DK142419B

DK142419B - N-nitrosohetacillinsulfoxidester til anvendelse som mellemprodukt til fremstilling af cephalexin.

N-nitrosohetacillinsulfoxidester til anvendelse som mellemprodukt til fremstilling af cephalexin. Download PDF

Info

Publication number: DK142419B
Authority: DK; Denmark
Prior art keywords: acid; sulfoxide; cephalexin; nitroso; nitrosohetacillin
Prior art date: 1972-07-26

Application number

DK13074A

Other languages

Danish (da)

English (en)

Other versions

DK142419C (enExample

Inventor

Jun Okumura

Takayuki Naito

Hideaki Hoshi

Original Assignee

Bristol Myers Co

Priority date

1972-07-26

Filing date

1974-01-10

Publication date

1980-10-27

1973-07-24 Priority claimed from DK408573AA external-priority patent/DK138745B/da

1974-01-10 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1974-01-10 Priority to DK13074A priority Critical patent/DK142419B/da

1980-10-27 Publication of DK142419B publication Critical patent/DK142419B/da

1981-03-23 Application granted granted Critical

1981-03-23 Publication of DK142419C publication Critical patent/DK142419C/da

Links

-1 sulfoxide ester Chemical class 0.000 title description 50
ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 title description 21
229940106164 cephalexin Drugs 0.000 title description 21
238000002360 preparation method Methods 0.000 title description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
150000003462 sulfoxides Chemical class 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
229910001868 water Inorganic materials 0.000 description 22
239000002253 acid Substances 0.000 description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
239000003054 catalyst Substances 0.000 description 20
239000000243 solution Substances 0.000 description 20
238000000034 method Methods 0.000 description 16
230000008707 rearrangement Effects 0.000 description 16
239000002904 solvent Substances 0.000 description 16
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 14
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
229960003884 hetacillin Drugs 0.000 description 11
239000000543 intermediate Substances 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
DXVUYOAEDJXBPY-NFFDBFGFSA-N hetacillin Chemical compound C1([C@@H]2C(=O)N(C(N2)(C)C)[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 DXVUYOAEDJXBPY-NFFDBFGFSA-N 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
230000002378 acidificating effect Effects 0.000 description 9
230000008569 process Effects 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
235000011007 phosphoric acid Nutrition 0.000 description 7
239000000047 product Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
238000009835 boiling Methods 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
229910000041 hydrogen chloride Inorganic materials 0.000 description 6
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
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 5
230000003197 catalytic effect Effects 0.000 description 5
229910052736 halogen Inorganic materials 0.000 description 5
150000002367 halogens Chemical class 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
229930182555 Penicillin Natural products 0.000 description 4
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
150000001875 compounds Chemical class 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
230000009935 nitrosation Effects 0.000 description 4
238000007034 nitrosation reaction Methods 0.000 description 4
229940049954 penicillin Drugs 0.000 description 4
229910052698 phosphorus Inorganic materials 0.000 description 4
239000011574 phosphorus Substances 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical class CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
125000002632 imidazolidinyl group Chemical group 0.000 description 3
125000000018 nitroso group Chemical group N(=O)* 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000007800 oxidant agent Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000012360 testing method Methods 0.000 description 3
AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
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 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
229930195708 Penicillin V Natural products 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
238000005903 acid hydrolysis reaction Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
BSKHPKMHTQYZBB-UHFFFAOYSA-N alpha-methylpyridine Natural products CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229960001701 chloroform Drugs 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
230000032050 esterification Effects 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 2
238000000855 fermentation Methods 0.000 description 2
230000004151 fermentation Effects 0.000 description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
239000000463 material Substances 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
239000000203 mixture Substances 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
125000001477 organic nitrogen group Chemical group 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229940056367 penicillin v Drugs 0.000 description 2
XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 2
YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000007017 scission Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
235000010288 sodium nitrite Nutrition 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
239000007787 solid Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
KIYRSYYOVDHSPG-SSDOTTSWSA-N (2r)-2-amino-2-phenylacetamide Chemical compound NC(=O)[C@H](N)C1=CC=CC=C1 KIYRSYYOVDHSPG-SSDOTTSWSA-N 0.000 description 1
QZJPQJKWNFDQGY-SNVMCYLTSA-N (6R)-7-[(4R)-2,2-dimethyl-3-nitroso-5-oxo-4-phenylimidazolidin-1-yl]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1(N(C([C@H](N1N=O)C1=CC=CC=C1)=O)C1[C@@H]2N(C(=C(CS2)C)C(=O)O)C1=O)C QZJPQJKWNFDQGY-SNVMCYLTSA-N 0.000 description 1
UFQHIVIORIVWFP-ZYFOBHMOSA-N (6R)-7-[(4R)-2,2-dimethyl-5-oxo-4-phenylimidazolidin-1-yl]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1(N(C([C@H](N1)C1=CC=CC=C1)=O)C1[C@@H]2N(C(=C(CS2)C)C(=O)O)C1=O)C UFQHIVIORIVWFP-ZYFOBHMOSA-N 0.000 description 1
ZAIPMKNFIOOWCQ-QKFMDRJYSA-N (6r)-7-[(2-amino-2-phenylacetyl)amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)C)C(O)=O)NC(=O)C(N)C1=CC=CC=C1 ZAIPMKNFIOOWCQ-QKFMDRJYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 1
XFDUHJPVQKIXHO-UHFFFAOYSA-N 3-aminobenzoic acid Chemical compound NC1=CC=CC(C(O)=O)=C1 XFDUHJPVQKIXHO-UHFFFAOYSA-N 0.000 description 1
CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 1
PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 1
XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 1
QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical class C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 description 1
WNPVZANXRCPJPW-UHFFFAOYSA-N 5-[isocyano-(4-methylphenyl)sulfonylmethyl]-1,2,3-trimethoxybenzene Chemical compound COC1=C(OC)C(OC)=CC(C([N+]#[C-])S(=O)(=O)C=2C=CC(C)=CC=2)=C1 WNPVZANXRCPJPW-UHFFFAOYSA-N 0.000 description 1
NVIAYEIXYQCDAN-UHFFFAOYSA-N 7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical class S1CC(C)=C(C(O)=O)N2C(=O)C(N)C12 NVIAYEIXYQCDAN-UHFFFAOYSA-N 0.000 description 1
NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical class S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 description 1
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
PODHJIQSMSGBRQ-UHFFFAOYSA-N C1=CC=CC=C1.P(O)(O)=O Chemical class C1=CC=CC=C1.P(O)(O)=O PODHJIQSMSGBRQ-UHFFFAOYSA-N 0.000 description 1
RFAGAGYCSREFDN-UHFFFAOYSA-N CI.P(O)(O)=O Chemical compound CI.P(O)(O)=O RFAGAGYCSREFDN-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
DQBOPCBRGHFTSN-UHFFFAOYSA-N P(O)(O)=O.BrC1=CC=CC=C1 Chemical class P(O)(O)=O.BrC1=CC=CC=C1 DQBOPCBRGHFTSN-UHFFFAOYSA-N 0.000 description 1
PMIGJHGQHKWNMH-UHFFFAOYSA-N P(O)(O)=O.ClC(Cl)Cl Chemical compound P(O)(O)=O.ClC(Cl)Cl PMIGJHGQHKWNMH-UHFFFAOYSA-N 0.000 description 1
XJMFIMBSWLGRQW-UHFFFAOYSA-N P(O)(O)=O.ClCCl Chemical compound P(O)(O)=O.ClCCl XJMFIMBSWLGRQW-UHFFFAOYSA-N 0.000 description 1
IQTYUGSHUITLHX-UHFFFAOYSA-N P([O-])(O)=O.ClCCl.[NH+]1=CC=CC=C1 Chemical compound P([O-])(O)=O.ClCCl.[NH+]1=CC=CC=C1 IQTYUGSHUITLHX-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
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125000004429 atom Chemical group 0.000 description 1
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125000004432 carbon atom Chemical group C* 0.000 description 1
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238000010494 dissociation reaction Methods 0.000 description 1
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238000002329 infrared spectrum Methods 0.000 description 1
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150000002537 isoquinolines Chemical class 0.000 description 1
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125000000468 ketone group Chemical group 0.000 description 1
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PKAUVIXBZJUYRV-UHFFFAOYSA-N methane;hydroiodide Chemical compound C.I PKAUVIXBZJUYRV-UHFFFAOYSA-N 0.000 description 1
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PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
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238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
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230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
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YCOFRPYSZKIPBQ-UHFFFAOYSA-N penicillic acid Natural products COC1=CC(=O)OC1(O)C(C)=C YCOFRPYSZKIPBQ-UHFFFAOYSA-N 0.000 description 1
VOUGEZYPVGAPBB-UHFFFAOYSA-N penicillin acid Natural products OC(=O)C=C(OC)C(=O)C(C)=C VOUGEZYPVGAPBB-UHFFFAOYSA-N 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
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150000003952 β-lactams Chemical class 0.000 description 1