CA2596668A1 - Novel processes for the preparation of a benzofuran - Google Patents
Novel processes for the preparation of a benzofuran Download PDFInfo
- Publication number
- CA2596668A1 CA2596668A1 CA002596668A CA2596668A CA2596668A1 CA 2596668 A1 CA2596668 A1 CA 2596668A1 CA 002596668 A CA002596668 A CA 002596668A CA 2596668 A CA2596668 A CA 2596668A CA 2596668 A1 CA2596668 A1 CA 2596668A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- pyrimidin
- dimethyl
- indole
- 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 13
- 230000008569 process Effects 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title abstract description 39
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 98
- 239000000543 intermediate Substances 0.000 claims abstract description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 37
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 31
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 17
- 239000012279 sodium borohydride Substances 0.000 claims description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- WZBXJDSDRVUINM-UHFFFAOYSA-N 5-chloro-3-[4-[(2,4-diaminopyrimidin-5-yl)methyl]-6,7-dimethoxy-1-benzofuran-2-carbonyl]-n,n-dimethyl-1h-indole-2-carboxamide Chemical compound C=12C=C(C(=O)C=3C4=CC(Cl)=CC=C4NC=3C(=O)N(C)C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N WZBXJDSDRVUINM-UHFFFAOYSA-N 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000468 ketone group Chemical group 0.000 claims description 4
- QAWZRNLQJHNKIN-UHFFFAOYSA-N 3-[[4-[[2,4-bis(2,2-dimethylpropanoylamino)pyrimidin-5-yl]methyl]-6,7-dimethoxy-1-benzofuran-2-yl]methyl]-5-chloro-n,n-dimethyl-1-(4-methylphenyl)sulfonylindole-2-carboxamide Chemical compound C=12C=C(CC=3C4=CC(Cl)=CC=C4N(C=3C(=O)N(C)C)S(=O)(=O)C=3C=CC(C)=CC=3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C QAWZRNLQJHNKIN-UHFFFAOYSA-N 0.000 claims description 3
- 229930194542 Keto Natural products 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- YQHKOVRQYOQBMQ-UHFFFAOYSA-N n-[2-(2,2-dimethylpropanoylamino)-5-[(2-formyl-3,4,5-trimethoxyphenyl)methyl]pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)(C)C)=NC=2)NC(=O)C(C)(C)C)=C1C=O YQHKOVRQYOQBMQ-UHFFFAOYSA-N 0.000 claims description 3
- BFYDHJGMGVPGEA-UHFFFAOYSA-N n-[5-[(2-formyl-3,4,5-trimethoxyphenyl)methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)C)=NC=2)NC(=O)C(C)C)=C1C=O BFYDHJGMGVPGEA-UHFFFAOYSA-N 0.000 claims description 3
- YYQAJVHVJBLONA-UHFFFAOYSA-N n-[5-[(2-formyl-3-hydroxy-4,5-dimethoxyphenyl)methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound OC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)C)=NC=2)NC(=O)C(C)C)=C1C=O YYQAJVHVJBLONA-UHFFFAOYSA-N 0.000 claims description 3
- MUZCTARMAPIEKB-UHFFFAOYSA-N 2-methyl-n-[2-(2-methylpropanoylamino)-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-4-yl]propanamide Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)C)=NC=2)NC(=O)C(C)C)=C1 MUZCTARMAPIEKB-UHFFFAOYSA-N 0.000 claims description 2
- MTRGYVUWRVFGOM-UHFFFAOYSA-N 3-(2-bromoacetyl)-5-chloro-n,n-dimethyl-1-(4-methylphenyl)sulfonylindole-2-carboxamide Chemical compound CN(C)C(=O)C1=C(C(=O)CBr)C2=CC(Cl)=CC=C2N1S(=O)(=O)C1=CC=C(C)C=C1 MTRGYVUWRVFGOM-UHFFFAOYSA-N 0.000 claims description 2
- FTXHJIVBKVOKES-UHFFFAOYSA-N 3-(2-bromoacetyl)-5-chloro-n,n-dimethyl-1h-indole-2-carboxamide Chemical compound C1=C(Cl)C=C2C(C(=O)CBr)=C(C(=O)N(C)C)NC2=C1 FTXHJIVBKVOKES-UHFFFAOYSA-N 0.000 claims description 2
