CA2647266A1 - Process for making cytokine inhibiting compounds containing 4- and 5- imidazolyl rings and the intermediates thereof - Google Patents
Process for making cytokine inhibiting compounds containing 4- and 5- imidazolyl rings and the intermediates thereof Download PDFInfo
- Publication number
- CA2647266A1 CA2647266A1 CA002647266A CA2647266A CA2647266A1 CA 2647266 A1 CA2647266 A1 CA 2647266A1 CA 002647266 A CA002647266 A CA 002647266A CA 2647266 A CA2647266 A CA 2647266A CA 2647266 A1 CA2647266 A1 CA 2647266A1
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- CA
- Canada
- Prior art keywords
- methyl
- phenyl
- cyclopropyl
- chosen
- nmr
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 23
- -1 5- imidazolyl rings Chemical group 0.000 title claims abstract description 19
- 150000001875 compounds Chemical class 0.000 title claims abstract description 18
- 239000000543 intermediate Substances 0.000 title abstract description 17
- 108090000695 Cytokines Proteins 0.000 title description 3
- 102000004127 Cytokines Human genes 0.000 title description 3
- 230000002401 inhibitory effect Effects 0.000 title description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 24
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 150000001879 copper Chemical class 0.000 claims description 7
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 7
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 7
- 229960005055 sodium ascorbate Drugs 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000001345 alkine derivatives Chemical class 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 150000003852 triazoles Chemical class 0.000 claims description 6
- LDDHMKANNXWUAK-UHFFFAOYSA-N 3-iodo-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1I LDDHMKANNXWUAK-UHFFFAOYSA-N 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 5
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 4
- 229930182821 L-proline Natural products 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229960002429 proline Drugs 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
- 229910000366 copper(II) sulfate Inorganic materials 0.000 claims description 3
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 3
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical group CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 claims description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 3
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012320 chlorinating reagent Substances 0.000 claims description 2
- 229940125890 compound Ia Drugs 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical group [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims 1
- 239000007787 solid Substances 0.000 description 29
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 27
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- CVWGFCNSHOZVQS-UHFFFAOYSA-N 2-cyclopropyl-1-methylimidazole Chemical compound CN1C=CN=C1C1CC1 CVWGFCNSHOZVQS-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-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
- 150000001540 azides Chemical class 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- VNVNOKAGAPDNHL-UHFFFAOYSA-N 4-(1H-imidazol-5-yl)-2H-triazole Chemical compound N1C=NC(C=2N=NNC=2)=C1 VNVNOKAGAPDNHL-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
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- CKPXLKWANYQNBL-WCCKRBBISA-N (2s)-pyrrolidine-2-carboxylic acid;sodium Chemical compound [Na].OC(=O)[C@@H]1CCCN1 CKPXLKWANYQNBL-WCCKRBBISA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- HYPFIEMTRKZPIC-UHFFFAOYSA-N 2-cyclopropyl-4,5-diiodo-1-methylimidazole Chemical compound CN1C(I)=C(I)N=C1C1CC1 HYPFIEMTRKZPIC-UHFFFAOYSA-N 0.000 description 1
