CS195286B2 - Method of preparing cephalosporin compounds - Google Patents
Method of preparing cephalosporin compounds Download PDFInfo
- Publication number
- CS195286B2 CS195286B2 CS752719A CS271975A CS195286B2 CS 195286 B2 CS195286 B2 CS 195286B2 CS 752719 A CS752719 A CS 752719A CS 271975 A CS271975 A CS 271975A CS 195286 B2 CS195286 B2 CS 195286B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- cephem
- acid
- carboxylate
- group
- ester
- Prior art date
Links
- -1 cephalosporin compounds Chemical class 0.000 title claims abstract description 201
- 238000000034 method Methods 0.000 title claims abstract description 56
- 229930186147 Cephalosporin Natural products 0.000 title claims description 18
- 229940124587 cephalosporin Drugs 0.000 title claims description 18
- 239000002253 acid Substances 0.000 claims abstract description 60
- 238000002360 preparation method Methods 0.000 claims abstract description 43
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims abstract description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 8
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 48
- 150000001875 compounds Chemical class 0.000 claims description 45
- 150000002148 esters Chemical class 0.000 claims description 45
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000002252 acyl group Chemical group 0.000 claims description 16
- 150000007513 acids Chemical class 0.000 claims description 14
- 150000001780 cephalosporins Chemical class 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 7
- FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 claims description 5
- SXBDXXFTJVHSAF-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-3-en-8-one Chemical class S1C=CCN2C(=O)C[C@H]21 SXBDXXFTJVHSAF-ZCFIWIBFSA-N 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 150000003462 sulfoxides Chemical class 0.000 claims description 3
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 125000004429 atom Chemical group 0.000 claims 2
- 125000005907 alkyl ester group Chemical group 0.000 claims 1
- 229910002092 carbon dioxide Inorganic materials 0.000 claims 1
- 239000001569 carbon dioxide Substances 0.000 claims 1
- 230000037213 diet Effects 0.000 claims 1
- 235000005911 diet Nutrition 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 239000004460 silage Substances 0.000 claims 1
- 239000000080 wetting agent Substances 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 12
- 239000003242 anti bacterial agent Substances 0.000 abstract description 8
- 229940088710 antibiotic agent Drugs 0.000 abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 abstract description 7
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 abstract description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 abstract description 5
- 125000004442 acylamino group Chemical group 0.000 abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 abstract description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 abstract description 3
- 125000005843 halogen group Chemical group 0.000 abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 abstract description 3
- 125000003342 alkenyl group Chemical group 0.000 abstract description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 abstract description 2
- MKFLFZPSOCGNJJ-PUUKEUDRSA-N benzhydryl (6r)-3-(1,3-dioxolan-2-yl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound S([C@@H]12)C=C(C3OCCO3)C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2NC(=O)CC1=CC=CS1 MKFLFZPSOCGNJJ-PUUKEUDRSA-N 0.000 abstract description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 abstract description 2
- 125000004970 halomethyl group Chemical group 0.000 abstract description 2
- 150000004702 methyl esters Chemical class 0.000 abstract description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 5
- 229910052799 carbon Inorganic materials 0.000 abstract 3
- 125000003545 alkoxy group Chemical group 0.000 abstract 2
- VWKZOTOKKINGGP-GCZXYKMCSA-N (6r)-3-formyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(C(=CS2)C=O)C(=O)O)NC(=O)CC1=CC=CS1 VWKZOTOKKINGGP-GCZXYKMCSA-N 0.000 abstract 1
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 abstract 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract 1
- 125000005042 acyloxymethyl group Chemical group 0.000 abstract 1
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 abstract 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract 1
- 229910052794 bromium Inorganic materials 0.000 abstract 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 abstract 1
- 150000001768 cations Chemical class 0.000 abstract 1
- ZGNIYAPHJAPRMA-UHFFFAOYSA-N chlorine azide Chemical group ClN=[N+]=[N-] ZGNIYAPHJAPRMA-UHFFFAOYSA-N 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000006502 nitrobenzyl group Chemical group 0.000 abstract 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000003944 tolyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 35
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 28
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 28
- 239000000047 product Substances 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 14
- 238000003776 cleavage reaction Methods 0.000 description 14
- 230000007017 scission Effects 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 125000004185 ester group Chemical group 0.000 description 12
- 230000003647 oxidation Effects 0.000 description 12
- 238000007254 oxidation reaction Methods 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical class CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 150000005690 diesters Chemical class 0.000 description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 7
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
- 235000013772 propylene glycol Nutrition 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 230000010933 acylation Effects 0.000 description 5
- 238000005917 acylation reaction Methods 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 5
- 150000002431 hydrogen Chemical group 0.000 description 5
- 239000003999 initiator Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 4
- 125000002015 acyclic group Chemical group 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 4
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 4
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 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 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-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
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 3
- 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
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 3
- 239000003377 acid catalyst Substances 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- DNQSSESRMZLVCL-QGPIEZSZSA-N benzhydryl (6r)-3-formyl-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate Chemical compound C1([C@H]2SC=C(C(N2C1=O)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)C=O)NC(=O)CC1=CC=CS1 DNQSSESRMZLVCL-QGPIEZSZSA-N 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 150000001782 cephems Chemical class 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
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- 230000020477 pH reduction Effects 0.000 description 1
- XLMFDCKSFJWJTP-UHFFFAOYSA-N pentane-2,3-diol Chemical compound CCC(O)C(C)O XLMFDCKSFJWJTP-UHFFFAOYSA-N 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
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- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- JBSALINYNVABSI-FFFFSGIJSA-N tert-butyl (6r)-7-[(2-chloroacetyl)amino]-3-formyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=C(C=O)CS[C@@H]2C(NC(=O)CCl)C(=O)N12 JBSALINYNVABSI-FFFFSGIJSA-N 0.000 description 1
- CLZWAWBPWVRRGI-UHFFFAOYSA-N tert-butyl 2-[2-[2-[2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-5-bromophenoxy]ethoxy]-4-methyl-n-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]anilino]acetate Chemical compound CC1=CC=C(N(CC(=O)OC(C)(C)C)CC(=O)OC(C)(C)C)C(OCCOC=2C(=CC=C(Br)C=2)N(CC(=O)OC(C)(C)C)CC(=O)OC(C)(C)C)=C1 CLZWAWBPWVRRGI-UHFFFAOYSA-N 0.000 description 1
- XBHUHMNGCIVZHX-UHFFFAOYSA-N tert-butyl 3-chloro-3-oxo-2-phenylpropanoate Chemical compound CC(C)(C)OC(=O)C(C(Cl)=O)C1=CC=CC=C1 XBHUHMNGCIVZHX-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
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- 238000006257 total synthesis reaction Methods 0.000 description 1
- LXEXBJXDGVGRAR-UHFFFAOYSA-N trichloro(trichlorosilyl)silane Chemical compound Cl[Si](Cl)(Cl)[Si](Cl)(Cl)Cl LXEXBJXDGVGRAR-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS777943A CS195289B2 (en) | 1974-04-19 | 1977-11-30 | Method of preparing cephalosporin compounds |
| CS777941A CS195287B2 (cs) | 1974-04-19 | 1977-11-30 | Způsob přípravy cefalósporinových Sloučenin |
