74578-69-1

Basic information

• Product Name: Ceftriaxone sodium
• Synonyms: CEFATRIAXONE;2,5,6-tetrahydro-2-methyl-5,6-dioxo-)(methoxyimino)acetyl)amino)-8-oxo-3-(((;4-triazin-3-yl)thio)methyl)-,sodiumsalt,hydrate(2:4:7)(6r-(6-alpha,7-2;beta(z)))-;cefatriaxonehydrate;cephtriaxone;ro13-9904;rocephin
• CAS NO: 74578-69-1
• Molecular Formula: C₁₈H₁₆N₈O₇S₃*2Na
• Molecular Weight: 554.58
• EINECS: 277-930-0
• Product Categories: Pharma;Pharmaceutical intermediate;Pharmaceutical intermediates, pharmaceutical raw materials;Pharmaceutical intermediates
• Mol File: 74578-69-1.mol
• Article Data: 12

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Ceftriaxone sodium(CAS DataBase Reference)
• NIST Chemistry Reference: Ceftriaxone sodium(74578-69-1)
• EPA Substance Registry System: Ceftriaxone sodium(74578-69-1)

Safety Data

• Hazardous Substances Data: 74578-69-1(Hazardous Substances Data)

Usage

Description

Ceftriaxone is a cephalosporin (SEF a low spor in) antibiotic that is used to treat conditions such as lower respiratory tract infections, skin and skin structure infections, urinary tract infections, pelvic inflammatory disease, bacterial septicemia, bone and joint infections, and meningitis.

Uses

Ceftriaxone sodium is antibacteria，an impurity of Ceftriaxone (C244995). It is an antibacterial, a third-generation cephalosporin.

Therapeutic Function

Antibacterial

Hazard

Moderately toxic. Low toxicity by inges- tion. Human systemic effects.

Clinical Use

Ceftriaxone sodium is a β-lactamase–resistantcephalosporin with an extremely long serum half-life.Once-daily dosing suffices for most indications. Two factorscontribute to the prolonged duration of action ofceftriaxone: high protein binding in the plasma and slowurinary excretion. Ceftriaxone is excreted in both the bileand the urine. Its urinary excretion is not affected byprobenecid. Despite its comparatively low volume ofdistribution, it reaches the cerebrospinal fluid in concentrationsthat are effective in meningitis. Nonlinear pharmacokineticsare observed. Ceftriaxone contains a highly acidic heterocyclic systemon the 3-thiomethyl group. This unusual dioxotriazine ringsystem is believed to confer the unique pharmacokineticproperties of this agent. Ceftriaxone has been associatedwith sonographically detected “sludge,” or pseudolithiasis,in the gallbladder and common bile duct. Symptoms ofcholecystitis may occur in susceptible patients, especiallythose on prolonged or high-dose ceftriaxone therapy. Theculprit has been identified as the calcium chelate. Ceftriaxone exhibits excellent broad-spectrum antibacterialactivity against both Gram-positive and Gram-negativeorganisms. It is highly resistant to most chromosomally andplasmid-mediated β-lactamases. The activity of ceftriaxoneagainst Enterobacter, Citrobacter, Serratia, indole-positiveProteus, and Pseudomonas spp. is particularly impressive. Itis also effective in the treatment of ampicillin-resistant gonorrheaand H. influenzae infections but generally less activethan cefotaxime against Gram-positive bacteria and B.fragilis.

Side effects

Different sources of media describe the Side effects of 74578-69-1 differently. You can refer to the following data:
1. Common side effects of Ceftriaxone sodium include:symptoms of a blood cell disorder;diarrhea;vaginal itching or discharge;warmth, tight feeling, or a hard lump where the injection was given;rash;abnormal?liver function tests.
2. Ceftriaxone sodium is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Synthesis

A solution of sodium-2-ethyl hexanoate (390 g) in acetone (2.0 Ltr) is added to the wet Ceftriaxone acid obtained in Example 2 is suspended in a mixture of acetone and water. The reaction mixture is charcoalized and filtered. To the clear filtrate is added acetone whereupon the product precipitated. The precipitated solid is filtered, washed with acetone and dried to get 515 g of Ceftriaxone sodium hemiheptahydrate. HPLC purity = Above 99.5%.