- FAAQIWWKGLYLMM-UHFFFAOYSA-N 2-cyclopropyl-4-iodo-1-methylimidazole Chemical compound CN1C=C(I)N=C1C1CC1 FAAQIWWKGLYLMM-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- FAODHOVOVRRPGS-UHFFFAOYSA-N 3-[4-(2-cyclopropyl-1-methylimidazol-4-yl)triazol-1-yl]-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N1N=NC(C=2N=C(N(C)C=2)C2CC2)=C1 FAODHOVOVRRPGS-UHFFFAOYSA-N 0.000 description 1
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- XBUNOQABRBHZER-UHFFFAOYSA-N 3-[4-(2-cyclopropyl-1-methylimidazol-4-yl)triazol-1-yl]-n-[3-(methanesulfonamido)phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC=2C=C(NS(C)(=O)=O)C=CC=2)C=C1N(N=N1)C=C1C(N=1)=CN(C)C=1C1CC1 XBUNOQABRBHZER-UHFFFAOYSA-N 0.000 description 1
- HRAQKRQBOZVMJN-UHFFFAOYSA-N 3-[4-(2-cyclopropyl-3-methylimidazol-4-yl)triazol-1-yl]-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N1N=NC(C=2N(C(C3CC3)=NC=2)C)=C1 HRAQKRQBOZVMJN-UHFFFAOYSA-N 0.000 description 1
- GFDOBHNKZQJERP-UHFFFAOYSA-N 3-[4-(2-cyclopropyl-3-methylimidazol-4-yl)triazol-1-yl]-n-[3-(methanesulfonamido)-2-methoxy-5-(1-methylcyclopropyl)phenyl]-4-methylbenzamide Chemical compound C1=C(C2(C)CC2)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C(C=1)=CC=C(C)C=1N(N=N1)C=C1C(N1C)=CN=C1C1CC1 GFDOBHNKZQJERP-UHFFFAOYSA-N 0.000 description 1
- NMVRYHVHAVALTM-UHFFFAOYSA-N 3-[4-(2-cyclopropyl-3-methylimidazol-4-yl)triazol-1-yl]-n-[3-(methanesulfonamido)phenyl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC=2C=C(NS(C)(=O)=O)C=CC=2)C=C1N(N=N1)C=C1C(N1C)=CN=C1C1CC1 NMVRYHVHAVALTM-UHFFFAOYSA-N 0.000 description 1
- MBASMSYMLJINKK-UHFFFAOYSA-N 3-[4-(2-cyclopropyl-3-methylimidazol-4-yl)triazol-1-yl]-n-[5-(1-hydroxy-2-methylpropan-2-yl)-3-(methanesulfonamido)-2-methoxyphenyl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)CO)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C=2N(C(C3CC3)=NC=2)C)=C1 MBASMSYMLJINKK-UHFFFAOYSA-N 0.000 description 1
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- JHBFTDRWNOPQOA-UHFFFAOYSA-N methyl 2-[3-[[3-[4-(2-cyclopropyl-3-methylimidazol-4-yl)triazol-1-yl]-4-methylbenzoyl]amino]-5-(methanesulfonamido)-4-methoxyphenyl]-2-methylpropanoate Chemical compound CS(=O)(=O)NC1=CC(C(C)(C)C(=O)OC)=CC(NC(=O)C=2C=C(C(C)=CC=2)N2N=NC(=C2)C=2N(C(C3CC3)=NC=2)C)=C1OC JHBFTDRWNOPQOA-UHFFFAOYSA-N 0.000 description 1
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- SMHOOUVVCHGBJO-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-(2-cyclopropyl-1-methylimidazol-4-yl)triazol-1-yl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C=2N=C(N(C)C=2)C2CC2)=C1 SMHOOUVVCHGBJO-UHFFFAOYSA-N 0.000 description 1
- HJQQAVJWAVJYKD-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-(2-cyclopropyl-3-methylimidazol-4-yl)triazol-1-yl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C=2N(C(C3CC3)=NC=2)C)=C1 HJQQAVJWAVJYKD-UHFFFAOYSA-N 0.000 description 1
- MELTVNIZQGUNBL-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-4-methyl-3-[4-(3-methyl-2-phenylimidazol-4-yl)triazol-1-yl]benzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C=2N(C(C=3C=CC=CC=3)=NC=2)C)=C1 MELTVNIZQGUNBL-UHFFFAOYSA-N 0.000 description 1
- UYXUUNPWGJMQCY-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-4-methyl-3-[4-[3-methyl-2-[4-(trifluoromethyl)phenyl]imidazol-4-yl]triazol-1-yl]benzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C=2N(C(C=3C=CC(=CC=3)C(F)(F)F)=NC=2)C)=C1 UYXUUNPWGJMQCY-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000000030 silines Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74501006P | 2006-04-18 | 2006-04-18 | |
| US60/745,010 | 2006-04-18 | ||
