CH401976A - Verfahren zur Herstellung von Penicillinderivaten - Google Patents
Verfahren zur Herstellung von PenicillinderivatenInfo
- Publication number
- CH401976A CH401976A CH371661A CH371661A CH401976A CH 401976 A CH401976 A CH 401976A CH 371661 A CH371661 A CH 371661A CH 371661 A CH371661 A CH 371661A CH 401976 A CH401976 A CH 401976A
- Authority
- CH
- Switzerland
- Prior art keywords
- methyl
- acid
- isoxazolylpenicillin
- dependent
- carboxylic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 32
- 150000002960 penicillins Chemical class 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000002253 acid Substances 0.000 claims description 34
- -1 heterocyclo Chemical group 0.000 claims description 30
- 229930182555 Penicillin Natural products 0.000 claims description 27
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 claims description 20
- 229940049954 penicillin Drugs 0.000 claims description 20
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 11
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 9
- 150000007513 acids Chemical class 0.000 claims description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- 230000010933 acylation Effects 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 238000000855 fermentation Methods 0.000 claims description 3
- 230000004151 fermentation Effects 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 9
- YSXGHSHJXCAZIN-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl chloride Chemical compound ClC(=O)C1=C(C)ON=C1C1=CC=C(Cl)C=C1 YSXGHSHJXCAZIN-UHFFFAOYSA-N 0.000 claims 1
- YVFYIVAJRVFJHR-UHFFFAOYSA-N 3-methyl-5-phenyl-1,2-oxazole-4-carbonyl chloride Chemical compound CC1=NOC(C=2C=CC=CC=2)=C1C(Cl)=O YVFYIVAJRVFJHR-UHFFFAOYSA-N 0.000 claims 1
- SWEIHMQQEWZRKQ-UHFFFAOYSA-N 3-methyl-5-thiophen-2-yl-1,2-oxazole-4-carbonyl chloride Chemical compound CC1=NOC(C=2SC=CC=2)=C1C(Cl)=O SWEIHMQQEWZRKQ-UHFFFAOYSA-N 0.000 claims 1
- CQXKKLRFOMKMHQ-UHFFFAOYSA-N 5-(4-chlorophenyl)-3-methyl-1,2-oxazole-4-carbonyl chloride Chemical compound CC1=NOC(C=2C=CC(Cl)=CC=2)=C1C(Cl)=O CQXKKLRFOMKMHQ-UHFFFAOYSA-N 0.000 claims 1
- BMRMMPVPESEVBE-UHFFFAOYSA-N 5-(furan-2-yl)-3-methyl-1,2-oxazole-4-carbonyl chloride Chemical compound CC1=NOC(C=2OC=CC=2)=C1C(Cl)=O BMRMMPVPESEVBE-UHFFFAOYSA-N 0.000 claims 1
- HXEVQMXCHCDPSO-UHFFFAOYSA-N 5-methyl-3-phenyl-1,2-oxazole-4-carbonyl chloride Chemical compound ClC(=O)C1=C(C)ON=C1C1=CC=CC=C1 HXEVQMXCHCDPSO-UHFFFAOYSA-N 0.000 claims 1
- VZJVEDRQJGLRNA-UHFFFAOYSA-N C(C)OC=1C(=NC2=CC=CC=C2C1C(=O)Cl)C Chemical compound C(C)OC=1C(=NC2=CC=CC=C2C1C(=O)Cl)C VZJVEDRQJGLRNA-UHFFFAOYSA-N 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 claims 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 14
- 229940056360 penicillin g Drugs 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000000047 product Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 235000019371 penicillin G benzathine Nutrition 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 229930195708 Penicillin V Natural products 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229940056367 penicillin v Drugs 0.000 description 4