Veterinary Drugs and Treatments

Ceftriaxone is used to treat serious infections, particularly against susceptible Enterobacteriaceae that are not susceptible to other less expensive agents or when aminoglycosides are not indicated (due to their potential toxicity). Its long half life, good CNS penetration, and activity against Borrelia burgdorferi also has made it a potential choice for treating Lyme’s disease.

InChI:InChI=1/C18H18N8O7S3.2Na/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7;;/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32);;/q;2*+1/p-2/b24-8-;;/t9-,15-;;/m1../s1

Synthetic route

C11H15N3O4S + C12H13N5O5S2*C5H13N3 → ceftriaxone disodium (74578-69-1)

Conditions	Yield
Stage #1: C11H15N3O4S; C12H13N5O5S2*C5H13N3 With sodium acetate In water at -50 - -40℃; for 1h; Stage #2: In acetone at 20 - 25℃; for 1h; Solvent; Reagent/catalyst;	97%

(Z)-S-benzo[d]thiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)ethanethioate (80756-85-0) + 7-aminoceftrizine (58909-56-1) → ceftriaxone disodium (74578-69-1)

Conditions	Yield
Stage #1: (Z)-S-benzo[d]thiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)ethanethioate; 7-aminoceftrizine With triethylamine In methanol at -2 - 3℃; Stage #2: With sodium 2-ethylhexanoic acid In water; isopropyl alcohol at 26 - 30℃; for 2h; Product distribution / selectivity;	95.5%
With sodium metabisulfite; edetate disodium; triethylamine In ethanol; water at 1 - 3℃; for 3h; Time;	91%

diethylthiophosphoryl-(Z)-(2-aminothiazol-4-yl)methoxyimino acetate + 7-aminoceftrizine (58909-56-1) → ceftriaxone disodium (74578-69-1)

Conditions	Yield
Stage #1: 7-aminoceftrizine With N,O-bis-(trimethylsilyl)-acetamide In dichloromethane at 20℃; for 2h; Stage #2: diethylthiophosphoryl-(Z)-(2-aminothiazol-4-yl)methoxyimino acetate In dichloromethane at 20℃; for 4h; Stage #3: With sodium hydroxide In dichloromethane; water at 15 - 20℃; pH=7.5 - 7.8;	94.6%
Stage #1: 7-aminoceftrizine With chloro-trimethyl-silane; 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane at 20℃; for 2h; Stage #2: diethylthiophosphoryl-(Z)-(2-aminothiazol-4-yl)methoxyimino acetate In dichloromethane at 20℃; for 18h;
Stage #1: 7-aminoceftrizine With N,O-bis-(trimethylsilyl)-acetamide In DMF (N,N-dimethyl-formamide) at 20℃; for 2h; Stage #2: diethylthiophosphoryl-(Z)-(2-aminothiazol-4-yl)methoxyimino acetate In DMF (N,N-dimethyl-formamide) at 20℃; for 4h; Stage #3: With sodium hydroxide In DMF (N,N-dimethyl-formamide); water at 15 - 20℃; pH=7.5 - 7.8;
Stage #1: 7-aminoceftrizine With N,N'-bis(trimethylsilyl)urea In dichloromethane at 20℃; for 2h; Stage #2: diethylthiophosphoryl-(Z)-(2-aminothiazol-4-yl)methoxyimino acetate In dichloromethane at 20℃; for 10h; Stage #3: With sodium hydroxide In dichloromethane; water at 15 - 20℃; pH=7.5 - 7.8;

2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetic acid (91868-79-0) + 7-aminoceftrizine (58909-56-1) → ceftriaxone disodium (74578-69-1)

Conditions	Yield
Stage #1: 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetic acid With isopropyl chloroformate; triethylamine In dichloromethane; acetonitrile at -5 - 20℃; for 5h; Stage #2: 7-aminoceftrizine In dichloromethane; acetonitrile at 20℃; for 6h;	89.18%

ceftriaxone (73384-59-5, 92143-31-2) → ceftriaxone disodium (74578-69-1)

Conditions	Yield
Stage #1: ceftriaxone With triethylamine In water at 0 - 5℃; Stage #2: With sodium 2-ethylhexanoic acid In water; acetone at 0 - 5℃;	77%
With sodium 2-ethylhexanoic acid In water; acetone at -10 - 20℃; for 1.5h;
Stage #1: ceftriaxone With sodium 2-ethylhexanoic acid In water at 10 - 15℃; Stage #2: In water; acetone at 18 - 20℃; for 1.5h;
Stage #1: ceftriaxone With RELITE CNS carboxylic resin; sodium form of In water; acetone at 10℃; for 4h; Stage #2: In water

