NL8101167A - 2-penem-3-carbonzuurverbindingen, hun bereiding en gebruik. - Google Patents

2-penem-3-carbonzuurverbindingen, hun bereiding en gebruik. Download PDF

Info

Publication number: NL8101167A
Authority: NL; Netherlands
Prior art keywords: group; formula; compound; alkyl; amino
Prior art date: 1980-03-10

Application number

NL8101167A

Other languages

English (en)

Dutch (nl)

Original Assignee

Sankyo 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.)

1980-03-10

Filing date

1981-03-10

Publication date

1981-10-01

1980-03-10 Priority claimed from JP3001380A external-priority patent/JPS56142282A/ja

1980-03-17 Priority claimed from JP3352980A external-priority patent/JPS56142283A/ja

1980-06-03 Priority claimed from JP7476180A external-priority patent/JPS572289A/ja

1981-03-10 Application filed by Sankyo Co filed Critical Sankyo Co

1981-10-01 Publication of NL8101167A publication Critical patent/NL8101167A/nl

Links

238000002360 preparation method Methods 0.000 title description 48
-1 hydroxy, amino, carbonyl Chemical group 0.000 claims description 473
150000001875 compounds Chemical class 0.000 claims description 293
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 147
238000006243 chemical reaction Methods 0.000 claims description 136
239000000203 mixture Substances 0.000 claims description 114
238000000034 method Methods 0.000 claims description 108
125000000217 alkyl group Chemical group 0.000 claims description 101
125000003277 amino group Chemical group 0.000 claims description 86
125000003545 alkoxy group Chemical group 0.000 claims description 52
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 46
125000003118 aryl group Chemical group 0.000 claims description 39
125000005843 halogen group Chemical group 0.000 claims description 38
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 36
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
125000003710 aryl alkyl group Chemical group 0.000 claims description 31
125000006239 protecting group Chemical group 0.000 claims description 31
150000003839 salts Chemical class 0.000 claims description 30
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 26
150000002148 esters Chemical class 0.000 claims description 25
159000000000 sodium salts Chemical class 0.000 claims description 25
125000004414 alkyl thio group Chemical group 0.000 claims description 24
125000004423 acyloxy group Chemical group 0.000 claims description 23
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 22
125000004442 acylamino group Chemical group 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 22
125000000623 heterocyclic group Chemical group 0.000 claims description 19
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
229920006395 saturated elastomer Polymers 0.000 claims description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 16
125000001424 substituent group Chemical group 0.000 claims description 16
125000001931 aliphatic group Chemical group 0.000 claims description 15
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 15
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 14
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 14
YQCIWBXEVYWRCW-UHFFFAOYSA-N methane;sulfane Chemical compound C.S YQCIWBXEVYWRCW-UHFFFAOYSA-N 0.000 claims description 13
125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
125000005035 acylthio group Chemical group 0.000 claims description 10
125000004122 cyclic group Chemical group 0.000 claims description 10
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
125000005389 trialkylsiloxy group Chemical group 0.000 claims description 10
GJEAMHAFPYZYDE-UHFFFAOYSA-N [C].[S] Chemical compound [C].[S] GJEAMHAFPYZYDE-UHFFFAOYSA-N 0.000 claims description 9
125000000033 alkoxyamino group Chemical group 0.000 claims description 9
239000003242 anti bacterial agent Substances 0.000 claims description 9
239000000126 substance Substances 0.000 claims description 9
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
230000003115 biocidal effect Effects 0.000 claims description 7
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 7
125000003396 thiol group Chemical group [H]S* 0.000 claims description 7
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
229910052708 sodium Inorganic materials 0.000 claims description 6
239000011734 sodium Substances 0.000 claims description 6
229940088710 antibiotic agent Drugs 0.000 claims description 5
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
125000004104 aryloxy group Chemical group 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 3
230000015572 biosynthetic process Effects 0.000 claims description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
125000001769 aryl amino group Chemical group 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
239000000543 intermediate Substances 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
239000011591 potassium Substances 0.000 claims description 2
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
241001331845 Equus asinus x caballus Species 0.000 claims 1
101001114407 Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) 30S ribosomal protein S6e Proteins 0.000 claims 1
101000718286 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) 30S ribosomal protein S13 Proteins 0.000 claims 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 1
ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 claims 1
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
239000000243 solution Substances 0.000 description 103
238000000862 absorption spectrum Methods 0.000 description 95
239000000047 product Substances 0.000 description 94
239000002904 solvent Substances 0.000 description 86
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 69
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 68
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
229960000583 acetic acid Drugs 0.000 description 56
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
241000786363 Rhampholeon spectrum Species 0.000 description 53
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 45
235000011054 acetic acid Nutrition 0.000 description 45
238000001228 spectrum Methods 0.000 description 35
239000002585 base Substances 0.000 description 34
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 31
230000002829 reductive effect Effects 0.000 description 30
239000000460 chlorine Chemical group 0.000 description 29
229910052801 chlorine Inorganic materials 0.000 description 29
239000007864 aqueous solution Substances 0.000 description 28
239000003480 eluent Substances 0.000 description 28
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 27
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
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 25
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 23
239000011780 sodium chloride Substances 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
238000003756 stirring Methods 0.000 description 21
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 17
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
238000010898 silica gel chromatography Methods 0.000 description 16
239000003795 chemical substances by application Substances 0.000 description 15
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 15
VQFAIAKCILWQPZ-UHFFFAOYSA-N bromoacetone Chemical compound CC(=O)CBr VQFAIAKCILWQPZ-UHFFFAOYSA-N 0.000 description 14
238000004440 column chromatography Methods 0.000 description 14
239000007858 starting material Substances 0.000 description 14
229910021529 ammonia Inorganic materials 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
239000003638 chemical reducing agent Substances 0.000 description 12
238000001816 cooling Methods 0.000 description 12
239000003960 organic solvent Substances 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
150000004702 methyl esters Chemical class 0.000 description 11
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 10
230000002411 adverse Effects 0.000 description 10
229910052731 fluorine Inorganic materials 0.000 description 10
239000011737 fluorine Substances 0.000 description 10
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 10
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 10
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
238000012746 preparative thin layer chromatography Methods 0.000 description 9
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
KTQYRXHQQNGZGC-UHFFFAOYSA-N 2-(2-methylsulfanyl-4-oxoazetidin-1-yl)acetic acid Chemical compound CSC1CC(=O)N1CC(O)=O KTQYRXHQQNGZGC-UHFFFAOYSA-N 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
229910052794 bromium Chemical group 0.000 description 8
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
239000013078 crystal Substances 0.000 description 8
230000002140 halogenating effect Effects 0.000 description 8
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
150000002170 ethers Chemical class 0.000 description 7
238000001819 mass spectrum Methods 0.000 description 7
244000005700 microbiome Species 0.000 description 7
238000000746 purification Methods 0.000 description 7
125000000446 sulfanediyl group Chemical group *S* 0.000 description 7
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
235000014113 dietary fatty acids Nutrition 0.000 description 6
239000000194 fatty acid Substances 0.000 description 6
229930195729 fatty acid Natural products 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
238000011084 recovery Methods 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
239000008096 xylene Substances 0.000 description 6
ZMXDDKWLCZADIW-YYWVXINBSA-N DMF-d7 Substances [2H]C(=O)N(C([2H])([2H])[2H])C([2H])([2H])[2H] ZMXDDKWLCZADIW-YYWVXINBSA-N 0.000 description 5
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
229940113088 dimethylacetamide Drugs 0.000 description 5
150000004665 fatty acids Chemical class 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
150000007530 organic bases Chemical class 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
238000005406 washing Methods 0.000 description 5
JYBFBEHQCOUIFO-SYPWQXSBSA-N (5r)-7-oxo-3-sulfanylidene-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound S1C(=S)C(C(=O)O)N2C(=O)C[C@H]21 JYBFBEHQCOUIFO-SYPWQXSBSA-N 0.000 description 4
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
229930182555 Penicillin Natural products 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
239000002168 alkylating agent Substances 0.000 description 4
229940100198 alkylating agent Drugs 0.000 description 4
230000000694 effects Effects 0.000 description 4
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 4
150000008282 halocarbons Chemical class 0.000 description 4
238000005658 halogenation reaction Methods 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
150000002960 penicillins Chemical group 0.000 description 4
238000000039 preparative column chromatography Methods 0.000 description 4
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
238000007086 side reaction Methods 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
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 4
USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical compound OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000012043 crude product Substances 0.000 description 3
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 3
230000026030 halogenation Effects 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
WSHJJCPTKWSMRR-RXMQYKEDSA-N penam Chemical compound S1CCN2C(=O)C[C@H]21 WSHJJCPTKWSMRR-RXMQYKEDSA-N 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000000376 reactant Substances 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
235000009518 sodium iodide Nutrition 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
DMEYZPJEFHGESJ-CPWLGJMPSA-M (5R,6Z)-6-(6,8-dihydro-5H-imidazo[2,1-c][1,4]oxazin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [O-]C(=O)C1=CS[C@H]2N1C(=O)\C2=C\C1=CN2CCOCC2=N1 DMEYZPJEFHGESJ-CPWLGJMPSA-M 0.000 description 2
OGEIIQUGVBIEGI-OBBYJWLBSA-N (5r)-6-(1-hydroxyethyl)-7-oxo-3-sulfanylidene-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound S1C(=S)C(C(O)=O)N2C(=O)C(C(O)C)[C@H]21 OGEIIQUGVBIEGI-OBBYJWLBSA-N 0.000 description 2
DUNKKIRUWZSMPT-RXMQYKEDSA-N (5r)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical class OC(=O)C1=CS[C@@H]2CC(=O)N12 DUNKKIRUWZSMPT-RXMQYKEDSA-N 0.000 description 2
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 2
LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 2
ILLHORFDXDLILE-UHFFFAOYSA-N 2-bromopropanoyl bromide Chemical compound CC(Br)C(Br)=O ILLHORFDXDLILE-UHFFFAOYSA-N 0.000 description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
WZPSXMPWJCIGAY-UHFFFAOYSA-N 4-methylsulfanylazetidin-2-one Chemical compound CSC1CC(=O)N1 WZPSXMPWJCIGAY-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229910052770 Uranium Inorganic materials 0.000 description 2
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
230000007059 acute toxicity Effects 0.000 description 2
