JPS6135995B2 - - Google Patents

Info

Publication number: JPS6135995B2
Authority: JP; Japan
Prior art keywords: apa; general formula; chloride; acid; alkyl
Prior art date: 1976-01-15
Legal status (The legal status 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 status listed.): Expired

Application number

JP52002519A

Other languages

English (en)

Japanese (ja)

Other versions

JPS5287190A (en

Inventor

Kurochi Maruko

Kotsuchi Jino

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Glaxo Laboratories Ltd

Original Assignee

Glaxo Laboratories Ltd

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.)

1976-01-15

Filing date

1977-01-14

Publication date

1986-08-15

1977-01-14 Application filed by Glaxo Laboratories Ltd filed Critical Glaxo Laboratories Ltd

1977-07-20 Publication of JPS5287190A publication Critical patent/JPS5287190A/ja

1986-08-15 Publication of JPS6135995B2 publication Critical patent/JPS6135995B2/ja

Status Granted legal-status Critical Current

Links

YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
238000000034 method Methods 0.000 claims description 34
NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 claims description 31
NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 claims description 25
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 24
150000001875 compounds Chemical class 0.000 claims description 20
230000003115 biocidal effect Effects 0.000 claims description 19
-1 aralkyl radical Chemical class 0.000 claims description 17
229930182555 Penicillin Natural products 0.000 claims description 15
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 claims description 15
239000002253 acid Substances 0.000 claims description 15
229940049954 penicillin Drugs 0.000 claims description 14
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 13
238000004519 manufacturing process Methods 0.000 claims description 13
YFAGHNZHGGCZAX-JKIFEVAISA-N dicloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl YFAGHNZHGGCZAX-JKIFEVAISA-N 0.000 claims description 11
229960001585 dicloxacillin Drugs 0.000 claims description 11
238000006243 chemical reaction Methods 0.000 claims description 10
LQOLIRLGBULYKD-JKIFEVAISA-N cloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl LQOLIRLGBULYKD-JKIFEVAISA-N 0.000 claims description 9
229960003326 cloxacillin Drugs 0.000 claims description 9
229910000039 hydrogen halide Inorganic materials 0.000 claims description 9
239000012433 hydrogen halide Substances 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 6
239000003960 organic solvent Substances 0.000 claims description 5
OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims description 2
150000003254 radicals Chemical class 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000002585 base Substances 0.000 description 22
238000005917 acylation reaction Methods 0.000 description 19
239000000725 suspension Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 17
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 16
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 16
239000000047 product Substances 0.000 description 16
230000010933 acylation Effects 0.000 description 14
239000000203 mixture Substances 0.000 description 14
238000002798 spectrophotometry method Methods 0.000 description 14
239000003795 chemical substances by application Substances 0.000 description 13
238000006884 silylation reaction Methods 0.000 description 13
238000002360 preparation method Methods 0.000 description 11
229960000723 ampicillin Drugs 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
238000004458 analytical method Methods 0.000 description 8
239000003242 anti bacterial agent Substances 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 8
239000005051 trimethylchlorosilane Substances 0.000 description 8
229940088710 antibiotic agent Drugs 0.000 description 7
239000000243 solution Substances 0.000 description 7
239000002904 solvent Substances 0.000 description 7
238000004448 titration Methods 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 6
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000000370 acceptor Substances 0.000 description 6
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
229960003311 ampicillin trihydrate Drugs 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
150000001263 acyl chlorides Chemical class 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
239000012535 impurity Substances 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
YBBLOADPFWKNGS-UHFFFAOYSA-N 1,1-dimethylurea Chemical compound CN(C)C(N)=O YBBLOADPFWKNGS-UHFFFAOYSA-N 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
229940057054 1,3-dimethylurea Drugs 0.000 description 2
WKQLCSGGVPLSRN-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound NC(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1Cl WKQLCSGGVPLSRN-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
MGJKQDOBUOMPEZ-UHFFFAOYSA-N N,N'-dimethylurea Chemical compound CNC(=O)NC MGJKQDOBUOMPEZ-UHFFFAOYSA-N 0.000 description 2
XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000002274 desiccant Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
150000004684 trihydrates Chemical class 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
LOIDZCCUOOVZFG-UHFFFAOYSA-N 1-[amino(dipropyl)silyl]propane Chemical compound CCC[Si](N)(CCC)CCC LOIDZCCUOOVZFG-UHFFFAOYSA-N 0.000 description 1
QSPBUUIVOLBPBO-UHFFFAOYSA-N 1-[bis(4-methylphenyl)-[tris(4-methylphenyl)silylamino]silyl]-4-methylbenzene Chemical compound C1(=CC=C(C=C1)[Si](N[Si](C1=CC=C(C=C1)C)(C1=CC=C(C=C1)C)C1=CC=C(C=C1)C)(C1=CC=C(C=C1)C)C1=CC=C(C=C1)C)C QSPBUUIVOLBPBO-UHFFFAOYSA-N 0.000 description 1