- LALOZSQSGLXLKC-UHFFFAOYSA-N 3-acetyl-5-chloro-n,n-dimethyl-1-(4-methylphenyl)sulfonylindole-2-carboxamide Chemical compound CN(C)C(=O)C1=C(C(C)=O)C2=CC(Cl)=CC=C2N1S(=O)(=O)C1=CC=C(C)C=C1 LALOZSQSGLXLKC-UHFFFAOYSA-N 0.000 claims description 2
- AWECPUZOTCMHMP-UHFFFAOYSA-N 3-acetyl-5-chloro-n,n-dimethyl-1h-indole-2-carboxamide Chemical compound C1=C(Cl)C=C2C(C(C)=O)=C(C(=O)N(C)C)NC2=C1 AWECPUZOTCMHMP-UHFFFAOYSA-N 0.000 claims description 2
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- OQBPNKPSHJYTQF-UHFFFAOYSA-N n-[2-(2,2-dimethylpropanoylamino)-5-[(2-formyl-3-hydroxy-4,5-dimethoxyphenyl)methyl]pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound OC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)(C)C)=NC=2)NC(=O)C(C)(C)C)=C1C=O OQBPNKPSHJYTQF-UHFFFAOYSA-N 0.000 claims description 2
- DCZWZARHHVYRSA-UHFFFAOYSA-N n-[2-(2,2-dimethylpropanoylamino)-5-[(2-iodo-3,4,5-trimethoxyphenyl)methyl]pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)(C)C)=NC=2)NC(=O)C(C)(C)C)=C1I DCZWZARHHVYRSA-UHFFFAOYSA-N 0.000 claims description 2
- INFXPVQENJOZPC-UHFFFAOYSA-N n-[2-(2,2-dimethylpropanoylamino)-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)(C)C)=NC=2)NC(=O)C(C)(C)C)=C1 INFXPVQENJOZPC-UHFFFAOYSA-N 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- ISKSYUMWYHSYAT-UHFFFAOYSA-N tert-butyl 3-(2-bromoacetyl)-5-chloro-2-(dimethylcarbamoyl)indole-1-carboxylate Chemical compound ClC1=CC=C2N(C(=O)OC(C)(C)C)C(C(=O)N(C)C)=C(C(=O)CBr)C2=C1 ISKSYUMWYHSYAT-UHFFFAOYSA-N 0.000 claims description 2
- FEYWRWKTJVSPLU-UHFFFAOYSA-N tert-butyl 3-[4-[[2,4-bis(2-methylpropanoylamino)pyrimidin-5-yl]methyl]-6,7-dimethoxy-1-benzofuran-2-carbonyl]-5-chloro-2-(dimethylcarbamoyl)indole-1-carboxylate Chemical compound C=12C=C(C(=O)C=3C4=CC(Cl)=CC=C4N(C(=O)OC(C)(C)C)C=3C(=O)N(C)C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C FEYWRWKTJVSPLU-UHFFFAOYSA-N 0.000 claims description 2
- OVAZQJLNFYUSPM-UHFFFAOYSA-N tert-butyl 3-[[4-[[2,4-bis(2,2-dimethylpropanoylamino)pyrimidin-5-yl]methyl]-6,7-dimethoxy-1-benzofuran-2-yl]methyl]-5-chloro-2-(dimethylcarbamoyl)indole-1-carboxylate Chemical compound C=12C=C(CC=3C4=CC(Cl)=CC=C4N(C(=O)OC(C)(C)C)C=3C(=O)N(C)C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C OVAZQJLNFYUSPM-UHFFFAOYSA-N 0.000 claims description 2
- PCYHRPSFYGFARO-UHFFFAOYSA-N 3-[4-[[2,4-bis(2-methylpropanoylamino)pyrimidin-5-yl]methyl]-6,7-dimethoxy-1-benzofuran-2-carbonyl]-5-chloro-n,n-dimethyl-1-(4-methylphenyl)sulfonylindole-2-carboxamide Chemical compound C=12C=C(C(=O)C=3C4=CC(Cl)=CC=C4N(C=3C(=O)N(C)C)S(=O)(=O)C=3C=CC(C)=CC=3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C PCYHRPSFYGFARO-UHFFFAOYSA-N 0.000 claims 1
- NXEYKWNYKVKUDM-UHFFFAOYSA-N 3-[[4-[[2,4-bis(2-methylpropanoylamino)pyrimidin-5-yl]methyl]-6,7-dimethoxy-1-benzofuran-2-yl]methyl]-5-chloro-n,n-dimethyl-1-(4-methylphenyl)sulfonylindole-2-carboxamide Chemical compound C=12C=C(CC=3C4=CC(Cl)=CC=C4N(C=3C(=O)N(C)C)S(=O)(=O)C=3C=CC(C)=CC=3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C NXEYKWNYKVKUDM-UHFFFAOYSA-N 0.000 claims 1
- KYSCILSNRJBNJJ-UHFFFAOYSA-N n-[5-[(2-iodo-3,4,5-trimethoxyphenyl)methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)C)=NC=2)NC(=O)C(C)C)=C1I KYSCILSNRJBNJJ-UHFFFAOYSA-N 0.000 claims 1
