NO891044L - Fremgangsmaate for fremstilling av 3-exometylencefamderivater. - Google Patents

Fremgangsmaate for fremstilling av 3-exometylencefamderivater. Download PDF

Info

Publication number: NO891044L
Authority: NO; Norway
Prior art keywords: cephem; formula; methylene; oxo; carboxylate
Prior art date: 1987-07-13

Application number

NO89891044A

Other languages

English (en)

Norwegian (no)

Other versions

NO891044D0 (no

Inventor

Jan Verweij

Jan Jacobus De Koning

Hendrik Adrianus Witkamp

Original Assignee

Gist Brocades Nv

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.)

1987-07-13

Filing date

1989-03-10

Publication date

1989-03-10

1989-03-10 Application filed by Gist Brocades Nv filed Critical Gist Brocades Nv

1989-03-10 Publication of NO891044D0 publication Critical patent/NO891044D0/no

1989-03-10 Publication of NO891044L publication Critical patent/NO891044L/no

Links

238000002360 preparation method Methods 0.000 title claims abstract description 53
238000000034 method Methods 0.000 title claims abstract description 41
-1 phosphonium cephem compounds Chemical class 0.000 claims abstract description 41
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 22
150000001781 cephams Chemical class 0.000 claims abstract description 11
JJYMUNWZKXXYFU-SSDOTTSWSA-N (6R)-3-(phosphanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(CP)=CN2C(=O)C[C@H]21 JJYMUNWZKXXYFU-SSDOTTSWSA-N 0.000 claims abstract description 8
229910052751 metal Inorganic materials 0.000 claims abstract description 8
239000002184 metal Substances 0.000 claims abstract description 8
229910052725 zinc Inorganic materials 0.000 claims abstract description 7
239000011701 zinc Substances 0.000 claims abstract description 7
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 4
239000011777 magnesium Substances 0.000 claims abstract description 3
229910052749 magnesium Inorganic materials 0.000 claims abstract description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 80
150000001875 compounds Chemical class 0.000 claims description 62
239000011541 reaction mixture Substances 0.000 claims description 47
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical group [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 34
239000000725 suspension Substances 0.000 claims description 32
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 32
238000006243 chemical reaction Methods 0.000 claims description 27
235000019270 ammonium chloride Nutrition 0.000 claims description 17
238000004519 manufacturing process Methods 0.000 claims description 17
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
125000003277 amino group Chemical group 0.000 claims description 8
229910052736 halogen Chemical group 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
150000002367 halogens Chemical group 0.000 claims description 7
229910017053 inorganic salt Inorganic materials 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 5
229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 5
150000003863 ammonium salts Chemical class 0.000 claims description 5
235000011150 stannous chloride Nutrition 0.000 claims description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 4
239000000908 ammonium hydroxide Substances 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
KYRUBSWVBPYWEF-UHFFFAOYSA-N copper;iron;sulfane;tin Chemical compound S.S.S.S.[Fe].[Cu].[Cu].[Sn] KYRUBSWVBPYWEF-UHFFFAOYSA-N 0.000 claims description 4
229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
JHJAKUBFZCFDCP-DKSCNQEISA-N (6r)-3-methylidene-5-oxo-5$l^{4}-thia-1-azabicyclo[4.2.0]octan-8-one Chemical compound O=S1CC(=C)CN2C(=O)C[C@H]21 JHJAKUBFZCFDCP-DKSCNQEISA-N 0.000 claims description 3
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
229910052796 boron Inorganic materials 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
ZODSKWVZQXADRY-SSDOTTSWSA-N (6r)-3-methylidene-5,5-dioxo-5$l^{6}-thia-1-azabicyclo[4.2.0]octan-8-one Chemical class O=S1(=O)CC(=C)CN2C(=O)C[C@H]21 ZODSKWVZQXADRY-SSDOTTSWSA-N 0.000 claims description 2
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
ZSUXOVNWDZTCFN-UHFFFAOYSA-L Tin(II) bromide Inorganic materials Br[Sn]Br ZSUXOVNWDZTCFN-UHFFFAOYSA-L 0.000 claims description 2
229910052782 aluminium Inorganic materials 0.000 claims description 2
239000004411 aluminium Substances 0.000 claims description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
239000011574 phosphorus Substances 0.000 claims description 2
239000011591 potassium Substances 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
229910052708 sodium Inorganic materials 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
150000003497 tellurium Chemical class 0.000 claims description 2
229910052718 tin Inorganic materials 0.000 claims description 2
239000011135 tin Substances 0.000 claims description 2
238000004090 dissolution Methods 0.000 claims 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical group [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
239000000243 solution Substances 0.000 description 99
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 59
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 52
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 35
239000000203 mixture Substances 0.000 description 33
239000000047 product Substances 0.000 description 29
238000001228 spectrum Methods 0.000 description 29
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 28
238000003756 stirring Methods 0.000 description 25
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
239000010410 layer Substances 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
238000002329 infrared spectrum Methods 0.000 description 22
239000012044 organic layer Substances 0.000 description 22
238000001035 drying Methods 0.000 description 19
238000002955 isolation Methods 0.000 description 17
238000005406 washing Methods 0.000 description 17
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
239000002244 precipitate Substances 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
239000012267 brine Substances 0.000 description 13
238000005119 centrifugation Methods 0.000 description 13
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
239000002904 solvent Substances 0.000 description 13
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
238000001914 filtration Methods 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
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 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
239000013078 crystal Substances 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
238000004611 spectroscopical analysis Methods 0.000 description 6
DBPOBORYRQTVSQ-SSDOTTSWSA-N (6r)-3-(bromomethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(CBr)=CN2C(=O)C[C@H]21 DBPOBORYRQTVSQ-SSDOTTSWSA-N 0.000 description 5
238000005893 bromination reaction Methods 0.000 description 5
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
150000004714 phosphonium salts Chemical class 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000012258 stirred mixture Substances 0.000 description 5
FJJNRKHLRYUGJW-OKRNOHDPSA-N tert-butyl (5s,6r,7r)-3-(bromomethyl)-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@H]2[S@@](=O)CC(CBr)=C(N2C1=O)C(=O)OC(C)(C)C)C(=O)CC1=CC=CC=C1 FJJNRKHLRYUGJW-OKRNOHDPSA-N 0.000 description 5
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 5
WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 5
229910052721 tungsten Inorganic materials 0.000 description 5
239000010937 tungsten Substances 0.000 description 5
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
238000001556 precipitation Methods 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000001119 stannous chloride Substances 0.000 description 4
238000001665 trituration Methods 0.000 description 4
HTFTURZHXAWZPC-SSDOTTSWSA-N (6r)-3-methylidene-5-thia-1-azabicyclo[4.2.0]octan-8-one Chemical class C1C(=C)CS[C@@H]2CC(=O)N21 HTFTURZHXAWZPC-SSDOTTSWSA-N 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
229930186147 Cephalosporin Natural products 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
229930182555 Penicillin Natural products 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
125000004442 acylamino group Chemical group 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
BADZRCFXXWKZIS-CMUXQDGESA-N benzhydryl (5s,6r,7r)-3-(bromomethyl)-7-formamido-5,8-dioxo-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C([S@](=O)[C@H]1N2C([C@H]1NC=O)=O)C(CBr)=C2C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 BADZRCFXXWKZIS-CMUXQDGESA-N 0.000 description 3
230000031709 bromination Effects 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
229940124587 cephalosporin Drugs 0.000 description 3
150000001780 cephalosporins Chemical class 0.000 description 3
238000001816 cooling Methods 0.000 description 3
229940049954 penicillin Drugs 0.000 description 3
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
238000000926 separation method Methods 0.000 description 3
150000003462 sulfoxides Chemical class 0.000 description 3
SSYFNDAJKNKLRW-CRAIPNDOSA-N tert-butyl (6r,7r)-3-(bromomethyl)-5,5,8-trioxo-7-[(2-phenylacetyl)amino]-5$l^{6}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@H]2S(=O)(=O)CC(CBr)=C(N2C1=O)C(=O)OC(C)(C)C)C(=O)CC1=CC=CC=C1 SSYFNDAJKNKLRW-CRAIPNDOSA-N 0.000 description 3
XTTGYFREQJCEML-UHFFFAOYSA-N tributyl phosphite Chemical compound CCCCOP(OCCCC)OCCCC XTTGYFREQJCEML-UHFFFAOYSA-N 0.000 description 3
XFHPQHSRXBBCDM-KGMSYRRLSA-N (6r)-7-amino-3-methylidene-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acid Chemical compound S1CC(=C)C(C(O)=O)N2C(=O)C(N)[C@H]21 XFHPQHSRXBBCDM-KGMSYRRLSA-N 0.000 description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
239000002585 base Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000001475 halogen functional group Chemical group 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
SCWIYGAIDORPGH-GZVCGHTCSA-N methyl (5s,6r,7r)-3-(bromomethyl)-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@H]2[S@@](=O)CC(CBr)=C(N2C1=O)C(=O)OC)C(=O)COC1=CC=CC=C1 SCWIYGAIDORPGH-GZVCGHTCSA-N 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
150000003003 phosphines Chemical class 0.000 description 2
238000000746 purification Methods 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
JPMNZLQVEIRUPV-VSDHEAMUSA-N tert-butyl (2r,5s,6r,7r)-3-methylidene-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound N([C@H]1[C@@H]2N(C1=O)[C@H](C(C[S@@]2=O)=C)C(=O)OC(C)(C)C)C(=O)CC1=CC=CC=C1 JPMNZLQVEIRUPV-VSDHEAMUSA-N 0.000 description 2
NNISIBHHOUUFFS-KPMSDPLLSA-N tert-butyl (6r)-3-(bromomethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@H]2SCC(CBr)=C(N2C1=O)C(=O)OC(C)(C)C)NC(=O)CC1=CC=CC=C1 NNISIBHHOUUFFS-KPMSDPLLSA-N 0.000 description 2
150000003568 thioethers Chemical class 0.000 description 2
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
JIGZRWHUGNBUOY-ZFJIDCOJSA-N (2r,5s,6r,7r)-3-methylidene-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acid Chemical compound N([C@H]1[C@@H]2N(C1=O)[C@H](C(C[S@@]2=O)=C)C(=O)O)C(=O)CC1=CC=CC=C1 JIGZRWHUGNBUOY-ZFJIDCOJSA-N 0.000 description 1
BYWDLGZGDJHATF-OTHANADMSA-N (4-methoxyphenyl)methyl (5s,6r,7r)-3-(bromomethyl)-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)C1=C(CBr)C[S@](=O)[C@H]2N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1 BYWDLGZGDJHATF-OTHANADMSA-N 0.000 description 1
QTZCBLVGJAMOBF-NLLPHEHUSA-N (4-nitrophenyl)methyl (5s,6r,7r)-3-(bromomethyl)-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(CBr)C[S@](=O)[C@H]2N1C(=O)[C@H]2NC(=O)COC1=CC=CC=C1 QTZCBLVGJAMOBF-NLLPHEHUSA-N 0.000 description 1
MLMISORMRJEVPQ-DTNGWZOYSA-N (4-nitrophenyl)methyl (5s,6r,7r)-3-(bromomethyl)-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(CBr)C[S@](=O)[C@H]2N1C(=O)[C@H]2NC(=O)CC1=CC=CC=C1 MLMISORMRJEVPQ-DTNGWZOYSA-N 0.000 description 1
GMRXPNMXBLJKGX-YFBHESTHSA-N (4-nitrophenyl)methyl (5s,6r,7r)-3-(bromomethyl)-7-formamido-5,8-dioxo-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=C(CBr)C[S@](=O)[C@H]2N1C(=O)[C@H]2NC=O GMRXPNMXBLJKGX-YFBHESTHSA-N 0.000 description 1
GSPKFXHTXPJXMV-DTNGWZOYSA-N (4-nitrophenyl)methyl (5s,6r,7r)-3-methyl-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(C[S@@]2=O)C)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)C(=O)COC1=CC=CC=C1 GSPKFXHTXPJXMV-DTNGWZOYSA-N 0.000 description 1
YUXVFVWGTIJWOE-HCALTAMKSA-N (4-nitrophenyl)methyl (5s,6r,7r)-3-methyl-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(C[S@@]2=O)C)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)C(=O)CC1=CC=CC=C1 YUXVFVWGTIJWOE-HCALTAMKSA-N 0.000 description 1
PGUMSXPBQQVEQX-YDWCZGDXSA-N (4-nitrophenyl)methyl (5s,6r,7r)-7-formamido-3-methyl-5,8-dioxo-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C([S@](=O)[C@H]1N2C([C@H]1NC=O)=O)C(C)=C2C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 PGUMSXPBQQVEQX-YDWCZGDXSA-N 0.000 description 1
BSVCOWCOTXUYDV-HWZXHQHMSA-N (6R)-4-methyl-3-phosphanyl-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class C1=C(P)C(C)S[C@@H]2CC(=O)N21 BSVCOWCOTXUYDV-HWZXHQHMSA-N 0.000 description 1
RIZZJGXAMBMULM-ZCFIWIBFSA-N (6r)-3-bromo-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(Br)=CN2C(=O)C[C@H]21 RIZZJGXAMBMULM-ZCFIWIBFSA-N 0.000 description 1
LFMBIMXJWIQULB-SSDOTTSWSA-N (6r)-3-methyl-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1CC(C)=CN2C(=O)C[C@H]21 LFMBIMXJWIQULB-SSDOTTSWSA-N 0.000 description 1
IYHNOYKXEDYSAZ-ULUSZKPHSA-N (6r)-4-bromo-3-(bromomethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical class S1C(Br)C(CBr)=CN2C(=O)C[C@H]21 IYHNOYKXEDYSAZ-ULUSZKPHSA-N 0.000 description 1
YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
OFDISMSWWNOGFW-UHFFFAOYSA-N 1-(4-ethoxy-3-fluorophenyl)ethanamine Chemical compound CCOC1=CC=C(C(C)N)C=C1F OFDISMSWWNOGFW-UHFFFAOYSA-N 0.000 description 1
NRGFURRDSZTMHG-LRYSPDEDSA-N 2,2,2-trichloroethyl (2r,5s,6r,7r)-3-(bromomethyl)-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound N([C@H]1[C@H]2[S@@](=O)CC(CBr)[C@@H](N2C1=O)C(=O)OCC(Cl)(Cl)Cl)C(=O)CC1=CC=CC=C1 NRGFURRDSZTMHG-LRYSPDEDSA-N 0.000 description 1
LRJNWZCLYAJVAM-MQBVLLCXSA-N 2,2-dichloroethyl (2r,5s,6r,7r)-3-methylidene-5,8-dioxo-7-[(2-phenylacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]octane-2-carboxylate Chemical compound N([C@H]1[C@@H]2N(C1=O)[C@H](C(C[S@@]2=O)=C)C(=O)OCC(Cl)Cl)C(=O)CC1=CC=CC=C1 LRJNWZCLYAJVAM-MQBVLLCXSA-N 0.000 description 1
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 1
NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
YECYMGRFPRRUDN-UIVUJYCXSA-N BrC1[S@]([C@H]2N(C(=C1CBr)C(=O)OC(C)(C)C)C([C@H]2NC=O)=O)=O Chemical compound BrC1[S@]([C@H]2N(C(=C1CBr)C(=O)OC(C)(C)C)C([C@H]2NC=O)=O)=O YECYMGRFPRRUDN-UIVUJYCXSA-N 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
229910021623 Tin(IV) bromide Inorganic materials 0.000 description 1
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
