89786-04-9

Basic information

• Product Name: Tazobactam acid
• Synonyms: 4,4-dioxide,(2s-(2-alpha,3-beta,5-alpha))--triazol-1-ylmethyl);cl298741;ytr83oh;TAZOBACTAM;tazobactam acid;TAZOBACTAN ACID;(2S,3S,5R)-3-METHYL-4,4,7-TRIOXO-3-[1,2,3]TRIAZOL-1-YLMETHYL-4LAMBDA6-THIA-1-AZA-BICYCLO[3.2.0]HEPTANE-2-CARBOXYLIC ACID;Tazobactam, Free acid
• CAS NO: 89786-04-9
• Molecular Formula: C₁₀H₁₂N₄O₅S
• Molecular Weight: 300.29
• EINECS: 1312995-182-4
• Product Categories: pharmaceutical;Amino Acid Derivatives;Peptide Synthesis/Antibiotics;TAZOCIN
• Mol File: 89786-04-9.mol

Chemical Properties

• Melting Point: 115-145℃
• Boiling Point: 77℃
• Flash Point: >110°(230°F)
• Appearance: White or off-white powder
• Density: 1.92 g/cm³
• Vapor Pressure: 5.55E-21mmHg at 25°C
• Refractive Index: 1.817
• Storage Temp.: Store at?0-5°C
• Solubility: DMSO (Slightly, Heated), Methanol (Slightly, Heated, Sonicated)
• PKA: 2.33±0.40(Predicted)
• Water Solubility: Soluble in water
• Stability: Light Sensitive
• CAS DataBase Reference: Tazobactam acid(CAS DataBase Reference)
• NIST Chemistry Reference: Tazobactam acid(89786-04-9)
• EPA Substance Registry System: Tazobactam acid(89786-04-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: XI0191400
• Hazardous Substances Data: 89786-04-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Tazobactam acid is used as a β-lactamase inhibitor for enhancing the effectiveness of β-lactam antibiotics. It is particularly used in combination with ceftolozane sulfate for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. Its ability to inhibit β-lactamases allows for a more potent and targeted approach to treating bacterial infections, overcoming the resistance posed by these enzymes.

Originator

CL-307579,China Pharm Chemical Co.,,China

Therapeutic Function

Antibiotic

Antimicrobial activity

Tazobactam exhibits little useful antimicrobial activity, although weak activity against Acinetobacter spp. and Borrelia burgdorferi has been reported.

Clinical Use

Tazobactam is a penicillanic acid sulfone that is similar instructure to sulbactam. It is a more potent β-lactamaseinhibitor than sulbactam and has a slightly broader spectrumof activity than clavulanic acid. It has very weak antibacterialactivity. Tazobactam is available in fixed-dose, injectablecombinations with piperacillin, a broad-spectrum penicillinconsisting of an 8:1 ratio of piperacillin sodium to tazobactamsodium by weight and marketed under the trade name Zosyn.The pharmacokinetics of the two drugs are very similar. Bothhave short half-lives (t1/2 ～1 hour), are minimally proteinbound, experience very little metabolism, and are excreted inactive forms in the urine in high concentrations.Approved indications for the piperacillin–tazobactamcombination include the treatment of appendicitis, postpartumendometritis, and pelvic inflammatory disease caused byβ-lactamase–producing E. coli and Bacteroides spp., skin andskin structure infections caused by β-lactamase–producingS. aureus, and pneumonia caused by β-lactamase–producingstrains of H. influenzae.

Veterinary Drugs and Treatments

Although veterinary experience is limited with piperacillin or piperacillin/ tazobactam, these drugs have expanded coverage against many bacteria and may be suitable for empiric use until culture and susceptibility data are available, or for surgical prophylaxis when gram-negative or mixed aerobic/anaerobic infections are concerns.

Drug interactions

Potentially hazardous interactions with other drugs Reduced excretion of methotrexate - monitor methotrexate levels during concomitant treatment. Enhanced action of vecuronium and similar neuromuscular blocking agents.

Metabolism

Piperacillin is metabolised to a minor microbiologically active desethyl metabolite. Tazobactam is metabolised to a single metabolite that has been found to be microbiologically inactive. Piperacillin and tazobactam are eliminated via the kidney by glomerular filtration and tubular secretion. Piperacillin, tazobactam, and desethyl piperacillin are also secreted into the bile.

