30246-33-4

Basic information

• Product Name: 7-AMINO-3-[(5-METHYL-1,3,4-THIADIAZOL-2-YL)THIOMETHYL]CEPHALOSPHORANIC ACID
• Synonyms: 7-AMINO-3-[(5-METHYL-1,3,4-THIADIAZOL-2-YL)THIOMETHYL]CEPHALOSPHORANIC ACID;TDA;(7r)-7-amino-3-[(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl]-3-cephem-4-carboxylicacid;(7r)-7-amino-3[(5-methyl-1,3,4-thiadiazole-2-yl)thiomethyl]-3-cephem-4-carboxylic acid;7-Amino-3-([5-methyl-1,3,4-thiadiazol-2-yl] thiomethyl)-3-cephem-4-carboxylic acid;7-Amino-3-[(5-methyl-1,3,4-thiadiazol-2-yl)-thiomethyl]-cephalosporanic aci;(6R)-7α-Amino-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;Parent nucleus of cefazedone (7-TDA)
• CAS NO: 30246-33-4
• Molecular Formula: C₁₁H₁₂N₄O₃S₃
• Molecular Weight: 344.43
• EINECS: 250-099-1
• Mol File: 30246-33-4.mol
• Article Data: 30

Chemical Properties

• Boiling Point: 678.2 °C at 760 mmHg
• Flash Point: 364 °C
• Appearance: /
• Density: 1.72 g/cm³
• Vapor Pressure: 2.53E-19mmHg at 25°C
• Refractive Index: 1.768
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
• Solubility: CHCl3 (Slightly, Heated), DMF (Very Slightly), DMSO (Slightly)
• PKA: 2.52±0.50(Predicted)
• CAS DataBase Reference: 7-AMINO-3-[(5-METHYL-1,3,4-THIADIAZOL-2-YL)THIOMETHYL]CEPHALOSPHORANIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 7-AMINO-3-[(5-METHYL-1,3,4-THIADIAZOL-2-YL)THIOMETHYL]CEPHALOSPHORANIC ACID(30246-33-4)
• EPA Substance Registry System: 7-AMINO-3-[(5-METHYL-1,3,4-THIADIAZOL-2-YL)THIOMETHYL]CEPHALOSPHORANIC ACID(30246-33-4)

Safety Data

• Hazardous Substances Data: 30246-33-4(Hazardous Substances Data)

Usage

Chemical Properties

Beige Solid

Uses

7-Amino-3-[(5-methyl-1,3,4-thiadiazol-2-ylthio)methyl]-3-cephem-4-carboxylic Acid is a substrate used in the assessment of immobilized PGA orientation and in the synthesis of beta lactam antibiotics.

InChI:InChI=1/C11H12N4O3S3/c1-4-13-14-11(21-4)20-3-5-2-19-9-6(12)8(16)15(9)7(5)10(17)18/h6,9H,2-3,12H2,1H3,(H,17,18)/t6-,9-/m0/s1

Synthetic route

2-mercapto-5-methyl-1,3,4-thiadiazole (29490-19-5) + 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylic acid → 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4)

Conditions	Yield
With boric acid; triethylamine In water	96%
In water; acetone
In water; acetone

3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0 ]oct-2-ene-2-carboxylic acid sodium salt (3855-09-2) + 2-mercapto-5-methyl-1,3,4-thiadiazole (29490-19-5) → 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4)

Conditions	Yield
With sodium hydrogencarbonate In water
With sodium hydrogencarbonate In water
With sodium hydrogencarbonate In water
With sodium hydrogencarbonate In water

pyrrolidine (123-75-1) + 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-2-(pyrrolidine-1-carbonyl)-5-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one

Conditions	Yield
With aluminum oxide at 120℃; for 0.0333333h; microwave irradiation;	93%

2-amino-5-(3-pyridyl)-1,3,4-thiadiazole (68787-52-0) + 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (5-pyridin-3-yl-[1,3,4]thiadiazol-2-yl)-amide

Conditions	Yield
With aluminum oxide at 120℃; for 0.0166667h; microwave irradiation;	92%

2-amino-5-undecyl-1,3,4-thiadiazole (100539-95-5) + 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (5-undecyl-[1,3,4]thiadiazol-2-yl)-amide