231100000403 acute toxicity Toxicity 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
125000001118 alkylidene group Chemical group 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
150000001768 cations Chemical class 0.000 description 2
150000001805 chlorine compounds Chemical class 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000002274 desiccant Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
238000001035 drying Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
125000005842 heteroatom Chemical group 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
150000002440 hydroxy compounds Chemical class 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
150000002497 iodine compounds Chemical class 0.000 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 description 2
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
229940087646 methanolamine Drugs 0.000 description 2
244000000010 microbial pathogen Species 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 description 2
150000002961 penems Chemical class 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
125000004344 phenylpropyl group Chemical group 0.000 description 2
239000008055 phosphate buffer solution Substances 0.000 description 2
229910000073 phosphorus hydride Inorganic materials 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
IWSWFVNUXDVDLT-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-aminoacetate Chemical compound NCC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 IWSWFVNUXDVDLT-UHFFFAOYSA-N 0.000 description 1
BELYDNDBYRAPBP-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-iodoacetate Chemical compound [O-][N+](=O)C1=CC=C(COC(=O)CI)C=C1 BELYDNDBYRAPBP-UHFFFAOYSA-N 0.000 description 1
HVRMNEPIBIGCNZ-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-oxoacetate Chemical compound [O-][N+](=O)C1=CC=C(COC(=O)C=O)C=C1 HVRMNEPIBIGCNZ-UHFFFAOYSA-N 0.000 description 1
OIHLWKOVIJPVHC-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-oxoacetate;hydrate Chemical compound O.[O-][N+](=O)C1=CC=C(COC(=O)C=O)C=C1 OIHLWKOVIJPVHC-UHFFFAOYSA-N 0.000 description 1
HFIDQRIALLFMBE-ZCFIWIBFSA-N (5R)-3-(2-amino-2-oxoethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carbothioic S-acid Chemical compound C(N)(=O)CC=1S[C@H]2N(C=1C(=S)O)C(C2)=O HFIDQRIALLFMBE-ZCFIWIBFSA-N 0.000 description 1
PTKYNPNEWCBHIO-SSDOTTSWSA-N (5R)-3-(2-ethoxy-2-oxoethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carbothioic S-acid Chemical compound C(C)OC(=O)CC=1S[C@H]2N(C=1C(=S)O)C(C2)=O PTKYNPNEWCBHIO-SSDOTTSWSA-N 0.000 description 1
YGRKLYNTPUJJRY-ZCFIWIBFSA-N (5R)-3-(2-hydrazinyl-2-oxoethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carbothioic S-acid Chemical compound N(N)C(=O)CC=1S[C@H]2N(C=1C(=S)O)C(C2)=O YGRKLYNTPUJJRY-ZCFIWIBFSA-N 0.000 description 1
RYXLZLYKNJGDCY-SSDOTTSWSA-N (5R)-3-(morpholine-4-carbonyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carbothioic S-acid Chemical compound O1CCN(CC1)C(=O)C=1S[C@H]2N(C=1C(=S)O)C(C2)=O RYXLZLYKNJGDCY-SSDOTTSWSA-N 0.000 description 1
BMJITHLQVLBNNE-RXMQYKEDSA-N (5R)-3-methyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carbothioic S-acid Chemical compound CC1=C(N2[C@H](S1)CC2=O)C(=O)S BMJITHLQVLBNNE-RXMQYKEDSA-N 0.000 description 1
UVFCHWTUYSKMFS-YBIVKOOQSA-N (5R)-6-(1-acetyloxyethyl)-7-oxo-3-sulfanylidene-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound CC(C1[C@@H]2N(C1=O)C(C(=S)S2)C(=O)O)OC(=O)C UVFCHWTUYSKMFS-YBIVKOOQSA-N 0.000 description 1
SUQYIDHCMVXBNU-LNFLDPOISA-N (5r)-3-(1-amino-1-oxopropan-2-yl)sulfanyl-6-(1-hydroxyethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1C(SC(C)C(N)=O)=C(C(O)=O)N2C(=O)C(C(O)C)[C@H]21 SUQYIDHCMVXBNU-LNFLDPOISA-N 0.000 description 1
BMGIXMGNSJJMIK-NERYYWBQSA-N (5r)-3-(1-amino-1-oxopropan-2-yl)sulfanyl-6-(hydroxymethyl)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1C(SC(C)C(N)=O)=C(C(O)=O)N2C(=O)C(CO)[C@@H]12 BMGIXMGNSJJMIK-NERYYWBQSA-N 0.000 description 1
LASNHXXZDAIHGQ-PACJAATDSA-N (5r)-3-(1-amino-1-oxopropan-2-yl)sulfanyl-6-ethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound S1C(SC(C)C(N)=O)=C(C(O)=O)N2C(=O)C(CC)[C@H]21 LASNHXXZDAIHGQ-PACJAATDSA-N 0.000 description 1
QVFKXIGCRPORSQ-VUYXPMRHSA-N (5r)-6-methoxy-7-oxo-3-sulfanylidene-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound S1C(=S)C(C(O)=O)N2C(=O)C(OC)[C@H]21 QVFKXIGCRPORSQ-VUYXPMRHSA-N 0.000 description 1
ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
ZRSKKRWCHNPOPE-UHFFFAOYSA-N 1,1-dibromobutane Chemical compound CCCC(Br)Br ZRSKKRWCHNPOPE-UHFFFAOYSA-N 0.000 description 1
DOBKWAAQCPDCBB-UHFFFAOYSA-N 1,3-dithiolan-4-ol Chemical compound OC1CSCS1 DOBKWAAQCPDCBB-UHFFFAOYSA-N 0.000 description 1
TZTGIYRFLYRDHP-UHFFFAOYSA-N 1,3-dithiolan-4-one Chemical compound O=C1CSCS1 TZTGIYRFLYRDHP-UHFFFAOYSA-N 0.000 description 1
CJXQAYQWVNXIQE-UHFFFAOYSA-N 2,2-dimethylpropanedioyl dichloride Chemical compound ClC(=O)C(C)(C)C(Cl)=O CJXQAYQWVNXIQE-UHFFFAOYSA-N 0.000 description 1
OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 1
KJIISCSBODNHIG-RXMQYKEDSA-N 2-[(5R)-7-oxo-2-sulfanylcarbonyl-4-thia-1-azabicyclo[3.2.0]hept-2-en-3-yl]acetic acid Chemical compound C(=O)(O)CC=1S[C@H]2N(C=1C(=S)O)C(C2)=O KJIISCSBODNHIG-RXMQYKEDSA-N 0.000 description 1
LAGJFIZOWYYHDP-UHFFFAOYSA-N 2-hydroxy-2-(2-methylsulfanyl-4-oxoazetidin-1-yl)acetic acid Chemical compound CSC1CC(=O)N1C(O)C(O)=O LAGJFIZOWYYHDP-UHFFFAOYSA-N 0.000 description 1
XQCWOAMYQRDOQY-UHFFFAOYSA-N 2-iodoacetaldehyde Chemical compound ICC=O XQCWOAMYQRDOQY-UHFFFAOYSA-N 0.000 description 1
QKSBEDINHRIOJR-UHFFFAOYSA-N 2-iodopropanamide Chemical compound CC(I)C(N)=O QKSBEDINHRIOJR-UHFFFAOYSA-N 0.000 description 1
LLWADFLAOKUBDR-UHFFFAOYSA-N 2-methyl-4-chlorophenoxybutyric acid Chemical compound CC1=CC(Cl)=CC=C1OCCCC(O)=O LLWADFLAOKUBDR-UHFFFAOYSA-N 0.000 description 1
ICNCZFQYZKPYMS-UHFFFAOYSA-N 2-methylpropanoyl bromide Chemical compound CC(C)C(Br)=O ICNCZFQYZKPYMS-UHFFFAOYSA-N 0.000 description 1
FUAKCPWOVKGAFN-UHFFFAOYSA-N 3-[1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-methylsulfanylazetidin-2-one Chemical compound CSC1NC(=O)C1C(C)O[Si](C)(C)C(C)(C)C FUAKCPWOVKGAFN-UHFFFAOYSA-N 0.000 description 1
ONZQYZKCUHFORE-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)CBr ONZQYZKCUHFORE-UHFFFAOYSA-N 0.000 description 1
IHBVNSPHKMCPST-UHFFFAOYSA-N 3-bromopropanoyl chloride Chemical compound ClC(=O)CCBr IHBVNSPHKMCPST-UHFFFAOYSA-N 0.000 description 1
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 1
RMBXKBYYWPXMDU-UHFFFAOYSA-N 4-[2-[[[2-(4-bromothiophen-2-yl)-2-hydroxyethyl]amino]methyl]phenoxy]butanoic acid Chemical compound C=1C(Br)=CSC=1C(O)CNCC1=CC=CC=C1OCCCC(O)=O RMBXKBYYWPXMDU-UHFFFAOYSA-N 0.000 description 1
JKTYGPATCNUWKN-UHFFFAOYSA-N 4-nitrobenzyl alcohol Chemical compound OCC1=CC=C([N+]([O-])=O)C=C1 JKTYGPATCNUWKN-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
244000063299 Bacillus subtilis Species 0.000 description 1
235000014469 Bacillus subtilis Nutrition 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
235000017647 Brassica oleracea var italica Nutrition 0.000 description 1
240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
101100352919 Caenorhabditis elegans ppm-2 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
241000588722 Escherichia Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
HHLFWLYXYJOTON-UHFFFAOYSA-N Glyoxylic acid Natural products OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
241000588748 Klebsiella Species 0.000 description 1
241000588747 Klebsiella pneumoniae Species 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
235000011613 Pinus brutia Nutrition 0.000 description 1
241000018646 Pinus brutia Species 0.000 description 1
241000588769 Proteus <enterobacteria> Species 0.000 description 1
241000588767 Proteus vulgaris Species 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
241000589517 Pseudomonas aeruginosa Species 0.000 description 1
241000607142 Salmonella Species 0.000 description 1
241000607762 Shigella flexneri Species 0.000 description 1
241000147000 Shigella flexneri 2a Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
241000191940 Staphylococcus Species 0.000 description 1
241000191967 Staphylococcus aureus Species 0.000 description 1
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
GWHDKFODLYVMQG-UHFFFAOYSA-N [3-[1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidin-2-yl] acetate Chemical compound CC(C)(C)[Si](C)(C)OC(C)C1C(OC(C)=O)NC1=O GWHDKFODLYVMQG-UHFFFAOYSA-N 0.000 description 1
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001263 acyl chlorides Chemical class 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000015107 ale Nutrition 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910052977 alkali metal sulfide Inorganic materials 0.000 description 1
125000005276 alkyl hydrazino group Chemical group 0.000 description 1
YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
UYJXRRSPUVSSMN-UHFFFAOYSA-P ammonium sulfide Chemical compound [NH4+].[NH4+].[S-2] UYJXRRSPUVSSMN-UHFFFAOYSA-P 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
150000003974 aralkylamines Chemical class 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
125000001691 aryl alkyl amino group Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
FYXKZNLBZKRYSS-UHFFFAOYSA-N benzene-1,2-dicarbonyl chloride Chemical compound ClC(=O)C1=CC=CC=C1C(Cl)=O FYXKZNLBZKRYSS-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
150000001639 boron compounds Chemical class 0.000 description 1
244000309464 bull Species 0.000 description 1
QAWBXZYPFCFQLA-UHFFFAOYSA-N butanoyl bromide Chemical compound CCCC(Br)=O QAWBXZYPFCFQLA-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
229940106681 chloroacetic acid Drugs 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
PAFZNILMFXTMIY-UHFFFAOYSA-O cyclohexylammonium Chemical compound [NH3+]C1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-O 0.000 description 1
125000001142 dicarboxylic acid group Chemical group 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000003113 dilution method Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
125000005949 ethanesulfonyloxy group Chemical group 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
239000006260 foam Substances 0.000 description 1
239000011888 foil Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
150000002366 halogen compounds Chemical class 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
235000015243 ice cream Nutrition 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910001503 inorganic bromide Inorganic materials 0.000 description 1
229910001505 inorganic iodide Inorganic materials 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical class NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
BEMHKVUNDGZRBB-UHFFFAOYSA-N methyl 2-(methanethioylamino)acetate Chemical compound COC(=O)CNC=S BEMHKVUNDGZRBB-UHFFFAOYSA-N 0.000 description 1
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
MBXNQZHITVCSLJ-UHFFFAOYSA-N methyl fluorosulfonate Chemical compound COS(F)(=O)=O MBXNQZHITVCSLJ-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
HLYVNXRHROOICH-UHFFFAOYSA-N o-propan-2-ylhydroxylamine Chemical group CC(C)ON HLYVNXRHROOICH-UHFFFAOYSA-N 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
RFPMGSKVEAUNMZ-UHFFFAOYSA-N pentylidene Chemical group [CH2+]CCC[CH-] RFPMGSKVEAUNMZ-UHFFFAOYSA-N 0.000 description 1
LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
125000006247 phenyl propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
229960003424 phenylacetic acid Drugs 0.000 description 1
239000003279 phenylacetic acid Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
150000003003 phosphines Chemical class 0.000 description 1
125000005633 phthalidyl group Chemical group 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
DPLVEEXVKBWGHE-UHFFFAOYSA-N potassium sulfide Chemical compound [S-2].[K+].[K+] DPLVEEXVKBWGHE-UHFFFAOYSA-N 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000011027 product recovery Methods 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 description 1
229940007042 proteus vulgaris Drugs 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
239000012429 reaction media Substances 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000000565 sealant Substances 0.000 description 1
125000003198 secondary alcohol group Chemical group 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000005055 short column chromatography Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 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
235000011152 sodium sulphate Nutrition 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
239000007787 solid Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
125000005323 thioketone group Chemical group 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical class CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000011800 void material Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
150000003952 β-lactams Chemical class 0.000 description 1

Classifications

- 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
- C07F7/18—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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Cephalosporin Compounds (AREA)

NL8101167A 1980-03-10 1981-03-10 2-penem-3-carbonzuurverbindingen, hun bereiding en gebruik. NL8101167A (nl)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
JP3001380		1980-03-10
JP3001380A JPS56142282A (en)	1980-03-10	1980-03-10	Penem-3-carboxylic acid derivative and its preparation
JP3352980		1980-03-17
JP3352980A JPS56142283A (en)	1980-03-17	1980-03-17	Penem-3-carboxylic acid derivative and its preparation
JP7476180		1980-06-03
JP7476180A JPS572289A (en)	1980-06-03	1980-06-03	Production of penem-3-carboxylic derivative

Publications (1)

Publication Number	Publication Date
NL8101167A true NL8101167A (nl)	1981-10-01

Family

ID=27286805

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL8101167A NL8101167A (nl)	1980-03-10	1981-03-10	2-penem-3-carbonzuurverbindingen, hun bereiding en gebruik.

Country Status (12)

Country	Link
US (1)	US4639441A (es)
CH (1)	CH653034A5 (es)
DD (1)	DD157801A5 (es)
DE (1)	DE3109086A1 (es)
DK (1)	DK108581A (es)
ES (1)	ES8205808A1 (es)
FR (1)	FR2477547A1 (es)
GB (1)	GB2074563B (es)
IT (1)	IT1172228B (es)
NL (1)	NL8101167A (es)
PL (1)	PL230074A1 (es)
SE (1)	SE8101464L (es)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3175042D1 (en) *	1980-11-06	1986-09-04	Hoechst Uk Ltd	7-oxo-4-thia-1-aza(3,2,0)heptane and 7-oxo-4-thia-1-aza(3,2,0)hept-2-ene derivatives
EP0185651A1 (en) *	1981-07-08	1986-06-25	Hoechst Uk Limited	Intermediates for the production of antibacterial penem derivates
US4748162A (en) *	1982-03-01	1988-05-31	Merck & Co., Inc.	6-substituted-2-carbaminidoyl-pen-2-em-3-carboxylic acids
EP0087792A1 (en) *	1982-03-01	1983-09-07	Merck & Co. Inc.	6-Substituted-2-carbamimidoyl-pen-2-em-3-carboxylic acids, process for preparing them and antibiotic compositions comprising them
ATE28648T1 (de) *	1982-03-26	1987-08-15	Hoechst Uk Ltd	7-oxo-4-thia-1-azabicyclo(3,2,0)heptan-derivate
GB2159519B (en) *	1982-03-26	1986-08-20	Hoechst Uk Ltd	7-oxo-4-thia-1-azabicyclo3,2,0heptane derivatives; azetidinones
US4443373A (en) *	1982-03-30	1984-04-17	Schering Corporation	Process for the production of antibiotic penems
US4456609A (en) *	1983-01-31	1984-06-26	Schering Corporation	(5R, 6S, 8R-6-(1-Hydroxyethyl)-2-(2-[methylaminocarbonyl]-ethylthio)-penem-3-carboxylic acid
US4530793A (en) *	1982-11-29	1985-07-23	Schering Corporation	Processes for the production of penems
ATE112778T1 (de) *	1982-11-29	1994-10-15	Schering Corp	Verfahren zur herstellung von penem-verbindungen.
EP0115308A3 (en) *	1983-01-25	1984-10-10	Merck & Co. Inc.	2-unsaturated alkylthio-pen-2-em-3-carboxylic acids and process for preparing substituted 2-thioxopenams and 2-substituted thiopenems
US4675317A (en) *	1983-01-25	1987-06-23	Merck & Co., Inc.	2-unsaturated alkylthio-pen-2-em-3-carboxylic acids
US4610823A (en) *	1983-01-25	1986-09-09	Merck & Co., Inc.	Process for preparing substituted 2-thioxopenams and 2-substituted thiopenems
GB9421816D0 (en) *	1994-10-29	1994-12-14	Smithkline Beecham Plc	Novel compounds
JPH09202789A (ja) *	1995-11-20	1997-08-05	Suntory Ltd	ペネム誘導体およびこれを含有する抗菌剤

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5466695A (en) *	1977-11-08	1979-05-29	Sankyo Co Ltd	Azetidinone derivative and its preparation
US4301074A (en) *	1977-11-17	1981-11-17	Merck & Co., Inc.	6-(1'-Hydroxyethyl)-2-substituted-pen-2-em-3-carboxylic acid
US4168314A (en) *	1977-11-17	1979-09-18	Merck & Co., Inc.	6-(1'-Hydroxyethyl)-2-aminoethylthio-pen-2-em-3-carboxylic acid
EP0003960B1 (de) *	1978-02-02	1983-06-29	Ciba-Geigy Ag	6-Substituierte Thia-Azaverbindungen, ihre Herstellung und diese enthaltende pharmazeutische Präparate
JPS559034A (en) *	1978-07-05	1980-01-22	Sankyo Co Ltd	Penem derivative and its preparation
US4272437A (en) *	1978-12-18	1981-06-09	Bristol-Myers Company	Antibacterial agents, and 4-thio azetidinone intermediates
IL59081A0 (en) *	1979-01-10	1980-05-30	Schering Corp	2-penem compounds and a method for preparing them
DE3175042D1 (en) *	1980-11-06	1986-09-04	Hoechst Uk Ltd	7-oxo-4-thia-1-aza(3,2,0)heptane and 7-oxo-4-thia-1-aza(3,2,0)hept-2-ene derivatives