- FRHYOQPCGDMYJC-UHFFFAOYSA-N tert-butyl 3-[4-[[2,4-bis(2,2-dimethylpropanoylamino)pyrimidin-5-yl]methyl]-6,7-dimethoxy-1-benzofuran-2-carbonyl]-5-chloro-2-(dimethylcarbamoyl)indole-1-carboxylate Chemical compound C=12C=C(C(=O)C=3C4=CC(Cl)=CC=C4N(C(=O)OC(C)(C)C)C=3C(=O)N(C)C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C FRHYOQPCGDMYJC-UHFFFAOYSA-N 0.000 claims 1
- BJUQQUUMFZMXSX-UHFFFAOYSA-N tert-butyl 3-[[4-[[2,4-bis(2-methylpropanoylamino)pyrimidin-5-yl]methyl]-6,7-dimethoxy-1-benzofuran-2-yl]methyl]-5-chloro-2-(dimethylcarbamoyl)indole-1-carboxylate Chemical compound C=12C=C(CC=3C4=CC(Cl)=CC=C4N(C(=O)OC(C)(C)C)C=3C(=O)N(C)C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C BJUQQUUMFZMXSX-UHFFFAOYSA-N 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 239000003166 dihydrofolate reductase inhibitor Substances 0.000 abstract description 2
- 229940117937 Dihydrofolate reductase inhibitor Drugs 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 71
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 67
- 239000000203 mixture Substances 0.000 description 61
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 53
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 33
- 239000012267 brine Substances 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000013078 crystal Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 16
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 13
- 239000002002 slurry Substances 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 10
- 229910052794 bromium Inorganic materials 0.000 description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000013058 crude material Substances 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- ASSNCSVJAZEMQG-UHFFFAOYSA-N 5-chloro-3-[[4-[(2,4-diaminopyrimidin-5-yl)methyl]-6,7-dimethoxy-1-benzofuran-2-yl]methyl]-n,n-dimethyl-1h-indole-2-carboxamide Chemical compound C=12C=C(CC=3C4=CC(Cl)=CC=C4NC=3C(=O)N(C)C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N ASSNCSVJAZEMQG-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 5
- 229940126543 compound 14 Drugs 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 5
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 5
- 229960001082 trimethoprim Drugs 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
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- 230000002265 prevention Effects 0.000 description 1
- 150000003195 pteridines Chemical class 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- COEZWFYORILMOM-UHFFFAOYSA-M sodium 4-[(2,4-dihydroxyphenyl)diazenyl]benzenesulfonate Chemical compound [Na+].OC1=CC(O)=CC=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 COEZWFYORILMOM-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229910000083 tin tetrahydride Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 229940094989 trimethylsilane Drugs 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EPPCT/EP2005/001695 | 2005-02-18 | ||
| EP2005001695 | 2005-02-18 | ||
| PCT/EP2006/001179 WO2006087140A1 (en) | 2005-02-18 | 2006-02-10 | Novell processes for the preparation of a benzofuran |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2596668A1 true CA2596668A1 (en) | 2006-08-24 |
Family
ID=36283919
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002596668A Abandoned CA2596668A1 (en) | 2005-02-18 | 2006-02-10 | Novel processes for the preparation of a benzofuran |
