KR20070106636A - 벤조퓨란의 제조를 위한 신규한 방법들 - Google Patents
벤조퓨란의 제조를 위한 신규한 방법들 Download PDFInfo
- Publication number
- KR20070106636A KR20070106636A KR1020077021395A KR20077021395A KR20070106636A KR 20070106636 A KR20070106636 A KR 20070106636A KR 1020077021395 A KR1020077021395 A KR 1020077021395A KR 20077021395 A KR20077021395 A KR 20077021395A KR 20070106636 A KR20070106636 A KR 20070106636A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- pyrimidin
- compound
- 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.)
- Withdrawn
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 14
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 239000000543 intermediate Substances 0.000 claims abstract description 20
- -1 2,4-bis-isobutyrylamino-pyrimidin-5-ylmethyl Chemical group 0.000 claims description 45
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 15
- 230000009467 reduction Effects 0.000 claims description 7
- 239000012279 sodium borohydride Substances 0.000 claims description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-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
- 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 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
- 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
- 230000008569 process Effects 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
- 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 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
- 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 1
- 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 1
- 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 1
- 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 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
- 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 1
- 239000003166 dihydrofolate reductase inhibitor Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 67
- 239000000203 mixture Substances 0.000 description 61
- 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 53
- 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 39
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 33
- 239000012267 brine Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 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 25
- XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 238000003756 stirring Methods 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000013078 crystal Substances 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
- 239000002002 slurry Substances 0.000 description 13
- QFIIYDCCJIXNCD-UHFFFAOYSA-N N,N-dimethyl-1-(4-methylphenyl)sulfonylindole-2-carboxamide Chemical compound CN(C(=O)C=1N(C2=CC=CC=C2C=1)S(=O)(=O)C1=CC=C(C)C=C1)C QFIIYDCCJIXNCD-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 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
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 239000002994 raw material Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- AYVIZFVTRRWODF-UHFFFAOYSA-N n,n-dimethyl-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N(C)C)=CC2=C1 AYVIZFVTRRWODF-UHFFFAOYSA-N 0.000 description 9
- 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 9
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 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 6
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-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
- 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
- 229940126543 compound 14 Drugs 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 150000008065 acid anhydrides Chemical class 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 235000009518 sodium iodide Nutrition 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 229960001082 trimethoprim Drugs 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-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
- 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
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 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
- 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
- 235000019253 formic acid Nutrition 0.000 description 4
