MX2012010678A - Procedimientos e intermediarios para preparar un inhibidor macrociclico de proteasa del virus de la hepatitis c. - Google Patents
Procedimientos e intermediarios para preparar un inhibidor macrociclico de proteasa del virus de la hepatitis c.Info
- Publication number
- MX2012010678A MX2012010678A MX2012010678A MX2012010678A MX2012010678A MX 2012010678 A MX2012010678 A MX 2012010678A MX 2012010678 A MX2012010678 A MX 2012010678A MX 2012010678 A MX2012010678 A MX 2012010678A MX 2012010678 A MX2012010678 A MX 2012010678A
- Authority
- MX
- Mexico
- Prior art keywords
- acid
- oxo
- compound
- mixture
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- 239000000543 intermediate Substances 0.000 title description 33
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 title description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 2
- 239000002253 acid Substances 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims abstract description 31
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 claims abstract description 29
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 claims abstract description 27
- CJSMOECOKYPHSC-UHFFFAOYSA-N 4-oxocyclopentane-1,2-dicarboxylic acid Chemical compound OC(=O)C1CC(=O)CC1C(O)=O CJSMOECOKYPHSC-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- KWGRBVOPPLSCSI-PSASIEDQSA-N (1s,2r)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-PSASIEDQSA-N 0.000 claims abstract description 7
- 230000001376 precipitating effect Effects 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 89
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 81
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 75
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 41
- -1 bicyclic lactone Chemical class 0.000 claims description 38
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 24
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 18
- WMWOMMJQVXRFAP-UHFFFAOYSA-N 5-chloro-4,6-dimethoxytriazine Chemical compound COC1=NN=NC(OC)=C1Cl WMWOMMJQVXRFAP-UHFFFAOYSA-N 0.000 claims description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 11
- 150000002596 lactones Chemical class 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 9
- 238000007363 ring formation reaction Methods 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- RJLBLEIPNSPREJ-UHFFFAOYSA-N 4-hydroxycyclopentane-1,2-dicarboxylic acid Chemical compound OC1CC(C(O)=O)C(C(O)=O)C1 RJLBLEIPNSPREJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000006751 Mitsunobu reaction Methods 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 125000000468 ketone group Chemical group 0.000 claims description 6
- FKSHZARYGBOZDO-UHFFFAOYSA-N 4,5-dichloro-6-methoxytriazine Chemical compound COC1=NN=NC(Cl)=C1Cl FKSHZARYGBOZDO-UHFFFAOYSA-N 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 4
- 150000004702 methyl esters Chemical class 0.000 claims description 4
- QLSTWGZDXAHREY-UHFFFAOYSA-N n-methylhex-1-en-1-amine Chemical compound CCCCC=CNC QLSTWGZDXAHREY-UHFFFAOYSA-N 0.000 claims description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- 239000004280 Sodium formate Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 claims description 3
- 235000019254 sodium formate Nutrition 0.000 claims description 3
- 238000005809 transesterification reaction Methods 0.000 claims description 3
- 150000003918 triazines Chemical class 0.000 claims description 3
- MGNCLNQXLYJVJD-VMIGTVKRSA-N 2,4,6-trichloro-1,3,5-triazine Chemical group Cl[13C]1=N[13C](Cl)=N[13C](Cl)=N1 MGNCLNQXLYJVJD-VMIGTVKRSA-N 0.000 claims description 2
- GSUKVTZXJFHNEU-UHFFFAOYSA-N 2-quinolin-2-yloxyquinoline Chemical group C1=CC=CC2=NC(OC=3N=C4C=CC=CC4=CC=3)=CC=C21 GSUKVTZXJFHNEU-UHFFFAOYSA-N 0.000 claims description 2
- NQVRMIOCJAWYNB-UHFFFAOYSA-N 3-oxocyclopentane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCC(=O)C1 NQVRMIOCJAWYNB-UHFFFAOYSA-N 0.000 claims description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 2
- 125000005604 azodicarboxylate group Chemical group 0.000 claims description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 150000001940 cyclopentanes Chemical class 0.000 claims description 2
- 125000000686 lactone group Chemical group 0.000 claims description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims 1
- KVJUPZXQTMRLQJ-UHFFFAOYSA-M 4-(3,5-dimethoxy-2h-triazin-4-yl)-4-methylmorpholin-4-ium;chloride Chemical compound [Cl-].CON1NN=CC(OC)=C1[N+]1(C)CCOCC1 KVJUPZXQTMRLQJ-UHFFFAOYSA-M 0.000 claims 1
