DK148261B - Fremgangsmaade til fremstilling af 3-chlormethyl-3-cephem-forbindelser - Google Patents

Fremgangsmaade til fremstilling af 3-chlormethyl-3-cephem-forbindelser Download PDF

Info

Publication number: DK148261B
Authority: DK; Denmark
Prior art keywords: compounds; cephem; acid; preparation; halogen
Prior art date: 1976-03-22

Application number

DK123177AA

Other languages

Danish (da)

English (en)

Other versions

DK123177A (da

Inventor

Gary Allen Koppel

Original Assignee

Lilly Co Eli

Priority date (The priority date 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 date listed.)

1976-03-22

Filing date

1977-03-21

Publication date

1985-05-20

1977-03-21 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1977-09-23 Publication of DK123177A publication Critical patent/DK123177A/da

1985-05-20 Publication of DK148261B publication Critical patent/DK148261B/da

Links

238000000034 method Methods 0.000 title description 28
238000002360 preparation method Methods 0.000 title description 7
REJZMNMWWGNGIJ-SSDOTTSWSA-N (6r)-3-(chloromethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(CCl)=CN2C(=O)C[C@H]21 REJZMNMWWGNGIJ-SSDOTTSWSA-N 0.000 title description 6
238000006243 chemical reaction Methods 0.000 description 13
150000001875 compounds Chemical class 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
-1 cephem compounds Chemical class 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
229910052736 halogen Inorganic materials 0.000 description 10
150000002367 halogens Chemical class 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
239000011230 binding agent Substances 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
229940124587 cephalosporin Drugs 0.000 description 7
239000012320 chlorinating reagent Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000007858 starting material Substances 0.000 description 7
239000000243 solution Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
229930186147 Cephalosporin Natural products 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
239000003242 anti bacterial agent Substances 0.000 description 5
229940088710 antibiotic agent Drugs 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
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 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
150000001780 cephalosporins Chemical class 0.000 description 4
150000001782 cephems Chemical class 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
125000001475 halogen functional group Chemical group 0.000 description 4
239000000203 mixture Substances 0.000 description 4
IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
238000005660 chlorination reaction Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
229910003002 lithium salt Inorganic materials 0.000 description 3
159000000002 lithium salts Chemical class 0.000 description 3
150000003138 primary alcohols Chemical class 0.000 description 3
239000000376 reactant Substances 0.000 description 3
UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
PZHCIOIEYLIJHX-QXPUDEPPSA-N benzhydryl (6r)-3-(chloromethyl)-7-methoxy-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]12)CC(CCl)=C(C(=O)OC(C=3C=CC=CC=3)C=3C=CC=CC=3)N1C(=O)C2(OC)NC(=O)CC1=CC=CS1 PZHCIOIEYLIJHX-QXPUDEPPSA-N 0.000 description 2
QHTOIDKCEPKVCM-ZCFIWIBFSA-N cepham Chemical compound S1CCCN2C(=O)C[C@H]21 QHTOIDKCEPKVCM-ZCFIWIBFSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
230000026030 halogenation Effects 0.000 description 2
238000005658 halogenation reaction Methods 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
238000010534 nucleophilic substitution reaction Methods 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
230000007017 scission Effects 0.000 description 2
238000007086 side reaction Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
239000011701 zinc Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
HTFTURZHXAWZPC-SSDOTTSWSA-N (6r)-3-methylidene-5-thia-1-azabicyclo[4.2.0]octan-8-one Chemical class C1C(=C)CS[C@@H]2CC(=O)N21 HTFTURZHXAWZPC-SSDOTTSWSA-N 0.000 description 1
CWWPRUSTCGPZGJ-NQPNHJOESA-N (6r)-4-methyl-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class C1=CC(C)S[C@@H]2CC(=O)N21 CWWPRUSTCGPZGJ-NQPNHJOESA-N 0.000 description 1
WEBVTPPSMMFBQU-UHFFFAOYSA-N 1,1-dibromo-2-chloroethane Chemical compound ClCC(Br)Br WEBVTPPSMMFBQU-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
UEVPKMPAHXHIEF-SECBINFHSA-N [(6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl acetate Chemical group S1CC(COC(=O)C)=CN2C(=O)C[C@H]21 UEVPKMPAHXHIEF-SECBINFHSA-N 0.000 description 1
FAGLETQHUJYDMO-SSDOTTSWSA-N [(6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl carbamate Chemical class S1CC(COC(=O)N)=CN2C(=O)C[C@H]21 FAGLETQHUJYDMO-SSDOTTSWSA-N 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
125000000746 allylic group Chemical group 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
UIJGNTRUPZPVNG-UHFFFAOYSA-N benzenecarbothioic s-acid Chemical compound SC(=O)C1=CC=CC=C1 UIJGNTRUPZPVNG-UHFFFAOYSA-N 0.000 description 1
SXNLKNCFTNRXKD-QGPIEZSZSA-N benzhydryl (6r)-3-methylidene-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound C1([C@H]2SCC(C(N2C1=O)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)=C)NC(=O)CC1=CC=CS1 SXNLKNCFTNRXKD-QGPIEZSZSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
QCVZVMTWFMXZEU-UHFFFAOYSA-L calcium;dicarbamate Chemical compound [Ca+2].NC([O-])=O.NC([O-])=O QCVZVMTWFMXZEU-UHFFFAOYSA-L 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
125000006244 carboxylic acid protecting group Chemical group 0.000 description 1
229960002682 cefoxitin Drugs 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
UZEDIBTVIIJELN-UHFFFAOYSA-N chromium(2+) Chemical class [Cr+2] UZEDIBTVIIJELN-UHFFFAOYSA-N 0.000 description 1
229940125758 compound 15 Drugs 0.000 description 1
229940125846 compound 25 Drugs 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000007257 deesterification reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical class [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000002534 ethynyl group Chemical class [H]C#C* 0.000 description 1
238000001914 filtration Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
238000007710 freezing Methods 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
238000006198 methoxylation reaction Methods 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 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
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000009877 rendering Methods 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
150000003839 salts Chemical class 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003464 sulfur compounds Chemical class 0.000 description 1
DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
239000000725 suspension Substances 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
239000008096 xylene Substances 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
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/57—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with a further substituent in position 7, e.g. cephamycines

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Cephalosporin Compounds (AREA)

DK123177AA 1976-03-22 1977-03-21 Fremgangsmaade til fremstilling af 3-chlormethyl-3-cephem-forbindelser DK148261B (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US05/669,368 US4048163A (en)	1976-03-22	1976-03-22	Process for preparation of 7-alkoxy-3-chloromethylcephems
US66936876		1976-03-22

Publications (2)

Publication Number	Publication Date
DK123177A DK123177A (da)	1977-09-23
DK148261B true DK148261B (da)	1985-05-20

Family

ID=24686091

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK123177AA DK148261B (da)	1976-03-22	1977-03-21	Fremgangsmaade til fremstilling af 3-chlormethyl-3-cephem-forbindelser

Country Status (30)

Country	Link
US (1)	US4048163A (es)
JP (1)	JPS52113996A (es)
AR (1)	AR228336A1 (es)
AT (1)	AT351676B (es)
AU (1)	AU505101B2 (es)
BE (1)	BE852670A (es)
BG (1)	BG27755A3 (es)
CA (1)	CA1109459A (es)
CH (1)	CH632515A5 (es)
CS (1)	CS194795B2 (es)
DD (1)	DD129915A5 (es)
DE (1)	DE2712047C2 (es)
DK (1)	DK148261B (es)
ES (1)	ES457059A1 (es)
GB (1)	GB1573026A (es)
GR (1)	GR66423B (es)
HU (1)	HU176659B (es)
IE (1)	IE44600B1 (es)
IL (1)	IL51433A (es)
MX (1)	MX4449E (es)
NL (1)	NL7703061A (es)
NZ (1)	NZ183309A (es)
PH (1)	PH12938A (es)
PL (1)	PL108101B1 (es)
PT (1)	PT66318B (es)
RO (1)	RO70052A (es)
SE (1)	SE428801B (es)
SU (1)	SU845790A3 (es)
YU (1)	YU68477A (es)
ZA (1)	ZA77714B (es)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS62242730A (ja) *	1986-04-14	1987-10-23	Mitsubishi Electric Corp	温水加熱装置
JPS62252848A (ja) *	1986-04-24	1987-11-04	Rinnai Corp	給湯器
KR20020017380A (ko) *	2000-08-30	2002-03-07	구자홍	티브이씨알의 캡스턴모터 고속 제어장치
CN107118224B (zh) *	2017-06-15	2019-09-17	浙江新和成股份有限公司	一种氧头孢母核中间体的制备方法、其溶剂化合物及其制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1241657A (en) *	1967-08-21	1971-08-04	Glaxo Lab Ltd	Improvements in or relating to cephalosporin compounds
US3637678A (en) *	1969-01-13	1972-01-25	Lilly Co Eli	Delta-2 cephalosporin compounds
US3705897A (en) *	1970-07-07	1972-12-12	Lilly Co Eli	Method for converting delta2 cephalosporin to delta3 cephalosporin
BE794554A (fr) *	1972-01-31	1973-07-26	Lilly Co Eli	Nouveaux derives de penicilline et de cephalusporine
US3883518A (en) *	1972-05-15	1975-05-13	Merck & Co Inc	3-Methylene cephalosporins

1976
- 1976-03-22 US US05/669,368 patent/US4048163A/en not_active Expired - Lifetime
1977
- 1977-02-08 ZA ZA00770714A patent/ZA77714B/xx unknown
- 1977-02-08 IE IE264/77A patent/IE44600B1/en unknown
- 1977-02-09 CA CA271,405A patent/CA1109459A/en not_active Expired
- 1977-02-09 GR GR52756A patent/GR66423B/el unknown
- 1977-02-10 NZ NZ183309A patent/NZ183309A/xx unknown
- 1977-02-11 AU AU22199/77A patent/AU505101B2/en not_active Expired
- 1977-02-11 IL IL51433A patent/IL51433A/xx unknown
- 1977-03-10 SE SE7702736A patent/SE428801B/xx not_active IP Right Cessation
- 1977-03-16 GB GB11150/77A patent/GB1573026A/en not_active Expired
- 1977-03-16 YU YU00684/77A patent/YU68477A/xx unknown
- 1977-03-17 PT PT66318A patent/PT66318B/pt unknown
- 1977-03-17 AR AR266895A patent/AR228336A1/es active
- 1977-03-18 JP JP3098677A patent/JPS52113996A/ja active Granted
- 1977-03-18 DE DE2712047A patent/DE2712047C2/de not_active Expired
- 1977-03-18 BE BE1008028A patent/BE852670A/xx not_active IP Right Cessation
- 1977-03-18 MX MX775557U patent/MX4449E/es unknown
- 1977-03-18 PH PH19572A patent/PH12938A/en unknown
- 1977-03-21 ES ES457059A patent/ES457059A1/es not_active Expired
- 1977-03-21 RO RO7789740A patent/RO70052A/ro unknown
- 1977-03-21 NL NL7703061A patent/NL7703061A/xx not_active Application Discontinuation
- 1977-03-21 SU SU772462783A patent/SU845790A3/ru active
- 1977-03-21 AT AT194677A patent/AT351676B/de not_active IP Right Cessation
- 1977-03-21 HU HU77EI734A patent/HU176659B/hu unknown
- 1977-03-21 DK DK123177AA patent/DK148261B/da not_active Application Discontinuation
- 1977-03-22 CH CH359577A patent/CH632515A5/de not_active IP Right Cessation
- 1977-03-22 BG BG7735757A patent/BG27755A3/xx unknown
- 1977-03-22 PL PL1977196822A patent/PL108101B1/pl unknown
- 1977-03-22 DD DD7700197991A patent/DD129915A5/xx unknown
- 1977-03-22 CS CS771900A patent/CS194795B2/cs unknown