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 238000005810 carbonylation reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- JMFBVEWGVFCOKD-UHFFFAOYSA-N 2-n,4-n-bis(3-bromophenyl)-5-fluoropyrimidine-2,4-diamine Chemical compound N1=C(NC=2C=C(Br)C=CC=2)C(F)=CN=C1NC1=CC=CC(Br)=C1 JMFBVEWGVFCOKD-UHFFFAOYSA-N 0.000 description 1
- 125000005806 3,4,5-trimethoxybenzyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1C([H])([H])* 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- ASSNCSVJAZEMQG-UHFFFAOYSA-N CN(C)C(c1c(Cc2cc(c(Cc3c(N)nc(N)nc3)cc(OC)c3OC)c3[o]2)c(cc(cc2)Cl)c2[nH]1)=O Chemical compound CN(C)C(c1c(Cc2cc(c(Cc3c(N)nc(N)nc3)cc(OC)c3OC)c3[o]2)c(cc(cc2)Cl)c2[nH]1)=O ASSNCSVJAZEMQG-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical compound BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical group 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- QWYFOIJABGVEFP-UHFFFAOYSA-L manganese(ii) iodide Chemical compound [Mn+2].[I-].[I-] QWYFOIJABGVEFP-UHFFFAOYSA-L 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 150000003195 pteridines Chemical class 0.000 description 1
- MISVBCMQSJUHMH-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical group NC1=CC(N)=NC=N1 MISVBCMQSJUHMH-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 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
- 235000002906 tartaric acid Nutrition 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
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)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| WOEP/2005/001695 | 2005-02-18 | ||
| EP2005001695 | 2005-02-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20070106636A true KR20070106636A (ko) | 2007-11-02 |
Family
ID=36283919
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020077021395A Withdrawn KR20070106636A (ko) | 2005-02-18 | 2006-02-10 | 벤조퓨란의 제조를 위한 신규한 방법들 |
| KR1020077021394A Ceased KR20070106635A (ko) | 2005-02-18 | 2006-02-10 | 2ｈ-크로멘의 제조를 위한 신규한 방법들 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020077021394A Ceased KR20070106635A (ko) | 2005-02-18 | 2006-02-10 | 2ｈ-크로멘의 제조를 위한 신규한 방법들 |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20080161561A1 (enExample) |
| EP (3) | EP1856106A1 (enExample) |
| JP (2) | JP2008530156A (enExample) |
| KR (2) | KR20070106636A (enExample) |
| CN (4) | CN101115746A (enExample) |
| AU (2) | AU2006215785A1 (enExample) |
| BG (2) | BG109937A (enExample) |
| BR (2) | BRPI0607758A2 (enExample) |
| CA (2) | CA2596668A1 (enExample) |
| CZ (2) | CZ2007537A3 (enExample) |
| EE (2) | EE200700051A (enExample) |
| HU (2) | HUP0700604A3 (enExample) |
| IL (2) | IL184404A0 (enExample) |
| MX (2) | MX2007009282A (enExample) |
| NO (2) | NO20073678L (enExample) |
| NZ (1) | NZ556800A (enExample) |
| RO (2) | RO122912B8 (enExample) |
| RU (2) | RU2397980C2 (enExample) |
| TR (1) | TR200705187T1 (enExample) |
| TW (2) | TW200640912A (enExample) |
| WO (2) | WO2006087143A1 (enExample) |
| ZA (2) | ZA200706421B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101115746A (zh) * | 2005-02-18 | 2008-01-30 | 阿皮德公开股份有限公司 | 用于制备苯并呋喃的新方法 |
| US7947293B2 (en) | 2008-04-08 | 2011-05-24 | Arpida Ag | Aqueous pharmaceutical formulation |
| MX2010011117A (es) * | 2008-04-08 | 2011-02-24 | Acino Pharma Ag | Formulacion farmaceutica acuosa. |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| CA2238521C (en) * | 1995-12-04 | 2005-08-16 | F. Hoffmann-La Roche Ag | Diaminopyrimidines, pharmaceutical compositions containing them and their use as antibacterial |
| WO2002010156A1 (en) * | 2000-07-29 | 2002-02-07 | Arpida Ag | Benzofuran derivatives and their use as antibacterial agents |
| WO2003000657A1 (en) * | 2001-06-20 | 2003-01-03 | Daiichi Pharmaceutical Co., Ltd. | 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 |
| CN101115746A (zh) * | 2005-02-18 | 2008-01-30 | 阿皮德公开股份有限公司 | 用于制备苯并呋喃的新方法 |
-
2006
- 2006-02-10 CN CNA2006800039630A patent/CN101115746A/zh active Pending
- 2006-02-10 WO PCT/EP2006/001185 patent/WO2006087143A1/en not_active Ceased
- 2006-02-10 TR TR2007/05187T patent/TR200705187T1/xx unknown
- 2006-02-10 MX MX2007009282A patent/MX2007009282A/es not_active Application Discontinuation
