CH643265A5 - Antibacterial penem compounds - Google Patents

Antibacterial penem compounds Download PDF

Info

Publication number: CH643265A5
Authority: CH; Switzerland
Prior art keywords: sep; alkyl; mmol; alkylamino; ethyl
Prior art date: 1978-12-18

Application number

CH1121979A

Other languages

German (de)

English (en)

Inventor

Marcel Menard

Alain Martel

Original Assignee

Bristol Myers Co

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.)

1978-12-18

Filing date

1979-12-18

Publication date

1984-05-30

1979-12-18 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1984-05-30 Publication of CH643265A5 publication Critical patent/CH643265A5/de

Links

150000002961 penems Chemical class 0.000 title claims abstract description 14
230000000844 anti-bacterial effect Effects 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 182
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 52
239000001257 hydrogen Substances 0.000 claims abstract description 45
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
239000003242 anti bacterial agent Substances 0.000 claims abstract description 4
239000000203 mixture Substances 0.000 claims description 224
-1 carboxy, carboxy Chemical group 0.000 claims description 148
125000000217 alkyl group Chemical group 0.000 claims description 113
238000000034 method Methods 0.000 claims description 100
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 88
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 86
239000002904 solvent Substances 0.000 claims description 78
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 76
150000002148 esters Chemical group 0.000 claims description 61
238000002360 preparation method Methods 0.000 claims description 61
125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
229910052757 nitrogen Inorganic materials 0.000 claims description 46
125000000623 heterocyclic group Chemical class 0.000 claims description 38
125000001424 substituent group Chemical group 0.000 claims description 36
125000003282 alkyl amino group Chemical group 0.000 claims description 33
150000003839 salts Chemical class 0.000 claims description 33
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 31
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
125000004432 carbon atom Chemical group C* 0.000 claims description 23
238000010992 reflux Methods 0.000 claims description 22
125000001931 aliphatic group Chemical group 0.000 claims description 21
HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 claims description 20
150000002367 halogens Chemical class 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 18
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
239000000543 intermediate Substances 0.000 claims description 18
229910052736 halogen Inorganic materials 0.000 claims description 17
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
150000003254 radicals Chemical class 0.000 claims description 13
238000004519 manufacturing process Methods 0.000 claims description 10
239000003960 organic solvent Substances 0.000 claims description 10
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 10
125000005236 alkanoylamino group Chemical group 0.000 claims description 9
229920006395 saturated elastomer Polymers 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
125000004423 acyloxy group Chemical group 0.000 claims description 6
150000002431 hydrogen Chemical group 0.000 claims description 6
125000004468 heterocyclylthio group Chemical group 0.000 claims description 5
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000002217 penem group Chemical group 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
229930195734 saturated hydrocarbon Natural products 0.000 claims description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
229910052702 rhenium Inorganic materials 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
229920002554 vinyl polymer Polymers 0.000 claims description 3
125000006022 2-methyl-2-propenyl group Chemical group 0.000 claims description 2
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000002015 acyclic group Chemical group 0.000 claims description 2
125000002723 alicyclic group Chemical group 0.000 claims description 2
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
230000003115 biocidal effect Effects 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims 3
229910004727 OSO3H Inorganic materials 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
HHXMXAQDOUCLDN-UHFFFAOYSA-N 4-thia-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical compound S1C=CN2C(=O)CC21 HHXMXAQDOUCLDN-UHFFFAOYSA-N 0.000 claims 1
229910006069 SO3H Inorganic materials 0.000 claims 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000006239 protecting group Chemical class 0.000 abstract description 10
230000000694 effects Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 399
239000000243 solution Substances 0.000 description 320
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 286
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 230
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 221
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 210
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 210
229910001868 water Inorganic materials 0.000 description 193
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 190
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 175
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 134
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 120
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 112
125000003118 aryl group Chemical group 0.000 description 106
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 100
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 90
239000012267 brine Substances 0.000 description 78
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 78
235000019439 ethyl acetate Nutrition 0.000 description 76
239000007787 solid Substances 0.000 description 76
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 72
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
239000003921 oil Substances 0.000 description 68
239000000047 product Substances 0.000 description 68
239000011541 reaction mixture Substances 0.000 description 64
239000000741 silica gel Substances 0.000 description 63
229910002027 silica gel Inorganic materials 0.000 description 63
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 61
229910000030 sodium bicarbonate Inorganic materials 0.000 description 58
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 57
235000017557 sodium bicarbonate Nutrition 0.000 description 57
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 56
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 52
238000006243 chemical reaction Methods 0.000 description 52
229910052943 magnesium sulfate Inorganic materials 0.000 description 50
235000019341 magnesium sulphate Nutrition 0.000 description 49
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 48
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 47
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 47
238000001704 evaporation Methods 0.000 description 46
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 46
230000008020 evaporation Effects 0.000 description 41
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 39
239000000706 filtrate Substances 0.000 description 37
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 36
238000003756 stirring Methods 0.000 description 35
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 34
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 34
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 34
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
239000002253 acid Substances 0.000 description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 28
229910052709 silver Inorganic materials 0.000 description 28
239000004332 silver Substances 0.000 description 28
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 27
238000004458 analytical method Methods 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
239000008346 aqueous phase Substances 0.000 description 23
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 22
239000000284 extract Substances 0.000 description 22
239000012074 organic phase Substances 0.000 description 22
229910052763 palladium Inorganic materials 0.000 description 22
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
238000001816 cooling Methods 0.000 description 21
238000010828 elution Methods 0.000 description 21
239000003054 catalyst Substances 0.000 description 20
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 19
239000002585 base Substances 0.000 description 19
238000004440 column chromatography Methods 0.000 description 19
229940043279 diisopropylamine Drugs 0.000 description 19
238000001035 drying Methods 0.000 description 19
150000003952 β-lactams Chemical class 0.000 description 19
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 18
ZCTHWZKWCUEIHN-UHFFFAOYSA-N 4-tritylsulfanylazetidin-2-one Chemical compound N1C(=O)CC1SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ZCTHWZKWCUEIHN-UHFFFAOYSA-N 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
238000007792 addition Methods 0.000 description 17
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 17
229910052799 carbon Inorganic materials 0.000 description 17
150000001732 carboxylic acid derivatives Chemical class 0.000 description 17
239000000725 suspension Substances 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 16
229910052938 sodium sulfate Inorganic materials 0.000 description 16
235000011152 sodium sulphate Nutrition 0.000 description 16
239000006188 syrup Substances 0.000 description 16
235000020357 syrup Nutrition 0.000 description 16
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 15
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 15
WPUJEWVVTKLMQI-UHFFFAOYSA-N benzene;ethoxyethane Chemical compound CCOCC.C1=CC=CC=C1 WPUJEWVVTKLMQI-UHFFFAOYSA-N 0.000 description 15
239000012039 electrophile Substances 0.000 description 15
229960002510 mandelic acid Drugs 0.000 description 15
238000005406 washing Methods 0.000 description 15
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 14
238000004587 chromatography analysis Methods 0.000 description 14
239000006260 foam Substances 0.000 description 14
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
229910001961 silver nitrate Inorganic materials 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
235000019270 ammonium chloride Nutrition 0.000 description 13
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 13
239000012071 phase Substances 0.000 description 13
239000002244 precipitate Substances 0.000 description 13
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 12
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 12
239000012346 acetyl chloride Substances 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 12
239000003480 eluent Substances 0.000 description 12
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
239000000843 powder Substances 0.000 description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
239000002808 molecular sieve Substances 0.000 description 11
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 11
239000007832 Na2SO4 Substances 0.000 description 10
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 10
150000001450 anions Chemical class 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
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125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
239000010413 mother solution Substances 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
WPLLIZNSPJDMRC-UHFFFAOYSA-N n-[dimethyl-(2,3,4,5-tetramethylcyclopenta-2,4-dien-1-ylidene)-$l^{5}-phosphanyl]adamantan-1-amine Chemical compound CC1=C(C)C(C)=C(C)C1=P(C)(C)NC1(C2)CC(C3)CC2CC3C1 WPLLIZNSPJDMRC-UHFFFAOYSA-N 0.000 description 1
125000002004 n-butylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004708 n-butylthio group Chemical group C(CCC)S* 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000004533 oil dispersion Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
229940116315 oxalic acid Drugs 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
238000006303 photolysis reaction Methods 0.000 description 1
230000015843 photosynthesis, light reaction Effects 0.000 description 1
238000011176 pooling Methods 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
HQHLWYMGKLFSKO-PFEQFJNWSA-M potassium;(5r)-5-[(2-hydroxyphenyl)methyl]-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [K+].C([C@@]12CC(=O)N1C(=C(S2)C)C([O-])=O)C1=CC=CC=C1O HQHLWYMGKLFSKO-PFEQFJNWSA-M 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000004007 reversed phase HPLC 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
102220047090 rs6152 Human genes 0.000 description 1
ZADZMOWCAUMICY-UHFFFAOYSA-N s-(2-oxoazetidin-1-yl) ethanethioate Chemical compound CC(=O)SN1CCC1=O ZADZMOWCAUMICY-UHFFFAOYSA-N 0.000 description 1
NYOUQWVIMBQOJL-UHFFFAOYSA-N s-(4-oxoazetidin-2-yl) ethanethioate Chemical compound CC(=O)SC1CC(=O)N1 NYOUQWVIMBQOJL-UHFFFAOYSA-N 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
150000003378 silver Chemical class 0.000 description 1
AXFFSUQSXMBCOS-NNCSWIEZSA-M sodium (5R)-6-(1-hydroxyethyl)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound OC(C)C1[C@@H]2N(C(=C(S2)C)C(=O)[O-])C1=O.[Na+] AXFFSUQSXMBCOS-NNCSWIEZSA-M 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 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
VWMRHWQOUZWXNN-UHFFFAOYSA-M sodium;5-methyl-1,3-thiazole-4-carboxylate Chemical compound [Na+].CC=1SC=NC=1C([O-])=O VWMRHWQOUZWXNN-UHFFFAOYSA-M 0.000 description 1
XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
RBBWNXJFTBCLKT-UHFFFAOYSA-M sodium;ethanethioate Chemical compound [Na+].CC([S-])=O RBBWNXJFTBCLKT-UHFFFAOYSA-M 0.000 description 1
238000007614 solvation Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
WRYRBZBPAFNIMX-UHFFFAOYSA-N sulfanide;triethylazanium Chemical compound S.CCN(CC)CC WRYRBZBPAFNIMX-UHFFFAOYSA-N 0.000 description 1
QXKXDIKCIPXUPL-UHFFFAOYSA-N sulfanylidenemercury Chemical compound [Hg]=S QXKXDIKCIPXUPL-UHFFFAOYSA-N 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
150000003553 thiiranes Chemical class 0.000 description 1
239000010409 thin film Substances 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
150000007944 thiolates Chemical class 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
230000017105 transposition Effects 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
238000005866 tritylation reaction Methods 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
229920001567 vinyl ester resin Polymers 0.000 description 1
239000008096 xylene Substances 0.000 description 1
239000002132 β-lactam antibiotic Substances 0.000 description 1
229940124586 β-lactam antibiotics Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C247/00—Compounds containing azido groups
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/88—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- 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
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
- 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
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
- 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
- C07F7/1804—Compounds having Si-O-C linkages
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/568—Four-membered rings
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
- C07F9/6539—Five-membered rings
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65611—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system (X = CH2, O, S, NH) optionally with an additional double bond and/or substituents, e.g. penicillins and analogs
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Communicable Diseases (AREA)
Chemical Kinetics & Catalysis (AREA)
Oncology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Saccharide Compounds (AREA)
Cephalosporin Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CH1121979A 1978-12-18 1979-12-18 Antibacterial penem compounds CH643265A5 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US96866378A	1978-12-18	1978-12-18

Publications (1)

Publication Number	Publication Date
CH643265A5 true CH643265A5 (en)	1984-05-30

Family

ID=25514601

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CH1121979A CH643265A5 (en)	1978-12-18	1979-12-18	Antibacterial penem compounds
CH1121879A CH643846A5 (en)	1978-12-18	1979-12-18	Antibacterial penem compounds

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CH1121879A CH643846A5 (en)	1978-12-18	1979-12-18	Antibacterial penem compounds

Country Status (13)

Country	Link
JP (1)	JPS60222486A (fr)
AU (4)	AU541717B2 (fr)
CA (2)	CA1286661C (fr)
CH (2)	CH643265A5 (fr)
DK (5)	DK161520C (fr)
ES (1)	ES8101594A1 (fr)
FI (2)	FI69845C (fr)
GR (2)	GR81420B (fr)
IE (3)	IE50597B1 (fr)
IL (2)	IL58576A (fr)
SE (5)	SE448995B (fr)
YU (4)	YU43628B (fr)
ZA (2)	ZA796813B (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8509180D0 (en) *	1985-04-10	1985-05-15	Erba Farmitalia	Penem derivatives
US4826832A (en) *	1986-05-06	1989-05-02	Ciba-Geigy Corporation	Penen compounds
EP0757051B1 (fr) *	1995-02-17	2003-10-29	Daiichi Suntory Pharma Co., Ltd.	Derives de peneme et agent anti-microbien les contenant
WO1999036098A1 (fr)	1998-01-13	1999-07-22	Suntory Limited	Composition antibacterienne contenant des antibiotiques et destinee a l'administration topique
JP2005239696A (ja)	2004-01-30	2005-09-08	Daiichi Suntory Pharma Co Ltd	無機物質を配合した医薬硬質カプセル剤
CN112746066B (zh) *	2021-01-25	2023-10-31	洛阳华荣生物技术有限公司	一种l-赖氨酸脱羧酶突变体及其应用

1979
- 1979-10-29 IL IL58576A patent/IL58576A/xx unknown
- 1979-11-07 GR GR60450A patent/GR81420B/el unknown
- 1979-11-12 YU YU2760/79A patent/YU43628B/xx unknown
- 1979-11-26 IL IL58804A patent/IL58804A/xx unknown
- 1979-11-29 GR GR60633A patent/GR74491B/el unknown
- 1979-12-10 JP JP79159315D patent/JPS60222486A/ja active Pending
- 1979-12-11 AU AU53710/79A patent/AU541717B2/en not_active Ceased
- 1979-12-13 FI FI793903A patent/FI69845C/fi not_active IP Right Cessation
- 1979-12-13 AU AU53787/79A patent/AU539983B2/en not_active Ceased
- 1979-12-13 FI FI793905A patent/FI67853C/fi not_active IP Right Cessation
- 1979-12-14 ZA ZA00796813A patent/ZA796813B/xx unknown
- 1979-12-14 DK DK533779A patent/DK161520C/da not_active IP Right Cessation
- 1979-12-14 ZA ZA00796812A patent/ZA796812B/xx unknown
- 1979-12-14 DK DK533879A patent/DK533879A/da not_active Application Discontinuation
- 1979-12-17 YU YU3076/79A patent/YU43464B/xx unknown
- 1979-12-17 SE SE7910391A patent/SE448995B/sv not_active IP Right Cessation
- 1979-12-17 SE SE7910390A patent/SE454779B/sv not_active IP Right Cessation
- 1979-12-17 CA CA000342069A patent/CA1286661C/fr not_active Expired - Fee Related
- 1979-12-18 ES ES487034A patent/ES8101594A1/es not_active Expired
- 1979-12-18 CH CH1121979A patent/CH643265A5/de not_active IP Right Cessation
- 1979-12-18 IE IE1853/85A patent/IE50597B1/en unknown
- 1979-12-18 CH CH1121879A patent/CH643846A5/de not_active IP Right Cessation
- 1979-12-18 IE IE2462/79A patent/IE49876B1/en unknown
- 1979-12-18 IE IE2246/85A patent/IE49877B1/en unknown
1982
- 1982-09-27 YU YU2153/82A patent/YU43280B/xx unknown
- 1982-09-27 YU YU2157/82A patent/YU42125B/xx unknown
1983
- 1983-03-08 CA CA000423146A patent/CA1268183A/fr not_active Expired - Fee Related
1984
- 1984-08-24 AU AU32408/84A patent/AU557545B2/en not_active Ceased
- 1984-09-10 AU AU32884/84A patent/AU563015B2/en not_active Ceased
- 1984-11-14 SE SE8405719A patent/SE461395B/sv not_active IP Right Cessation
- 1984-11-19 SE SE8405812A patent/SE8405812D0/xx not_active Application Discontinuation
- 1984-11-19 SE SE8405813A patent/SE464027B/sv not_active IP Right Cessation
1990
- 1990-10-01 DK DK236590A patent/DK161970C/da not_active IP Right Cessation
- 1990-10-01 DK DK237690A patent/DK237690A/da not_active Application Discontinuation
1991
- 1991-07-15 DK DK135291A patent/DK135291A/da not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA1268183A (fr)	1990-04-24
AU563015B2 (en)	1987-06-25
SE8405719D0 (sv)	1984-11-14
FI793905A7 (fi)	1980-06-19
SE8405813L (sv)	1984-11-19
AU557545B2 (en)	1986-12-24
YU43628B (en)	1989-10-31
IL58804A0 (en)	1980-02-29
AU541717B2 (en)	1985-01-17
DK161520B (da)	1991-07-15
AU5371079A (en)	1980-06-26
CA1286661C (fr)	1991-07-23
SE448995B (sv)	1987-03-30
DK135291D0 (da)	1991-07-15
SE461395B (sv)	1990-02-12
AU3288484A (en)	1985-03-07
SE8405812L (sv)	1984-11-19
IL58576A0 (en)	1980-01-31
YU276079A (en)	1983-02-28
DK533879A (da)	1980-06-19
CH643846A5 (en)	1984-06-29
FI67853C (fi)	1985-06-10
ES487034A0 (es)	1980-12-16
FI69845B (fi)	1985-12-31
SE8405813D0 (sv)	1984-11-19
DK236590D0 (da)	1990-10-01
ZA796813B (en)	1981-05-27
FI67853B (fi)	1985-02-28
AU5378779A (en)	1980-08-28
SE7910391L (sv)	1981-06-18
DK237690D0 (da)	1990-10-01
YU215782A (en)	1983-06-30
AU3240884A (en)	1984-12-13
YU43464B (en)	1989-08-31
SE8405719L (sv)	1984-11-14
GR81420B (fr)	1984-12-11
IL58576A (en)	1985-12-31
AU539983B2 (en)	1984-10-25
IE792462L (en)	1980-06-18
ES8101594A1 (es)	1980-12-16
JPS60222486A (ja)	1985-11-07
IE50597B1 (en)	1986-05-28
DK533779A (da)	1980-06-19
YU43280B (en)	1989-06-30
SE7910390L (sv)	1981-06-18
DK161970C (da)	1992-02-03
GR74491B (fr)	1984-06-28
YU215382A (en)	1983-06-30
IL58804A (en)	1986-03-31
IE851853L (en)	1980-06-18
IE852246L (en)	1980-06-18
YU42125B (en)	1988-04-30
YU307679A (en)	1983-02-28
IE49877B1 (en)	1986-01-08
SE464027B (sv)	1991-02-25
DK236590A (da)	1990-10-01
IE49876B1 (en)	1986-01-08
DK135291A (da)	1991-07-15
SE8405812D0 (sv)	1984-11-19
FI793903A7 (fi)	1980-06-19
DK237690A (da)	1990-10-01
DK161520C (da)	1991-12-23
FI69845C (fi)	1986-05-26
DK161970B (da)	1991-09-02
SE454779B (sv)	1988-05-30
ZA796812B (en)	1981-05-27

Legal Events

Date	Code	Title	Description
1992-08-31	PL	Patent ceased
2024-10-31	PL	Patent ceased

Publication	Publication Date	Title
DE2950898A1 (de)	1980-07-03	Neue penemverbindungen, verfahren zu deren herstellung und arzneimittel
DE2751624C2 (fr)	1988-09-08
EP0002210A1 (fr)	1979-06-13	Acides pen-2-em-3-carboxyliques substitués en position 6- et 2- ou en position 6,6- et 2-; leurs procédés de préparation et compositions pharmaceutiques les contenant
JPH0329789B2 (fr)	1991-04-25
JPH0440357B2 (fr)	1992-07-02
DD152339A5 (de)	1981-11-25	Verfahren zur herstellung von 2-penem-verbindungen
JPH0545596B2 (fr)	1993-07-09
DE2529941A1 (de)	1976-04-08	Azetidinonderivate und verfahren zu ihrer herstellung
DE3429102A1 (de)	1985-02-28	Verfahren zur herstellung von penem-verbindungen
DE3109086C2 (fr)	1991-05-02
DE3854874T2 (de)	1996-05-23	Diastereomere 5R,6S-6-(1R-hydroxyethyl)-2-(Cis-1-oxo-3-thiolanylthio)-2-Penem-3-Carbonsäuren
DD152561A5 (de)	1981-12-02	Verfahren zur herstellung von penizillinderivaten
EP0074599A1 (fr)	1983-03-23	Dérivés de 5,6-cis-carbapénème, leurs préparation et utilisation
DE3122523C2 (fr)	1990-10-18
EP0247431A1 (fr)	1987-12-02	Antibiotiques du 6-hydroxyméthylcarbapénème substitués, leur procédé de préparation et leur application
CA1136617A (fr)	1982-11-30	Composes penem substitues en positions 2 et 6
DE3344317C2 (fr)	1992-02-27
NO159796B (no)	1988-10-31	Fremgangsmaate ved fremstilling av terapeutisk aktive 2- (fluoralkylthio)substituerte penemer.
DE3007298A1 (de)	1981-09-03	Verfahren zur herstellung von azetidinonen und deren verwendung
CH643846A5 (en)	1984-06-29	Antibacterial penem compounds
DE2751597A1 (de)	1978-05-24	3-(2-aminoaethylthio)-6-(1-hydroxyaethyl)-7-oxo-1-azabicyclo eckige klammer auf 3.2.0 eckige klammer zu hept-2-en- 2-carbonsaeure
DE69125015T2 (de)	1997-06-19	Cephalosporin-derivate und deren homologe
EP0010358A1 (fr)	1980-04-30	Composés de bêta-lactame, procédés pour leur préparation, compositions les contenant, intermédiaires utilisables dans leur préparation et méthodes pour leur production
EP0125208A1 (fr)	1984-11-14	Dérivés d'amino-alcoyl-inférieur-pénème, procédé pour leur préparation, compositions pharmaceutiques les contenant et leur application
EP0112283B1 (fr)	1987-08-12	Dérivés hétérocyclylthio, procédé pour leur préparation, compositions pharmaceutiques les contenant et leur application