYSA-M tetrapropylazanium;iodide Chemical compound [I-].CCC[N+](CCC)(CCC)CCC GKXDJYKZFZVASJ-UHFFFAOYSA-M 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 125000006343 heptafluoro propyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 238000005580 one pot reaction Methods 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- UDWHYAPPVOEOMP-UHFFFAOYSA-L dichloro(phenylsulfanylmethylidene)ruthenium;tricyclohexylphosphane Chemical compound Cl[Ru](Cl)=CSC1=CC=CC=C1.C1CCCCC1P(C1CCCCC1)C1CCCCC1.C1CCCCC1P(C1CCCCC1)C1CCCCC1 UDWHYAPPVOEOMP-UHFFFAOYSA-L 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 9
- RUKVGXGTVPPWDD-UHFFFAOYSA-N 1,3-bis(2,4,6-trimethylphenyl)imidazolidine Chemical group CC1=CC(C)=CC(C)=C1N1CN(C=2C(=CC(C)=CC=2C)C)CC1 RUKVGXGTVPPWDD-UHFFFAOYSA-N 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- XELFHNUFJMCUIG-UHFFFAOYSA-N [Ru].CC1=C(C(=CC(=C1)C)C)N1C(N(CC1)C1=C(C=C(C=C1C)C)C)=C1C(C(=C(C=C1)P(C1=CC=CC=C1)(C1=CC=CC=C1)=C1C=C(C2=CC=CC=C12)C1=CC=CC=C1)Cl)Cl Chemical compound [Ru].CC1=C(C(=CC(=C1)C)C)N1C(N(CC1)C1=C(C=C(C=C1C)C)C)=C1C(C(=C(C=C1)P(C1=CC=CC=C1)(C1=CC=CC=C1)=C1C=C(C2=CC=CC=C12)C1=CC=CC=C1)Cl)Cl XELFHNUFJMCUIG-UHFFFAOYSA-N 0.000 claims 1
- FCDPQMAOJARMTG-UHFFFAOYSA-L benzylidene-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-dichlororuthenium;tricyclohexylphosphane Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1.CC1=CC(C)=CC(C)=C1N(CCN1C=2C(=CC(C)=CC=2C)C)C1=[Ru](Cl)(Cl)=CC1=CC=CC=C1 FCDPQMAOJARMTG-UHFFFAOYSA-L 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 claims 1
- 150000002678 macrocyclic compounds Chemical class 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 241000711549 Hepacivirus C Species 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 108091005804 Peptidases Proteins 0.000 abstract description 3
- 239000004365 Protease Substances 0.000 abstract description 3
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 125000004494 ethyl ester group Chemical group 0.000 abstract description 2
- 230000010076 replication Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 113
- 239000000243 solution Substances 0.000 description 74
- 239000000203 mixture Substances 0.000 description 27
- 238000010992 reflux Methods 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000011550 stock solution Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- VBJIFLOSOQGDRZ-UHFFFAOYSA-N (2-chloro-2,2-difluoroacetyl) 2-chloro-2,2-difluoroacetate Chemical compound FC(F)(Cl)C(=O)OC(=O)C(F)(F)Cl VBJIFLOSOQGDRZ-UHFFFAOYSA-N 0.000 description 9
- WYKHFQKONWMWQM-UHFFFAOYSA-N 2-sulfanylidene-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1S WYKHFQKONWMWQM-UHFFFAOYSA-N 0.000 description 9
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- LYUUVYQGUMRKOV-UHFFFAOYSA-N Diethyl diallylmalonate Chemical compound CCOC(=O)C(CC=C)(CC=C)C(=O)OCC LYUUVYQGUMRKOV-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000011065 in-situ storage Methods 0.000 description 7
- 238000005649 metathesis reaction Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- 238000003760 magnetic stirring Methods 0.000 description 5
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- ZRPFJAPZDXQHSM-UHFFFAOYSA-L 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazole;dichloro-[(2-propan-2-yloxyphenyl)methylidene]ruthenium Chemical compound CC(C)OC1=CC=CC=C1C=[Ru](Cl)(Cl)=C1N(C=2C(=CC(C)=CC=2C)C)CCN1C1=C(C)C=C(C)C=C1C ZRPFJAPZDXQHSM-UHFFFAOYSA-L 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 150000001993 dienes Chemical class 0.000 description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 150000003334 secondary amides Chemical group 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229940122604 HCV protease inhibitor Drugs 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
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- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 2
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
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- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
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- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
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- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
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- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- BPPVUXSMLBXYGG-UHFFFAOYSA-N 4-[3-(4,5-dihydro-1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl]-2-methyl-1h-pyrazol-3-one Chemical compound CC1=C(C(=O)C=2C(N(C)NC=2)=O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 BPPVUXSMLBXYGG-UHFFFAOYSA-N 0.000 description 1
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- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 1
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- 150000003147 proline derivatives Chemical class 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 125000002348 vinylic group Chemical group 0.000 description 1
- 238000010626 work up procedure Methods 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