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- CJSMOECOKYPHSC-RFZPGFLSSA-N (1r,2r)-4-oxocyclopentane-1,2-dicarboxylic acid Chemical compound OC(=O)[C@@H]1CC(=O)C[C@H]1C(O)=O CJSMOECOKYPHSC-RFZPGFLSSA-N 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 description 110
- 239000000243 solution Substances 0.000 description 76
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 65
- 239000007787 solid Substances 0.000 description 42
- 230000015572 biosynthetic process Effects 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
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- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 17
- 239000007864 aqueous solution Substances 0.000 description 17
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- 238000010992 reflux Methods 0.000 description 13
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 241000711549 Hepacivirus C Species 0.000 description 8
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- 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 3
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- RVWUHFFPEOKYLB-UHFFFAOYSA-N 2,2,6,6-tetramethyl-1-oxidopiperidin-1-ium Chemical compound CC1(C)CCCC(C)(C)[NH+]1[O-] RVWUHFFPEOKYLB-UHFFFAOYSA-N 0.000 description 1
- MLFXJCXPSODAIS-UHFFFAOYSA-N 2-[[2-[(2-hydroxyphenyl)methylamino]ethylamino]methyl]phenol Chemical compound OC1=CC=CC=C1CNCCNCC1=CC=CC=C1O MLFXJCXPSODAIS-UHFFFAOYSA-N 0.000 description 1
- DMHXELXBORNSQN-JHJVBQTASA-N 2-o-benzyl 1-o-methyl (1r,2r,4r)-4-hydroxycyclopentane-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@@H](O)C[C@H]1C(=O)OCC1=CC=CC=C1 DMHXELXBORNSQN-JHJVBQTASA-N 0.000 description 1
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- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- LPPRPUJPNUYIKH-UHFFFAOYSA-N 7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)-1h-quinolin-4-one Chemical compound N=1C2=C(C)C(OC)=CC=C2C(O)=CC=1C1=NC(C(C)C)=CS1 LPPRPUJPNUYIKH-UHFFFAOYSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
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- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
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- 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 1
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- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000002152 aqueous-organic solution Substances 0.000 description 1
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- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 1
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 1
- 230000005587 bubbling Effects 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
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- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
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- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
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- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- BYGAVIIEJSUUHA-UHFFFAOYSA-N cyclopentane-1,1-dicarboxamide Chemical compound NC(=O)C1(C(N)=O)CCCC1 BYGAVIIEJSUUHA-UHFFFAOYSA-N 0.000 description 1
- YZFOGXKZTWZVFN-UHFFFAOYSA-N cyclopentane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCCC1 YZFOGXKZTWZVFN-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- GMKJWKXCHOWVDN-UHFFFAOYSA-N dimethyl 4-oxocyclopentane-1,2-dicarboxylate Chemical compound COC(=O)C1CC(=O)CC1C(=O)OC GMKJWKXCHOWVDN-UHFFFAOYSA-N 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
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- 229950000038 interferon alfa Drugs 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- YOJAHJGBFDPSDI-UHFFFAOYSA-N methyl 4-nitrobenzoate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C=C1 YOJAHJGBFDPSDI-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 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
- XDYRBRLMIGIKQW-UHFFFAOYSA-N n-cyclopentylhydroxylamine Chemical compound ONC1CCCC1 XDYRBRLMIGIKQW-UHFFFAOYSA-N 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
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- 150000004322 quinolinols Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
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- 230000000284 resting effect Effects 0.000 description 1
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- 229920006395 saturated elastomer Polymers 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
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- MBDNRNMVTZADMQ-UHFFFAOYSA-N sulfolene Chemical compound O=S1(=O)CC=CC1 MBDNRNMVTZADMQ-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
