DE2728578A1 - Verfahren zur herstellung einer beta-lactamsaeure - Google Patents
Verfahren zur herstellung einer beta-lactamsaeureInfo
- Publication number
- DE2728578A1 DE2728578A1 DE19772728578 DE2728578A DE2728578A1 DE 2728578 A1 DE2728578 A1 DE 2728578A1 DE 19772728578 DE19772728578 DE 19772728578 DE 2728578 A DE2728578 A DE 2728578A DE 2728578 A1 DE2728578 A1 DE 2728578A1
- Authority
- DE
- Germany
- Prior art keywords
- formula
- zinc
- nitrobenzyl
- organothiol
- cephem
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims description 89
- 239000002253 acid Substances 0.000 title description 30
- 150000003952 β-lactams Chemical class 0.000 title 1
- -1 cyanoacetyl Chemical group 0.000 claims description 124
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 81
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 71
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 63
- 239000011701 zinc Substances 0.000 claims description 55
- 229910052725 zinc Inorganic materials 0.000 claims description 55
- 150000002148 esters Chemical class 0.000 claims description 33
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000004442 acylamino group Chemical group 0.000 claims description 17
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 claims description 4
- DCEYEVIPFIUTBZ-NNNOSOPVSA-N Cl.[N+](=O)([O-])C1=CC=C(CC2S[C@H]3N(C(=C2C)C(=O)O)C(C3N)=O)C=C1 Chemical compound Cl.[N+](=O)([O-])C1=CC=C(CC2S[C@H]3N(C(=C2C)C(=O)O)C(C3N)=O)C=C1 DCEYEVIPFIUTBZ-NNNOSOPVSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- IWAAXRFPRHQKAZ-RKOYOZNISA-N (6R)-3-methyl-4-[(4-nitrophenyl)methyl]-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound [N+](=O)([O-])C1=CC=C(CC2S[C@H]3N(C(=C2C)C(=O)O)C(C3NC(COC3=CC=CC=C3)=O)=O)C=C1 IWAAXRFPRHQKAZ-RKOYOZNISA-N 0.000 claims description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- QIULLHZMZMGGFH-UHFFFAOYSA-N 2,5-dichlorobenzenethiol Chemical compound SC1=CC(Cl)=CC=C1Cl QIULLHZMZMGGFH-UHFFFAOYSA-N 0.000 claims description 2
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- HCXJFMDOHDNDCC-UHFFFAOYSA-N 5-$l^{1}-oxidanyl-3,4-dihydropyrrol-2-one Chemical group O=C1CCC(=O)[N]1 HCXJFMDOHDNDCC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005544 phthalimido group Chemical group 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003536 tetrazoles Chemical class 0.000 claims description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 claims description 2
- LDNUMTPCFCUXNJ-LTXLLRJYSA-N phenacyl (6r)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;hydrochloride Chemical compound Cl.S([C@H]1N2C(C1N)=O)CC(C)=C2C(=O)OCC(=O)C1=CC=CC=C1 LDNUMTPCFCUXNJ-LTXLLRJYSA-N 0.000 claims 2
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical compound COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- 229930186147 Cephalosporin Natural products 0.000 description 20
- 229940124587 cephalosporin Drugs 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 125000004185 ester group Chemical group 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 150000001780 cephalosporins Chemical class 0.000 description 14
- 229930182555 Penicillin Natural products 0.000 description 13
- 238000007257 deesterification reaction Methods 0.000 description 13
- 150000003573 thiols Chemical class 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 229940049954 penicillin Drugs 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 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 7
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 229940088710 antibiotic agent Drugs 0.000 description 7
- 229940106164 cephalexin Drugs 0.000 description 7
