Bristol-myers Company

Yukio Narita

Takayuki Naito

Jun Okumura

Shimpei Aburaki

Hajime Kamachi

Seiji Iimura

Kiyoto Imae

Donald G Walker

Temperature stable crystalline mono-hydrochloric and sulfuric acid addition salts of 7-amino-3-(1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate substantially free of .DELTA..sup.2 isomer are intermediates for the preparation of broad spectrum 7-[.alpha.-(2-aminothiazol-4-yl)-.alpha.-(Z)-methoxyiminoacetamido]-3-[(1- methyl-1-pyrrolidinio)methyl]-3-cephem-4-carboxylates. The monohydrochloric acid addition salt intermediate is prepared by a process comprising the steps of (1) neutralizing diphenylmethyl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride, (2) reacting the resulting free base with benzaldehyde to produce diphenylmethyl 7-benzylideneamino-3-chloromethyl-3-cephem-4-carboxylate, (3) reacting the resulting product with sodium iodide to convert the chloromethyl group to iodomethyl, (4) reacting the resulting product with N-methylpyrrolidine to give the quaternized product diphenylmethyl 7-benzylideneamino-3-(1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate iodide, and (5) reacting with hydrochloric acid to form said intermediate.

Cephalosporin intermediates

Compounds of the formula ##STR1## wherein R.sup.1 is hydrogen or a conventional amino-protecting group, R.sup.2 is a straight or branched chain alkyl, alkenyl or alkynyl containing from 1 to 4 carbon atoms, and ##STR2## is a quaternary ammonio group as described herein, and nontoxic pharmaceutically acceptable salts, physiologically hydrolyzable esters and solvates thereof, as well as processes for their preparation, are disclosed. The compounds in which R.sup.1 is hydrogen are potent antibacterial agents.

Cephalosporins

Compounds of the formula ##STR1## wherein R.sup.1 is hydrogen or a conventional amino-protecting group, R.sup.2 is one of various alkyl, alkenyl, alkynyl, cycloalkyl, carboxyalkyl or carboxycycloalkyl moieties described herein, and R.sup.5 is hydrogen, amino, carboxy, formyl, carbamoyl, guanidino, amidino or one of various alkyl, alkoxy, alkylthio or substituted amino moieties described herein, and nontoxic pharmaceutically acceptable acid addition salts, physiologically hydrolyzable esters and solvates thereof, as well as processes for their preparation, are disclosed. The compounds in which R.sup.1 is hydrogen are potent antibacterial agents.

Cephalosporin derivatives

7-{(Z)-2-(2-Aminothiazol-4-yl)-2-[(substituted)oxyimino]acetamido}-3-[3-(qu aternary ammonio)-1-propen-1-yl]-3-cephem-4-carboxylates and salts, esters and solvates thereof, having potent antibacterial activity, are provided. Processes for their preparation and intermediates in their preparation also are disclosed.

Compounds of the formula ##STR1## wherein R.sup.1 is hydrogen or a conventional amino-protecting group, and R.sup.2 is a straight or branched chain alkyl group containing from 1 to 4 carbon atoms, allyl, 2-butenyl or 3-butenyl, and nontoxic pharmaceutically acceptable salts and solvates thereof, as well as processes for their preparation, are disclosed. The compounds in which R.sup.1 is hydrogen are potent antibacterial agents.

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Yokohama, Japan

Yukio Narita