Cemandil sodium salt CAS 42540-40-9

Introduction：Basic information about Cemandil sodium salt CAS 42540-40-9, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Cemandil sodium salt Basic information

• Product Name: Cemandil sodium salt
• Synonyms: ,(6r-(6-alpha,7-beta(r)))-;Cefamandole Nafate -Delta-3- Isomer;Cemandil sodium salt;Sodium [6R-[6alpha,7beta(R*)]]-7-[[(formyloxy)phenylacetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;CEFAMANDOLE NAFATE;Cefamandole nafate,Cefamandole formate sodium salt;Cefamandole Nafate (250 mg);Cefamandole Nafate (200 mg)
• CAS: 42540-40-9
• MF: C19H17N6NaO6S2
• MW: 512.49
• EINECS: 255-877-4
• Product Categories: MANDOL;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 42540-40-9.mol

Cemandil sodium salt Chemical Properties

• Melting point: 190-193°C
• storage temp.: Inert atmosphere,Store in freezer, under -20°C
• solubility: Freely soluble in water, sparingly soluble in methanol.
• pka: 2.6-3.0(at 25℃)
• form: Solid
• color: White to Off-White
• Water Solubility: Freely soluble in water. Sparingly soluble in methanol
• Major Application: pharmaceutical (small molecule)
• InChIKey: ICZOIXFFVKYXOM-YCLOEFEOSA-M
• SMILES: [Na+].Cn1nnnc1SCC2=C(N3C(SC2)[C@H](NC(=O)[C@H](OC=O)c4ccccc4)C3=O)C([O-])=O
• CAS DataBase Reference: 42540-40-9(CAS DataBase Reference)

Safety Information

• Hazard Codes: Xn
• Risk Statements: 36/37/38-42/43
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: XI0380000
• HS Code: 2941906000
• Storage Class: 11 - Combustible Solids
• Hazard Classifications: Eye Irrit. 2 Resp. Sens. 1 Skin Irrit. 2 Skin Sens. 1 STOT SE 3

Cemandil sodium salt Usage And Synthesis

Chemical Properties

White Solid

Originator

Mandokef,Lilly,W. Germany,1977

Uses

A second generation cephalosporin antibiotic.

Uses

Cephalosporin antibacterial.

Definition

ChEBI: A cephalosporin prodrug having (R)-O-formylmandelamido and N-methylthiotetrazole side-groups.

Manufacturing Process

To 21.6 kg (17.8 l) of 98% formic acid was added 1.14 kg (7.5 mols) of D-(-)-mandelic acid and the reaction mixture was heated for 4 hours at 70°C withstirring. The excess formic acid was evaporated off in vacuo and the residualsyrup was dissolved in 6 l of benzene. The solution was washed twice with 6 lportions of water and was dried over magnesium sulfate. The drying agentwas filtered and washed with 1.5 l of benzene, the washes being added to thefiltrate. The dried filtrate was evaporated in vacuo to obtain the D-(-)-mandelic acid formate ether as a syrup. The product can be crystallized fromcyclohexane to yield material melting at about 55°C to 58°C.
The mandelic acid formate ester obtained as a syrup as described above isstirred for 2 hours with 2.9 kg (~1.75 l) of thionyl chloride at a temperatureof about 70°C. The excess thionyl chloride is removed by evaporation and theresidual green solution is vacuum distilled. The product, O-formyl mandeloylchloride, distills over at 127°C to 130°C (15 mm) or at 108°C to 112°C (7mm).
To 13 l of ethyl acetate were added 85.1 g (2.59 mols) of 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid and 1,361 g(10.37 mols) of monotrimethylsilyl acetamide, and the mixture was stirred at50°C until a clear solution was obtained. The solution was cooled to 20°C and514 g (2.59 mold of O-formyl mandeloyl chloride was added at a rate suchthat the temperature of the reaction solution was maintained between about20°C to 25% with ice-cooling.
The reaction mixture was stirred for 1.5 hours at about room temperatureafter the addition of the mandeloyl chloride was completed. Five liters ofwater were then added to the reaction mixture and the diluted mixture wasstirred for about 10 minutes. The organic layer was separated and waswashed twice with water. The combined washes are extracted with 1.5 l ofethyl acetate and the extract is combined with the washed organic layer. Thewhole was dried over magnesium sulfate, filtered and evaporated in vacuo ona 25°C water bath to yield 1,460 g of product, 7-(D-2-formyloxy-2-phenylacetamido)-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid, as a yellow foam.
The product was dissolved in 5 l of acetone and the solution was mixed with asolution of 430 g (2.59 mols) of sodium 2-ethylhexanoate in 5.4 l of acetone.The combined solutions were seeded and stirred in an ice bath for 1.5 hours.The crystalline precipitate of sodium 7-(D-2-formyloxy-2-phenylacetamido)-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate was filteredand washed with 5 l of acetone. The crystalline salt was dried overnight in avacuum oven at 40°C to yield 1,060 g (80%)of product, melting at 182°C to184°C.

Brand name

Mandol (Lilly).

Therapeutic Function

Antibiotic

Mechanism of action

Cefamandole nafate has a formylated D-mandelic amide moiety at C-7. The formate ester is cleaved rapidlyin the host to release the more active cefamandole. The esterification also apparently overcomes theinstability of cefamandole when it is stored in dry form. This agent has increased activity againstHaemophil us influenzae and some Gram-negative bacilli as compared with the first-generationcephalosporins. Loss of the 5-thio-l-methyl-l-H-tetrazole moiety (referred to sometimes by the acronym MT T)from C-3 is associated with prothrombin deficiency and bleeding problems as well as with an Antabuse-likeacute alcohol intolerance. On the other hand, this grouping enhances potency and prevents metabolism bydeacetylation. Like the other second-generation cephalosporins, cefamandole is more active againstGram-negative bacteria. The principle clinical use is for lower respiratory tract, skin and skin structures, andbone and joint infections as well as septicemia and urinary tract infections when the organisms are sensitive.

Clinical Use

The D-mandeloyl moiety of Cemandil sodium salt appears toconfer resistance to a few β-lactamases, since some β-lactamase–producing, Gram-negative bacteria (particularlyEnterobacteriaceae) that show resistance to cefazolin andother first-generation cephalosporins are sensitive tocefamandole. Additionally, it is active against some ampicillin-resistant strains of Neisseria and Haemophilus spp.Although resistance to β-lactamases may be a factor in determiningthe sensitivity of individual bacterial strains tocefamandole, an early study indicated that other factors,such as permeability and intrinsic activity, are frequentlymore important. The L-mandeloyl isomer is significantlyless active than the D-isomer.

Cemandil sodium salt Preparation Products And Raw materials

• Raw materials: Sodium 2-ethylhexanoate-->Thionyl chloride-->Formic acid-->Mandelic acid-->[6R-[6alpha,7beta(R*)]]-7-[(formyloxy)phenylacetamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-->(R)-(formyloxy)phenylacetic acid-->O-FORMYLMANDELOYL CHLORIDE-->7-TMCA-->(R)-(-)-Methyl mandelate