75028-24-9

Usage

Uses

Used in Pharmaceutical Industry:
(Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetic acid is used as a key intermediate in the preparation of Ceftaroline, a potent antibiotic with broad-spectrum antibacterial activity. It is particularly effective against methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa, two of the most common and dangerous antibiotic-resistant bacteria. The development of (Z)-2-(5-AMino-1,2,4-thiadiazol-3-yl)-2-ethoxyiMinoacetic acid has contributed to the fight against antibiotic resistance and the improvement of public health.

Upstream product

• 344302-24-5 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(ethoxyimino) acetonitrile 
• 57967-25-6 2-cyano-2-ethoxyiminoacetamide 
• 84981-58-8 ethoxymethylenemalononitrile 
• 1618104-04-3 (Z)-N-(3-(2-acetamido-1-(ethoxyimino)-2-oxoethyl)-1,2,4-thiadiazol-5-yl)pivalamide 
• 113080-37-8 (Z)-2-(5-amino-1,2,4-thiadiazole-3-yl)-2-ethoxyiminoacetonitrile 

Downstream Products

• 106962-96-3 benzhydryl 2-<(4S)-4-<2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-(ethoxyimino)acetylamino>-3-oxo-2-isoxazolidinyl>-5-oxo-2-tetrahydrofurancarboxylate 
• 142266-02-2 p-methoxybenzyl (6R,7R)-7-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(ethoxyimino)acetamido]-3-chloromethyl-3-cephem-4-carboxylate 
• 90211-01-1 2-[[5-(dichlorophosphinyl)amino]-1,2,4-thiadiazole-3-yl]-2(Z)-ethoxyiminoacetyl chloride 

Relevant academic research and scientific papers

(Z) - 2 - (5- two chlorine phosphinylidynes amino -1, 2, 4-thiadiazol-3-yl) - 2-ethoxy imidogen acetyl chloride preparation method (by machine translation)

The invention relates to a preparation method of (Z)-2-(5-dichlorophosphorylamino-1,2,4-thiadiazolyl-3-yl)-2-ethoxyiminoacetyl chloride. The invention discloses a preparation method of ceftaroline fosamil side chain ATDE-Cl, which comprises the following steps: oximation reaction, dehydration reaction, ammonification reaction, cyclization reaction, hydrolysis reaction and acyl-chlorination reaction. The method has the advantages of short reaction steps, accessible raw materials and high yield; and the content of the prepared ceftaroline fosamil is higher than 93%, thereby conforming to the requirements for medicinal intermediates and satisfying the demands for ceftaroline fosamil production. The preparation method is low in cost, and can create considerable economic benefits for the enterprise.

(Z) - 5-amino-α-(ethoxy-imino) - 1, 2, 4-thiadiazol-3-process for the preparation of acetic acid

The invention discloses a method for preparing (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid. The method comprises steps of firstly, carrying out oximation reaction on malononitrile and sodium nitrite under the action of acetic acid so as to obtain a compound A, then carrying out Williamson synthesis on the compound A and bromoethane or diethyl sulfate under alkaline condition, so as to obtain a compound B, then carrying out amidine reaction on the compound B and ammonia water, so as to obtain a compound C, carrying out cyclization reaction on the compound C and potassium rhodanide for ring closing so as to obtain a compound D, and finally, hydrolyzing the compound D under the action of a strong base, so as to obtain (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid. The method has few synthesis steps, has low cost, uses the materials which are cheap and easy to obtain, is beneficial to industrial production, and has light contamination; the purity of the product can reach 99%, so that synthesis of high-purity ceftaroline fosamil in the subsequent step is guaranteed.

An improved synthesis of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2- (ethoxyimino) acetic acid

An improved synthetic route of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2- (ethoxyimino)acetic acid (2a), an important intermediate for the preparation of Ceftaroline, from N-(3-aminoisoxazol-5-yl)acetamide (8) in total yield of 47% has been developed. The key intermediate (Z)-N-(3-(2-acetamido-1-(ethoxyimino)- 2-oxoethyl)-1,2,4-thiadiazol-5- yl)pivalamide (12a) was easily isolated from (Z/E)-N-(3-(2-acetamido-1-(ethoxyimino)-2-oxoethyl)-1,2,4 -thiadiazol-5- yl)pivalamide. The title compound 2a was obtained from the hydrolysis of 12a with a yield of 83%, and its structure was comfirmed by X-ray single crystal diffraction analysis. Moreover, (E)- and (Z)-N-(3-(2-acetamido-1-(ethoxyimino)-2 -oxoethyl)-1,2,4-thiadiazol-5-yl)pivalamide were prepared respectively from the etherification of oxime hydroxyl group under different conditions. This improved procedure has many appealing attributes such as convenient separation, good yields, and easy access to large scale.

The synthesis of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetic acid

The objective was to synthesize (Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2- ethoxyiminoacetic acid (the side chain for Ceftaroline fosamil). Oximation and alkylation were used on cyanoacetamide to get 2-cyano-2-hydroxyiminoacetamide, which became 2-ethyoxyiminopropanedinitrile through reaction with phosphorus oxychloride, and then aminolysis to get 2-ethoxyiminopropanedinitrile, which became 2-ethoxyimion-2-(5-amino-1,2,4 thiadiazol-3-yl) acetonitrile by brominating and with KSCN, followed by hydrolysis to get (Z)-2-(5-Amino-1,2,4- thiadiazol-3-yl)-2-ethoxyiminoacetic acid.