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-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 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108010087702 Penicillinase Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 229950009506 penicillinase Drugs 0.000 description 3
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 3
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 3
- 229960004919 procaine Drugs 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- MOTLBIPBNZTCMS-UHFFFAOYSA-N 2,4-dimethoxyquinoline-3-carboxylic acid Chemical compound C1=CC=C2C(OC)=C(C(O)=O)C(OC)=NC2=C1 MOTLBIPBNZTCMS-UHFFFAOYSA-N 0.000 description 2
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
- KXCBWEJWVBHYKF-UHFFFAOYSA-N 3-methylquinoline-4-carboxylic acid Chemical compound C1=CC=CC2=C(C(O)=O)C(C)=CN=C21 KXCBWEJWVBHYKF-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- VOUGEZYPVGAPBB-UHFFFAOYSA-N penicillin acid Natural products OC(=O)C=C(OC)C(=O)C(C)=C VOUGEZYPVGAPBB-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- NEKPMJJGBBGVII-UHFFFAOYSA-N 2,4-dimethoxyquinoline-3-carbonyl chloride Chemical compound COC1=NC2=CC=CC=C2C(=C1C(=O)Cl)OC NEKPMJJGBBGVII-UHFFFAOYSA-N 0.000 description 1
- NQIBQILAMKZKFE-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3-fluoropyridine Chemical compound FC1=CC=C(Br)C=C1C1=NC=CC=C1F NQIBQILAMKZKFE-UHFFFAOYSA-N 0.000 description 1
- DWQIFUQLSDIOAR-UHFFFAOYSA-N 2-ethyl-3-methylquinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(O)=O)=C(C)C(CC)=NC2=C1 DWQIFUQLSDIOAR-UHFFFAOYSA-N 0.000 description 1
- OYQCYEOVMBWTMV-UHFFFAOYSA-N 2-methyl-3-propoxyquinoline-4-carboxylic acid Chemical compound CC1=NC2=CC=CC=C2C(=C1OCCC)C(=O)O OYQCYEOVMBWTMV-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- UVEPOHNXGXVOJE-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl UVEPOHNXGXVOJE-UHFFFAOYSA-N 0.000 description 1
- KOQSJBSGCNLIJY-UHFFFAOYSA-N 3-(2-methoxyphenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound COC1=CC=CC=C1C1=NOC(C)=C1C(O)=O KOQSJBSGCNLIJY-UHFFFAOYSA-N 0.000 description 1
- BYJATVZZRGMSPH-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=CC(Cl)=C1 BYJATVZZRGMSPH-UHFFFAOYSA-N 0.000 description 1
- DTWRRPFCWHWFSM-UHFFFAOYSA-N 3-(4-bromophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=C(Br)C=C1 DTWRRPFCWHWFSM-UHFFFAOYSA-N 0.000 description 1
- VMCAZKHMYAGXPM-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-ethyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(CC)ON=C1C1=CC=C(Cl)C=C1 VMCAZKHMYAGXPM-UHFFFAOYSA-N 0.000 description 1
- PDEGBONVUJDOFN-UHFFFAOYSA-N 3-(4-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=C(F)C=C1 PDEGBONVUJDOFN-UHFFFAOYSA-N 0.000 description 1
- IKDPECCMAKOJTK-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=NOC(C)=C1C(O)=O IKDPECCMAKOJTK-UHFFFAOYSA-N 0.000 description 1
