CH628635A5 - Process for the preparation of semisynthetic penicillin antibiotics - Google Patents

Process for the preparation of semisynthetic penicillin antibiotics Download PDF

Info

Publication number: CH628635A5
Authority: CH; Switzerland
Prior art keywords: compound; apa; formula; chloride; alkyl
Prior art date: 1976-01-15

Application number

CH43277A

Other languages

German (de)

English (en)

Inventor

Marco Croci

Gino Cotti

Original Assignee

Glaxo Lab 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

1977-01-13

Publication date

1982-03-15

1977-01-13 Application filed by Glaxo Lab Ltd filed Critical Glaxo Lab Ltd

1982-03-15 Publication of CH628635A5 publication Critical patent/CH628635A5/de

Links

238000000034 method Methods 0.000 title claims description 37
238000002360 preparation method Methods 0.000 title claims description 19
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 title claims description 16
229930182555 Penicillin Natural products 0.000 title claims description 15
229940049954 penicillin Drugs 0.000 title claims description 14
239000003242 anti bacterial agent Substances 0.000 title description 7
229940088710 antibiotic agent Drugs 0.000 title description 7
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 44
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 39
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 34
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 29
150000001875 compounds Chemical class 0.000 claims description 24
-1 2,6-dichlorophenyl Chemical group 0.000 claims description 23
238000005917 acylation reaction Methods 0.000 claims description 20
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 claims description 18
230000003115 biocidal effect Effects 0.000 claims description 18
230000010933 acylation Effects 0.000 claims description 15
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 14
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 12
229960001585 dicloxacillin Drugs 0.000 claims description 12
229960000723 ampicillin 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
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 7
125000003710 aryl 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
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
125000003118 aryl group Chemical group 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims description 2
150000007513 acids Chemical class 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
239000002585 base Substances 0.000 description 33
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 18
239000000725 suspension Substances 0.000 description 18
239000000203 mixture Substances 0.000 description 17
239000000047 product Substances 0.000 description 14
239000003795 chemical substances by application Substances 0.000 description 13
238000003756 stirring Methods 0.000 description 12
238000006884 silylation reaction Methods 0.000 description 11
239000005051 trimethylchlorosilane Substances 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 8
238000004519 manufacturing process Methods 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
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
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000000370 acceptor Substances 0.000 description 6
229960003311 ampicillin trihydrate Drugs 0.000 description 6
239000002904 solvent Substances 0.000 description 6
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 5
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 4
XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 4
150000001263 acyl chlorides Chemical class 0.000 description 4
239000000356 contaminant Substances 0.000 description 4
230000000694 effects 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
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
238000000926 separation method Methods 0.000 description 3
238000002798 spectrophotometry method Methods 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
AVKUERGKIZMTKX-ZIOCXDFPSA-N (5R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N[C@@H](C(=O)NC1[C@@H]2N(C(C(S2)(C)C)C(=O)O)C1=O)C1=CC=CC=C1 AVKUERGKIZMTKX-ZIOCXDFPSA-N 0.000 description 2
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
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
MGJKQDOBUOMPEZ-UHFFFAOYSA-N N,N'-dimethylurea Chemical compound CNC(=O)NC MGJKQDOBUOMPEZ-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
238000004166 bioassay Methods 0.000 description 2
239000007795 chemical reaction product Substances 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
150000004820 halides Chemical class 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
150000002960 penicillins Chemical class 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
LQOLIRLGBULYKD-MQBCKMQZSA-N (5R)-6-[[3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound S([C@@H]12)C(C)(C)C(C(O)=O)N1C(=O)C2NC(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl LQOLIRLGBULYKD-MQBCKMQZSA-N 0.000 description 1
MASDFXZJIDNRTR-UHFFFAOYSA-N 1,3-bis(trimethylsilyl)urea Chemical compound C[Si](C)(C)NC(=O)N[Si](C)(C)C MASDFXZJIDNRTR-UHFFFAOYSA-N 0.000 description 1
LOIDZCCUOOVZFG-UHFFFAOYSA-N 1-[amino(dipropyl)silyl]propane Chemical compound CCC[Si](N)(CCC)CCC LOIDZCCUOOVZFG-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
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
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
238000003109 Karl Fischer titration Methods 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
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
206010041349 Somnolence Diseases 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
APDDLLVYBXGBRF-UHFFFAOYSA-N [diethyl-(triethylsilylamino)silyl]ethane Chemical compound CC[Si](CC)(CC)N[Si](CC)(CC)CC APDDLLVYBXGBRF-UHFFFAOYSA-N 0.000 description 1
AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
238000001632 acidimetric titration Methods 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
239000000010 aprotic solvent Substances 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
238000012455 bioassay technique 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
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
229960003669 carbenicillin Drugs 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
229940124587 cephalosporin Drugs 0.000 description 1
150000001780 cephalosporins Chemical class 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
MNKYQPOFRKPUAE-UHFFFAOYSA-N chloro(triphenyl)silane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 MNKYQPOFRKPUAE-UHFFFAOYSA-N 0.000 description 1
ACTAPAGNZPZLEF-UHFFFAOYSA-N chloro(tripropyl)silane Chemical compound CCC[Si](Cl)(CCC)CCC ACTAPAGNZPZLEF-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
238000005828 desilylation reaction Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
231100000869 headache Toxicity 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
239000002198 insoluble material Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
229960003085 meticillin Drugs 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
LMSCAPYDLTUYDG-UHFFFAOYSA-N n-triethylsilylethanamine Chemical compound CCN[Si](CC)(CC)CC LMSCAPYDLTUYDG-UHFFFAOYSA-N 0.000 description 1
LWFWUJCJKPUZLV-UHFFFAOYSA-N n-trimethylsilylacetamide Chemical compound CC(=O)N[Si](C)(C)C LWFWUJCJKPUZLV-UHFFFAOYSA-N 0.000 description 1
230000008693 nausea Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 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
239000012044 organic layer Substances 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
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product 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
150000003053 piperidines Chemical class 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
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000011541 reaction mixture Substances 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
238000007086 side reaction Methods 0.000 description 1
FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical compound [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
229910000077 silane Inorganic materials 0.000 description 1
IYMSIPPWHNIMGE-UHFFFAOYSA-N silylurea Chemical compound NC(=O)N[SiH3] IYMSIPPWHNIMGE-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
238000005063 solubilization Methods 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
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
ZUJHPDSXDJCNNL-UHFFFAOYSA-N triethylsilylurea Chemical compound CC[Si](CC)(CC)NC(N)=O ZUJHPDSXDJCNNL-UHFFFAOYSA-N 0.000 description 1
150000004684 trihydrates Chemical class 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)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Cephalosporin Compounds (AREA)

CH43277A 1976-01-15 1977-01-13 Process for the preparation of semisynthetic penicillin antibiotics CH628635A5 (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 (1)

Publication Number	Publication Date
CH628635A5 true CH628635A5 (en)	1982-03-15

Family

ID=11261615

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH43277A CH628635A5 (en)	1976-01-15	1977-01-13	Process for the preparation of semisynthetic penicillin antibiotics

Country Status (14)

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

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0953569A1 (fr) *	1998-04-29	1999-11-03	Gist-Brocades B.V.	Préparation d'antibiotiques béta-lactamiques en présence d'urée ou d'amide

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* 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 (fr) *	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 GB GB1540/77A patent/GB1569426A/en not_active Expired
- 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 DE DE19772701407 patent/DE2701407A1/de not_active Withdrawn
- 1977-01-14 ZA ZA770194A patent/ZA77194B/xx unknown
- 1977-01-14 JP JP251977A patent/JPS5287190A/ja active Granted
- 1977-01-14 FR FR7701122A patent/FR2338278A1/fr active Granted
- 1977-01-14 DK DK13877A patent/DK143705C/da 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 ES ES455025A patent/ES455025A1/es not_active Expired
- 1977-01-14 BE BE174078A patent/BE850381A/fr not_active IP Right Cessation