- 150000002960 penicillins Chemical class 0.000 description 7
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 6
- 229960000723 ampicillin Drugs 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 6
- NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 125000006004 trihaloethyl group Chemical group 0.000 description 5
- 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 description 4
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical group 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- NVIAYEIXYQCDAN-HWZXHQHMSA-N (6r)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)C(N)[C@@H]12 NVIAYEIXYQCDAN-HWZXHQHMSA-N 0.000 description 2
- YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 2
- PMBXCGGQNSVESQ-UHFFFAOYSA-N 1-Hexanethiol Chemical compound CCCCCCS PMBXCGGQNSVESQ-UHFFFAOYSA-N 0.000 description 2
- ZRKMQKLGEQPLNS-UHFFFAOYSA-N 1-Pentanethiol Chemical compound CCCCCS ZRKMQKLGEQPLNS-UHFFFAOYSA-N 0.000 description 2
- ORLCYMQZIPSODD-UHFFFAOYSA-N 1-chloro-2-[chloro(2,2,2-trichloroethoxy)phosphoryl]oxybenzene Chemical group ClC1=CC=CC=C1OP(Cl)(=O)OCC(Cl)(Cl)Cl ORLCYMQZIPSODD-UHFFFAOYSA-N 0.000 description 2
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 2
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- ZJWGSGAUTAIUJL-DMWIINFCSA-N CC(C(CC(C=C1)=CC=C1[N+]([O-])=O)S[C@@H]1C2NC([C@@H](C3=CC=CC=C3)N)=O)=C(C(O)=O)N1C2=O Chemical compound CC(C(CC(C=C1)=CC=C1[N+]([O-])=O)S[C@@H]1C2NC([C@@H](C3=CC=CC=C3)N)=O)=C(C(O)=O)N1C2=O ZJWGSGAUTAIUJL-DMWIINFCSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- GIJGXNFNUUFEGH-UHFFFAOYSA-N Isopentyl mercaptan Chemical compound CC(C)CCS GIJGXNFNUUFEGH-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 150000001356 alkyl thiols Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 2
- 238000006894 reductive elimination reaction Methods 0.000 description 2
- 238000006049 ring expansion reaction Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- FCZNNHHXCFARDY-WQRUCBPWSA-N (2s,5r,6r)-3,3-dimethyl-4,7-dioxo-6-[(2-phenylacetyl)amino]-4$l^{4}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@H]1[C@@H]2N(C1=O)[C@H](C(S2=O)(C)C)C(O)=O)C(=O)CC1=CC=CC=C1 FCZNNHHXCFARDY-WQRUCBPWSA-N 0.000 description 1
- LNVKHOIUIPPOFH-ISTVAULSSA-N (2s,5r,6r)-6-(1,3-dioxoisoindol-2-yl)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1[C@H]1[C@H]2SC(C)(C)[C@H](C(O)=O)N2C1=O LNVKHOIUIPPOFH-ISTVAULSSA-N 0.000 description 1
- GKQXPTHQTXCXEV-UHFFFAOYSA-N (4-chlorophenyl)methanethiol Chemical compound SCC1=CC=C(Cl)C=C1 GKQXPTHQTXCXEV-UHFFFAOYSA-N 0.000 description 1
- ZNPGKOOTUCWRTM-FQNRMIAFSA-N (4-nitrophenyl)methyl (6R)-7-formamido-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C(=O)NC1[C@@H]2N(C(=C(CS2)COC)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C1=O ZNPGKOOTUCWRTM-FQNRMIAFSA-N 0.000 description 1
- AFQZHFSVATUELX-FBLFFUNLSA-N (4-nitrophenyl)methyl (6r)-7-[(4-aminobenzoyl)amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)C)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)C1=CC=C(N)C=C1 AFQZHFSVATUELX-FBLFFUNLSA-N 0.000 description 1
- ABTUPEBOWRKQLD-SBXXRYSUSA-N (4-nitrophenyl)methyl (6r)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@H]1N2C(C1N)=O)CC(C)=C2C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 ABTUPEBOWRKQLD-SBXXRYSUSA-N 0.000 description 1
- YLIOIMWNSIRKDG-ZWNOBZJWSA-N (4-nitrophenyl)methyl (6r,7r)-7-amino-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N11)=O)N)CC(Cl)=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 YLIOIMWNSIRKDG-ZWNOBZJWSA-N 0.000 description 1
- XSTURBLIFLHNPH-RKOYOZNISA-N (6R)-3-methyl-4-[(4-nitrophenyl)methyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1=C(N2[C@@H](C(C2=O)NC(=O)CC3=CC=CC=C3)SC1CC4=CC=C(C=C4)[N+](=O)[O-])C(=O)O XSTURBLIFLHNPH-RKOYOZNISA-N 0.000 description 1