| CA002596669A Abandoned CA2596669A1 (en) | 2005-02-18 | 2006-02-10 | Novel processes for the preparation of a 2h-chromene |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002596669A Abandoned CA2596669A1 (en) | 2005-02-18 | 2006-02-10 | Novel processes for the preparation of a 2h-chromene |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20080221324A1 (https=) |
| EP (3) | EP1856109A1 (https=) |
| JP (2) | JP2008530156A (https=) |
| KR (2) | KR20070106635A (https=) |
| CN (4) | CN101115746A (https=) |
| AU (2) | AU2006215788B2 (https=) |
| BG (2) | BG109938A (https=) |
| BR (2) | BRPI0607797A2 (https=) |
| CA (2) | CA2596668A1 (https=) |
| CZ (2) | CZ2007536A3 (https=) |
| EE (2) | EE200700050A (https=) |
| HU (2) | HUP0700604A3 (https=) |
| IL (2) | IL184405A0 (https=) |
| MX (2) | MX2007009283A (https=) |
| NO (2) | NO20073678L (https=) |
| NZ (1) | NZ556800A (https=) |
| RO (2) | RO122912B8 (https=) |
| RU (2) | RU2397980C2 (https=) |
| TR (1) | TR200705187T1 (https=) |
| TW (2) | TW200640914A (https=) |
| WO (2) | WO2006087143A1 (https=) |
| ZA (2) | ZA200706422B (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20070106635A (ko) * | 2005-02-18 | 2007-11-02 | 아르피다 아게 | 2ｈ-크로멘의 제조를 위한 신규한 방법들 |
| CN102112108A (zh) * | 2008-04-08 | 2011-06-29 | 阿西诺药品有限公司 | 水性医药剂型 |
| US7947293B2 (en) | 2008-04-08 | 2011-05-24 | Arpida Ag | Aqueous pharmaceutical formulation |
| FR2949465B1 (fr) * | 2009-09-01 | 2011-08-12 | Pf Medicament | Derives chromones, leur procede de preparation et leurs applications therapeutiques |
| CN110606831A (zh) * | 2018-06-14 | 2019-12-24 | 上海度德医药科技有限公司 | 一种Iclaprim的新中间体及其制备方法和应用 |
| CN110818693B (zh) * | 2018-08-07 | 2023-06-02 | 上海度德医药科技有限公司 | 一种艾拉普林甲磺酸盐晶型b及其制备方法 |
| CN109988156B (zh) * | 2019-03-12 | 2021-12-28 | 广东中科药物研究有限公司 | 一种氨基嘧啶化合物 |
| CN110372746A (zh) * | 2019-07-11 | 2019-10-25 | 辽宁石油化工大学 | 一种合成β-胺基膦氧化合物的方法 |
| CN110642792B (zh) * | 2019-11-18 | 2023-04-21 | 上海医药工业研究院有限公司 | 艾拉普林中间体的制备方法 |
| CN110724135B (zh) * | 2019-11-18 | 2023-04-28 | 上海医药工业研究院有限公司 | 一种艾拉普林中间体及其制备方法 |
| CN110724108B (zh) * | 2019-11-18 | 2023-04-28 | 上海医药工业研究院有限公司 | 一种艾拉普林中间体及其制备方法 |
| CN110746361B (zh) * | 2019-11-18 | 2023-04-21 | 上海医药工业研究院有限公司 | 一种艾拉普林中间体及其制备方法 |
| CN110713483B (zh) * | 2019-11-18 | 2023-04-07 | 上海医药工业研究院 | 艾拉普林中间体及艾拉普林的制备方法 |
| CN110790753B (zh) * | 2019-11-18 | 2023-04-07 | 上海医药工业研究院 | 艾拉普林对甲苯磺酸盐、其制备方法和应用 |
| CN110818694B (zh) * | 2019-11-18 | 2023-04-21 | 上海医药工业研究院有限公司 | 艾拉普林中间体及其应用 |
| CN113493461A (zh) * | 2020-04-01 | 2021-10-12 | 上海医药工业研究院 | 一种七元杂环化合物或其盐、其制备方法及应用 |
| CN117700410B (zh) * | 2023-05-20 | 2025-07-04 | 山东康诺生物工程有限公司 | 一种3-(2-氯乙基)-2-甲基-9-羟基-4H-吡啶并[1,2-a]嘧啶-4-酮的制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2709634A1 (de) * | 1977-03-05 | 1978-09-07 | Basf Ag | Benzylpyrimidine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| US4438267A (en) * | 1980-11-11 | 1984-03-20 | Daluge Susan M | Monoheteroring compounds and their use |
| DE69618986T2 (de) * | 1995-12-04 | 2002-06-20 | Arpida Ag, Muenchenstein | Diaminopyrimidine, diese enthaltende pharmazeutische zusammensetzungen und ihre verwendung als antibakterielle mittel |
| WO2002010156A1 (en) * | 2000-07-29 | 2002-02-07 | Arpida Ag | Benzofuran derivatives and their use as antibacterial agents |
| US7365205B2 (en) * | 2001-06-20 | 2008-04-29 | Daiichi Sankyo Company, Limited | Diamine derivatives |
| CN100443482C (zh) * | 2003-07-11 | 2008-12-17 | 阿皮德公开股份有限公司 | 苯并呋喃衍生物及其在制备治疗由细菌引起的感染的药物中的用途 |