Also Published As

Publication number	Publication date
SE7702736L (sv)	1977-09-23
PT66318A (en)	1977-04-01
HU176659B (en)	1981-04-28
MX4449E (es)	1982-05-11
RO70052A (ro)	1980-07-15
NZ183309A (en)	1978-07-28
PH12938A (en)	1979-10-18
IE44600B1 (en)	1982-01-27
AU2219977A (en)	1978-08-17
IE44600L (en)	1977-09-22
DE2712047A1 (de)	1977-09-29
US4048163A (en)	1977-09-13
GR66423B (es)	1981-03-20
PL108101B1 (pl)	1980-03-31
BE852670A (fr)	1977-09-19
CS194795B2 (en)	1979-12-31
NL7703061A (nl)	1977-09-26
GB1573026A (en)	1980-08-13
SE428801B (sv)	1983-07-25
CA1109459A (en)	1981-09-22
YU68477A (en)	1982-06-30
PT66318B (en)	1978-08-14
CH632515A5 (de)	1982-10-15
IL51433A (en)	1979-11-30
DK123177A (da)	1977-09-23
AU505101B2 (en)	1979-11-08
JPS52113996A (en)	1977-09-24
IL51433A0 (en)	1977-04-29
ZA77714B (en)	1978-09-27
DE2712047C2 (de)	1985-09-19
SU845790A3 (ru)	1981-07-07
BG27755A3 (en)	1979-12-12
AR228336A1 (es)	1983-02-28
DD129915A5 (de)	1978-02-15
JPS613353B2 (es)	1986-01-31
ES457059A1 (es)	1978-06-01
AT351676B (de)	1979-08-10
ATA194677A (de)	1979-01-15

Legal Events

Date	Code	Title	Description
1985-12-02	PHB	Application deemed withdrawn due to non-payment or other reasons

Publication	Publication Date	Title
NO881531L (no)	1988-10-11	Acylderivater.
DK148261B (da)	1985-05-20	Fremgangsmaade til fremstilling af 3-chlormethyl-3-cephem-forbindelser
US4042585A (en)	1977-08-16	Process for preparation of 3-halomethylcephems
JP2973143B2 (ja)	1999-11-08	３−アシルアミノ−６−フェニルオキシ−７−アルキルスルホニルアミノ−４ｈ−１−ベンゾピラン−４−オンまたはその塩の製造法
EP0958286A1 (en)	1999-11-24	Process for the preparation of thiazole derivatives
US4008229A (en)	1977-02-15	Halo substituted β-lactam antibiotics
CA2174797C (en)	2007-01-09	Cyanobenzenesulfenyl halide and process for preparation of 3-substituted benzisothiazole using the same
HU192469B (en)	1987-06-29	Process for production of derivatives of cefem-carbonic acid and their intermediers
DK148097B (da)	1985-03-04	Fremgangsmaade til fremstilling af 3-brommethyl-3-cephem-forbindelser
US4366315A (en)	1982-12-28	Process for preparing 3'bromo-desacetoxycephalosporanic acid sulfoxide compounds
CZ20023843A3 (cs)	2003-05-14	Způsob přípravy 2-chlor-5-chlormethyl-1,3-thiazolu
KR890002107B1 (ko)	1989-06-19	세팔로스포린 유도체의 제조방법
NO159658B (no)	1988-10-17	Mellomprodukt for fremstilling av 1,1-diokso-penicillanoyloksymetyl-6-(2-amino-2-fenyl-acetamido)penicillanat-antibiotika.
KR840002142B1 (ko)	1984-11-23	7α-메톡시세팔로스포린 유도체의 제조방법
CA2564300C (en)	2010-09-14	Process for preparation of 3-substituted benzisothiazole
PL126906B1 (en)	1983-09-30	Method of obtaining /2-aminothiazole-4-ilo/-acetic acid hydrochloride
CZ2016611A3 (cs)	2018-05-09	Způsob výroby 2-(5-brom-4-(1-cyklopropylnaftalen-4-yl)-4H-1,2,4-triazol-3-ylthio)octové kyseliny - lesinuradu
EP0120094B1 (en)	1989-04-19	Azetidinone compounds
CA1201433A (en)	1986-03-04	Penicillin derivatives and process for preparation of the same
DK159157B (da)	1990-09-10	Krystallinske 3-hydroxy-cephalosporin-solvater
US3956291A (en)	1976-05-11	7-Thioacetamido cephalosporanic acid derivatives
CA1133470A (en)	1982-10-12	Cephapirine esters, salts thereof and processes for producing the same
KR950008321B1 (ko)	1995-07-27	세펨 유도체
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JPH06321953A (ja)	1994-11-22	セファロスポラン酸誘導体