- KKLSUWDVMGAXKC-UHFFFAOYSA-N 3-benzylquinoline-4-carboxylic acid Chemical compound C1=NC2=CC=CC=C2C(C(=O)O)=C1CC1=CC=CC=C1 KKLSUWDVMGAXKC-UHFFFAOYSA-N 0.000 description 1
- PPRTZXNLFVNWGC-UHFFFAOYSA-N 3-bromoquinoline-4-carboxylic acid Chemical compound BrC=1C=NC2=CC=CC=C2C=1C(=O)O PPRTZXNLFVNWGC-UHFFFAOYSA-N 0.000 description 1
- HPZDUHCNNYTHIA-UHFFFAOYSA-N 3-butoxy-2-ethylquinoline-4-carboxylic acid Chemical compound C(C)C1=NC2=CC=CC=C2C(=C1OCCCC)C(=O)O HPZDUHCNNYTHIA-UHFFFAOYSA-N 0.000 description 1
- ZYCDJLZFOUQYKT-UHFFFAOYSA-N 3-cyclohexyl-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1CCCCC1 ZYCDJLZFOUQYKT-UHFFFAOYSA-N 0.000 description 1
- KSZWTKQFLIGPEE-UHFFFAOYSA-N 3-ethoxyquinoline-4-carboxylic acid Chemical compound C1=CC=CC2=C(C(O)=O)C(OCC)=CN=C21 KSZWTKQFLIGPEE-UHFFFAOYSA-N 0.000 description 1
- UVUBXMWGFOOGNP-UHFFFAOYSA-N 3-ethyl-2-propylquinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(O)=O)=C(CC)C(CCC)=NC2=C1 UVUBXMWGFOOGNP-UHFFFAOYSA-N 0.000 description 1
- PRYKGZVEXSTAGZ-UHFFFAOYSA-N 3-ethyl-5-phenyl-1,2-oxazole-4-carboxylic acid Chemical compound CCC1=NOC(C=2C=CC=CC=2)=C1C(O)=O PRYKGZVEXSTAGZ-UHFFFAOYSA-N 0.000 description 1
- VZNJFRIPRWNVLS-UHFFFAOYSA-N 3-ethylquinoline-4-carboxylic acid Chemical compound C1=CC=CC2=C(C(O)=O)C(CC)=CN=C21 VZNJFRIPRWNVLS-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OTBBTOKYRSDPGP-UHFFFAOYSA-N 3-methoxy-2-methylquinoline-4-carboxylic acid Chemical compound C1=CC=CC2=C(C(O)=O)C(OC)=C(C)N=C21 OTBBTOKYRSDPGP-UHFFFAOYSA-N 0.000 description 1
- ZEDCFLNCVWDQHW-UHFFFAOYSA-N 3-methoxyquinoline-4-carboxylic acid Chemical compound C1=CC=CC2=C(C(O)=O)C(OC)=CN=C21 ZEDCFLNCVWDQHW-UHFFFAOYSA-N 0.000 description 1
- ZSVACLAZDFXWQG-UHFFFAOYSA-N 3-methyl-2-phenylquinoline-4-carboxylic acid Chemical compound N1=C2C=CC=CC2=C(C(O)=O)C(C)=C1C1=CC=CC=C1 ZSVACLAZDFXWQG-UHFFFAOYSA-N 0.000 description 1
- MKEBQUUKCDZLBM-UHFFFAOYSA-N 3-methyl-5-(3-nitrophenyl)-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(=C1C(=O)O)C1=CC(=CC=C1)[N+](=O)[O-] MKEBQUUKCDZLBM-UHFFFAOYSA-N 0.000 description 1
- HAIMCHXZWFJELA-UHFFFAOYSA-N 3-methyl-5-(4-methylphenyl)-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=CC(C)=CC=2)=C1C(O)=O HAIMCHXZWFJELA-UHFFFAOYSA-N 0.000 description 1
- DPKUEPACPHWTDS-UHFFFAOYSA-N 3-methyl-5-(4-nitrophenyl)-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=CC(=CC=2)[N+]([O-])=O)=C1C(O)=O DPKUEPACPHWTDS-UHFFFAOYSA-N 0.000 description 1
- CGLYUMRYFOEGNE-UHFFFAOYSA-N 3-phenylquinoline-4-carboxylic acid Chemical compound C1=NC2=CC=CC=C2C(C(=O)O)=C1C1=CC=CC=C1 CGLYUMRYFOEGNE-UHFFFAOYSA-N 0.000 description 1
- UKBDFVBVJCUFQV-UHFFFAOYSA-N 3-tert-butyl-5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC=1ON=C(C(C)(C)C)C=1C(O)=O UKBDFVBVJCUFQV-UHFFFAOYSA-N 0.000 description 1
- HTJGMCGLOGVXHP-UHFFFAOYSA-N 5-(2-chlorophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C(=CC=CC=2)Cl)=C1C(O)=O HTJGMCGLOGVXHP-UHFFFAOYSA-N 0.000 description 1