- 2006-02-10 KR KR1020077021395A patent/KR20070106636A/ko not_active Withdrawn
- 2006-02-10 CZ CZ20070537A patent/CZ2007537A3/cs 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 NZ NZ556800A patent/NZ556800A/en not_active IP Right Cessation
- 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 RU RU2007134584/04A patent/RU2397980C2/ru not_active IP Right Cessation
- 2006-02-10 WO PCT/EP2006/001179 patent/WO2006087140A1/en not_active Ceased
- 2006-02-10 RU RU2007134583/04A patent/RU2007134583A/ru not_active Application Discontinuation
- 2006-02-10 JP JP2007555504A patent/JP2008530156A/ja active Pending
- 2006-02-10 EE EEP200700050A patent/EE200700050A/xx unknown
- 2006-02-10 AU AU2006215785A patent/AU2006215785A1/en not_active Abandoned
- 2006-02-10 CA CA002596668A patent/CA2596668A1/en not_active Abandoned
- 2006-02-10 BR BRPI0607758-7A patent/BRPI0607758A2/pt not_active IP Right Cessation
- 2006-02-10 EP EP06706809A patent/EP1856109A1/en not_active Withdrawn
- 2006-02-10 KR KR1020077021394A patent/KR20070106635A/ko not_active Ceased
- 2006-02-10 AU AU2006215788A patent/AU2006215788B2/en not_active Ceased
- 2006-02-10 US US11/816,150 patent/US20080221324A1/en not_active Abandoned
- 2006-02-10 CN CN2006800039626A patent/CN101115743B/zh not_active Expired - Fee Related
- 2006-02-10 RO ROA200700589A patent/RO122912B8/ro unknown
- 2006-02-10 MX MX2007009283A patent/MX2007009283A/es unknown
- 2006-02-10 JP JP2007555507A patent/JP2009505943A/ja active Pending
- 2006-02-10 BR BRPI0607797-8A patent/BRPI0607797A2/pt not_active IP Right Cessation
- 2006-02-10 HU HU0700604A patent/HUP0700604A3/hu unknown
- 2006-02-10 CA CA002596669A patent/CA2596669A1/en not_active Abandoned
- 2006-02-10 HU HU0700605A patent/HUP0700605A3/hu unknown
- 2006-02-10 CN CN2011100324952A patent/CN102079727A/zh active Pending
- 2006-02-10 EP EP10184131A patent/EP2270003A1/en not_active Withdrawn
- 2006-02-10 RO ROA200700590A patent/RO122853B1/ro unknown
- 2006-02-10 CZ CZ20070536A patent/CZ2007536A3/cs unknown
- 2006-02-17 TW TW095105426A patent/TW200640912A/zh unknown
- 2006-02-17 TW TW095105425A patent/TW200640914A/zh unknown
-
2007
- 2007-07-04 IL IL184404A patent/IL184404A0/en unknown
- 2007-07-04 IL IL184405A patent/IL184405A0/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 ZA200706421A patent/ZA200706421B/xx unknown
- 2007-08-01 ZA ZA200706422A patent/ZA200706422B/xx unknown
- 2007-08-10 BG BG109937A patent/BG109937A/bg unknown
- 2007-08-10 BG BG109938A patent/BG109938A/bg unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BG109938A (bg) | Нови методи за получаване на бензофуран | |
| FR2748026A1 (fr) | Nouveaux inhibiteurs de metalloproteases, leur procede de preparation et les compositions pharmaceutiques qui les contiennent | |
| JP2000516588A (ja) | 細胞増殖阻害のための置換ビスインドリルマレイミド | |
| EP3418273A1 (fr) | Dérivés de flavaglines | |
| KR100753353B1 (ko) | 졸미트립탄 화합물의 제조방법 | |
| CA2443585A1 (fr) | Nouveaux derives de (3,4-a:3,4-c) carbazole, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent | |
| KR100755625B1 (ko) | 신경이완 활성을 갖는 5-(2-(4-(1,2벤즈이소티아졸-3-일)-1-피페라지닐)에틸)-6-클로로-1,3-디히드로-2ｈ-인돌-2-온의 아실 유도체 | |
| HU208966B (en) | Process for producing 6-(substituted amino-propionyl)-forskoline derivatives | |
| IE913576A1 (en) | A process(ii) for preparing 5-aroyl-2,3¹dihydro-1h-pyrrolizine-1,1-dicarboxylates | |
| US6710185B2 (en) | Process for the preparation of cell proliferation inhibitors | |
| CA2220995C (fr) | Nouveaux derives 7,12-dioxa-benzo¬a|anthraceniques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent | |
| HK1111996A (en) | Novell processes for the preparation of a benzofuran | |
| JPH08325265A (ja) | チアゾリルベンゾフラン誘導体の製造方法、および該製造方法に用いられる化合物 | |
| KINOSHITA et al. | Synthesis and Reactions of 2, 3-Dihydrothiazolo [3, 2-a] pyrimidine Derivatives | |
| WO2014003694A1 (en) | Synthesis of thiosemicarbazides and triazoles derived from etodolac | |
| JPH02233676A (ja) | ジベンゾオキセピン誘導体および製造法 | |
| HK1141948A (en) | Benzimidazoles and pharmaceutical compositions thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20070918 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |