58909-56-1

Basic information

• Product Name: (6R-trans)-7-amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• Synonyms: 7-Amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl;7-AMINOCEPHALOSPORANIC TRIAZINE;(6R,7R)-7-Amino-8-oxo-3-[[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin)-3-yl]thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;(6R-trans)-7-Amino-8-oxo-3-(((1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio)methyl)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid;Einecs 261-491-7;Ceftriaxone IMpurity E;(7R)-7-amino-3-(((6-hydroxy-2-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;(6R-trans)-7-amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS NO: 58909-56-1
• Molecular Formula: C₁₂H₁₃N₅O₅S₂
• Molecular Weight: 371.39212
• EINECS: 261-491-7
• Product Categories: Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 58909-56-1.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 718℃[at 101 325 Pa]
• Appearance: /
• Density: 2.03g/cm³
• Vapor Pressure: 0Pa at 25℃
• Refractive Index: 1.913
• PKA: 2.49±0.50(Predicted)
• Water Solubility: 200mg/L at 20℃
• CAS DataBase Reference: (6R-trans)-7-amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (6R-trans)-7-amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid(58909-56-1)
• EPA Substance Registry System: (6R-trans)-7-amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid(58909-56-1)

Safety Data

• Hazardous Substances Data: 58909-56-1(Hazardous Substances Data)

Usage

Uses

An intermediate in the synthesis of cephalosporin antibiotics, Ceftriaxone (C245000) and Cefixime (C242800).

Flammability and Explosibility

Notclassified

InChI:InChI=1/C12H13N5O5S2/c1-16-12(14-7(18)8(19)15-16)24-3-4-2-23-10-5(13)9(20)17(10)6(4)11(21)22/h5,10H,2-3,13H2,1H3,(H,15,19)(H,21,22)/t5-,10-/m0/s1

Synthetic route

2-methyl-3-mercapto-5-oxo-6-hydroxy-2,5-dihydro-1,2,4-triazine (58909-39-0) + 7-Aminocephalosporanic acid (957-68-6) → 7-aminoceftrizine (58909-56-1)

Conditions	Yield
With boron trifluoride dimethyl carbonate complex; methanesulfonic acid at 10 - 12℃; for 0.383333h; Reagent/catalyst;	95.1%
With boron trifluoride dimethyl carbonate complex; edetate disodium at 30℃; for 0.833333h; Time;	90%
With boron trifluoride In acetonitrile at 10 - 30℃; for 0.5h;	85.71%

7-Aminocephalosporanic acid (957-68-6) + 1,2,3,4-Tetrahydro-2-methyl-3-thioxo-1,2,4-triazine-5,6-dione → 7-aminoceftrizine (58909-56-1)

Conditions	Yield
With ethylenediaminetetraacetic acid; acetonitrile boron trifluoride complex at 30℃; for 0.333333h;	88%

(6R,7R)-7-(4-Carboxy-butyrylamino)-3-(6-hydroxy-2-methyl-5-oxo-2,5-dihydro-[1,2,4]triazin-3-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid → 7-aminoceftrizine (58909-56-1)

Conditions	Yield
With sodium hydroxide; glutaryl-7-aminocephalosporanic acid acylase In water at 25℃; pH=8.0; Enzyme kinetics; Enzymatic reaction;

C18H14N5O9PS2 + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;	95.7%

(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;

C14H24N3O5PS2 + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;	93.4%

C18H14N5O10PS + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;	93.3%

diethylthiophosphoryl-(Z)-(2-aminothiazol-4-yl)methoxyimino acetate + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;	92.8%

4-(diethylphosphoryl)-2-(2-amino-4-thiazolyl)-2-syn-(2-methoxyimino)acetate (179258-53-8) + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;	91.7%

C20H20N3O5PS2 + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;	91.6%

C8H12N3O5PS2 + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;	91.2%

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%

2-mercapto-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetate + 7-aminoceftrizine (58909-56-1) → 7-[[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino]acetamido]-3-[[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazin-3-yl)thio]methyl]-3-cephem-4-carboxylic acid disodium salt

Conditions	Yield
Stage #1: 2-mercapto-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetate; 7-aminoceftrizine With triethylamine In tetrahydrofuran; water at 0 - 5℃; Stage #2: With sodium 2-ethylhexanoic acid

chloro-trimethyl-silane (75-77-4) + 1,1,1,3,3,3-hexamethyl-disilazane (999-97-3) + 7-aminoceftrizine (58909-56-1) → C18H29N5O5S2Si2 (847835-82-9)

Conditions	Yield
In dichloromethane for 8h; Heating / reflux;
In dichloromethane at 20℃; for 8h; Product distribution / selectivity; Heating / reflux;

N,O-bis-(trimethylsilyl)-acetamide (10416-59-8) + 7-aminoceftrizine (58909-56-1) → C18H29N5O5S2Si2 (847835-82-9)

Conditions	Yield
In dichloromethane at 25 - 30℃; for 2h;

N,O-bis-(trimethylsilyl)-acetamide (10416-59-8) + 7-aminoceftrizine (58909-56-1) → (7R,8R)-7-(trimethylsilylamino)-3-[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazin-3-yl)thiomethyl]-3-cephem-4-carboxylic acid

Conditions	Yield
In dichloromethane at 20℃; for 2 - 3h;

2-amino-4-thiazoleglyoxylic acid (Z)-O-[[(3,4-dihydroxyphenyl)sulphonyl]methyl] oxime (121170-86-3) + 7-aminoceftrizine (58909-56-1) → (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[[(3,4-dihydroxyphenyl)sulphonyl]methoxy]imino]acetamido]-3-[[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt

2-Bromoacetyl bromide (598-21-0) + 7-aminoceftrizine (58909-56-1) → 7-bromoacetamido-3-(((1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio)methyl)cephalosporanic acid

Conditions	Yield
Stage #1: 2-Bromoacetyl bromide; 7-aminoceftrizine With sodium hydrogencarbonate; triethylamine In water; toluene for 2h; Stage #2: In water pH=3; Product distribution / selectivity; Acidic conditions;
Stage #1: 2-Bromoacetyl bromide; 7-aminoceftrizine With triethylamine In water; ethyl acetate at 0 - 10℃; Stage #2: In water; ethyl acetate pH=3; Product distribution / selectivity; Acidic conditions;
Stage #1: 2-Bromoacetyl bromide; 7-aminoceftrizine With sodium hydrogencarbonate; triethylamine In water; acetone for 1h; Stage #2: With hydrogenchloride In water; acetone pH=3; Product distribution / selectivity;
Stage #1: 2-Bromoacetyl bromide; 7-aminoceftrizine With sodium hydrogencarbonate; triethylamine In water; propiononitrile at 0 - 10℃; Stage #2: In water; propiononitrile pH=3; Product distribution / selectivity; Acidic conditions;
Stage #1: 2-Bromoacetyl bromide; 7-aminoceftrizine With triethylamine In dichloromethane; water for 2h; Stage #2: With hydrogenchloride In water pH=3; Product distribution / selectivity;

4-chloro-2(Z)-metoxyimino-3-oxobutyric acid chloride (117683-58-6) + 7-aminoceftrizine (58909-56-1) → C17H17ClN6O8S2 (614751-38-1)

Conditions	Yield
Stage #1: 7-aminoceftrizine With N,O-bis-(trimethylsilyl)-acetamide In dichloromethane at 35 - 40℃; for 1.5h; Stage #2: 4-chloro-2(Z)-metoxyimino-3-oxobutyric acid chloride In dichloromethane at -10℃; for 0.25h; Stage #3: With sodium carbonate In dichloromethane; water at 4 - 7℃; for 1h; pH=5 - 6;
Stage #1: 7-aminoceftrizine With N,N'-bis(trimethylsilyl)urea In dichloromethane at 35 - 40℃; for 5h; Stage #2: 4-chloro-2(Z)-metoxyimino-3-oxobutyric acid chloride In dichloromethane at -15℃; for 0.25h; Stage #3: With sodium carbonate In dichloromethane; water at 4 - 7℃; pH=5.8 - 6;

C18H16N3O5PS2 + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;

(Z)-S-benzo[d]thiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)ethanethioate (80756-85-0) + 7-aminoceftrizine (58909-56-1) → ceftriaxone (73384-59-5, 92143-31-2)

Conditions	Yield
With ethylenediaminetetraacetic acid; sulphurous acid; sodium hydrogensulfite; triethylamine In ethanol; dichloromethane at 0 - 5℃; for 4h;

2-(2-amino-1,3-thiazol-4-yl)-1-(1,3-benzothiazol-2-ylsulfanyl)-2-(methoxyimino)ethan-1-one (94088-75-2) + 7-aminoceftrizine (58909-56-1) → ceftriaxone

Conditions	Yield
With N,N,N',N'-tetramethylguanidine In ethanol; dichloromethane at -10 - -5℃; for 4h; Reagent/catalyst;

7-aminoceftrizine (58909-56-1) → 7-(α-((N,N'-diisopropylamidino)thio)acetylamino)-3-(((1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio)methyl) cephalosporanic acid

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / water; ethyl acetate / 0 - 10 °C 1.2: pH 3 / Acidic conditions 2.1: diethylamine / dichloromethane; acetone / pH 5.0 - 7.5 / Heating / reflux View Scheme

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

Conditions	Yield
With sulfuryl dichloride; pyrographite; sodium hydrogensulfite; N,N,N',N'-tetramethylguanidine In dichloromethane; water; N,N-dimethyl-formamide at 20℃; for 0.5h;

Upstream product

• 957-68-6 7-Aminocephalosporanic acid 
• 58909-39-0 2-methyl-3-mercapto-5-oxo-6-hydroxy-2,5-dihydro-1,2,4-triazine 

Downstream Products

• 74578-69-1 ceftriaxone disodium 
• 74578-69-1 (6R,7R)-7-<2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido>-3-<<(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio>methyl>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid disodium salt (Z isomer) 
• 73384-59-5 ceftriaxone 
• 149-30-4 2-Mercaptobenzothiazole 
• 73384-59-5 Ceftriaxone 

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