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- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
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- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
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- GNXBFFHXJDZGEK-UHFFFAOYSA-N 4-tert-butylbenzenethiol Chemical compound CC(C)(C)C1=CC=C(S)C=C1 GNXBFFHXJDZGEK-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
- MDQGTDMBVJCTBN-JCGDXUMPSA-N 6-formamidopenicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2[C@H](NC=O)C(=O)N21 MDQGTDMBVJCTBN-JCGDXUMPSA-N 0.000 description 1
- OQSAFIZCBAZPMY-UHFFFAOYSA-N 7-azaniumyl-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC(Cl)=C(C(O)=O)N2C(=O)C(N)C21 OQSAFIZCBAZPMY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- WVDYBOADDMMFIY-UHFFFAOYSA-N Cyclopentanethiol Chemical compound SC1CCCC1 WVDYBOADDMMFIY-UHFFFAOYSA-N 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- VPIAKHNXCOTPAY-UHFFFAOYSA-N Heptane-1-thiol Chemical compound CCCCCCCS VPIAKHNXCOTPAY-UHFFFAOYSA-N 0.000 description 1
- YRLTXBOEZLJQPC-XARDSYGASA-N N[C@@H](C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=CN=NN2)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C1=O)C1=CC=CC=C1 Chemical compound N[C@@H](C(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=CN=NN2)C(=O)OCC2=CC=C(C=C2)[N+](=O)[O-])C1=O)C1=CC=CC=C1 YRLTXBOEZLJQPC-XARDSYGASA-N 0.000 description 1
- 229930195708 Penicillin V Natural products 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- CSGFFYNMTALICU-ZWNOBZJWSA-N adipyl-7-aminodesacetoxycephalosporanic acid Natural products CC1=C(N2[C@H](SC1)[C@H](NC(=O)CCCCC(O)=O)C2=O)C(O)=O CSGFFYNMTALICU-ZWNOBZJWSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- LOCHFZBWPCLPAN-UHFFFAOYSA-N butane-2-thiol Chemical compound CCC(C)S LOCHFZBWPCLPAN-UHFFFAOYSA-N 0.000 description 1
- WQAQPCDUOCURKW-UHFFFAOYSA-N butanethiol Chemical compound CCCCS WQAQPCDUOCURKW-UHFFFAOYSA-N 0.000 description 1
- 125000006244 carboxylic acid protecting group Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- QHTOIDKCEPKVCM-ZCFIWIBFSA-N cepham group Chemical group S1CCCN2[C@H]1CC2=O QHTOIDKCEPKVCM-ZCFIWIBFSA-N 0.000 description 1
- 150000001782 cephems Chemical group 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- JRVFLEPKNRTFHN-UHFFFAOYSA-N cycloheptanethiol Chemical compound SC1CCCCCC1 JRVFLEPKNRTFHN-UHFFFAOYSA-N 0.000 description 1
- CMKBCTPCXZNQKX-UHFFFAOYSA-N cyclohexanethiol Chemical compound SC1CCCCC1 CMKBCTPCXZNQKX-UHFFFAOYSA-N 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- VTXVGVNLYGSIAR-UHFFFAOYSA-N decane-1-thiol Chemical compound CCCCCCCCCCS VTXVGVNLYGSIAR-UHFFFAOYSA-N 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- WNAHIZMDSQCWRP-UHFFFAOYSA-N dodecane-1-thiol Chemical compound CCCCCCCCCCCCS WNAHIZMDSQCWRP-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- VIBDJEWPNNCFQO-UHFFFAOYSA-N ethane-1,1,2-triol Chemical compound OCC(O)O VIBDJEWPNNCFQO-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- IAQLJCYTGRMXMA-UHFFFAOYSA-M lithium;acetate;dihydrate Chemical compound [Li+].O.O.CC([O-])=O IAQLJCYTGRMXMA-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HQOQSFITXGQQDM-SSDOTTSWSA-N methyl (6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound COC(=O)C1=CCS[C@@H]2CC(=O)N12 HQOQSFITXGQQDM-SSDOTTSWSA-N 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XMFGKICZZHDQGH-UHFFFAOYSA-N naphthalen-1-ylmethanethiol Chemical compound C1=CC=C2C(CS)=CC=CC2=C1 XMFGKICZZHDQGH-UHFFFAOYSA-N 0.000 description 1