| WO2005014586A1 (en) * | 2003-08-08 | 2005-02-17 | Arpida Ag | Novel process for the preparation of 2h-chromenes |
| KR20070106635A (ko) * | 2005-02-18 | 2007-11-02 | 아르피다 아게 | 2ｈ-크로멘의 제조를 위한 신규한 방법들 |
-
2006
- 2006-02-10 KR KR1020077021394A patent/KR20070106635A/ko not_active Ceased
- 2006-02-10 RO ROA200700589A patent/RO122912B8/ro unknown
- 2006-02-10 RO ROA200700590A patent/RO122853B1/ro unknown
- 2006-02-10 KR KR1020077021395A patent/KR20070106636A/ko not_active Withdrawn
- 2006-02-10 JP JP2007555504A patent/JP2008530156A/ja active Pending
- 2006-02-10 JP JP2007555507A patent/JP2009505943A/ja active Pending
- 2006-02-10 WO PCT/EP2006/001185 patent/WO2006087143A1/en not_active Ceased
- 2006-02-10 CZ CZ20070536A patent/CZ2007536A3/cs unknown
- 2006-02-10 US US11/816,150 patent/US20080221324A1/en not_active Abandoned
- 2006-02-10 CN CNA2006800039630A patent/CN101115746A/zh active Pending
- 2006-02-10 AU AU2006215788A patent/AU2006215788B2/en not_active Ceased
- 2006-02-10 CA CA002596668A patent/CA2596668A1/en not_active Abandoned
- 2006-02-10 TR TR2007/05187T patent/TR200705187T1/xx unknown
- 2006-02-10 RU RU2007134584/04A patent/RU2397980C2/ru not_active IP Right Cessation
- 2006-02-10 EP EP06706809A patent/EP1856109A1/en not_active Withdrawn
- 2006-02-10 RU RU2007134583/04A patent/RU2007134583A/ru not_active Application Discontinuation
- 2006-02-10 BR BRPI0607797-8A patent/BRPI0607797A2/pt not_active IP Right Cessation
- 2006-02-10 CN CN2011100324952A patent/CN102079727A/zh active Pending
- 2006-02-10 AU AU2006215785A patent/AU2006215785A1/en not_active Abandoned
- 2006-02-10 CA CA002596669A patent/CA2596669A1/en not_active Abandoned
- 2006-02-10 EE EEP200700050A patent/EE200700050A/xx unknown
- 2006-02-10 CZ CZ20070537A patent/CZ2007537A3/cs unknown
- 2006-02-10 HU HU0700604A patent/HUP0700604A3/hu unknown
- 2006-02-10 EP EP10184131A patent/EP2270003A1/en not_active Withdrawn
- 2006-02-10 CN CN2006800039626A patent/CN101115743B/zh not_active Expired - Fee Related
- 2006-02-10 EP EP06706815A patent/EP1856106A1/en not_active Withdrawn
- 2006-02-10 US US11/816,157 patent/US20080161561A1/en not_active Abandoned
- 2006-02-10 WO PCT/EP2006/001179 patent/WO2006087140A1/en not_active Ceased
- 2006-02-10 BR BRPI0607758-7A patent/BRPI0607758A2/pt not_active IP Right Cessation
- 2006-02-10 HU HU0700605A patent/HUP0700605A3/hu unknown
- 2006-02-10 NZ NZ556800A patent/NZ556800A/en not_active IP Right Cessation
- 2006-02-10 MX MX2007009283A patent/MX2007009283A/es unknown
- 2006-02-10 CN CN2011100324933A patent/CN102140094B/zh not_active Expired - Fee Related
- 2006-02-10 EE EEP200700051A patent/EE200700051A/xx unknown
- 2006-02-10 MX MX2007009282A patent/MX2007009282A/es not_active Application Discontinuation
- 2006-02-17 TW TW095105425A patent/TW200640914A/zh unknown
- 2006-02-17 TW TW095105426A patent/TW200640912A/zh unknown
-
2007
- 2007-07-04 IL IL184405A patent/IL184405A0/en unknown
- 2007-07-04 IL IL184404A patent/IL184404A0/en unknown
- 2007-07-17 NO NO20073678A patent/NO20073678L/no not_active Application Discontinuation
- 2007-07-18 NO NO20073701A patent/NO20073701L/no not_active Application Discontinuation
- 2007-08-01 ZA ZA200706422A patent/ZA200706422B/xx unknown
- 2007-08-01 ZA ZA200706421A patent/ZA200706421B/xx unknown
- 2007-08-10 BG BG109938A patent/BG109938A/bg unknown
- 2007-08-10 BG BG109937A patent/BG109937A/bg unknown
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |