FI63583C - Azetidinderivat foer anvaendning som mellanfoereningar till frmstaellning av terapeutiskt aktiva 3-desacetoxi-cefalosp aorsyraderivat och foerfarande foer framstaellning av azeti ndierivaten - Google Patents
Azetidinderivat foer anvaendning som mellanfoereningar till frmstaellning av terapeutiskt aktiva 3-desacetoxi-cefalosp aorsyraderivat och foerfarande foer framstaellning av azeti ndierivaten Download PDFInfo
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- FI63583C FI63583C FI364/74A FI36474A FI63583C FI 63583 C FI63583 C FI 63583C FI 364/74 A FI364/74 A FI 364/74A FI 36474 A FI36474 A FI 36474A FI 63583 C FI63583 C FI 63583C
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- mmol
- mixture
- phenylacetamido
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 122
- -1 nitrosubstituted phenyl groups Chemical group 0.000 claims description 42
- 239000011541 reaction mixture Substances 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 33
- 150000001539 azetidines Chemical class 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 22
- 150000003462 sulfoxides Chemical class 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 13
- 239000003960 organic solvent Substances 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 239000000543 intermediate Substances 0.000 claims description 8
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000005544 phthalimido group Chemical group 0.000 claims description 3
- QHUNJMXHQHHWQP-UHFFFAOYSA-N trimethylsilyl acetate Chemical compound CC(=O)O[Si](C)(C)C QHUNJMXHQHHWQP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical class C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 2
- 239000002798 polar solvent Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 105
- 239000000203 mixture Substances 0.000 description 65
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 229940113088 dimethylacetamide Drugs 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000003480 eluent Substances 0.000 description 16
- 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 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- 239000002210 silicon-based material Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 11
- ZRAPHEBMDYQXKR-UHFFFAOYSA-N 2-trimethylsilylisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N([Si](C)(C)C)C(=O)C2=C1 ZRAPHEBMDYQXKR-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 238000004566 IR spectroscopy Methods 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- YUWVMABNHZEMGO-UHFFFAOYSA-N 1-trimethylsilylpyrrolidine-2,5-dione Chemical compound C[Si](C)(C)N1C(=O)CCC1=O YUWVMABNHZEMGO-UHFFFAOYSA-N 0.000 description 8
- MLSIOVIWWMNVQR-UHFFFAOYSA-N 2-[2-(2,5-dioxopyrrolidin-1-yl)sulfanyl-4-oxo-3-[(2-phenylacetyl)amino]azetidin-1-yl]-3-methylbut-3-enoic acid Chemical compound C=1C=CC=CC=1CC(=O)NC1C(=O)N(C(C(=C)C)C(O)=O)C1SN1C(=O)CCC1=O MLSIOVIWWMNVQR-UHFFFAOYSA-N 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 7
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 229930186147 Cephalosporin Natural products 0.000 description 6
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229940124587 cephalosporin Drugs 0.000 description 6
- 150000001780 cephalosporins Chemical class 0.000 description 6
- 239000003610 charcoal Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- RHLBOBPOIZROJX-UHFFFAOYSA-N 1-acetylpyrrolidine-2,5-dione Chemical compound CC(=O)N1C(=O)CCC1=O RHLBOBPOIZROJX-UHFFFAOYSA-N 0.000 description 5
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000001384 succinic acid Substances 0.000 description 5
- 229960002317 succinimide Drugs 0.000 description 5
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 4
- SFZQZAQRMKDJHP-UHFFFAOYSA-N 1,5,5-trimethyl-3-trimethylsilylimidazolidine-2,4-dione Chemical compound CN1C(=O)N([Si](C)(C)C)C(=O)C1(C)C SFZQZAQRMKDJHP-UHFFFAOYSA-N 0.000 description 4
- UQJMXAVBXDCOHE-UHFFFAOYSA-N 2-[2-(1,3-dioxoisoindol-2-yl)sulfanyl-4-oxo-3-[(2-phenylacetyl)amino]azetidin-1-yl]-3-methylbut-3-enoic acid Chemical compound O=C1N(C(C(=C)C)C(O)=O)C(SN2C(C3=CC=CC=C3C2=O)=O)C1NC(=O)CC1=CC=CC=C1 UQJMXAVBXDCOHE-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 229950005499 carbon tetrachloride Drugs 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- INZUQGFQRYAKQQ-UHFFFAOYSA-N 2-acetylisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(C(=O)C)C(=O)C2=C1 INZUQGFQRYAKQQ-UHFFFAOYSA-N 0.000 description 3
- MFDDZPYSXOECQJ-UHFFFAOYSA-N 3-acetyl-1,5,5-trimethylimidazolidine-2,4-dione Chemical compound CN1C(=O)N(C(C)=O)C(=O)C1(C)C MFDDZPYSXOECQJ-UHFFFAOYSA-N 0.000 description 3
- FTWWABXHBBWBNV-UHFFFAOYSA-N 4,4-dimethyl-1-trimethylsilylpiperidine-2,6-dione Chemical compound CC1(C)CC(=O)N([Si](C)(C)C)C(=O)C1 FTWWABXHBBWBNV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical group 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 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical class S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- VHEIRTVLOQHBQL-UHFFFAOYSA-N methyl 2-[2-(2,5-dioxopyrrolidin-1-yl)sulfanyl-4-oxo-3-[(2-phenylacetyl)amino]azetidin-1-yl]-3-methylbut-3-enoate Chemical compound C=1C=CC=CC=1CC(=O)NC1C(=O)N(C(C(=O)OC)C(C)=C)C1SN1C(=O)CCC1=O VHEIRTVLOQHBQL-UHFFFAOYSA-N 0.000 description 3
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical class OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- HYBDSXBLGCQKRE-UHFFFAOYSA-N 1-(2,6-dichlorophenyl)ethanone Chemical compound CC(=O)C1=C(Cl)C=CC=C1Cl HYBDSXBLGCQKRE-UHFFFAOYSA-N 0.000 description 2
- HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2,5-dimethylpyridine Chemical compound CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 2
- HORNYPOIDVXNQZ-UHFFFAOYSA-N 2-[2-(2,5-dioxopyrrolidin-1-yl)sulfanyl-4-oxo-3-[(2-phenoxyacetyl)amino]azetidin-1-yl]-3-methylbut-3-enoic acid Chemical compound C=1C=CC=CC=1OCC(=O)NC1C(=O)N(C(C(=C)C)C(O)=O)C1SN1C(=O)CCC1=O HORNYPOIDVXNQZ-UHFFFAOYSA-N 0.000 description 2
- OBETXYAYXDNJHR-UHFFFAOYSA-M 2-ethylhexanoate Chemical compound CCCCC(CC)C([O-])=O OBETXYAYXDNJHR-UHFFFAOYSA-M 0.000 description 2
- BKFNEOXRGFXAML-UHFFFAOYSA-N 2-methylpyridin-1-ium;bromide Chemical compound Br.CC1=CC=CC=N1 BKFNEOXRGFXAML-UHFFFAOYSA-N 0.000 description 2
- GCBXXRPFVSAYKI-UHFFFAOYSA-N 2-trimethylsilyl-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione Chemical compound C1CCCC2C(=O)N([Si](C)(C)C)C(=O)C21 GCBXXRPFVSAYKI-UHFFFAOYSA-N 0.000 description 2
- FVVXWRGARUACNW-UHFFFAOYSA-N 3-methylisoquinoline Chemical compound C1=CC=C2C=NC(C)=CC2=C1 FVVXWRGARUACNW-UHFFFAOYSA-N 0.000 description 2
- HTUBIXOOXNBTCK-UHFFFAOYSA-N 4-ethyl-4-methyl-1-trimethylsilylpiperidine-2,6-dione Chemical compound CCC1(C)CC(=O)N([Si](C)(C)C)C(=O)C1 HTUBIXOOXNBTCK-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical group NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical group CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- 229930195708 Penicillin V Natural products 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- SMRRYUGQTFYZGD-UHFFFAOYSA-K diacetyloxythallanyl acetate Chemical compound [Tl+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SMRRYUGQTFYZGD-UHFFFAOYSA-K 0.000 description 2
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical group C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical group C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- MLFHJEHSLIIPHL-UHFFFAOYSA-N isoamyl acetate Chemical compound CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 229940056367 penicillin v Drugs 0.000 description 2
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- 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 2
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- AHSBSUVHXDIAEY-UHFFFAOYSA-K manganese(iii) acetate Chemical compound [Mn+3].CC([O-])=O.CC([O-])=O.CC([O-])=O AHSBSUVHXDIAEY-UHFFFAOYSA-K 0.000 description 1
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- WOKQHKJYVONEMQ-UHFFFAOYSA-N methyl 2-[2-(1,3-dioxoisoindol-2-yl)sulfanyl-4-oxo-3-[(2-phenylacetyl)amino]azetidin-1-yl]-3-methylbut-3-enoate Chemical compound O=C1N(C(C(=O)OC)C(C)=C)C(SN2C(C3=CC=CC=C3C2=O)=O)C1NC(=O)CC1=CC=CC=C1 WOKQHKJYVONEMQ-UHFFFAOYSA-N 0.000 description 1
- CKXVRPBHWDRPFU-UHFFFAOYSA-N methyl 2-[2-(2,5-dioxopyrrolidin-1-yl)sulfanyl-4-oxo-3-[(2-phenylacetyl)amino]azetidin-1-yl]-3-methylbut-2-enoate Chemical compound C=1C=CC=CC=1CC(=O)NC1C(=O)N(C(C(=O)OC)=C(C)C)C1SN1C(=O)CCC1=O CKXVRPBHWDRPFU-UHFFFAOYSA-N 0.000 description 1
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- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 125000005543 phthalimide group Chemical class 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- KNCYXPMJDCCGSJ-UHFFFAOYSA-N piperidine-2,6-dione Chemical class O=C1CCCC(=O)N1 KNCYXPMJDCCGSJ-UHFFFAOYSA-N 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
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- 125000006239 protecting group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000006049 ring expansion reaction Methods 0.000 description 1
- QYHFIVBSNOWOCQ-UHFFFAOYSA-N selenic acid Chemical compound O[Se](O)(=O)=O QYHFIVBSNOWOCQ-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 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
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- JFHIHGKRIMGLJR-UHFFFAOYSA-N trimethylsilyl 2-[2-(1,3-dioxoisoindol-2-yl)sulfanyl-4-oxo-3-[(2-phenoxyacetyl)amino]azetidin-1-yl]-3-methylbut-3-enoate Chemical compound O=C1N(C(C(=C)C)C(=O)O[Si](C)(C)C)C(SN2C(C3=CC=CC=C3C2=O)=O)C1NC(=O)COC1=CC=CC=C1 JFHIHGKRIMGLJR-UHFFFAOYSA-N 0.000 description 1
- FSVVUUZLGDYIHR-UHFFFAOYSA-N trimethylsilyl 2-[3-(1,3-dioxoisoindol-2-yl)-2-(1,3-dioxoisoindol-2-yl)sulfanyl-4-oxoazetidin-1-yl]-3-methylbut-3-enoate Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1C(SN2C(C3=CC=CC=C3C2=O)=O)N(C(C(=C)C)C(=O)O[Si](C)(C)C)C1=O FSVVUUZLGDYIHR-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052720 vanadium Inorganic materials 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
- C07D501/02—Preparation
- C07D501/08—Preparation by forming the ring or condensed ring systems
- C07D501/10—Preparation by forming the ring or condensed ring systems from compounds containing the penicillin ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/09—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4
- C07D205/095—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4 and with a nitrogen atom directly attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1896—Compounds having one or more Si-O-acyl linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB657673A GB1465893A (en) | 1973-02-09 | 1973-02-09 | I-carboxypropenyl-4-iminothio-azetidine-2-one derivatives methods for their preparation and use |
GB657673 | 1973-02-09 |
Publications (2)
Publication Number | Publication Date |
---|---|
FI63583B FI63583B (fi) | 1983-03-31 |
FI63583C true FI63583C (fi) | 1983-07-11 |
Family
ID=9817015
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI364/74A FI63583C (fi) | 1973-02-09 | 1974-02-08 | Azetidinderivat foer anvaendning som mellanfoereningar till frmstaellning av terapeutiskt aktiva 3-desacetoxi-cefalosp aorsyraderivat och foerfarande foer framstaellning av azeti ndierivaten |
Country Status (30)
Country | Link |
---|---|
US (2) | US3966738A (hu) |
JP (1) | JPS5734836B2 (hu) |
AR (1) | AR204821A1 (hu) |
AT (1) | AT331399B (hu) |
AU (1) | AU6540874A (hu) |
BE (1) | BE810808A (hu) |
BR (1) | BR7400904D0 (hu) |
CA (1) | CA1042873A (hu) |
CH (1) | CH615675A5 (hu) |
CS (1) | CS189623B2 (hu) |
DD (1) | DD111580A5 (hu) |
DE (1) | DE2406165A1 (hu) |
DK (1) | DK153949C (hu) |
ES (1) | ES423051A1 (hu) |
FI (1) | FI63583C (hu) |
FR (1) | FR2260583B1 (hu) |
GB (1) | GB1465893A (hu) |
HU (1) | HU167925B (hu) |
IE (1) | IE38833B1 (hu) |
IL (1) | IL44176A (hu) |
IN (1) | IN139732B (hu) |
IT (1) | IT1055549B (hu) |
LU (1) | LU69361A1 (hu) |
NL (1) | NL181991C (hu) |
NO (1) | NO142815C (hu) |
PH (1) | PH9901A (hu) |
RO (1) | RO67307A (hu) |
SE (1) | SE417958B (hu) |
YU (1) | YU36723B (hu) |
ZA (1) | ZA74831B (hu) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1465893A (en) * | 1973-02-09 | 1977-03-02 | Gist Brocades Nv | I-carboxypropenyl-4-iminothio-azetidine-2-one derivatives methods for their preparation and use |
US4046761A (en) * | 1974-02-08 | 1977-09-06 | Gist-Brocades N.V. | Process for preparing cephalosporin derivatives |
US4159266A (en) * | 1974-12-24 | 1979-06-26 | Eli Lilly And Company | Method of preparation of 3-methylenecephams |
US4018761A (en) * | 1975-02-19 | 1977-04-19 | E. R. Squibb & Sons, Inc. | Thio-β-lactam cephalosporins |
GB1472864A (en) * | 1975-04-05 | 1977-05-11 | Farmaceutici Italia | Method of preparing cephalosporins |
IT1063088B (it) * | 1976-06-01 | 1985-02-11 | Dobfar Spa | Derivati azetidinonici e procedimento per la preparazione di cefalosporine |
US4322347A (en) * | 1978-04-03 | 1982-03-30 | Bristol-Myers Company | 2-Carbamoyloxymethyl-penicillin derivatives |
GB2045236A (en) * | 1979-03-26 | 1980-10-29 | Hoechst Uk Ltd | Oxapenem derivatives |
GB2099817B (en) * | 1981-04-10 | 1985-05-15 | Otsuka Kagaku Yakuhin | Azetidinone derivatives and process for the preparation of the same |
US6383773B2 (en) | 1998-04-23 | 2002-05-07 | Massachusetts Institute Of Technology | Penicillin conversion |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2011376B2 (de) * | 1969-03-11 | 1975-08-28 | Glaxo Laboratories Ltd., Greenford, Middlesex (Grossbritannien) | Verfahren zur Herstellung von 7beta-Acylamido-S-methylceph-S-em^-carbonsäureestern |
US3853861A (en) * | 1969-03-18 | 1974-12-10 | Lilly Co Eli | Cephalexin intermediate |
GB1312233A (en) * | 1969-12-05 | 1973-04-04 | Glaxo Lab Ltd | Cephalosporin compounds |
US3843637A (en) * | 1971-05-11 | 1974-10-22 | Bristol Myers Co | Process for rearranging 6-acylamidopenicillanic acid-1-oxides to 7-acyla mido-3-methyl-ceph-3-em-4-carboxylic acids |
US3840556A (en) * | 1971-05-28 | 1974-10-08 | Lilly Co Eli | Penicillin conversion by halogen electrophiles and anti-bacterials derived thereby |
US3720666A (en) * | 1971-09-02 | 1973-03-13 | American Home Prod | 6-(substituted-4-oxouretidino-1-yl)penicillanic acids |
US3736318A (en) * | 1971-09-09 | 1973-05-29 | American Home Prod | 6-(2-substituted-3-phenyl-2h-isoindole-1-carboxamido)penicillanic acids |
US3944545A (en) * | 1972-05-10 | 1976-03-16 | Eli Lilly And Company | Process for preparing desacetoxycephalosporins |
GB1431174A (en) * | 1972-06-30 | 1976-04-07 | Clin Midy | Process for the conversion of a penicillin s-oxide into a corresponding desacetoxycephalosporin |
JPS4988892A (hu) * | 1972-12-28 | 1974-08-24 | ||
GB1465893A (en) * | 1973-02-09 | 1977-03-02 | Gist Brocades Nv | I-carboxypropenyl-4-iminothio-azetidine-2-one derivatives methods for their preparation and use |
US3962277A (en) * | 1973-02-09 | 1976-06-08 | Gist-Brocades N.V. | Acetidine derivatives |
US4008221A (en) * | 1973-11-07 | 1977-02-15 | Richardson-Merrell Inc. | 6-[(2,4-Dioxo-1-pyrimidinyl)acylamino]penicillin derivatives |
GB1483526A (en) * | 1974-02-08 | 1977-08-24 | Gist Brocades Nv | Azetidine derivatives |
CH602746A5 (hu) * | 1974-03-12 | 1978-07-31 | Hoffmann La Roche | |
DE2440268A1 (de) * | 1974-08-22 | 1976-03-04 | Bayer Ag | Beta-lactamantibiotika, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
US4009160A (en) * | 1974-11-12 | 1977-02-22 | Pfizer Inc. | Aminomethylarylmethylpenicillin derivatives |
DE2457464A1 (de) * | 1974-12-05 | 1976-06-10 | Hoechst Ag | Acylaminopenicillansaeuren und verfahren zu ihrer herstellung |
US3953440A (en) * | 1974-12-13 | 1976-04-27 | Eli Lilly And Company | Deacetoxycephalosporins via penicillin sulfoxide rearrangement |
JPS5195090A (en) * | 1975-02-14 | 1976-08-20 | 66 * dd22 * 33 hidorokishipiridajin 44 karubokishiamido * 22 * paraahidorokishifueniru * asetoamido * penishiransanno seiho |
-
1973
- 1973-02-09 GB GB657673A patent/GB1465893A/en not_active Expired
-
1974
- 1974-01-01 AR AR252251A patent/AR204821A1/es active
- 1974-02-08 YU YU0336/74A patent/YU36723B/xx unknown
- 1974-02-08 PH PH15491*A patent/PH9901A/en unknown
- 1974-02-08 NO NO740431A patent/NO142815C/no unknown
- 1974-02-08 AT AT100774A patent/AT331399B/de not_active IP Right Cessation
- 1974-02-08 IE IE243/74A patent/IE38833B1/xx unknown
- 1974-02-08 ZA ZA740831A patent/ZA74831B/xx unknown
- 1974-02-08 FR FR7404359A patent/FR2260583B1/fr not_active Expired
- 1974-02-08 BE BE140725A patent/BE810808A/xx not_active IP Right Cessation
- 1974-02-08 IL IL44176A patent/IL44176A/en unknown
- 1974-02-08 DE DE19742406165 patent/DE2406165A1/de not_active Withdrawn
- 1974-02-08 ES ES423051A patent/ES423051A1/es not_active Expired
- 1974-02-08 BR BR74904A patent/BR7400904D0/pt unknown
- 1974-02-08 NL NLAANVRAGE7401730,A patent/NL181991C/xx not_active IP Right Cessation
- 1974-02-08 DD DD176471A patent/DD111580A5/xx unknown
- 1974-02-08 CH CH180574A patent/CH615675A5/de not_active IP Right Cessation
- 1974-02-08 RO RO7477586A patent/RO67307A/ro unknown
- 1974-02-08 CA CA192,253A patent/CA1042873A/en not_active Expired
- 1974-02-08 IN IN264/CAL/74A patent/IN139732B/en unknown
- 1974-02-08 IT IT67350/74A patent/IT1055549B/it active
- 1974-02-08 AU AU65408/74A patent/AU6540874A/en not_active Expired
- 1974-02-08 LU LU69361A patent/LU69361A1/xx unknown
- 1974-02-08 JP JP1612274A patent/JPS5734836B2/ja not_active Expired
- 1974-02-08 CS CS74918A patent/CS189623B2/cs unknown
- 1974-02-08 DK DK069174A patent/DK153949C/da not_active IP Right Cessation
- 1974-02-08 US US05/440,725 patent/US3966738A/en not_active Expired - Lifetime
- 1974-02-08 SE SE7401707A patent/SE417958B/xx not_active IP Right Cessation
- 1974-02-08 FI FI364/74A patent/FI63583C/fi active
- 1974-02-08 HU HUGI199A patent/HU167925B/hu unknown
-
1975
- 1975-10-21 US US05/624,332 patent/US4282145A/en not_active Expired - Lifetime
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