| CS777942A CS195288B2 (cs) | 1974-04-19 | 1977-11-30 | Způsob přípravy cefalosporinových sloučenin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/462,459 US3953436A (en) | 1974-04-19 | 1974-04-19 | 3,4-Dicarboxycephalosporins and derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS195286B2 true CS195286B2 (en) | 1980-01-31 |
Family
ID=23836483
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS752719A CS195286B2 (en) | 1974-04-19 | 1975-04-18 | Method of preparing cephalosporin compounds |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US3953436A (OSRAM) |
| JP (1) | JPS50148382A (OSRAM) |
| AR (4) | AR224221A1 (OSRAM) |
| AT (1) | AT341669B (OSRAM) |
| BE (1) | BE828066A (OSRAM) |
| BG (1) | BG26538A3 (OSRAM) |
| CA (1) | CA1043332A (OSRAM) |
| CS (1) | CS195286B2 (OSRAM) |
| DD (1) | DD118650A5 (OSRAM) |
| DE (1) | DE2517047A1 (OSRAM) |
| DK (1) | DK164775A (OSRAM) |
| ES (4) | ES436737A1 (OSRAM) |
| FR (1) | FR2267785B1 (OSRAM) |
| GB (1) | GB1505848A (OSRAM) |
| HU (1) | HU171887B (OSRAM) |
| IE (1) | IE41005B1 (OSRAM) |
| IL (1) | IL47111A (OSRAM) |
| NL (1) | NL7504607A (OSRAM) |
| NZ (1) | NZ177260A (OSRAM) |
| PL (4) | PL100075B1 (OSRAM) |
| RO (4) | RO66822A (OSRAM) |
| SE (1) | SE7504535L (OSRAM) |
| SU (3) | SU735169A3 (OSRAM) |
| YU (1) | YU98775A (OSRAM) |
| ZA (1) | ZA752472B (OSRAM) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI760756A7 (OSRAM) * | 1975-03-26 | 1976-09-27 | Novo Industri As | |
| WO2021041583A1 (en) * | 2019-08-29 | 2021-03-04 | The Regents Of The University Of California | Compounds to identify beta-lactamases, and methods of use thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3864338A (en) * | 1970-08-11 | 1975-02-04 | Squibb & Sons Inc | Process for the preparation of {66 {hu 2{b -cephalosporin aldehydes |
| GB1368235A (en) * | 1970-11-03 | 1974-09-25 | Glaxo Lab Ltd | Azetidinone disulphides and their preparation |
-
1974
- 1974-04-19 US US05/462,459 patent/US3953436A/en not_active Expired - Lifetime
-
1975
- 1975-04-17 BE BE1006597A patent/BE828066A/xx unknown
- 1975-04-17 JP JP50047380A patent/JPS50148382A/ja active Pending
- 1975-04-17 ZA ZA752472A patent/ZA752472B/xx unknown
- 1975-04-17 DE DE19752517047 patent/DE2517047A1/de not_active Withdrawn
- 1975-04-17 NZ NZ177260A patent/NZ177260A/xx unknown
- 1975-04-17 NL NL7504607A patent/NL7504607A/xx not_active Application Discontinuation
- 1975-04-17 FR FR7512026A patent/FR2267785B1/fr not_active Expired
- 1975-04-17 GB GB15803/75A patent/GB1505848A/en not_active Expired
- 1975-04-17 DK DK164775A patent/DK164775A/da not_active Application Discontinuation
- 1975-04-17 CA CA224,856A patent/CA1043332A/en not_active Expired
- 1975-04-18 RO RO7582025A patent/RO66822A/ro unknown
- 1975-04-18 CS CS752719A patent/CS195286B2/cs unknown
- 1975-04-18 SE SE7504535A patent/SE7504535L/xx unknown
- 1975-04-18 AR AR258427A patent/AR224221A1/es active
- 1975-04-18 RO RO7591731A patent/RO70019A/ro unknown
- 1975-04-18 YU YU00987/75A patent/YU98775A/xx unknown
- 1975-04-18 PL PL1975179756A patent/PL100075B1/pl unknown
- 1975-04-18 ES ES436737A patent/ES436737A1/es not_active Expired
- 1975-04-18 IL IL47111A patent/IL47111A/xx unknown
- 1975-04-18 SU SU752127589A patent/SU735169A3/ru active
- 1975-04-18 RO RO7591730A patent/RO69983A/ro unknown
- 1975-04-18 AT AT299575A patent/AT341669B/de not_active IP Right Cessation
- 1975-04-18 DD DD185554A patent/DD118650A5/xx unknown
- 1975-04-18 PL PL1975197694A patent/PL103478B1/pl unknown
- 1975-04-18 PL PL1975197695A patent/PL103475B1/pl unknown
- 1975-04-18 PL PL1975197696A patent/PL103474B1/pl unknown
- 1975-04-18 HU HU75EI00000614A patent/HU171887B/hu unknown
- 1975-04-18 IE IE884/75A patent/IE41005B1/xx unknown
- 1975-04-19 RO RO7591729A patent/RO69982A/ro unknown
- 1975-04-19 BG BG029721A patent/BG26538A3/xx unknown
-
1976
- 1976-05-25 SU SU762361850A patent/SU677663A3/ru active
- 1976-05-27 SU SU762362203A patent/SU639455A3/ru active
- 1976-12-01 ES ES453860A patent/ES453860A1/es not_active Expired
- 1976-12-01 ES ES453859A patent/ES453859A1/es not_active Expired
- 1976-12-01 ES ES453858A patent/ES453858A1/es not_active Expired
- 1976-12-30 AR AR266090A patent/AR218238A1/es active
- 1976-12-30 AR AR266092A patent/AR219910A1/es active
- 1976-12-30 AR AR266091A patent/AR221325A1/es active
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