Conditions	Yield
With aluminum oxide at 120℃; for 0.0333333h; microwave irradiation;	90%

piperidine (110-89-4) + 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-2-(piperidine-1-carbonyl)-5-thia-1-aza-bicyclo[4.2.0]oct-2-en-8-one

Conditions	Yield
With aluminum oxide at 120℃; for 0.025h; microwave irradiation;	89%

2-amino-5-phenyl-1,3,4-thiadiazole (2002-03-1) + 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (5-phenyl-[1,3,4]thiadiazol-2-yl)-amide

Conditions	Yield
With aluminum oxide at 120℃; for 0.0166667h; microwave irradiation;	87%

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) + 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazole (28004-62-8) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid [5-(4-chloro-phenyl)-[1,3,4]thiadiazol-2-yl]-amide

Conditions	Yield
With aluminum oxide at 120℃; for 0.025h; microwave irradiation;	86%

5-methyl-1,3,4-thiadiazol-2-amine (108-33-8) + 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide

Conditions	Yield
With aluminum oxide at 120℃; for 0.025h; microwave irradiation;	85%

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) + 5-nonyl-[1,3,4]thiadiazol-2-ylamine (113836-51-4) → 7-amino-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (5-nonyl-[1,3,4]thiadiazol-2-yl)-amide

Conditions	Yield
With aluminum oxide at 120℃; for 0.025h; microwave irradiation;	83%

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-methylenecepham-4-carboxylic acid (36996-01-7, 51795-31-4) + 7-aminodesacetoxycephalosporanic acid (26395-99-3)

Conditions	Yield
With N,N-Bis(trimethylsilyl)urea; ammonium chloride; zinc In N,N-dimethyl-formamide 1.) 25 deg C, 13 min, 2.) 5 deg C, 18 min, 3.) 5 deg C, 30 min;	A 66.5% B 3.0 % Chromat.

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-hydroxycepham-4-carboxylic acid (68403-70-3, 115889-60-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 66.5 percent / bis(trimethylsilyl)urea (BSU), NH4Cl, zinc dust / dimethylformamide / 1.) 25 deg C, 13 min, 2.) 5 deg C, 18 min, 3.) 5 deg C, 30 min 2: 1.) MsOH, ozone, 2.) NaBH4, NaOH / 1.) MeOH, -75 deg C, 2.) MeOH/H2O, 0 - 10 deg C View Scheme

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 3-methylene-7-phenylacetamidocepham-4-carboxylic acid 1-sulfoxide (115824-01-6, 121055-15-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 66.5 percent / bis(trimethylsilyl)urea (BSU), NH4Cl, zinc dust / dimethylformamide / 1.) 25 deg C, 13 min, 2.) 5 deg C, 18 min, 3.) 5 deg C, 30 min 2: 1.) ozone, MsOH, 2.) NaBH4 / 1.) MeOH, -40 deg C, 2.) MeOH/H2O, 3.) pH 6.5 - 7.5 View Scheme

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 3-hydroxy-7-phenylacetamido-cepham-4-carboxylic acid (90305-32-1, 115889-59-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 66.5 percent / bis(trimethylsilyl)urea (BSU), NH4Cl, zinc dust / dimethylformamide / 1.) 25 deg C, 13 min, 2.) 5 deg C, 18 min, 3.) 5 deg C, 30 min 2: 1.) ozone, MsOH, 2.) NaBH4 / 1.) MeOH, -40 deg C, 2.) MeOH/H2O, 3.) pH 6.5 - 7.5 View Scheme

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-[[2-carboethoxy-2-(1-pyrryl)acetyl]amino]-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

7-aminocephalosporanic acid (108260-00-0) + 7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) + isobutene (115-11-7) → 3-[(Acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester (6187-87-7, 102253-55-4)

Conditions	Yield
With sulfuric acid; sodium hydrogencarbonate In 1,4-dioxane; ethyl acetate; 7-aminodesacetoxycephalosporanic acid

7-amino-3-(5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl)cephalosporanic acid (30246-33-4) → 7-amino-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid t-butyl ester (54895-35-1) + 3-[(Acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester (6187-87-7, 102253-55-4)