1981
- 1981-03-09 SE SE8101464A patent/SE8101464L/xx not_active Application Discontinuation
- 1981-03-10 DE DE19813109086 patent/DE3109086A1/de active Granted
- 1981-03-10 NL NL8101167A patent/NL8101167A/nl not_active Application Discontinuation
- 1981-03-10 PL PL23007481A patent/PL230074A1/xx unknown
- 1981-03-10 DK DK108581A patent/DK108581A/da unknown
- 1981-03-10 FR FR8104709A patent/FR2477547A1/fr active Granted
- 1981-03-10 ES ES500253A patent/ES8205808A1/es not_active Expired
- 1981-03-10 GB GB8107415A patent/GB2074563B/en not_active Expired
- 1981-03-10 DD DD81228171A patent/DD157801A5/de unknown
- 1981-03-10 CH CH1634/81A patent/CH653034A5/de not_active IP Right Cessation
- 1981-03-10 IT IT67330/81A patent/IT1172228B/it active
1984
- 1984-02-24 US US06/582,152 patent/US4639441A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
SE8101464L (sv)	1981-09-11
CH653034A5 (de)	1985-12-13
IT8167330A0 (it)	1981-03-10
DK108581A (da)	1981-09-11
US4639441A (en)	1987-01-27
FR2477547B1 (es)	1983-11-25
ES500253A0 (es)	1982-08-01
DE3109086C2 (es)	1991-05-02
ES8205808A1 (es)	1982-08-01
IT1172228B (it)	1987-06-18
GB2074563A (en)	1981-11-04
GB2074563B (en)	1984-05-10
PL230074A1 (es)	1982-06-21
FR2477547A1 (fr)	1981-09-11
DE3109086A1 (de)	1981-12-24
DD157801A5 (de)	1982-12-08

Legal Events

Date	Code	Title	Description
1985-01-01	A85	Still pending on 85-01-01
1985-11-01	BV	The patent application has lapsed

Publication	Publication Date	Title
NL8101167A (nl)	1981-10-01	2-penem-3-carbonzuurverbindingen, hun bereiding en gebruik.
EP0070204B1 (en)	1987-11-19	Carboxylic beta-lactam compounds and the preparation thereof
FI74966C (fi)	1988-04-11	Foerfarande foer framstaellning av en 2-penem-foerening eller dess salt.
US4350631A (en)	1982-09-21	6- and 4-Substituted-1-azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylates
NL8105470A (nl)	1982-07-01	1-sulfo 2-oxoazetidinederivaten, alsmede bereiding en toepassing daarvan.
EP0037081A1 (en)	1981-10-07	Process for the preparation of 1-carbapenems and intermediates via trithioorthoacetates
JPS5826887A (ja)	1983-02-17	１−，及び１，１−ジ置換−６−置換−２−カルバムイミドイル−１−カルバデチアペン−２−エム−３−カルボン酸類
JPS60233076A (ja)	1985-11-19	新規なβ−ラクタム化合物およびその製造法
JPH0745500B2 (ja)	1995-05-17	１−メチルカルバペネム誘導体及びその製法
NL8101039A (nl)	1981-10-01	7-oxo-1-azabicyclo3,2,0 hept-2-een-2-carbonzuurverbindingen, hun gebruik en bereiding.
NL8102736A (nl)	1982-01-04	Penem-3-carbonzuurverbindingen en hun bereiding.
Shibata et al.	1989	Synthetic studies of 1-β-methylcarbapenem antibiotics
JPH0532668A (ja)	1993-02-09	置換２−チオキソペナムおよび２−置換チオペネムの製造方法
FI69845B (fi)	1985-12-31	Foerfarande foer framstaellning av nya antibakteriella penemderivat
US4410533A (en)	1983-10-18	β-Lactam antibiotics, their preparation and use
CA1206148A (en)	1986-06-17	7-oxo-4-thia-1-azabicyclo¬3,2,0\|heptane derivatives
JPH0316356B2 (es)	1991-03-05
JPH0525181A (ja)	1993-02-02	ペネム−３−カルボン酸誘導体の製法
AU745980B2 (en)	2002-04-11	Titanium catalyzed preparation of carbapenem intermediates
JPH0625243A (ja)	1994-02-01	１−メチルカルバペネム誘導体の製造法
JPH0328434B2 (es)	1991-04-19
JPH0325435B2 (es)	1991-04-05
JPH0224832B2 (es)	1990-05-30
JPH045037B2 (es)	1992-01-30
JPH06211858A (ja)	1994-08-02	４−アリルアゼチジノンを経由する１−カルバペネム類の中間体の製造方法