HIRUGLIVSKMROK-ZDXFNXCESA-N [(5s,6r,7r)-2-methoxycarbonyl-5,8-dioxo-7-[(2-phenoxyacetyl)amino]-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl-triphenylphosphanium;bromide Chemical compound [Br-].O=C([C@@H](NC(=O)COC=1C=CC=CC=1)[C@H]1[S@@](=O)C2)N1C(C(=O)OC)=C2C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 HIRUGLIVSKMROK-ZDXFNXCESA-N 0.000 description 1
UEVPKMPAHXHIEF-SECBINFHSA-N [(6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl acetate Chemical class S1CC(COC(=O)C)=CN2C(=O)C[C@H]21 UEVPKMPAHXHIEF-SECBINFHSA-N 0.000 description 1
FYCKWYRVRFYWBL-LGWLCBCNSA-N [(6r,7r)-2-[(2-methylpropan-2-yl)oxycarbonyl]-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl-triphenylphosphanium;bromide Chemical compound [Br-].O=C([C@@H](NC(=O)CC=1C=CC=CC=1)[C@H]1SC2)N1C(C(=O)OC(C)(C)C)=C2C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 FYCKWYRVRFYWBL-LGWLCBCNSA-N 0.000 description 1
HFWLIBBBZYAYTP-YZUKSGEXSA-N [(6r,7r)-3-(bromomethyl)-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-7-yl]-propan-2-ylideneazanium;bromide Chemical compound [Br-].S1CC(CBr)=C(C(O)=O)N2C(=O)[C@@H]([NH+]=C(C)C)[C@H]21 HFWLIBBBZYAYTP-YZUKSGEXSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
235000012501 ammonium carbonate Nutrition 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
244000309464 bull Species 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
QHTOIDKCEPKVCM-ZCFIWIBFSA-N cepham Chemical compound S1CCCN2C(=O)C[C@H]21 QHTOIDKCEPKVCM-ZCFIWIBFSA-N 0.000 description 1
150000001782 cephems Chemical class 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
125000006003 dichloroethyl group Chemical group 0.000 description 1
238000007865 diluting Methods 0.000 description 1
JBVOSZYUSFDYIN-UHFFFAOYSA-N dimethyl cyclopropane-1,2-dicarboxylate Chemical compound COC(=O)C1CC1C(=O)OC JBVOSZYUSFDYIN-UHFFFAOYSA-N 0.000 description 1
PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
238000010828 elution Methods 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
238000000605 extraction Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000003999 initiator Substances 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
238000002386 leaching Methods 0.000 description 1
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
235000011285 magnesium acetate Nutrition 0.000 description 1
239000011654 magnesium acetate Substances 0.000 description 1
229940069446 magnesium acetate Drugs 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000005580 one pot reaction Methods 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
IYGZQRWNAFDQDO-XHKSWWFASA-N tert-butyl (5s,6r,7r)-3-(bromomethyl)-7-formamido-5,8-dioxo-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=C(CBr)C[S@](=O)[C@@H]2[C@H](NC=O)C(=O)N12 IYGZQRWNAFDQDO-XHKSWWFASA-N 0.000 description 1
GXOWMPBTTCRDEI-XVEBHNSPSA-N tert-butyl (5s,6r,7r)-3-(dibromomethyl)-7-formamido-5,8-dioxo-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=C(C(Br)Br)C[S@](=O)[C@@H]2[C@H](NC=O)C(=O)N12 GXOWMPBTTCRDEI-XVEBHNSPSA-N 0.000 description 1
HYXHTDNGFPNQPI-TZIQNSENSA-N tert-butyl (5s,6r,7r)-7-formamido-3-methyl-5,8-dioxo-5$l^{4}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound O=[S@]1CC(C)=C(C(=O)OC(C)(C)C)N2C(=O)[C@@H](NC=O)[C@H]21 HYXHTDNGFPNQPI-TZIQNSENSA-N 0.000 description 1
FFWRGQZDXNWMTG-CRAIPNDOSA-N tert-butyl (6r,7r)-3-methyl-5,5,8-trioxo-7-[(2-phenylacetyl)amino]-5$l^{6}-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2(=O)=O)C)C(=O)OC(C)(C)C)C(=O)CC1=CC=CC=C1 FFWRGQZDXNWMTG-CRAIPNDOSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
125000005425 toluyl group Chemical group 0.000 description 1
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Cephalosporin Compounds (AREA)
Steroid Compounds (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Investigating Or Analysing Biological Materials (AREA)
Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