- GFLKZFOUAHOGJF-UHFFFAOYSA-N 5-(4-bromophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=CC(Br)=CC=2)=C1C(O)=O GFLKZFOUAHOGJF-UHFFFAOYSA-N 0.000 description 1
- BHDJZDIKPZSMTM-UHFFFAOYSA-N 5-(4-chlorophenyl)-3-ethyl-1,2-oxazole-4-carboxylic acid Chemical compound CCC1=NOC(C=2C=CC(Cl)=CC=2)=C1C(O)=O BHDJZDIKPZSMTM-UHFFFAOYSA-N 0.000 description 1
- FLEZAJQFCZOVDO-UHFFFAOYSA-N 5-(4-cyanophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=CC(=CC=2)C#N)=C1C(O)=O FLEZAJQFCZOVDO-UHFFFAOYSA-N 0.000 description 1
- IXZFWSQFSYOAKK-UHFFFAOYSA-N 5-(4-ethoxyphenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound C1=CC(OCC)=CC=C1C1=C(C(O)=O)C(C)=NO1 IXZFWSQFSYOAKK-UHFFFAOYSA-N 0.000 description 1
- RQSKSTWEPHZKEO-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=CC(F)=CC=2)=C1C(O)=O RQSKSTWEPHZKEO-UHFFFAOYSA-N 0.000 description 1
- KHOOMTRVPBUDMG-UHFFFAOYSA-N 5-(4-methoxyphenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=C(C(O)=O)C(C)=NO1 KHOOMTRVPBUDMG-UHFFFAOYSA-N 0.000 description 1
- WNPVZANXRCPJPW-UHFFFAOYSA-N 5-[isocyano-(4-methylphenyl)sulfonylmethyl]-1,2,3-trimethoxybenzene Chemical compound COC1=C(OC)C(OC)=CC(C([N+]#[C-])S(=O)(=O)C=2C=CC(C)=CC=2)=C1 WNPVZANXRCPJPW-UHFFFAOYSA-N 0.000 description 1
- WEPNGPXMYYFCCV-UHFFFAOYSA-N 5-cyclohexyl-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C2CCCCC2)=C1C(O)=O WEPNGPXMYYFCCV-UHFFFAOYSA-N 0.000 description 1
- BKVNATITQUEJFR-UHFFFAOYSA-N 5-ethyl-3-phenyl-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(CC)ON=C1C1=CC=CC=C1 BKVNATITQUEJFR-UHFFFAOYSA-N 0.000 description 1
- HWQOLMPXSSJXJG-UHFFFAOYSA-N 5-methyl-3-(2-nitrophenyl)-1,2-oxazole-4-carboxylic acid Chemical compound [N+](=O)([O-])C1=C(C=CC=C1)C1=NOC(=C1C(=O)O)C HWQOLMPXSSJXJG-UHFFFAOYSA-N 0.000 description 1
- WRTHFIGWWRXPLR-UHFFFAOYSA-N 5-methyl-3-(3-nitrophenyl)-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=CC([N+]([O-])=O)=C1 WRTHFIGWWRXPLR-UHFFFAOYSA-N 0.000 description 1
- IAGFERXYANTCJG-UHFFFAOYSA-N 5-methyl-3-(4-methylphenyl)-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=C(C)C=C1 IAGFERXYANTCJG-UHFFFAOYSA-N 0.000 description 1
- VFJLIEUAOCAYLH-UHFFFAOYSA-N 5-methyl-3-(4-nitrophenyl)-1,2-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)ON=C1C1=CC=C([N+]([O-])=O)C=C1 VFJLIEUAOCAYLH-UHFFFAOYSA-N 0.000 description 1
- MVTWRDSURHGWBF-UHFFFAOYSA-N 5-methylsulfanyl-3-phenyl-1,2-oxazole-4-carboxylic acid Chemical compound C1(=CC=CC=C1)C1=NOC(=C1C(=O)O)SC MVTWRDSURHGWBF-UHFFFAOYSA-N 0.000 description 1
- ZRUXRSPPPCWPKP-UHFFFAOYSA-N 5-phenyl-3-propan-2-yl-1,2-oxazole-4-carboxylic acid Chemical compound CC(C)C1=NOC(C=2C=CC=CC=2)=C1C(O)=O ZRUXRSPPPCWPKP-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- KCMWDOZHOCZICJ-UHFFFAOYSA-N C(C)C1=NC2=CC=CC=C2C(=C1OCCC)C(=O)O Chemical compound C(C)C1=NC2=CC=CC=C2C(=C1OCCC)C(=O)O KCMWDOZHOCZICJ-UHFFFAOYSA-N 0.000 description 1
- LRPMDFBAWRLTEQ-UHFFFAOYSA-N C1=CC=CC2=C(C(O)=O)C(CCC)=CN=C21 Chemical compound C1=CC=CC2=C(C(O)=O)C(CCC)=CN=C21 LRPMDFBAWRLTEQ-UHFFFAOYSA-N 0.000 description 1
