CZ2007536A3 - Nové zpusoby prípravy 2H-chromenu - Google Patents
Nové zpusoby prípravy 2H-chromenu Download PDFInfo
- Publication number
- CZ2007536A3 CZ2007536A3 CZ20070536A CZ2007536A CZ2007536A3 CZ 2007536 A3 CZ2007536 A3 CZ 2007536A3 CZ 20070536 A CZ20070536 A CZ 20070536A CZ 2007536 A CZ2007536 A CZ 2007536A CZ 2007536 A3 CZ2007536 A3 CZ 2007536A3
- Authority
- CZ
- Czechia
- Prior art keywords
- formula
- compound
- pyrimidin
- isobutyramide
- cyclopropyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000008569 process Effects 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title claims description 40
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 239000000543 intermediate Substances 0.000 claims abstract description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- -1 2,2-Dimethyl-propionylamino Chemical group 0.000 claims description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 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
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 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
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 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 4
- 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
- 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
- 150000002576 ketones Chemical class 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
- 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
- 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
- 229940047889 isobutyramide Drugs 0.000 claims 8
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 4
- 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 claims 1
- 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 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
- 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
- 239000011877 solvent mixture Substances 0.000 claims 1
- 239000003166 dihydrofolate reductase inhibitor Substances 0.000 abstract description 3
- 229940117937 Dihydrofolate reductase inhibitor Drugs 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 89
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- 239000000243 solution Substances 0.000 description 41
- 239000000203 mixture Substances 0.000 description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 38
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 25
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 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
- 229910052786 argon Inorganic materials 0.000 description 21
- 239000012267 brine Substances 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 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 19
- 239000011541 reaction mixture Substances 0.000 description 18
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 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
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000013058 crude material Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-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
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 10
- 235000009518 sodium iodide Nutrition 0.000 description 10
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 229940125782 compound 2 Drugs 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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229940126214 compound 3 Drugs 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 229960001082 trimethoprim Drugs 0.000 description 6
- 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 6
- 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 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 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 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 229940125773 compound 10 Drugs 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 230000017858 demethylation Effects 0.000 description 4
- 238000010520 demethylation reaction Methods 0.000 description 4
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 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 4
- 238000000746 purification Methods 0.000 description 4