NO89891044A 1987-07-13 1989-03-10 Fremgangsmaate for fremstilling av 3-exometylencefamderivater. NO891044L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP87201323		1987-07-13
PCT/NL1988/000035 WO1989000572A1 (en)	1987-07-13	1988-07-13	Process for the preparation of 3-exomethylene cepham derivatives

Publications (2)

Publication Number	Publication Date
NO891044D0 NO891044D0 (no)	1989-03-10
NO891044L true NO891044L (no)	1989-03-10

Family

ID=8197638

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO89891044A NO891044L (no)	1987-07-13	1989-03-10	Fremgangsmaate for fremstilling av 3-exometylencefamderivater.

Country Status (19)

Country	Link
US (3)	US4985554A (de)
EP (1)	EP0299587B1 (de)
JP (1)	JPH0742291B2 (de)
KR (1)	KR0137221B1 (de)
CN (1)	CN1040441C (de)
AT (1)	ATE113952T1 (de)
AU (1)	AU619201B2 (de)
CA (1)	CA1338607C (de)
DE (1)	DE3852065T2 (de)
DK (1)	DK116889D0 (de)
ES (1)	ES2067465T3 (de)
FI (1)	FI891191A (de)
HU (1)	HU207865B (de)
IE (1)	IE66466B1 (de)
IL (1)	IL87110A (de)
NO (1)	NO891044L (de)
NZ (1)	NZ225388A (de)
PT (1)	PT87985B (de)
WO (1)	WO1989000572A1 (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0300546B1 (de) *	1987-07-10	1995-08-09	Gist-Brocades N.V.	Cephalosporinderivate und Verfahren zur Herstellung von Cephem-Verbindungen
US5159071A (en) *	1990-09-06	1992-10-27	Ranbaxy Laboratories Limited	Process for the manufacture of 7-amino-3-exomethylene-3-cepham-4-carboxylic acid ester
US6248881B1 (en)	1991-03-08	2001-06-19	Biochemie Gmbh	Intermediates and process for the production of 3-vinyl cephalosporins
US5604222A (en)	1993-12-27	1997-02-18	Lupin Laboratories, Ltd.	Method for the preparation of 2-chloro sulfinyl azetidinones
US5578721A (en)	1994-07-11	1996-11-26	Lupin Laboratories Limited	Process for preparation of 3-exomethylene cepham sulfoxide esters
AU7567596A (en) *	1995-11-06	1997-05-29	Gist-Brocades B.V.	De-esterification process

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4731443A (en) *	1979-11-19	1988-03-15	Fujisawa Pharmaceutical Co., Ltd.	7-acylamino-3-vinylcephalosporanic acid derivatives
US4354022A (en) *	1981-06-05	1982-10-12	Fujisawa Pharmaceutical Co., Ltd.	Process for preparing 3-methylenecepham compounds or a salt thereof
US4558123A (en) *	1983-07-22	1985-12-10	Eli Lilly And Company	3-Exomethylene cephalosporins
US4705851A (en) *	1984-09-28	1987-11-10	Fujisawa Pharmaceutical Co., Ltd.	Process for the preparation of 3-phosphoniummethyl-3-cephem compounds

1988
- 1988-07-13 AT AT88201495T patent/ATE113952T1/de not_active IP Right Cessation
- 1988-07-13 CA CA000571920A patent/CA1338607C/en not_active Expired - Fee Related
- 1988-07-13 IE IE213788A patent/IE66466B1/en not_active IP Right Cessation
- 1988-07-13 WO PCT/NL1988/000035 patent/WO1989000572A1/en active Application Filing
- 1988-07-13 HU HU884578A patent/HU207865B/hu not_active IP Right Cessation
- 1988-07-13 PT PT87985A patent/PT87985B/pt not_active IP Right Cessation
- 1988-07-13 CN CN88106371A patent/CN1040441C/zh not_active Expired - Fee Related
- 1988-07-13 US US07/337,525 patent/US4985554A/en not_active Expired - Fee Related
- 1988-07-13 KR KR1019890700458A patent/KR0137221B1/ko not_active IP Right Cessation
- 1988-07-13 NZ NZ225388A patent/NZ225388A/en unknown
- 1988-07-13 ES ES88201495T patent/ES2067465T3/es not_active Expired - Lifetime
- 1988-07-13 EP EP88201495A patent/EP0299587B1/de not_active Expired - Lifetime
- 1988-07-13 AU AU20783/88A patent/AU619201B2/en not_active Ceased
- 1988-07-13 JP JP63506023A patent/JPH0742291B2/ja not_active Expired - Lifetime
- 1988-07-13 DE DE3852065T patent/DE3852065T2/de not_active Expired - Fee Related
- 1988-07-14 IL IL87110A patent/IL87110A/xx unknown
1989
- 1989-03-10 DK DK116889A patent/DK116889D0/da not_active Application Discontinuation
- 1989-03-10 NO NO89891044A patent/NO891044L/no unknown
- 1989-03-13 FI FI891191A patent/FI891191A/fi not_active IP Right Cessation
- 1989-12-27 US US07/457,253 patent/US4994454A/en not_active Expired - Fee Related
1990
- 1990-09-10 US US07/581,518 patent/US5109132A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US5109132A (en)	1992-04-28
NO891044D0 (no)	1989-03-10
AU2078388A (en)	1989-02-13
US4994454A (en)	1991-02-19
HU207865B (en)	1993-06-28
HUT52512A (de)	1990-07-28
WO1989000572A1 (en)	1989-01-26
EP0299587A1 (de)	1989-01-18
JPH0742291B2 (ja)	1995-05-10
FI891191A0 (fi)	1989-03-13
DE3852065T2 (de)	1995-04-06
IL87110A (en)	1993-04-04
KR890701593A (ko)	1989-12-21
FI891191A (fi)	1989-03-13
NZ225388A (en)	1991-07-26
PT87985A (pt)	1989-06-30
KR0137221B1 (ko)	1998-04-25
US4985554A (en)	1991-01-15
JPH02500843A (ja)	1990-03-22
AU619201B2 (en)	1992-01-23
IL87110A0 (en)	1988-12-30
DK116889A (da)	1989-03-10
DE3852065D1 (de)	1994-12-15
CN1031534A (zh)	1989-03-08
IE882137L (en)	1989-01-13
DK116889D0 (da)	1989-03-10
PT87985B (pt)	1995-03-01
ES2067465T3 (es)	1995-04-01
CN1040441C (zh)	1998-10-28
ATE113952T1 (de)	1994-11-15
IE66466B1 (en)	1995-12-27
EP0299587B1 (de)	1994-11-09
CA1338607C (en)	1996-09-24

