CA1204436A - Monohydrate d'hydrochlorure de cephalosporine cristallise - Google Patents

Monohydrate d'hydrochlorure de cephalosporine cristallise

Info

Publication number: CA1204436A
Authority: CA; Canada
Prior art keywords: methyl; cephem; acid; naphthylglycylamido; carboxylic acid
Prior art date: 1983-09-30
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

CA000451714A

Other languages

English (en)

Inventor

Preston C. Conrad

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.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1983-09-30

Filing date

1984-04-11

Publication date

1986-05-13

1984-04-11 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1986-05-13 Application granted granted Critical

1986-05-13 Publication of CA1204436A publication Critical patent/CA1204436A/fr

Status Expired legal-status Critical Current

Links

-1 cephalosporin hydrochloride monohydrate Chemical class 0.000 title description 5
229930186147 Cephalosporin Natural products 0.000 title description 3
229940124587 cephalosporin Drugs 0.000 title description 3
239000002253 acid Substances 0.000 claims abstract description 33
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 claims abstract 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 39
238000000034 method Methods 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 1
239000000126 substance Substances 0.000 claims 1
239000013078 crystal Substances 0.000 abstract description 5
230000003115 biocidal effect Effects 0.000 abstract description 2
230000003389 potentiating effect Effects 0.000 abstract description 2
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
238000002360 preparation method Methods 0.000 description 18
239000000243 solution Substances 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
150000001875 compounds Chemical class 0.000 description 13
239000000203 mixture Substances 0.000 description 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-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
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000000047 product Substances 0.000 description 9
238000001914 filtration Methods 0.000 description 8
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 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
239000007787 solid Substances 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
150000004685 tetrahydrates Chemical class 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
241000282320 Panthera leo Species 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000010933 acylation Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
239000000725 suspension Substances 0.000 description 3
NVIAYEIXYQCDAN-HWZXHQHMSA-N (6r)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)C(N)[C@@H]12 NVIAYEIXYQCDAN-HWZXHQHMSA-N 0.000 description 2
NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 2
SEABHMYCRYLVKD-UHFFFAOYSA-N 2-(naphthalen-2-ylamino)acetic acid Chemical compound C1=CC=CC2=CC(NCC(=O)O)=CC=C21 SEABHMYCRYLVKD-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 2
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 2
230000002349 favourable effect Effects 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
238000004448 titration Methods 0.000 description 2
229940086542 triethylamine Drugs 0.000 description 2
OEUFXZDZKRPVAV-CZNRRTBNSA-N (6R)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid tetrahydrate Chemical compound O.O.O.O.CC1=C(N2[C@@H](CC2=O)SC1)C(O)=O OEUFXZDZKRPVAV-CZNRRTBNSA-N 0.000 description 1
NLZHNYNXJJFHRW-ZCFIWIBFSA-N (6r)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)C[C@H]21 NLZHNYNXJJFHRW-ZCFIWIBFSA-N 0.000 description 1
BAAYOXGQOJBERU-GUNDQUCTSA-N (6r)-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC(C)S[C@@H]2CC(=O)N21 BAAYOXGQOJBERU-GUNDQUCTSA-N 0.000 description 1
NYVVVBWEVRSKIU-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;n,n-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide Chemical compound OC(=O)C(O)C(O)C(O)=O.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 NYVVVBWEVRSKIU-UHFFFAOYSA-N 0.000 description 1
VSBLSZBSWQIDFL-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonyl-naphthalen-1-ylamino]acetic acid Chemical compound C1=CC=C2C(N(CC(O)=O)C(=O)OC(C)(C)C)=CC=CC2=C1 VSBLSZBSWQIDFL-UHFFFAOYSA-N 0.000 description 1
LRDIEHDJWYRVPT-UHFFFAOYSA-N 4-amino-5-hydroxynaphthalene-1-sulfonic acid Chemical compound C1=CC(O)=C2C(N)=CC=C(S(O)(=O)=O)C2=C1 LRDIEHDJWYRVPT-UHFFFAOYSA-N 0.000 description 1
UJTTUOLQLCQZEA-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(4-hydroxybutyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCCO)C3=CC=CC=C3C2=C1 UJTTUOLQLCQZEA-UHFFFAOYSA-N 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
238000005169 Debye-Scherrer Methods 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
241000243251 Hydra Species 0.000 description 1
238000003109 Karl Fischer titration Methods 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000191992 Peptostreptococcus Species 0.000 description 1
206010057190 Respiratory tract infections Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
229940059913 ammonium carbonate Drugs 0.000 description 1
235000012501 ammonium carbonate Nutrition 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001780 cephalosporins Chemical class 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
239000013505 freshwater Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000000227 grinding Methods 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
206010022000 influenza Diseases 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229940051374 intermezzo Drugs 0.000 description 1
QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
230000007774 longterm Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
238000003801 milling Methods 0.000 description 1
WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
150000004002 naphthaldehydes Chemical class 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
229940127249 oral antibiotic Drugs 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000008092 positive effect Effects 0.000 description 1
238000000634 powder X-ray diffraction Methods 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000011514 reflex Effects 0.000 description 1
208000020029 respiratory tract infectious disease Diseases 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1

Landscapes

Cephalosporin Compounds (AREA)

CA000451714A 1983-09-30 1984-04-11 Monohydrate d'hydrochlorure de cephalosporine cristallise Expired CA1204436A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US53805083A	1983-09-30	1983-09-30
US538,050		1983-09-30

Publications (1)

Publication Number	Publication Date
CA1204436A true CA1204436A (fr)	1986-05-13

Family

ID=24145231

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000451714A Expired CA1204436A (fr)	1983-09-30	1984-04-11	Monohydrate d'hydrochlorure de cephalosporine cristallise

Country Status (1)

Country	Link
CA (1)	CA1204436A (fr)

1984
- 1984-04-11 CA CA000451714A patent/CA1204436A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2004-04-11	MKEX	Expiry

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