- ODWQMRSOVQARSI-UHFFFAOYSA-N CC1=NOC(=C1C(=O)O)C2=CC=CC=C2I Chemical compound CC1=NOC(=C1C(=O)O)C2=CC=CC=C2I ODWQMRSOVQARSI-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-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
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000012431 aqueous reaction media Substances 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 235000010633 broth Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002021 butanolic extract Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- ULBLITMQCMVRMY-UHFFFAOYSA-N ethyl 2,4-dichloroquinoline-3-carboxylate Chemical compound C1=CC=CC2=C(Cl)C(C(=O)OCC)=C(Cl)N=C21 ULBLITMQCMVRMY-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 description 1
- YCOFRPYSZKIPBQ-UHFFFAOYSA-N penicillic acid Natural products COC1=CC(=O)OC1(O)C(C)=C YCOFRPYSZKIPBQ-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000012261 resinous substance Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1141260A GB905778A (en) | 1960-03-31 | 1960-03-31 | Improvements in or relating to penicillins |
| GB2504960 | 1960-07-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH401976A true CH401976A (de) | 1965-11-15 |
Family
ID=26248261
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH371661A CH401976A (de) | 1960-03-31 | 1961-03-29 | Verfahren zur Herstellung von Penicillinderivaten |
Country Status (11)
| Country | Link |
|---|---|
| BE (1) | BE601969A (en)van) |
| BR (1) | BR6127716D0 (en)van) |
| CH (1) | CH401976A (en)van) |
| CY (1) | CY262A (en)van) |
| DK (1) | DK137049B (en)van) |
| ES (1) | ES265959A1 (en)van) |
| FR (1) | FR1033M (en)van) |
| MY (1) | MY6300087A (en)van) |
| NO (1) | NO127106B (en)van) |
| OA (1) | OA01036A (en)van) |
| SE (1) | SE346003B (en)van) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1212089B (de) * | 1961-05-03 | 1966-03-10 | Smith Kline French Lab | Verfahren zur Herstellung heterocyclischer 6-Acylaminopenicillansaeuren |
-
1961
- 1961-03-10 NO NO00139438A patent/NO127106B/no unknown
- 1961-03-14 SE SE2737/61A patent/SE346003B/xx unknown
- 1961-03-17 BR BR127716/61A patent/BR6127716D0/pt unknown
- 1961-03-22 ES ES0265959A patent/ES265959A1/es not_active Expired
- 1961-03-28 DK DK132661AA patent/DK137049B/da unknown
- 1961-03-29 BE BE601969A patent/BE601969A/fr unknown
- 1961-03-29 CH CH371661A patent/CH401976A/de unknown
- 1961-03-30 FR FR857297A patent/FR1033M/fr active Active
-
1963
- 1963-08-09 CY CY26263A patent/CY262A/xx unknown
- 1963-12-30 MY MY87/63A patent/MY6300087A/xx unknown
-
1964
- 1964-12-18 OA OA50917A patent/OA01036A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK137049B (da) | 1978-01-09 |
| OA01036A (fr) | 1968-08-07 |
| CY262A (en) | 1963-08-09 |
| SE346003B (en)van) | 1972-06-19 |
| DK137049C (en)van) | 1978-06-12 |
| NO127106B (en)van) | 1973-05-07 |
| BE601969A (fr) | 1961-09-29 |
| ES265959A1 (es) | 1961-08-01 |
| BR6127716D0 (pt) | 1973-06-07 |
| FR1033M (fr) | 1962-01-02 |
| MY6300087A (en) | 1963-12-31 |
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