| PCT/US2007/066684 WO2007121390A1 (en) | 2006-04-18 | 2007-04-16 | Process for making cytokine inhibiting compounds containing 4- and 5- imidazolyl rings and the intermediates thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2647266A1 true CA2647266A1 (en) | 2007-10-25 |
Family
ID=38327037
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002647266A Abandoned CA2647266A1 (en) | 2006-04-18 | 2007-04-16 | Process for making cytokine inhibiting compounds containing 4- and 5- imidazolyl rings and the intermediates thereof |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7858804B2 (enExample) |
| EP (1) | EP2010522A1 (enExample) |
| JP (1) | JP2009536618A (enExample) |
| CA (1) | CA2647266A1 (enExample) |
| WO (1) | WO2007121390A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109553591A (zh) * | 2019-01-15 | 2019-04-02 | 齐鲁天和惠世制药有限公司 | 一种富马酸喹硫平中间体的制备方法 |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0712795A2 (pt) | 2006-07-07 | 2012-09-04 | Boehringer Ingelheim Int | derivados de heteroarila substituìdos com fenila e uso dos mesmos como agentes antitumorais |
| PE20090837A1 (es) * | 2007-07-02 | 2009-07-24 | Boehringer Ingelheim Int | Nuevos compuestos quimicos |
| TW201014860A (en) | 2008-09-08 | 2010-04-16 | Boehringer Ingelheim Int | New chemical compounds |
| EA201100564A1 (ru) | 2008-09-29 | 2011-12-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Антипролиферативные соединения |
| US8569316B2 (en) | 2009-02-17 | 2013-10-29 | Boehringer Ingelheim International Gmbh | Pyrimido [5,4-D] pyrimidine derivatives for the inhibition of tyrosine kinases |
| JP5871896B2 (ja) | 2010-03-26 | 2016-03-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｂ−ｒａｆキナーゼインヒビター |
| WO2011117382A1 (en) | 2010-03-26 | 2011-09-29 | Boehringer Ingelheim International Gmbh | Pyridyltriazoles |
| US8710055B2 (en) | 2010-12-21 | 2014-04-29 | Boehringer Ingelheim International Gmbh | Triazolylphenyl sulfonamides as serine/threonine kinase inhibitors |
| US8889684B2 (en) | 2011-02-02 | 2014-11-18 | Boehringer Ingelheim International Gmbh | Azaindolylphenyl sulfonamides as serine/threonine kinase inhibitors |
| EP2701511A4 (en) * | 2011-04-29 | 2015-06-10 | Univ Akron | ANTIQUE AND ANTIMICROBIAL AGENTS WITH AZOLIUM AND PURINIUM SALT |
| WO2013064231A1 (en) | 2011-10-31 | 2013-05-10 | Phenex Pharmaceuticals Ag | SEVEN-MEMBERED SULFONAMIDES AS MODULATORS OF RAR-RELATED ORPHAN RECEPTOR-GAMMA (RORγ, NR1F3) |
| PT2963037T (pt) | 2013-02-27 | 2019-04-23 | Mochida Pharm Co Ltd | Novo derivado de pirazole |
| WO2022188792A1 (zh) * | 2021-03-12 | 2022-09-15 | 四川科伦博泰生物医药股份有限公司 | 具有蛋白激酶抑制活性的杂环化合物、包含其的药物组合物及其制备方法和用途 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1725544T1 (sl) * | 2004-03-09 | 2009-10-31 | Boehringer Ingelheim Pharma | 3-(4-heterociklil-1,2,3-triazol-1-il)-N-aril-benzamidi kot inhibitorji proizvodnje citokinov za zdravljenje kroničnih vnetnih bolezni |
-
2007
- 2007-04-16 JP JP2009506701A patent/JP2009536618A/ja active Pending
- 2007-04-16 CA CA002647266A patent/CA2647266A1/en not_active Abandoned
- 2007-04-16 EP EP07760693A patent/EP2010522A1/en not_active Withdrawn
- 2007-04-16 US US12/295,636 patent/US7858804B2/en active Active
- 2007-04-16 WO PCT/US2007/066684 patent/WO2007121390A1/en not_active Ceased
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109553591A (zh) * | 2019-01-15 | 2019-04-02 | 齐鲁天和惠世制药有限公司 | 一种富马酸喹硫平中间体的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007121390A1 (en) | 2007-10-25 |
| JP2009536618A (ja) | 2009-10-15 |
| US20090137815A1 (en) | 2009-05-28 |
| EP2010522A1 (en) | 2009-01-07 |
| US7858804B2 (en) | 2010-12-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20130416 |