- 235000011150 stannous chloride Nutrition 0.000 description 4
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 4
- 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 3
- 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 3
- HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 3
- 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 3
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 3
- 229940126657 Compound 17 Drugs 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 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 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
- 229940125797 compound 12 Drugs 0.000 description 3
- 229940125758 compound 15 Drugs 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 229960001925 iclaprim Drugs 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
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- 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
- 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 description 1
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Classifications
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP2005001695 | 2005-02-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ2007536A3 true CZ2007536A3 (cs) | 2008-02-20 |
Family
ID=36283919
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20070536A CZ2007536A3 (cs) | 2005-02-18 | 2006-02-10 | Nové zpusoby prípravy 2H-chromenu |
| CZ20070537A CZ2007537A3 (cs) | 2005-02-18 | 2006-02-10 | Nové zpusoby výroby benzofuranové slouceniny |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20070537A CZ2007537A3 (cs) | 2005-02-18 | 2006-02-10 | Nové zpusoby výroby benzofuranové slouceniny |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20080221324A1 (https=) |
| EP (3) | EP1856109A1 (https=) |
| JP (2) | JP2008530156A (https=) |
| KR (2) | KR20070106635A (https=) |
| CN (4) | CN101115746A (https=) |
| AU (2) | AU2006215788B2 (https=) |
| BG (2) | BG109938A (https=) |
| BR (2) | BRPI0607797A2 (https=) |
| CA (2) | CA2596668A1 (https=) |
| CZ (2) | CZ2007536A3 (https=) |
| EE (2) | EE200700050A (https=) |
| HU (2) | HUP0700604A3 (https=) |
| IL (2) | IL184405A0 (https=) |
| MX (2) | MX2007009283A (https=) |
| NO (2) | NO20073678L (https=) |
| NZ (1) | NZ556800A (https=) |
| RO (2) | RO122912B8 (https=) |
| RU (2) | RU2397980C2 (https=) |
| TR (1) | TR200705187T1 (https=) |
| TW (2) | TW200640914A (https=) |
| WO (2) | WO2006087143A1 (https=) |
| ZA (2) | ZA200706422B (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20070106635A (ko) * | 2005-02-18 | 2007-11-02 | 아르피다 아게 | 2ｈ-크로멘의 제조를 위한 신규한 방법들 |
| CN102112108A (zh) * | 2008-04-08 | 2011-06-29 | 阿西诺药品有限公司 | 水性医药剂型 |
| US7947293B2 (en) | 2008-04-08 | 2011-05-24 | Arpida Ag | Aqueous pharmaceutical formulation |
| FR2949465B1 (fr) * | 2009-09-01 | 2011-08-12 | Pf Medicament | Derives chromones, leur procede de preparation et leurs applications therapeutiques |
| CN110606831A (zh) * | 2018-06-14 | 2019-12-24 | 上海度德医药科技有限公司 | 一种Iclaprim的新中间体及其制备方法和应用 |
| CN110818693B (zh) * | 2018-08-07 | 2023-06-02 | 上海度德医药科技有限公司 | 一种艾拉普林甲磺酸盐晶型b及其制备方法 |
| CN109988156B (zh) * | 2019-03-12 | 2021-12-28 | 广东中科药物研究有限公司 | 一种氨基嘧啶化合物 |
| CN110372746A (zh) * | 2019-07-11 | 2019-10-25 | 辽宁石油化工大学 | 一种合成β-胺基膦氧化合物的方法 |
| CN110642792B (zh) * | 2019-11-18 | 2023-04-21 | 上海医药工业研究院有限公司 | 艾拉普林中间体的制备方法 |
| CN110724135B (zh) * | 2019-11-18 | 2023-04-28 | 上海医药工业研究院有限公司 | 一种艾拉普林中间体及其制备方法 |
| CN110724108B (zh) * | 2019-11-18 | 2023-04-28 | 上海医药工业研究院有限公司 | 一种艾拉普林中间体及其制备方法 |
| CN110746361B (zh) * | 2019-11-18 | 2023-04-21 | 上海医药工业研究院有限公司 | 一种艾拉普林中间体及其制备方法 |
| CN110713483B (zh) * | 2019-11-18 | 2023-04-07 | 上海医药工业研究院 | 艾拉普林中间体及艾拉普林的制备方法 |
| CN110790753B (zh) * | 2019-11-18 | 2023-04-07 | 上海医药工业研究院 | 艾拉普林对甲苯磺酸盐、其制备方法和应用 |
| CN110818694B (zh) * | 2019-11-18 | 2023-04-21 | 上海医药工业研究院有限公司 | 艾拉普林中间体及其应用 |
| CN113493461A (zh) * | 2020-04-01 | 2021-10-12 | 上海医药工业研究院 | 一种七元杂环化合物或其盐、其制备方法及应用 |
| CN117700410B (zh) * | 2023-05-20 | 2025-07-04 | 山东康诺生物工程有限公司 | 一种3-(2-氯乙基)-2-甲基-9-羟基-4H-吡啶并[1,2-a]嘧啶-4-酮的制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2709634A1 (de) * | 1977-03-05 | 1978-09-07 | Basf Ag | Benzylpyrimidine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| US4438267A (en) * | 1980-11-11 | 1984-03-20 | Daluge Susan M | Monoheteroring compounds and their use |