InChI:InChI=1/C10H12N4O5S/c1-10(5-13-3-2-11-12-13)8(9(16)17)14-6(15)4-7(14)20(10,18)19/h2-3,7-8H,4-5H2,1H3,(H,16,17)/t7-,8+,10+/m1/s1

Upstream product

• 87-53-6 penicillanic acid 
• 24138-28-1 6-bromopenicillanic acid 
• 80353-26-0 6α-bromopenicillan-3α-carboxylic acid diphenylmethyl ester-1β-oxide 
• 74189-25-6 diphenylmethyl 6α-bromopenicillanate 
• 551-16-6 6-Aminopenicillanic Acid 
• 793625-09-9 C₈H₁₁NO₄S 
• 78378-75-3 2β-acetoxymethyl-2α-methyl-(5R)penam-3α-carboxylic acid 
• 76911-22-3 6,6-dihydropenam-3α-carboxylic acid benzyl ester-1β-oxide 
• 80078-08-6 6α-bromopenam-3α-carboxylic acid benzyl ester-1β-oxide 
• 79703-02-9 6α-bromopenicillan-3α-carboxylic acid-1β-oxide 

Downstream Products

• 89785-84-2 tazobactam sodium 
• 59703-84-3 sodium piperacillin 

Relevant articles and documents

Application of Continuous Flow in Tazobactam Synthesis

Tazobactam is a β-lactamase inhibitor. In this work, a combination of continuous flow and batch experiments for the synthesis of tazobactam has been developed. The first three steps and the preparation of the peroxyacetic acid are continuously carried out in the microreactors, which improves the procedure safety and efficiency. There is also a final step of the deprotection reaction in the microreactor, which can increase the yield and reduce the formation of impurities. Under optimized process conditions, the total yield of the target product reached 37.09% (30.93% in batch). The continuous flow method not only greatly reduces the reaction time but also significantly improves procedure safety and increases the yield.

2 β -triazole methylpenicillanic acid dibenzoate. Preparation method of tazobactam intermediate and tazobactam

The invention provides a preparation method of 2 β -triazole methyl penicillanic acid dibenzoate, tazobactam intermediate and tazobactam. The preparation method comprises the following steps: reacting a reaction raw material comprising a double-sulfur ring opening compound, 1, 2, 3 - triazole and first oxidizing agent in first solvent to obtain a product system comprising 2 β - triazole methylpenicillanic acid dibenzoate. The structural formula of 2 β -triazole methylpenicillanic acid dibenzoate is shown. Under the action first oxidizing agent 1, 2 and 3 - triazole are used for directly closing the bicyclic ring opening compound, and the efficient and high-selectivity synthesis of the bis-sulfur ring-opening compound directly to the key intermediate 2 β - triazole methylpenicillanic acid dibenzoate is successfully realized. Further, 2 β - triazole methyl penicillanic acid dibenzoate is used as a key intermediate for synthesizing tazobactam, the yield of tazobactam is improved, and the cost is reduced.

2 β - Azidomethyl penicillanic acid dibenzoate. Preparation method of tazobactam intermediate and tazobactam

The invention provides a preparation method of 2 β -azipenicillanic acid dibenzoate, tazobactam intermediate and tazobactam. The preparation method comprises the following steps: carrying out free radical reaction in a solvent by using a reaction raw material comprising a double-sulfur open-loop compound, a stacked nitrogen source and an oxidant to obtain a product system comprising 2 β - azidomethyl penicillanic acid dibenzoate. By radical addition of the carbon-carbon double bonds of the double-sulfur ring-opening compound through the azide free radical, high-efficiency and high-selectivity synthesis of the disulphide ring-opening compound directly to 2 β - azimaapenem naphthenate is successfully realized through intramolecular radical substitution. Further, 2 β - azidomethyl penicillanic acid dibenzoate is taken as a key intermediate for synthesizing tazobactam, the yield of tazobactam is improved, and the cost is reduced.

Tazobactam intermediate, preparation method thereof and method for preparing tazobactam by using intermediate (by machine translation)

The intermediate V is prepared from glyoxal and hydrazine through dihydrazone of glyoxal, 1 - 2-triazole, and then reacted with (2S, 3S) 3 methyl -3 -methyl-3 -oxo -7 -thio -4 -methylpyridine-1 -thioxazabicyclo [3.2.0 -2 -] heptanoic acid to obtain an intermediate VII, and an intermediate VII is subjected to deprotection reaction to prepare the tazobarbazobactam intermediate V; the intermediate V is subjected to diazotization reaction to prepare the intermediate V. The preparation method of tazobactam is mild in reaction condition, simple in process, low in cost, high 90% in yield, high 99.0% in purity, environmentally friendly, good in economic benefit and suitable for industrial production. (by machine translation)

Self-Assembled Polymeric Pyridine Copper Catalysts for Huisgen Cycloaddition with Alkynes and Acetylene Gas: Application in Synthesis of Tazobactam

Novel convoluted polymeric pyridine copper(I) catalysts PVPy-Cu were developed for the Huisgen cyclization of organic azides using alkynes and acetylene gas. They were readily prepared based on our molecular convolution of CuSO4·5H2O and poly(4-vinylpyridine) (PVPy) in the presence of sodium ascorbate with and without various sodium salts in water. Their structural investigation was conducted using XANES and EXAFS, as well as DFT calculation. The Huisgen cycloaddition of a variety of alkynes and acetylene gas was carried out using 100 to 800 mol ppm of Cu of PVPy-Cu in water, whose turnover numbers reached up to 10 000. This catalytic system was applied to the synthesis of tazobactam, which is an inhibitor of bacterial β-lactamases.