- ZVEZMVFBMOOHAT-UHFFFAOYSA-N nonane-1-thiol Chemical compound CCCCCCCCCS ZVEZMVFBMOOHAT-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 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
- VOUGEZYPVGAPBB-UHFFFAOYSA-N penicillin acid Natural products OC(=O)C=C(OC)C(=O)C(C)=C VOUGEZYPVGAPBB-UHFFFAOYSA-N 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- WMXCDAVJEZZYLT-UHFFFAOYSA-N tert-butylthiol Chemical compound CC(C)(C)S WMXCDAVJEZZYLT-UHFFFAOYSA-N 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 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)
- Cephalosporin Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70185076A | 1976-07-01 | 1976-07-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2728578A1 true DE2728578A1 (de) | 1978-01-12 |
Family
ID=24818932
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19772728578 Withdrawn DE2728578A1 (de) | 1976-07-01 | 1977-06-24 | Verfahren zur herstellung einer beta-lactamsaeure |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS535194A (enExample) |
| BE (1) | BE856288A (enExample) |
| DE (1) | DE2728578A1 (enExample) |
| ES (1) | ES460338A1 (enExample) |
| FR (1) | FR2356653A1 (enExample) |
| GB (1) | GB1582960A (enExample) |
| IL (1) | IL52144A (enExample) |
| NL (1) | NL7707302A (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0197294A2 (de) | 1985-03-16 | 1986-10-15 | Bayer Ag | Beta-Lactam-Antibiotika, Verfahren zur Herstellung und ihre Verwendung als Arzneimittel |
| US4748163A (en) * | 1985-03-08 | 1988-05-31 | Bayer Aktiengesellschaft | Novel β-lactam antibiotics |
| EP0326887A1 (de) | 1988-02-03 | 1989-08-09 | Bayer Ag | Beta-Lactam-Antibiotika, Verfahren zu ihrer Herstellung und ihre Verwendung als und in Arzneimitteln |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL72412A (en) * | 1983-07-22 | 1988-05-31 | Lilly Co Eli | Deesterification of beta-lactam antibiotic esters |
| IN181697B (enExample) * | 1994-04-22 | 1998-09-05 | Ranbaxy Lab Ltd | |
| CN103588790A (zh) * | 2013-11-29 | 2014-02-19 | 中国科学院长春应用化学研究所 | 7-氨基-3-氯-3-头孢-4-羧酸-对硝基苄基酯的制备方法 |
-
1977
- 1977-05-22 IL IL52144A patent/IL52144A/xx unknown
- 1977-06-24 DE DE19772728578 patent/DE2728578A1/de not_active Withdrawn
- 1977-06-27 GB GB26788/77A patent/GB1582960A/en not_active Expired
- 1977-06-29 JP JP7847477A patent/JPS535194A/ja active Pending
- 1977-06-30 FR FR7720118A patent/FR2356653A1/fr active Granted
- 1977-06-30 BE BE1008237A patent/BE856288A/xx unknown
- 1977-06-30 NL NL7707302A patent/NL7707302A/xx not_active Application Discontinuation
- 1977-07-01 ES ES460338A patent/ES460338A1/es not_active Expired
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4748163A (en) * | 1985-03-08 | 1988-05-31 | Bayer Aktiengesellschaft | Novel β-lactam antibiotics |
| USRE33948E (en) * | 1985-03-08 | 1992-06-02 | Bayer Aktiengesellschaft | β-lactam antibiotics |
| EP0197294A2 (de) | 1985-03-16 | 1986-10-15 | Bayer Ag | Beta-Lactam-Antibiotika, Verfahren zur Herstellung und ihre Verwendung als Arzneimittel |
| US4734407A (en) * | 1985-03-16 | 1988-03-29 | Bayer Aktiengesellschaft | Alpha-aminoacyl-penicillins and cephalosporins |
| EP0326887A1 (de) | 1988-02-03 | 1989-08-09 | Bayer Ag | Beta-Lactam-Antibiotika, Verfahren zu ihrer Herstellung und ihre Verwendung als und in Arzneimitteln |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS535194A (en) | 1978-01-18 |
| ES460338A1 (es) | 1978-08-16 |
| IL52144A0 (en) | 1977-07-31 |
| NL7707302A (nl) | 1978-01-03 |
| FR2356653B1 (enExample) | 1980-01-04 |
| IL52144A (en) | 1979-10-31 |
| FR2356653A1 (fr) | 1978-01-27 |
| GB1582960A (en) | 1981-01-21 |
| BE856288A (fr) | 1977-12-30 |
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