| DE69618986T2 (de) * | 1995-12-04 | 2002-06-20 | Arpida Ag, Muenchenstein | Diaminopyrimidine, diese enthaltende pharmazeutische zusammensetzungen und ihre verwendung als antibakterielle mittel |
| WO2002010156A1 (en) * | 2000-07-29 | 2002-02-07 | Arpida Ag | Benzofuran derivatives and their use as antibacterial agents |
| US7365205B2 (en) * | 2001-06-20 | 2008-04-29 | Daiichi Sankyo Company, Limited | Diamine derivatives |
| CN100443482C (zh) * | 2003-07-11 | 2008-12-17 | 阿皮德公开股份有限公司 | 苯并呋喃衍生物及其在制备治疗由细菌引起的感染的药物中的用途 |
| WO2005014586A1 (en) * | 2003-08-08 | 2005-02-17 | Arpida Ag | Novel process for the preparation of 2h-chromenes |
| KR20070106635A (ko) * | 2005-02-18 | 2007-11-02 | 아르피다 아게 | 2ｈ-크로멘의 제조를 위한 신규한 방법들 |
-
2006
- 2006-02-10 KR KR1020077021394A patent/KR20070106635A/ko not_active Ceased
- 2006-02-10 RO ROA200700589A patent/RO122912B8/ro unknown
- 2006-02-10 RO ROA200700590A patent/RO122853B1/ro unknown
- 2006-02-10 KR KR1020077021395A patent/KR20070106636A/ko not_active Withdrawn
- 2006-02-10 JP JP2007555504A patent/JP2008530156A/ja active Pending
- 2006-02-10 JP JP2007555507A patent/JP2009505943A/ja active Pending
- 2006-02-10 WO PCT/EP2006/001185 patent/WO2006087143A1/en not_active Ceased
- 2006-02-10 CZ CZ20070536A patent/CZ2007536A3/cs unknown
- 2006-02-10 US US11/816,150 patent/US20080221324A1/en not_active Abandoned
- 2006-02-10 CN CNA2006800039630A patent/CN101115746A/zh active Pending
- 2006-02-10 AU AU2006215788A patent/AU2006215788B2/en not_active Ceased
- 2006-02-10 CA CA002596668A patent/CA2596668A1/en not_active Abandoned
- 2006-02-10 TR TR2007/05187T patent/TR200705187T1/xx unknown
- 2006-02-10 RU RU2007134584/04A patent/RU2397980C2/ru not_active IP Right Cessation
- 2006-02-10 EP EP06706809A patent/EP1856109A1/en not_active Withdrawn
- 2006-02-10 RU RU2007134583/04A patent/RU2007134583A/ru not_active Application Discontinuation
- 2006-02-10 BR BRPI0607797-8A patent/BRPI0607797A2/pt not_active IP Right Cessation
- 2006-02-10 CN CN2011100324952A patent/CN102079727A/zh active Pending
- 2006-02-10 AU AU2006215785A patent/AU2006215785A1/en not_active Abandoned
- 2006-02-10 CA CA002596669A patent/CA2596669A1/en not_active Abandoned
- 2006-02-10 EE EEP200700050A patent/EE200700050A/xx unknown
- 2006-02-10 CZ CZ20070537A patent/CZ2007537A3/cs unknown
- 2006-02-10 HU HU0700604A patent/HUP0700604A3/hu unknown
- 2006-02-10 EP EP10184131A patent/EP2270003A1/en not_active Withdrawn
- 2006-02-10 CN CN2006800039626A patent/CN101115743B/zh not_active Expired - Fee Related
- 2006-02-10 EP EP06706815A patent/EP1856106A1/en not_active Withdrawn
- 2006-02-10 US US11/816,157 patent/US20080161561A1/en not_active Abandoned
- 2006-02-10 WO PCT/EP2006/001179 patent/WO2006087140A1/en not_active Ceased
- 2006-02-10 BR BRPI0607758-7A patent/BRPI0607758A2/pt not_active IP Right Cessation
- 2006-02-10 HU HU0700605A patent/HUP0700605A3/hu unknown
- 2006-02-10 NZ NZ556800A patent/NZ556800A/en not_active IP Right Cessation
- 2006-02-10 MX MX2007009283A patent/MX2007009283A/es unknown
- 2006-02-10 CN CN2011100324933A patent/CN102140094B/zh not_active Expired - Fee Related
- 2006-02-10 EE EEP200700051A patent/EE200700051A/xx unknown
- 2006-02-10 MX MX2007009282A patent/MX2007009282A/es not_active Application Discontinuation
- 2006-02-17 TW TW095105425A patent/TW200640914A/zh unknown
- 2006-02-17 TW TW095105426A patent/TW200640912A/zh unknown
-
2007
- 2007-07-04 IL IL184405A patent/IL184405A0/en unknown
- 2007-07-04 IL IL184404A patent/IL184404A0/en unknown
- 2007-07-17 NO NO20073678A patent/NO20073678L/no not_active Application Discontinuation
- 2007-07-18 NO NO20073701A patent/NO20073701L/no not_active Application Discontinuation
- 2007-08-01 ZA ZA200706422A patent/ZA200706422B/xx unknown
- 2007-08-01 ZA ZA200706421A patent/ZA200706421B/xx unknown
- 2007-08-10 BG BG109938A patent/BG109938A/bg unknown
- 2007-08-10 BG BG109937A patent/BG109937A/bg unknown
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