Publication	Publication Date	Title
FI74019C (fi)	1987-12-10	Foerfarande foer framstaellning av 7 -acylamino-3-substitueradmetyl-3-cefem-4-karboxylsyraderivat.
US6388070B1 (en)	2002-05-14	Thioester derivatives of thiazolyl acetic acid and their use in the preparation of cephalosporin compounds
JPH0326197B2 (de)	1991-04-10
NO881531L (no)	1988-10-11	Acylderivater.
HU184799B (en)	1984-10-29	Process for producing 7-square bracket-bracket-2-aryl-bracket closed-2-hydroxy-imino-acetamido-sguare bracket closed-ceph-3-eme-4-carboxylic acid derivatives
NO801052L (no)	1980-10-13	Fremgangsmaate for fremstilling av cefem-derivater
EP0043546B1 (de)	1986-01-29	7-Oxo-cephalosporine und 6-Oxo-penicilline, ihre Analoge und Verfahren zu ihrer Herstellung
EP1016665B1 (de)	2002-08-07	Verfahren zur selektiven herstellung von z-isomeren von 3-(2-substituiertes vinyl)cephalosporinen
CS208116B2 (en)	1981-08-31	Method of making the delta up3 -cefem-4-carboxyl acid having in position 7,event.substituted aminogroup and in position 3 substituted thiomethyl group
NO891044L (no)	1989-03-10	Fremgangsmaate for fremstilling av 3-exometylencefamderivater.
DK159154B (da)	1990-09-10	Fremgangsmaade til fremstilling af cephalosporinderivater eller salte deraf
DK161521B (da)	1991-07-15	Fremgangsmaade til fremstilling af cephalosporiner samt thiestere til anvendelse som udgangsmateriale ved fremgangsmaaden
JPH02790A (ja)	1990-01-05	７―［２―（２―アミノチアゾール―４―イル）―２―ヒドロキシイミノアセトアミド］―３―セフェム化合物の製造法
IE59123B1 (en)	1994-01-12	Cephalosporanic acid derivatives
WO2003059908A1 (en)	2003-07-24	Novel thioester derivatives and process for preparation of cephalosporin
JPH0521912B2 (de)	1993-03-25
EP0791597B1 (de)	2000-07-12	Verfahren zur Herstellung von Cephalosporinderivaten und Zwischenverbindungen
US3767655A (en)	1973-10-23	Intermediates for the production of cephalosporin compounds
WO2000068234A2 (en)	2000-11-16	Process for the preparation of cefpodoxime acid
KR810000760B1 (ko)	1981-07-02	세팔로스포린 화합물의 제조법
JPS5951555B2 (ja)	1984-12-14	セフアロスポリン化合物の製造法
KR970005897B1 (ko)	1997-04-21	신규한 세팔로스포린계 항생제 및 이의 제조방법(ⅱ)
JPS6135198B2 (de)	1986-08-12
NO791788L (no)	1979-12-04	Cefalosporiner og fremgangsmaate til deres fremstilling
JPH06184166A (ja)	1994-07-05	新規なセファロスポリン化合物およびその製法