- C07C215/20—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated the carbon skeleton being saturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
- C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
- C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/82—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/02—Preparation of carboxylic acids or their salts, halides or anhydrides from salts of carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C69/757—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/28—Only halogen atoms, e.g. cyanuric chloride
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/30—Only oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/06—Saturated compounds having a carboxyl group bound to a five-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- 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
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Furan Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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| EP10156681 | 2010-03-16 | ||
| PCT/EP2011/053957 WO2011113859A1 (en) | 2010-03-16 | 2011-03-16 | Processes and intermediates for preparing a macrocyclic protease inhibitor of hcv |
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| MX2012010678A true MX2012010678A (es) | 2012-10-15 |
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| MX2012010678A MX2012010678A (es) | 2010-03-16 | 2011-03-16 | Procedimientos e intermediarios para preparar un inhibidor macrociclico de proteasa del virus de la hepatitis c. |
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| JP (2) | JP2013522273A (enExample) |
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| MX2012010678A (es) * | 2010-03-16 | 2012-10-15 | Janssen Pharmaceuticals Inc | Procedimientos e intermediarios para preparar un inhibidor macrociclico de proteasa del virus de la hepatitis c. |
| JP6235473B2 (ja) * | 2011-09-22 | 2017-11-22 | ヤンセン ファーマシューティカルズ,インコーポレーテッド | 大環状hcvプロテアーゼ阻害剤を製造するための方法および中間体 |
| MX2017007854A (es) * | 2014-12-22 | 2017-09-19 | Colgate Palmolive Co | Suavizante para telas de dosis unitaria. |
| 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 |
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| NL8300536A (nl) * | 1983-02-14 | 1984-09-03 | Oce Andeno Bv | Optisch actief alfa-azido-p-hydroxyfenylazijnzuur en zijn zouten alsmede de bereiding daarvan. |
| JPS6124539A (ja) * | 1984-07-11 | 1986-02-03 | Sagami Chem Res Center | 光学活性(r)−2,5,12−トリヒドロキシ−1,2,3,4−テトラヒドロナフタセン−6,11−ジオン−2−カルボン酸の取得方法 |
| JPH06124539A (ja) | 1992-10-08 | 1994-05-06 | Sony Corp | ディジタルvtr |
| JPH08231469A (ja) * | 1995-02-23 | 1996-09-10 | Nippon Kayaku Co Ltd | シクロペンタンカルボン酸誘導体及びその製造法 |
| JPH11180930A (ja) * | 1997-12-22 | 1999-07-06 | Sumitomo Chem Co Ltd | 光学活性trans−シクロブタンジカルボン酸類の製造方法 |
| DE10029139A1 (de) * | 2000-06-14 | 2002-01-03 | Sueddeutsche Kalkstickstoff | Verfahren zur Herstellung von Amiden oder Estern |
| MY153011A (en) | 2004-01-30 | 2014-12-31 | Medivir Ab | Hcv ns-3 serine protease inhibitors |
| CA2617099C (en) * | 2005-07-29 | 2014-03-25 | Tibotec Pharmaceuticals Ltd. | Macrocyclic inhibitors of hepatitis c virus |
| PE20070211A1 (es) * | 2005-07-29 | 2007-05-12 | Medivir Ab | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
| US20070185346A1 (en) * | 2006-02-03 | 2007-08-09 | Vaidya Niteen A | Kit for automated resolving agent selection and method thereof |
| TWI455936B (zh) * | 2007-02-01 | 2014-10-11 | Tibotec Pharm Ltd | 用於製備hcv之大環蛋白酶抑制劑之方法及中間物 |
| MX2012010678A (es) * | 2010-03-16 | 2012-10-15 | Janssen Pharmaceuticals Inc | Procedimientos e intermediarios para preparar un inhibidor macrociclico de proteasa del virus de la hepatitis c. |
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Also Published As
| Publication number | Publication date |
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| JP2016164143A (ja) | 2016-09-08 |
| CA2793129A1 (en) | 2011-09-22 |
| IL221242A0 (en) | 2012-10-31 |
| AU2011229164A1 (en) | 2012-08-30 |
| IL221242A (en) | 2016-04-21 |
| KR20130034012A (ko) | 2013-04-04 |
| US20130005976A1 (en) | 2013-01-03 |
| US20170152253A1 (en) | 2017-06-01 |
| EP3239129A1 (en) | 2017-11-01 |
| CN103249708A (zh) | 2013-08-14 |
| WO2011113859A1 (en) | 2011-09-22 |
| JP2013522273A (ja) | 2013-06-13 |
| BR112012023296A2 (pt) | 2016-10-18 |
| US9586893B2 (en) | 2017-03-07 |
| AU2011229164B2 (en) | 2015-11-26 |
| EP2547645B1 (en) | 2018-07-04 |
| BR112012023296B1 (pt) | 2018-07-03 |
| RU2012143977A (ru) | 2014-04-27 |
| EP2547645A1 (en) | 2013-01-23 |
| RU2628081C2 (ru) | 2017-08-14 |
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