VXWYQEYFYNAZOD-UHFFFAOYSA-N 2-[3-[(4,4-difluoropiperidin-1-yl)methyl]-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound FC1(F)CCN(CC2=NN(CC(=O)N3CCC4=C(C3)N=NN4)C=C2C2=CN=C(NC3CC4=C(C3)C=CC=C4)N=C2)CC1 VXWYQEYFYNAZOD-UHFFFAOYSA-N 0.000 description 1
MEAZEHJUPLREOQ-UHFFFAOYSA-N 2-amino-2-phenylacetyl chloride Chemical compound ClC(=O)C(N)C1=CC=CC=C1 MEAZEHJUPLREOQ-UHFFFAOYSA-N 0.000 description 1
XPJAACBOROWTBC-UHFFFAOYSA-N C(C)[Si](N[Si](C)(C)CC)(CC)CC Chemical compound C(C)[Si](N[Si](C)(C)CC)(CC)CC XPJAACBOROWTBC-UHFFFAOYSA-N 0.000 description 1
PVEWMXHRWYGMGN-UHFFFAOYSA-N CC[SiH](Cl)CCC1=CC=CC=C1 Chemical compound CC[SiH](Cl)CCC1=CC=CC=C1 PVEWMXHRWYGMGN-UHFFFAOYSA-N 0.000 description 1
ADVRQQNYDMZTEW-UHFFFAOYSA-N C[Si](N[Si](CC)(CC)C)(C)C Chemical compound C[Si](N[Si](CC)(CC)C)(C)C ADVRQQNYDMZTEW-UHFFFAOYSA-N 0.000 description 1
229930186147 Cephalosporin Natural products 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
206010041349 Somnolence Diseases 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
GLQOALGKMKUSBF-UHFFFAOYSA-N [amino(diphenyl)silyl]benzene Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(N)C1=CC=CC=C1 GLQOALGKMKUSBF-UHFFFAOYSA-N 0.000 description 1
TWSOFXCPBRATKD-UHFFFAOYSA-N [diphenyl-(triphenylsilylamino)silyl]benzene Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C=1C=CC=CC=1)N[Si](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 TWSOFXCPBRATKD-UHFFFAOYSA-N 0.000 description 1
DTJXCEOOTSOEJB-UHFFFAOYSA-N [methyl-phenyl-(trimethylsilylamino)silyl]benzene Chemical compound C=1C=CC=CC=1[Si](C)(N[Si](C)(C)C)C1=CC=CC=C1 DTJXCEOOTSOEJB-UHFFFAOYSA-N 0.000 description 1
AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
229960003022 amoxicillin Drugs 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
CBOXQJGHYXSYFT-UHFFFAOYSA-N bromo-dimethyl-phenylsilane Chemical compound C[Si](C)(Br)C1=CC=CC=C1 CBOXQJGHYXSYFT-UHFFFAOYSA-N 0.000 description 1
CAURZYXCQQWBJO-UHFFFAOYSA-N bromomethyl-chloro-dimethylsilane Chemical compound C[Si](C)(Cl)CBr CAURZYXCQQWBJO-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical class N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
229940124587 cephalosporin Drugs 0.000 description 1
150000001780 cephalosporins Chemical class 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
ACTAPAGNZPZLEF-UHFFFAOYSA-N chloro(tripropyl)silane Chemical compound CCC[Si](Cl)(CCC)CCC ACTAPAGNZPZLEF-UHFFFAOYSA-N 0.000 description 1
PDNUHAXBKKDGAM-UHFFFAOYSA-N chloro-diethyl-methylsilane Chemical compound CC[Si](C)(Cl)CC PDNUHAXBKKDGAM-UHFFFAOYSA-N 0.000 description 1
AVDUEHWPPXIAEB-UHFFFAOYSA-N chloro-ethyl-dimethylsilane Chemical compound CC[Si](C)(C)Cl AVDUEHWPPXIAEB-UHFFFAOYSA-N 0.000 description 1
UPSBFLYYMHIEJB-UHFFFAOYSA-N chloro-methyl-(2-phenylethyl)silane Chemical compound C[SiH](Cl)CCC1=CC=CC=C1 UPSBFLYYMHIEJB-UHFFFAOYSA-N 0.000 description 1
HPQGAYBKOJXAEZ-UHFFFAOYSA-N chloro-tris(2-methylphenyl)silane Chemical compound CC1=CC=CC=C1[Si](Cl)(C=1C(=CC=CC=1)C)C1=CC=CC=C1C HPQGAYBKOJXAEZ-UHFFFAOYSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
KCUWTKOTPIUBRI-VICXVTCVSA-M cloxacillin sodium monohydrate Chemical compound O.[Na+].N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C([O-])=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl KCUWTKOTPIUBRI-VICXVTCVSA-M 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000005828 desilylation reaction Methods 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000007788 liquid Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
229960003085 meticillin Drugs 0.000 description 1
239000011707 mineral Substances 0.000 description 1
QHUOBLDKFGCVCG-UHFFFAOYSA-N n-methyl-n-trimethylsilylacetamide Chemical compound CC(=O)N(C)[Si](C)(C)C QHUOBLDKFGCVCG-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
LMSCAPYDLTUYDG-UHFFFAOYSA-N n-triethylsilylethanamine Chemical compound CCN[Si](CC)(CC)CC LMSCAPYDLTUYDG-UHFFFAOYSA-N 0.000 description 1
230000008693 nausea Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000009965 odorless effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 1
229960001019 oxacillin Drugs 0.000 description 1
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
150000002960 penicillins Chemical class 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 1
238000000711 polarimetry Methods 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
150000003858 primary carboxamides Chemical class 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
150000003859 secondary carboxamides Chemical class 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical compound [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
HPGPMRDLVSYSGS-UHFFFAOYSA-N silane triphenyl-lambda3-chlorane Chemical compound [SiH4].C1(=CC=CC=C1)Cl(C1=CC=CC=C1)C1=CC=CC=C1 HPGPMRDLVSYSGS-UHFFFAOYSA-N 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
150000003511 tertiary amides Chemical class 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000010998 test method Methods 0.000 description 1
238000012360 testing method Methods 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
JSQJUDVTRRCSRU-UHFFFAOYSA-N tributyl(chloro)silane Chemical compound CCCC[Si](Cl)(CCCC)CCCC JSQJUDVTRRCSRU-UHFFFAOYSA-N 0.000 description 1
XEJUFRSVJVTIFW-UHFFFAOYSA-N triethyl(triethylsilyl)silane Chemical compound CC[Si](CC)(CC)[Si](CC)(CC)CC XEJUFRSVJVTIFW-UHFFFAOYSA-N 0.000 description 1
ZUJHPDSXDJCNNL-UHFFFAOYSA-N triethylsilylurea Chemical compound CC[Si](CC)(CC)NC(N)=O ZUJHPDSXDJCNNL-UHFFFAOYSA-N 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
150000003952 β-lactams Chemical class 0.000 description 1

