7-Amino-3-methyl-3-cephem-4-carboxylic

Amino-3-methyl-3-cephem-4-carboxylic acid Manufacturing Process... 

On the other hand, 1 g of 7-amino-3-methyl-3-cephem-4-carboxylic acid was suspended in 20 ml of methanol, and 1.4 g of triethylamine was added thereto to be dissolved, and 0,4 ml of acetic acid was further added thereto. This solution was cooled to -20°C and the mixed acid anhydride prepared previously was added thereto. After the mixture was reacted at -20°C for 1 hour, the temperature of the reaction mixture was raised to 0°C over a period of 1 hour, and the mixture was reacted for 3 hours at the same temperature. 

Cefazaflur (58) stands out among this group of analogues because it lacks an arylamide C-7 side chain (see cephacetri 1 e for another example).Cefazaflur (58) is synthesized by reaction of 3-(1-methyl-lB[-tetrazol-5-ylthiomethylene)-7-amino-cephem-4-carboxylic acid (56) with trifluoromethylthioacetyl chloride (57). ... 

Preparation of 7-(D-0t-phenyigiycyiamido)-3-chioro-3-cephem-4-carboxyiic acid To a suspension of 280 mg (1.2 mmol) of 7-amino-3-chloro-3-cephem-4-carboxylic acid in 14 ml of acetonitrile was added with stirring at room temperature 0.5 ml of N, 0-bis-(trimethylsilyl)acetamide to form the soluble disilylmethyl derivative thereof. The solution was cooled to 0°C and was slowly added to a solution of the mixed anhydride formed by reacting 408 mg (1.5 mmol) of methyl-3-a-carboxybenzylaminocrotonate sodium salt with 161 mg (1.7 mmol) of methyl chloroformate in the presence to 2 drops of N, N-dimethylbenzyl amine in 7 ml of acetonitrile. 

Amino-3-(1 -methyl-1 H-tetrazol-5-yI-thiomethyI)-3-cephem-4-carboxylic acid... 

C2,H2oCl2N20,S 107837-26-3) see t/.t-Cefprozil diphenylmethyl 7-amino-3-chloromethyl-3-cephem-4-carboxylate monohydrochloride (C2,H2oCl2N20,S 79349-53-4) see Cefixime diphenylmethyl 7-amino-7-methoxycephalosporanatc (C24H24N20 S 35565-04-9) see Cefoxitin diphenylmethyl 7(R)-7-amino-7-methoxy-3-(l-methyl-tetrazol-5-ylthiomethyl)-l-oxa-l-dethia-3-cephem-4-carb-oxylate... 

C24H24NSO5S 66510-99-4) see Latamoxef diphenylmethyl 7(/f)-amino-3-(l-methyl-lH-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate (C23H22N6O3S2 53090-86-1) see Cefbuperazone diphenylmethyl 7-amino-3-[(Z)-f -propenyl]-3-cephem-4-carboxylate... 

After the reaction, 1 ml of water was added to the reaction mixture, and the mixture was adjusted to a pH of 1.0 with concentrated hydrochloric acid while being cooled, and then stirred for 30 minutes, The insoluble matters were filtered off, and the filtrate was adjusted to a pH of 5.5 with triethylamine. This solution was concentrated under reduced pressure, and the residue was diluted with 20 ml of acetone to precipitate white crystals. The crystals were collected by filtration and washed with ethanol to obtain 1.46 g of white crystals of 7-[D(-)-a-amino-(4-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4-carboxylic acid having a decomposition point of 197°C. 

Amino-3-(l-methyl-lH-tetrazol-5-yl-thiomethyl)-3-cephem-4-carboxylic... 

Amino-3-[(Z)-2-(methyl-5-thiazolyl)vinyl]-3-cephem-4-carboxylic acid Triethylamine... 

D-(-)-a-Amino-p-hydroxyphenylacetamido]-3-[5-(l-methyl-l,2,3,4-tetrazolyl)-thiomethyl]-8(3)-cephem-4-carboxylic acid 4-Ethyl-2,3-dioxo-l-piperazinocarbonyl chloride... 

To a suspension of 3.0 g of 7-[D-(-)-a-amino-p-hydroxyphenylacetamido]-3-[5-(l-methyl-l,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylic acid in 29 ml of water was added 0.95 g of anhydrous potassium carbonate. After the solution was formed, 15 ml of ethyl acetate was added to the solution, and 1.35 g of 4-ethyl-2,3-dioxo-l-piperazinocarbonyl chloride was added to the resulting solution at 0°C to 5°C over a period of 15 minutes, and then the mixture was reacted at 0°C to 5°C for 30 minutes. After the reaction, an aqueous layer was separated off, 40 ml of ethyl acetate and 10 ml of acetone... 

Fig. 1 Chemical structure of 7-aminocephalosporanic acid [3-(acetyloxy-methyl)-7-amino-8-oxo-5-thia-l-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid or briefly 7-ACA] and cephem ring system.

ChemicalAbstracts indexes cephalosporins as 5-thia-l-azabicydo[4.2.0]oct-2-enes. Using this system then, cephalosporin C [61 -24-5]> C1(5H21N3OgS, (2) is 3-[(acetyloxy)methyl]-7- [(5-amino-5-carboxy-l-oxopentyl)amino]-8-oxo-5-thia-l-azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid Such names are too cumbersome for general use. One simplification defines the ring system of the cephalosporins as cepham (3) (1). Hence cephalosporins become 3-acetoxymethyl-7-acylamino-3-cephem-4-carboxylic acids. In this widely used nomenclature system, the numbering, as shown in structure (3), differs from that used by Chemical Abstracts shown in structure (2). In both systems, however, the important C-7, C-6, and C-3 positions remain unchanged. The cephem numbering system (3) is used herein. 

Cefminox. [6R-[6a,7thio]methyl]S-oxo-S-thia-I-azabicyc (o-[4.2.0]oct-2-ene-2-carboxytic add 7,5-t2-1 -amino -2-ea rb-oxyethy]thioacetamido)-7 -methoxy-3-[[(l -methyl-12f-tetrazol 5-yl)thio]methyl]-3-cephem -4 -carboxylic acid. C)6HnN707S3 mol wt 519.57. C 36.99%, H 4.07%, N 18.87%, O 21.56%, S 18.51 %. Semisynthetic broad spectrum cephamycin antibiotic. Prepn Belg. pat. 880,686, K. 

Cephaloglycin. 3-[(Acetyloxy>methyl]-7-[carboxylic acid 7-(2-amino-2-phenylacetamido)-3-[Pg.304]

To a suspension of 3.0 g of 7-[D-(-)-0 -amino-p-hydroxyphenyiacetamido] -3-[5-(1-methyi-1,2,3,4-tetrazoiyl)thiomethyl] -A3-cephem-4-carboxyiic acid in 29 mi of water was added 0.95 g of anhydrous potassium carbonate. After the solution was formed, 15 ml of ethyl acetate was added to the solution, and 1.35 g of 4-ethyl-2,3-dioxo-1 -piperazinocarbonyl chloride was added to the resulting solution at 0°C to 5°C over a period of 15 minutes, and then the mixture was reacted at 0°C to 5°C for 30 minutes. After the reaction, an aqueous layer was separated off, 40 ml of ethyl acetate and 10 ml of acetone were added to the aqueous layer, and then the resulting solution was adjusted to a pH of 2.0 by addition of dilute hydrochloric acid. Thereafter, an organic layer was separated off, the organic layer was washed two times with 10 ml of water, dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was dissolved in 10 ml of acetone, and 60 ml of 2-propanol was added to the solution to deposit crystals. The deposited crystals were collected by filtration, washed with 2-propanol,and then dried to obtain 3.27 gof 7-[D-(-)-a-(4-ethyl-2 A-dioxo)-1 -piperazinocarbonylamino)-p-hydroxyphenylacetamido] -3-[5-(1 -methyl-1,2,3,4-tetrazolyl)thiomethyl]-A -cephem-4-carboxylic acid, yield 80.7%. The product forms crystals, MP lOO C to lOO C (with decomposition). 

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