Preparation method of tazobactam

The invention discloses a preparation method of tazobactam. The preparation method comprises the following steps: performing double oxidization on 2beta-chloromethyl penicillanic acid diphenyl methylester by adopting a solution prepared from potassium permanganate, glacial acetic acid and concentrated sulfuric acid; then loading triazole by taking crown ether as a phase transfer catalyst and taking potassium iodide as a catalyst; then performing deprotection to obtain tazobactam. Compared with the prior art, the preparation method disclosed by the invention has the advantages that although sulfur atoms are oxidized into sulfone to lower chlorine atom activity, the use of the crown ether as the phase transfer catalyst and the potassium iodide as the catalyst compensates for the inactivation well. By adopting the method, the stability of the 2beta-chloromethyl penicillanic acid diphenyl methyl ester is improved, the reaction time is shortened, the reaction yield is improved, the operation risk is lowered, and the industrial production is facilitated.

Synthesis method of tazobactam acid

The invention provides a synthesis method of tazobactam acid, and the method comprises the following steps: performing deamination reaction on 6-APA to obtain a compound A; selectively oxidizing the compound A by a Ce(OTf)4/H2O2 oxidation system to obtain a compound B; reacting the compound B with acetic anhydride to obtain a compound C; reacting the compound C with hydrazine hydrate to obtain a compound D; reacting the compound D with methanesulfonyl chloride to obtain a compound E, reacting the compound E with triazole to obtain a compound F, and performing oxidation reaction on the compoundF to obtain the tazobactam acid. The method has the advantages of simple operation steps, cheap and easily available reaction raw materials, short reaction steps, high purity of obtained intermediateproducts and products, purity of the final product tazobactam acid white solid powder of more than 99.5%, high total molar yield, suitability for industrial production, and wide application prospect.

Preparation method of tazobactam

The invention discloses a preparation method of tazobactam. The method includes the steps that 6 alpha-bromine penicillium alkane-3 alpha-carboxylate-1 beta-oxide is used as a raw material, and the tazobactam is obtained through the steps of esterification, reduction, thermal cracking, chloromethylation, azidation, bi-oxidization, cyclization addition and deprotection. According to the method, benzyl bromide is adopted as a protecting group of a carboxylic acid group in an esterification reaction in the presence of sodium bicarbonate, and then benzyl protection is removed through a hydrogenolysis reaction. Compared with an existing process route, the carboxyl protection and removal method has the advantages that the process is simple, environmental friendliness is achieved, and byproductsare fewer.

Preparation method of tazobactam

The invention discloses a preparation method of tazobactam. The method includes: adopting 3, 5-dinitrobenzyl chloride as the carboxyl protection reagent for esterification reaction with 6alpha-bromopenam-3alpha-carboxylic acid-1beta-oxide; then carrying out reduction, thermal cracking, chloromethylation, azidation, double oxidation and cyclization addition to obtain tazobactam3, 5-dinitrobenzyl ester; then taking palladium carbon as the catalyst, and employing hydrogen to remove the protection of tazobactam3, 5-dinitrobenzyl ester so as to obtain tazobactam; and reacting the by-product 3, 5-dinitrotoluene with the chlorinating reagent N-chlorosuccinimide to prepare 3, 5-dinitrobenzyl chloride, thus realizing recycling of the protection reagent. The method provided by the invention uses 3,5-dinitrobenzyl chloride with stable chemical properties, high reaction activity and low price as the carboxyl protection reagent, avoids the use of peracetic acid that has poor stability and easily causes decomposition explosion, and realizes intrinsic safety of the process.

A β - lactam compound carboxy and hydroxy protecting group removing method (by machine translation)

The invention discloses a β - lactam compound carboxyl and hydroxyl protecting group removal method, the method is that the carboxyl and/or hydroxyl protected β - lactam compounds in the trichloro acetic acid and carbon is ion absorbent for removing protecting group and gets the role of β - lactam compound deprotected product. The method adopts the trichloro acetic acid instead of trifluoro acetic acid, trichloro acetic acid and phenol or cresol and, anisole together, can greatly reduce the consumption of the trichloroacetic acid; in addition, trichloro acetic acid in the cephalosporin into sodium salt in the follow-up process meets the volunteer fire brigade into chloroform and carbon dioxide, is easy to remove, does not exist the problem of residual of the trichloroacetic acid, the reaction yield is high, relatively few impurities; trichloro acetic acid is inexpensive and environmentally friendly, reduce the cost beneficial to industrial production. (by machine translation)