- C07D417/14—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 three or more hetero rings
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11187025 | 2011-10-28 | ||
| EP11187025.9 | 2011-10-28 | ||
| PCT/IB2012/055900 WO2013061285A1 (en) | 2011-10-28 | 2012-10-26 | Improved process for preparing an intermediate of the macrocyclic protease inhibitor tmc 435 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2848377A1 true CA2848377A1 (en) | 2013-05-02 |
Family
ID=47221505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2848377A Abandoned CA2848377A1 (en) | 2011-10-28 | 2012-10-26 | Improved process for preparing an intermediate of the macrocyclic protease inhibitor tmc 435 |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US8981082B2 (enExample) |
| EP (1) | EP2771339B1 (enExample) |
| JP (1) | JP6231482B2 (enExample) |
| KR (1) | KR20140086967A (enExample) |
| CN (1) | CN104053658B (enExample) |
| AR (1) | AR088568A1 (enExample) |
| AU (1) | AU2012327934B2 (enExample) |
| BR (1) | BR112014009849A2 (enExample) |
| CA (1) | CA2848377A1 (enExample) |
| CL (1) | CL2014001043A1 (enExample) |
| EA (1) | EA201490892A1 (enExample) |
| ES (1) | ES2671732T3 (enExample) |
| HK (1) | HK1202120A1 (enExample) |
| IL (1) | IL231892A (enExample) |
| MX (1) | MX347650B (enExample) |
| TW (1) | TWI574960B (enExample) |
| WO (1) | WO2013061285A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MA41812A (fr) | 2015-03-27 | 2018-01-30 | Janssen Pharmaceuticals Inc | Procédés et intermédiaires pour la préparation d'un inhibiteur de protéase macrocyclique du vhc |
| WO2017064680A1 (en) * | 2015-10-16 | 2017-04-20 | Lupin Limited | An improved process for the preparation of simeprevir sodium and intermediate thereof |
| CN109846883A (zh) * | 2017-11-30 | 2019-06-07 | 常州寅盛药业有限公司 | 苯并呋喃衍生物与tmc435联合用药物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060008877A (ko) | 2003-04-10 | 2006-01-27 | 베링거 인겔하임 인터내셔날 게엠베하 | 루테늄 착물 촉매 존재하의 복분해 반응에 의한거대사이클릭 화합물의 제조방법 |
| PE20070211A1 (es) * | 2005-07-29 | 2007-05-12 | Medivir Ab | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
| PL1934243T3 (pl) * | 2005-09-09 | 2011-10-31 | Boehringer Ingelheim Int | Proces metatezy z zamknięciem pierścienia w zastosowaniu do wytwarzania peptydów makrocyklicznych |
| EP2224920A4 (en) | 2007-12-06 | 2012-05-09 | Enanta Pharm Inc | PROCESS FOR THE PREPARATION OF MACROCYCLIC OXIMYL HEPATITIS C PROTEASE INHIBITORS |
| WO2010015545A1 (en) * | 2008-08-07 | 2010-02-11 | F. Hoffmann-La Roche Ag | Process for the preparation of a macrocycle |
| WO2010072742A1 (en) | 2008-12-23 | 2010-07-01 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc | Processes and intermediates for preparing a macrocyclic protease inhibitor of hcv |
-
2012
- 2012-10-26 JP JP2014537794A patent/JP6231482B2/ja not_active Expired - Fee Related
- 2012-10-26 AR ARP120104040A patent/AR088568A1/es unknown
- 2012-10-26 MX MX2014005070A patent/MX347650B/es active IP Right Grant
- 2012-10-26 ES ES12790677.4T patent/ES2671732T3/es active Active
- 2012-10-26 TW TW101139616A patent/TWI574960B/zh not_active IP Right Cessation
- 2012-10-26 CA CA2848377A patent/CA2848377A1/en not_active Abandoned
- 2012-10-26 HK HK15102687.7A patent/HK1202120A1/xx unknown
- 2012-10-26 KR KR1020147009887A patent/KR20140086967A/ko not_active Ceased
- 2012-10-26 WO PCT/IB2012/055900 patent/WO2013061285A1/en not_active Ceased
- 2012-10-26 CN CN201280052692.3A patent/CN104053658B/zh not_active Expired - Fee Related
- 2012-10-26 US US14/350,138 patent/US8981082B2/en not_active Expired - Fee Related
- 2012-10-26 EP EP12790677.4A patent/EP2771339B1/en active Active
- 2012-10-26 EA EA201490892A patent/EA201490892A1/ru unknown
- 2012-10-26 AU AU2012327934A patent/AU2012327934B2/en not_active Ceased
- 2012-10-26 BR BR112014009849A patent/BR112014009849A2/pt not_active IP Right Cessation
-
2014
- 2014-04-03 IL IL231892A patent/IL231892A/en not_active IP Right Cessation
- 2014-04-24 CL CL2014001043A patent/CL2014001043A1/es unknown
-
2015
- 2015-02-09 US US14/616,770 patent/US9328108B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AR088568A1 (es) | 2014-06-18 |
| HK1202120A1 (en) | 2015-09-18 |
| ES2671732T3 (es) | 2018-06-08 |
| AU2012327934B2 (en) | 2017-06-01 |
| CN104053658A (zh) | 2014-09-17 |
| BR112014009849A2 (pt) | 2016-07-05 |
| US8981082B2 (en) | 2015-03-17 |
| TWI574960B (zh) | 2017-03-21 |
| JP2014530901A (ja) | 2014-11-20 |
| US20150152098A1 (en) | 2015-06-04 |
| WO2013061285A1 (en) | 2013-05-02 |
| EP2771339B1 (en) | 2018-04-18 |
| AU2012327934A1 (en) | 2014-03-20 |
| US9328108B2 (en) | 2016-05-03 |
| US20140235852A1 (en) | 2014-08-21 |
| JP6231482B2 (ja) | 2017-11-15 |
| CN104053658B (zh) | 2018-03-13 |
| EA201490892A1 (ru) | 2014-08-29 |
| EP2771339A1 (en) | 2014-09-03 |
| IL231892A (en) | 2017-09-28 |
| MX347650B (es) | 2017-05-05 |
| KR20140086967A (ko) | 2014-07-08 |
| TW201323423A (zh) | 2013-06-16 |
| IL231892A0 (en) | 2014-05-28 |
| CL2014001043A1 (es) | 2014-07-25 |
| MX2014005070A (es) | 2014-08-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20191028 |