7-aminocephalosporanic acid (108260-00-0) → ceftriaxone disodium (74578-69-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetonitrile 1.2: -15 °C 2.1: sodium acetate / water / 1 h / -50 - -40 °C 2.2: 1 h / 20 - 25 °C View Scheme

gold(III) chloride + water (7732-18-5) + ceftriaxone disodium (74578-69-1) → C18H16AuN8O7S3(1+)*Cl(1-)*4H2O

Conditions	Yield
In methanol for 3h; Reflux;

water (7732-18-5) + palladium dichloride + ceftriaxone disodium (74578-69-1) → C18H16N8O7PdS3*3H2O

Conditions	Yield
In methanol for 3h; Reflux;

water (7732-18-5) + zinc(II) chloride (7646-85-7) + ceftriaxone disodium (74578-69-1) → C18H20N8O9S3Zn*7H2O

Conditions	Yield
In methanol for 3h; Reflux;

iron(III) chloride hexahydrate + water (7732-18-5) + ceftriaxone disodium (74578-69-1) → C18H18ClFeN8O8S3*7H2O

Conditions	Yield
In methanol for 3h; Reflux;

ceftriaxone disodium (74578-69-1) → C18H20CaN8O9S3

Conditions	Yield
With water; calcium chloride In methanol for 3h; Reflux;

Upstream product

• 108260-00-0 7-aminocephalosporanic acid 
• 91868-79-0 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetic acid 
• 58909-56-1 7-aminoceftrizine 
• 80756-85-0 (Z)-S-benzo[d]thiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)ethanethioate 
• 162208-27-7 diethylthiophosphoryl-(Z)-(2-aminothiazol-4-yl)methoxyimino acetate 
• 73384-59-5 ceftriaxone 
• 58909-56-1 7-amino-3-[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazine-3-mercapto)methyl]-3 cephalosporin-4-carboxylic acid 
• 94088-75-2 2-(2-amino-1,3-thiazol-4-yl)-1-(1,3-benzothiazol-2-ylsulfanyl)-2-(methoxyimino)ethan-1-one 
• 957-68-6 7-Aminocephalosporanic acid 

Relevant articles and documents

Preparation method of ceftriaxone sodium

The invention provides a preparation method of ceftriaxone sodium. The preparation method is characterized in that 7-ACA and triazinic acid are subjected to a condensation reaction to obtain 7-ACT, the 7-ACT is salified with an organic base catalyst, then 7-ACT guanidine salt and aminothiazoly loxime acetic anhydride are subjected to the condensation reaction to form ceftriaxone acid, and a prepared sodium salt aqueous solution is used for extraction to obtain a ceftriaxone sodium solid. According to the synthesis method, 7-ACT guanidine salt and aminothiazoleacetic anhydride are condensed, and no mercaptobenzothiazole byproduct with relatively high toxicity exists in the condensation process.

New indications of troxofine ceftriaxone sodium pharmaceutical preparation for treatment of infection of patients with immunodeficiency

The invention belongs to the technical field of drug preparation, and discloses new indications of a troxofine ceftriaxone sodium pharmaceutical preparation for treatment of infection of patients withimmunodeficiency. By improving a raw material synthesis process, ceftriaxone sodium with the high effective constituent content and the low impurity content is provided so as to solve the problems ofpoor stability and reducing of the antibacterial effect of a ceftriaxone sodium preparation due to impurities. The ceftriaxone sodium provided by the specific production process is very low in impurity content and significant in efficacy, the quality of a preparation product is improved advantageously, safety and effectiveness of the preparation product are ensured, and the preparation product has uses in the aspects of preparing drugs for treating infection of the patients with immunodeficiency.

A method of preparing ceftriazone sodium

The invention relates to a novel green low-cost method for synthesizing ceftriaxone sodium. Firstly, in the 7-ACT synthesis process, the dimethyl carbonate is used as the reaction solvent, and the boron trifluoride-dimethyl carbonate is used as the catalyst, thereby substituting the use of the high-cost high-toxicity acetonitrile; and secondly, in the ceftriaxone sodium synthesis process, the ethanol-water reaction system is adopted to obtain the high-yield high-quality ceftriaxone sodium.