RU2397980C2 - Новые способы получения 2н-хромена - Google Patents
Новые способы получения 2н-хромена Download PDFInfo
- Publication number
- RU2397980C2 RU2397980C2 RU2007134584/04A RU2007134584A RU2397980C2 RU 2397980 C2 RU2397980 C2 RU 2397980C2 RU 2007134584/04 A RU2007134584/04 A RU 2007134584/04A RU 2007134584 A RU2007134584 A RU 2007134584A RU 2397980 C2 RU2397980 C2 RU 2397980C2
- Authority
- RU
- Russia
- Prior art keywords
- formula
- compound
- pyrimidin
- isobutyramide
- dimethylpropionylamino
- Prior art date
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- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 title 1
- 238000001308 synthesis method Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 155
- 238000000034 method Methods 0.000 claims abstract description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 12
- 235000009518 sodium iodide Nutrition 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- -1 3-cyclopropyl-3-oxopropenyl Chemical group 0.000 claims description 9
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 230000017858 demethylation Effects 0.000 claims description 8
- 238000010520 demethylation reaction Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 229940047889 isobutyramide Drugs 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000007363 ring formation reaction Methods 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- MISVBCMQSJUHMH-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical group NC1=CC(N)=NC=N1 MISVBCMQSJUHMH-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
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction 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
- LFFUAILAMCMAEX-UHFFFAOYSA-N n-[5-[(2-cyclopropyl-7,8-dimethoxy-2h-chromen-5-yl)methyl]-2-(2,2-dimethylpropanoylamino)pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound C=12C=CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C LFFUAILAMCMAEX-UHFFFAOYSA-N 0.000 claims description 3
- JFKQCBNREHXNGN-UHFFFAOYSA-N n-[5-[(2-cyclopropyl-7,8-dimethoxy-4-oxo-2,3-dihydrochromen-5-yl)methyl]-2-(2,2-dimethylpropanoylamino)pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound C=12C(=O)CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C JFKQCBNREHXNGN-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
- IZDDGZZMOSNQAB-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropylprop-2-enoyl)-3,4,5-trimethoxyphenyl]methyl]-2-(2,2-dimethylpropanoylamino)pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound C1CC1C=CC(=O)C=1C(OC)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C IZDDGZZMOSNQAB-UHFFFAOYSA-N 0.000 claims description 3
- 230000006315 carbonylation Effects 0.000 claims description 2
- 238000005810 carbonylation reaction Methods 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000003776 cleavage reaction Methods 0.000 claims description 2
- 150000002576 ketones Chemical class 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
- AQGCZNUFGQRIDL-UHFFFAOYSA-N n-[2-(2,2-dimethylpropanoylamino)-5-[[2-formyl-4,5-dimethoxy-3-(methoxymethoxy)phenyl]methyl]pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound COCOC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)(C)C)=NC=2)NC(=O)C(C)(C)C)=C1C=O AQGCZNUFGQRIDL-UHFFFAOYSA-N 0.000 claims description 2
- QFYZYWLNQKSIRO-UHFFFAOYSA-N n-[5-[(2-acetyl-3,4,5-trimethoxyphenyl)methyl]-2-(2,2-dimethylpropanoylamino)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(C)=O QFYZYWLNQKSIRO-UHFFFAOYSA-N 0.000 claims description 2
- HHSFWVDEUAIIIY-UHFFFAOYSA-N n-[5-[(2-acetyl-3-hydroxy-4,5-dimethoxyphenyl)methyl]-2-(2,2-dimethylpropanoylamino)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(C)=O HHSFWVDEUAIIIY-UHFFFAOYSA-N 0.000 claims description 2
- OMRYBXGIAPRHRK-UHFFFAOYSA-N n-[5-[(2-cyclopropyl-4-hydroxy-7,8-dimethoxy-3,4-dihydro-2h-chromen-5-yl)methyl]-2-(2,2-dimethylpropanoylamino)pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound C=12C(O)CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C OMRYBXGIAPRHRK-UHFFFAOYSA-N 0.000 claims description 2
- KEYBPUBTCPPLCH-UHFFFAOYSA-N n-[5-[(2-cyclopropyl-7,8-dimethoxy-2h-chromen-5-yl)methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound C=12C=CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C KEYBPUBTCPPLCH-UHFFFAOYSA-N 0.000 claims description 2
- WTRFJGWDFILQOD-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropyl-3-hydroxyprop-1-enyl)-4,5-dimethoxy-3-(methoxymethoxy)phenyl]methyl]-2-(2,2-dimethylpropanoylamino)pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound C1CC1C(O)C=CC=1C(OCOC)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C WTRFJGWDFILQOD-UHFFFAOYSA-N 0.000 claims description 2
- GDHIWHVOHQBEAA-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropyl-3-iodopropanoyl)-3-hydroxy-4,5-dimethoxyphenyl]methyl]-2-(2,2-dimethylpropanoylamino)pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound C1CC1C(I)CC(=O)C=1C(O)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C GDHIWHVOHQBEAA-UHFFFAOYSA-N 0.000 claims description 2
- KMQQEQCYPANETP-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropyl-3-oxoprop-1-enyl)-4,5-dimethoxy-3-(methoxymethoxy)phenyl]methyl]-2-(2,2-dimethylpropanoylamino)pyrimidin-4-yl]-2,2-dimethylpropanamide Chemical compound C1CC1C(=O)C=CC=1C(OCOC)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)(C)C)N=C1NC(=O)C(C)(C)C KMQQEQCYPANETP-UHFFFAOYSA-N 0.000 claims description 2
- 230000007017 scission Effects 0.000 claims description 2
- 230000003993 interaction Effects 0.000 claims 2
- 230000022244 formylation Effects 0.000 claims 1
- 238000006170 formylation reaction Methods 0.000 claims 1
