JP2009505943A - ２ｈ−クロメンの製造のための新規方法 - Google Patents
２ｈ−クロメンの製造のための新規方法 Download PDFInfo
- Publication number
- JP2009505943A JP2009505943A JP2007555507A JP2007555507A JP2009505943A JP 2009505943 A JP2009505943 A JP 2009505943A JP 2007555507 A JP2007555507 A JP 2007555507A JP 2007555507 A JP2007555507 A JP 2007555507A JP 2009505943 A JP2009505943 A JP 2009505943A
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- JP
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- Prior art keywords
- formula
- dimethyl
- pyrimidin
- benzyl
- dimethoxy
- 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.)
- Pending
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- 238000000034 method Methods 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 107
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 42
- -1 2-Iodo-3,4,5-trimethoxy-benzyl Chemical group 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 12
- 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 11
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 238000010511 deprotection reaction Methods 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
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 2
- 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 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
- 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
- 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 2
- 229940047889 isobutyramide Drugs 0.000 claims 4
- 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
- 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 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
- 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 1
- 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 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
- 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 1
- 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 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
- 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 1
- 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 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
- 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 1
- 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 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
- 239000011877 solvent mixture Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 22
- 239000000543 intermediate Substances 0.000 abstract description 11
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
- 241000233872 Pneumocystis carinii Species 0.000 abstract description 3
- 208000035473 Communicable disease Diseases 0.000 abstract description 2
- 241000192125 Firmicutes Species 0.000 abstract description 2
- 230000000845 anti-microbial effect Effects 0.000 abstract description 2
- 239000003166 dihydrofolate reductase inhibitor Substances 0.000 abstract description 2
- 244000039328 opportunistic pathogen Species 0.000 abstract description 2
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- 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 45
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 34
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- 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
- 238000003756 stirring Methods 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 19
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- 229910052786 argon Inorganic materials 0.000 description 18
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- 235000009518 sodium iodide Nutrition 0.000 description 12
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- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 10
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 239000002904 solvent Substances 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
- 230000015572 biosynthetic process Effects 0.000 description 7
- 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
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
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- 238000004128 high performance liquid chromatography Methods 0.000 description 4
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- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 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
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- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 3
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
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- 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
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- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
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- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 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
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000002051 biphasic effect Effects 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
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 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
- YCIGMXVAUVFHGG-UHFFFAOYSA-N ditert-butyl-chloro-methylsilane Chemical compound CC(C)(C)[Si](C)(Cl)C(C)(C)C YCIGMXVAUVFHGG-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 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
- 239000007789 gas Substances 0.000 description 1
- 229960004275 glycolic acid Drugs 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
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 229960000448 lactic acid Drugs 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
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 150000003195 pteridines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 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
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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)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP2005001695 | 2005-02-18 | ||
| PCT/EP2006/001185 WO2006087143A1 (en) | 2005-02-18 | 2006-02-10 | Novel processes for the preparation of a 2h-chromene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2009505943A true JP2009505943A (ja) | 2009-02-12 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007555507A Pending JP2009505943A (ja) | 2005-02-18 | 2006-02-10 | ２ｈ−クロメンの製造のための新規方法 |
| JP2007555504A Pending JP2008530156A (ja) | 2005-02-18 | 2006-02-10 | ベンゾフランの製造のための新規方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007555504A Pending JP2008530156A (ja) | 2005-02-18 | 2006-02-10 | ベンゾフランの製造のための新規方法 |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20080161561A1 (enExample) |
| EP (3) | EP2270003A1 (enExample) |
| JP (2) | JP2009505943A (enExample) |
| KR (2) | KR20070106635A (enExample) |
| CN (4) | CN101115743B (enExample) |
| AU (2) | AU2006215788B2 (enExample) |
| BG (2) | BG109937A (enExample) |
| BR (2) | BRPI0607758A2 (enExample) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008530156A (ja) * | 2005-02-18 | 2008-08-07 | アルパイダ アーゲー | ベンゾフランの製造のための新規方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011516509A (ja) * | 2008-04-08 | 2011-05-26 | アシノ ファーマ アーゲー | 水性医薬製剤 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
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- 2006-02-10 CA CA002596669A patent/CA2596669A1/en not_active Abandoned
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