Classifications

- 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
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

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

JP251977A 1976-01-15 1977-01-14 Process for preparing semiisynthetic penicillin antibiotics Granted JPS5287190A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
IT47642/76A IT1053312B (it)	1976-01-15	1976-01-15	Procedimento per la produzione di antibiotici di penicillina semisintetici

Publications (2)

Publication Number	Publication Date
JPS5287190A JPS5287190A (en)	1977-07-20
JPS6135995B2 true JPS6135995B2 (da)	1986-08-15

Family

ID=11261615

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP251977A Granted JPS5287190A (en)	1976-01-15	1977-01-14	Process for preparing semiisynthetic penicillin antibiotics

Country Status (14)

Country	Link
JP (1)	JPS5287190A (da)
AU (1)	AU512149B2 (da)
BE (1)	BE850381A (da)
CH (1)	CH628635A5 (da)
DE (1)	DE2701407A1 (da)
DK (1)	DK143705C (da)
ES (1)	ES455025A1 (da)
FR (1)	FR2338278A1 (da)
GB (1)	GB1569426A (da)
IT (1)	IT1053312B (da)
NL (1)	NL7700395A (da)
SE (1)	SE7700392L (da)
YU (1)	YU9177A (da)
ZA (1)	ZA77194B (da)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0953569A1 (en) *	1998-04-29	1999-11-03	Gist-Brocades B.V.	Preparation of beta-lactam antibiotics in the presence of urea or amide

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB958478A (en) *	1962-03-13	1964-05-21	Beecham Res Lab	Production of penicillins
FR68F (da) *	1962-10-17
GB1104937A (en) *	1964-05-28	1968-03-06	Glaxo Lab Ltd	Improvements in or relating to the acylation of 7-aminocephalosporanic acid and derivatives thereof
US3351597A (en) *	1966-11-23	1967-11-07	Lilly Co Eli	Process for acylating 7-amino cephalosporanic acid
FR2220531A1 (en) *	1973-03-06	1974-10-04	Aries Robert	Synthesis of penicillins from 6-amino penicillanic acid - by acylation with acid chlorides using hexamethylphosphotriamide as solvent
GB1472746A (en) *	1973-07-05	1977-05-04	Glaxo Lab Ltd	Cephalosporin compounds
GB1459807A (en) *	1975-05-27	1976-12-31	Proter Spa	Process for the production of 7-d-a-amino-phenyl-acetamido-3- desacetoxy-cephalosporanic acid