- DKXBSABLPFJAGS-UHFFFAOYSA-N n-[5-[(2-acetyl-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(C)=O DKXBSABLPFJAGS-UHFFFAOYSA-N 0.000 claims 1
- PGNJVILWXITQTG-UHFFFAOYSA-N n-[5-[(2-cyclopropyl-4-hydroxy-7,8-dimethoxy-3,4-dihydro-2h-chromen-5-yl)methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound C=12C(O)CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C PGNJVILWXITQTG-UHFFFAOYSA-N 0.000 claims 1
- IUJCEPWBYKNDBO-UHFFFAOYSA-N n-[5-[(2-cyclopropyl-7,8-dimethoxy-4-oxo-2,3-dihydrochromen-5-yl)methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound C=12C(=O)CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C IUJCEPWBYKNDBO-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
- IBWFJIUPWAVYQZ-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropyl-3-hydroxyprop-1-enyl)-4,5-dimethoxy-3-(methoxymethoxy)phenyl]methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound C1CC1C(O)C=CC=1C(OCOC)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C IBWFJIUPWAVYQZ-UHFFFAOYSA-N 0.000 claims 1
- LGVWFLUJJNNABV-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropyl-3-iodopropanoyl)-3-hydroxy-4,5-dimethoxyphenyl]methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound C1CC1C(I)CC(=O)C=1C(O)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C LGVWFLUJJNNABV-UHFFFAOYSA-N 0.000 claims 1
- WDWYZVOCMRVEEU-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropyl-3-oxoprop-1-enyl)-4,5-dimethoxy-3-(methoxymethoxy)phenyl]methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound C1CC1C(=O)C=CC=1C(OCOC)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C WDWYZVOCMRVEEU-UHFFFAOYSA-N 0.000 claims 1
- VTEJQOQHOURSEI-UHFFFAOYSA-N n-[5-[[2-(3-cyclopropylprop-2-enoyl)-3,4,5-trimethoxyphenyl]methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound C1CC1C=CC(=O)C=1C(OC)=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)C(C)C)N=C1NC(=O)C(C)C VTEJQOQHOURSEI-UHFFFAOYSA-N 0.000 claims 1
- LOKFXEBZGCMWCX-UHFFFAOYSA-N n-[5-[[2-formyl-4,5-dimethoxy-3-(methoxymethoxy)phenyl]methyl]-2-(2-methylpropanoylamino)pyrimidin-4-yl]-2-methylpropanamide Chemical compound COCOC1=C(OC)C(OC)=CC(CC=2C(=NC(NC(=O)C(C)C)=NC=2)NC(=O)C(C)C)=C1C=O LOKFXEBZGCMWCX-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- HWJPWWYTGBZDEG-UHFFFAOYSA-N 5-[(2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N HWJPWWYTGBZDEG-UHFFFAOYSA-N 0.000 abstract description 5
- 229960001925 iclaprim Drugs 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 239000003166 dihydrofolate reductase inhibitor Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 86
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 38
- 238000002360 preparation method Methods 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 25
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- 239000012300 argon atmosphere Substances 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000012634 fragment Substances 0.000 description 17
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000013058 crude material Substances 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 10
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 229940125782 compound 2 Drugs 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229940126214 compound 3 Drugs 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 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 6
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 6
- 239000002841 Lewis acid Substances 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 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
- 150000007517 lewis acids Chemical class 0.000 description 6
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- 150000003512 tertiary amines Chemical class 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-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
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000003643 water by type Substances 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 |
|---|---|---|---|
| EPPCT/EP2005/001695 | 2005-02-18 | ||
| EP2005001695 | 2005-02-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2007134584A RU2007134584A (ru) | 2009-03-27 |
| RU2397980C2 true RU2397980C2 (ru) | 2010-08-27 |
Family
ID=36283919
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007134584/04A RU2397980C2 (ru) | 2005-02-18 | 2006-02-10 | Новые способы получения 2н-хромена |
| RU2007134583/04A RU2007134583A (ru) | 2005-02-18 | 2006-02-10 | Новые способы получения бензофурана |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007134583/04A RU2007134583A (ru) | 2005-02-18 | 2006-02-10 | Новые способы получения бензофурана |
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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5773446A (en) * | 1995-12-04 | 1998-06-30 | Hoffmann-La Roche Inc. | Diamino pyrimidines |
| RU2002107674A (ru) * | 1999-09-27 | 2003-10-10 | Оно Фармасьютикал Ко., Лтд. | Соединения пиримидина, способы их получения и фармацевтические композиции, содержащие соединения в качестве активного ингредиента |
Family Cites Families (7)
| 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 |
| 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
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5773446A (en) * | 1995-12-04 | 1998-06-30 | Hoffmann-La Roche Inc. | Diamino pyrimidines |
| EP1149834A1 (en) * | 1995-12-04 | 2001-10-31 | F. Hoffmann-La Roche Ag | Diaminopyrimidines, pharmaceutical compositions containing them and their use as antibacterial |
| RU2002107674A (ru) * | 1999-09-27 | 2003-10-10 | Оно Фармасьютикал Ко., Лтд. | Соединения пиримидина, способы их получения и фармацевтические композиции, содержащие соединения в качестве активного ингредиента |
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