Conditions	Yield
In 7-aminodesacetoxycephalosporanic acid

Upstream product

• 3855-09-2 3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0 ]oct-2-ene-2-carboxylic acid sodium salt 
• 29490-19-5 2-mercapto-5-methyl-1,3,4-thiadiazole 
• 7440-44-0 pyrographite 
• 107447-96-1 7-phenylacetylamino-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester 
• 31461-04-8 (6R,7R)-Trimethylsilyl 7-(Trimethylsilyl)amino-3-acetoxy methylceph-3-em-4-carboxylate 
• 111390-00-2 (6R,7R)-Trimethylsilyl 7-[((Trimethylsilyl)oxy)carbonyl]-amino-3-acetoxymethylceph-3-em-4-carboxylate 
• 957-68-6 7-Aminocephalosporanic acid 
• 111389-99-2 (6R,7R)-Trimethylsilyl 7-[((Trimethylsilyl)oxy)carbonyl]-amino-3-iodomethylceph-3-em-4-carboxylate 
• 106134-67-2 (6R,7R)-trimethylsilyl 7-(trimethylsilyl)amino-3-iodomethylceph-3-em-4-carboxylate 
• 98493-37-9 7-amino-3-<(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl>-Δ³-cephem-4-carboxylic acid hydrochloride 

Downstream Products

• 32944-72-2 7-(phenylacetamido)-3-(((2-methyl-1,3,4-thiadiazol-5-yl)thio)methyl)-3-cephem-4-carboxylic acid 
• 68403-70-3 7-amino-3-hydroxycepham-4-carboxylic acid 
• 115824-01-6 3-methylene-7-phenylacetamidocepham-4-carboxylic acid 1-sulfoxide 
• 90305-32-1 3-hydroxy-7-phenylacetamido-cepham-4-carboxylic acid 
• 63491-68-9 (6R)-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-5ξ,8-dioxo-(6rH)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 63491-71-4 (6R)-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid acetoxymethyl ester 
• 63491-69-0 (6R)-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-5ξ,8-dioxo-(6rH)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid acetoxymethyl ester 
• 63491-72-5 (6R)-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester 
• 63491-70-3 (6R)-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-5ξ,8-dioxo-(6rH)-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester 
• 61296-38-6 (6R)-7t-((R)-2-tert-butoxycarbonylamino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (Ξ)-3-oxo-1,3-dihydro-isobenzofuran-1-yl ester 
• 63491-75-8 (6R)-7t-((R)-2-amino-2-phenyl-acetylamino)-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (Ξ)-3-oxo-1,3-dihydro-isobenzofuran-1-yl ester; mono-(toluene-4-sulfonate) 
• 63521-15-3 (6R,7R)-3-[[(5-methyl-1,3,4-thiadiazolyl-2-yl)thio]methyl]-7-[2-(3,5-dichloro-4-pyridone-1-acetylamido)]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt 
• 139080-49-2 Potassium; (6R,7R)-7-{2-[(Z)-methoxyimino]-2-[2-(trityl-amino)-thiazol-4-yl]-acetylamino}-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate 
• 139112-06-4 (6R,7R)-7-{2-[(Z)-Methoxyimino]-2-[2-(trityl-amino)-thiazol-4-yl]-acetylamino}-3-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-5,8-dioxo-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 

Relevant articles and documents

A rapid and cheap synthesis of cephalosporins

A fast, cheap and pollution free microwave assisted method for the synthesis of cephalosporin and its comparison with conventional method in terms of yield and reaction time were described.

Preparation technology of cefazedone sodium

The invention belongs to the technical field of medicine, and discloses a preparation technology of cefazedone sodium. 3,5-dichloropyridone acetic acid and pivaloyl chloride are taken as the raw materials to synthesize mixed acid anhydrides; and then cefazedone sodium is obtained after salt forming reactions between mixed acid anhydrides and an intermediate prepared from 7-aminocephalosporanic acid and thiol tetrazole. A mixed solvent is used in 3-substitution, the reaction becomes more stable and softer, the byproducts are reduced; in acylation reactions, mixed acid anhydrides are used, the activity is high, 7-acylation reactions are promoted, and thus the yield and purity of cefazedone sodium are high.

Preparation method of cefazedone sodium compound

The invention discloses a preparation method of a cefazedone sodium compound. 7-ACA and a compound III react to prepare a compound IV, and the compound IV and a compound V have an amidation reaction,and are salified and refined to obtain a competitive product of cefazedone sodium (I). The process route of the reaction is simple, the total yield and the purity are high, and the method is suitablefor industrial production.