Also Published As

Publication number	Publication date
IT1053312B (it)	1981-08-31
DE2701407A1 (de)	1977-07-21
JPS6135995B2 (fr)	1986-08-15
DK13877A (da)	1977-07-16
SE7700392L (sv)	1977-07-16
ZA77194B (en)	1977-11-30
JPS5287190A (en)	1977-07-20
AU2133977A (en)	1978-07-20
AU512149B2 (en)	1980-09-25
NL7700395A (nl)	1977-07-19
BE850381A (fr)	1977-07-14
DK143705B (da)	1981-09-28
ES455025A1 (es)	1977-12-16
GB1569426A (en)	1980-06-18
YU9177A (en)	1982-06-30
DK143705C (da)	1982-03-08
FR2338278B1 (fr)	1981-06-12
FR2338278A1 (fr)	1977-08-12

Legal Events

Date	Code	Title	Description
1987-09-30	PL	Patent ceased
2024-10-31	PL	Patent ceased

Publication	Publication Date	Title
DE1923624C3 (de)	1979-11-08	Verfahren zur Herstellung von Penicillinen
DE1518934A1 (de)	1969-09-04	Verfahren zur Herstellung von Silylgruppenhaltigen Verbindungen
DE2462383A1 (de)	1976-12-02	Verfahren zur herstellung von antibiotischen mitteln
DE2432485C3 (de)	1981-01-22	Verfahren zur Herstellung von Cefalexin
DE2754743A1 (de)	1978-06-15	Thiooximcephalosporin- und -penicillin- derivate, verfahren zu ihrer herstellung und ihre verwendung als arzneistoffe
DE2205144C3 (de)	1982-02-11	Azetidino [3,2-d] thiazole und Verfahren zu ihrer Herstellung
DE2822876C2 (fr)	1988-01-07
DE3012669C2 (fr)	1991-05-08
DE1420981C3 (de)	1976-01-02	Verfahren zur Herstellung von 6-Acylaminopenicillansäuren
DE2809594A1 (de)	1979-09-20	Neue penicillinderivate, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
DE2701407A1 (de)	1977-07-21	Verfahren zur herstellung halbsynthetischer penicillinantibiotika
DE1695313C3 (de)	1975-04-10	Verfahren zur Herstellung von 6-Aminopenicillansäure
DE2145354C3 (de)	1980-02-21	Thioester und Verfahren zu ihrer Herstellung
CH627182A5 (en)	1981-12-31	Process for the preparation of semisynthetic penicillin antibiotics
DE3750023T2 (de)	1994-09-29	Verfahren zur Herstellung von 2-(1-Pentyl-3-guanidino)-4-(2-methyl-4-imidazolyl)Thiazol und dessen kristallinisches Dihydrochlorid-Trihydrat.
CH630640A5 (de)	1982-06-30	Verfahren zur herstellung von neuem bis-trimethylsilylcefamandol.
CH646435A5 (de)	1984-11-30	Verfahren zur herstellung halbsynthetischer penicillinantibiotika.
DE2503394A1 (de)	1975-07-31	Verfahren zur herstellung von antibakteriellen mitteln
EP0203216A1 (fr)	1986-12-03	Dérivés de pénicilline et procédé pour leur préparation
AT267051B (de)	1968-12-10	Verfahren zur Herstellung von neuen N-Acyl-6-aminopenicillansäuren
DE2408171C3 (de)	1977-11-17	Silyl-oxazolidinon-Verbindungen und Verfahren zu ihrer Herstellung
DE3330192A1 (de)	1985-03-07	4-alkylimidazol-derivate, ihre herstellung und verwendung
DE1941026C3 (de)	1975-07-31	6- eckige Klammer auf 2,2-Dimethyl-4-(p-hydroxyphenyl)-5-oxo-1-imidazolinyl eckige Klammer zu -penicHlansäure und Verfahren zu ihrer Herstellung
AT314081B (de)	1974-03-25	Verfahren zur Herstellung von Penicillinen
DE1695049B2 (de)	1979-06-21	Verfahren zur Herstellung von Cephalosporinderivaten