1976
- 1976-01-15 IT IT47642/76A patent/IT1053312B/it active
1977
- 1977-01-13 CH CH43277A patent/CH628635A5/de not_active IP Right Cessation
- 1977-01-14 AU AU21339/77A patent/AU512149B2/en not_active Expired
- 1977-01-14 SE SE7700392A patent/SE7700392L/xx not_active Application Discontinuation
- 1977-01-14 DK DK13877A patent/DK143705C/da not_active IP Right Cessation
- 1977-01-14 DE DE19772701407 patent/DE2701407A1/de not_active Withdrawn
- 1977-01-14 JP JP251977A patent/JPS5287190A/ja active Granted
- 1977-01-14 BE BE174078A patent/BE850381A/xx not_active IP Right Cessation
- 1977-01-14 YU YU00091/77A patent/YU9177A/xx unknown
- 1977-01-14 NL NL7700395A patent/NL7700395A/xx not_active Application Discontinuation
- 1977-01-14 FR FR7701122A patent/FR2338278A1/fr active Granted
- 1977-01-14 ES ES455025A patent/ES455025A1/es not_active Expired
- 1977-01-14 ZA ZA770194A patent/ZA77194B/xx unknown
- 1977-01-14 GB GB1540/77A patent/GB1569426A/en not_active Expired

Also Published As

Publication number	Publication date
GB1569426A (en)	1980-06-18
YU9177A (en)	1982-06-30
CH628635A5 (en)	1982-03-15
IT1053312B (it)	1981-08-31
FR2338278B1 (da)	1981-06-12
SE7700392L (sv)	1977-07-16
AU2133977A (en)	1978-07-20
BE850381A (fr)	1977-07-14
DK13877A (da)	1977-07-16
AU512149B2 (en)	1980-09-25
DK143705B (da)	1981-09-28
ES455025A1 (es)	1977-12-16
ZA77194B (en)	1977-11-30
NL7700395A (nl)	1977-07-19
JPS5287190A (en)	1977-07-20
DE2701407A1 (de)	1977-07-21
FR2338278A1 (fr)	1977-08-12
DK143705C (da)	1982-03-08

Publication	Publication Date	Title
US4234721A (en)	1980-11-18	Process for the preparation of the crystalline monohydrate of 7-[D-amino-(p-hydroxyphenyl]acetamido)-3-methyl-3-cephen-4-carboxylic acid
EP0019345B1 (en)	1985-06-19	Process for the preparation of a (d-alpha-amino-(p-hydroxyphenyl)-acetamido) group containing cephalosporanic acid derivatives
SU467521A3 (ru)	1975-04-15	Способ получени производных цефалоспорина или пенициллина
US3980637A (en)	1976-09-14	Production of amoxicillin
US4254029A (en)	1981-03-03	Process for preparing β-lactam antibiotics
US4160863A (en)	1979-07-10	Process for the preparation of the crystalline monohydrate of 7-[D-α-aα-(p-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4-carboxylic acid
US3957773A (en)	1976-05-18	Process for preparing cephalosporin compounds from 7-adca
NO146203B (no)	1982-05-10	Fremgangsmaate til fremstilling av cephalexin eller salter derav
KR20040008158A (ko)	2004-01-28	세프포독심 산의 제조 방법
KR830002454B1 (ko)	1983-10-26	7-아미노-데스아세톡시 세파로스포란산 유도체의 제조방법
JPS6135995B2 (da)	1986-08-15
US4182709A (en)	1980-01-08	Manufacture of semi-synthetic penicillin antibiotics
US4193918A (en)	1980-03-18	Process for the preparation of hydroxy-alpha-amino-benzyl penicillin
US4181656A (en)	1980-01-01	Manufacture of semi-synthetic penicillin antibiotics
KR810000856B1 (ko)	1981-08-10	반합성 페니실린의 제조방법
US3965098A (en)	1976-06-22	Intermediates for preparing cephalosporins and methods of production
US4051131A (en)	1977-09-27	Intermediates for preparing cephalosporins
HUT77102A (hu)	1998-03-02	Szililező eljárás
KR810001202B1 (ko)	1981-09-28	반합성 페니실린의 제조방법
US3676429A (en)	1972-07-11	Imino compounds of penicillins and silyl esters thereof
US4272438A (en)	1981-06-09	Manufacture of semi-synthetic penicillin antibiotics
KR920001769B1 (ko)	1992-03-02	클로로세파드록실 모노하이드레이트의 제조방법
KR840000482B1 (ko)	1984-04-12	세팔로 스포린 유도체의 제조방법
GB2034695A (en)	1980-06-11	Acylation of 6-APA via silyl intermediates
JPS6137787A (ja)	1986-02-22	高収率でベーター‐ラクタム抗生物質を製造するための方法