4928-88-5

Basic information

• Product Name: Methyl 1,2,4-triazole-3-carboxylate
• Synonyms: 1,2,4-Triazole-3-carboxylatem;1,2,4-triazole-3-carboxylicacidmethylester;METHYL 1H-TRIAZOLE-3-CARBOXYLATE;METHYL 1H-1,2,4-TRIAZOLE-3-CARBOXYLATE;METHYL 1,2,4-TRIAZOLE-3-CARBOXYLATE;1H-TRIAZOLE-3-CARBOXYLIC ACID METHYL ESTER;1H-1,2,4-TRIAZOLE-3-CARBOXYLIC ACID METHYL ESTER;1,2,4-Triatoze-3-carboxylic acid Methylester
• CAS NO: 4928-88-5
• Molecular Formula: C₄H₅N₃O₂
• Molecular Weight: 127.1
• EINECS: 480-470-5
• Product Categories: Aromatic Esters;Building Blocks;Heterocyclic Building Blocks;Triazoles;carboxylic ester;Thiophenes
• Mol File: 4928-88-5.mol
• Article Data: 7

Chemical Properties

• Melting Point: 196-199 °C(lit.)
• Boiling Point: 283.9 °C at 760 mmHg
• Flash Point: 125.5 °C
• Appearance: Clear colorless to yellow/Liquid
• Density: 1.38 g/cm³
• Vapor Pressure: 0.00307mmHg at 25°C
• Refractive Index: 1.534
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 7.96±0.20(Predicted)
• CAS DataBase Reference: Methyl 1,2,4-triazole-3-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl 1,2,4-triazole-3-carboxylate(4928-88-5)
• EPA Substance Registry System: Methyl 1,2,4-triazole-3-carboxylate(4928-88-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37
• WGK Germany: 3
• Hazardous Substances Data: 4928-88-5(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 4928-88-5 differently. You can refer to the following data:
1. Methyl 1,2,4-Triazole-3-carboxylate has been used as a reactant for the preparation of Ribavirin (1-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide, an antiviral agent.
2. Methyl-1H-1,2,4-triazole-3-carboxylate (1,2,4-Triazole-3-methylcarboxylate) may be used in the preparation of 1H-1,2,4-triazole-3-carbohydrazide.It may also be used in the synthesis of the following nucleoside analogues: 1-(2,2-dimethyl-6-trityloxymethyl-4,6a-dihydro-3aH-cyclopenta-[1,3]dioxol-4-yl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester methyl 4,6-O-benzylidene-2-(methyl 1H-1,2,4-triazol-1-yl-3-carboxylate)-2-deoxy-D-altrohexopyranoside1,5-anhydro-4,6-O-benzylidene-2-(methyl 1H-1,2,4-triazol-1-yl-3-carboxylate)-2-deoxy-D-altro-hexitol

Chemical Properties

White solid

General Description

Methyl-1H-1,2,4-triazole-3-carboxylate can be synthesized from 5-amino-1,2,4-triazole-3-carboxylic acid via esterification with methanol. It is utilized as precursor for preparing the nucleoside analogue, Ribavirin. The crystal structure of methyl-1H-1,2,4-triazole-3-carboxylate has been analyzed.

InChI:InChI=1/C4H5N3O2/c1-9-4(8)3-5-2-6-7-3/h2H,1H3,(H,5,6,7)

Synthetic route

methanol (67-56-1) + 1,2,4-triazole-3-carboxylic acid (4928-87-4) → methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5)

Conditions	Yield
With thionyl chloride at 0 - 65℃; for 3h;	97%
With thionyl chloride at 10 - 20℃;	80%
With hydrogenchloride

methanol (67-56-1) + sodium methylate (124-41-4) + C3H2Cl3N3 → methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5)

Conditions	Yield
at 50℃; for 3h;	91.2%

5-amino-1H-[1,2,4]-triazole-3-carboxylic acid methyl ester (3641-14-3) → methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5)

Conditions	Yield
With sodium hypophosphite; phosphoric acid; sodium nitrite In water at 0 - 20℃; for 1h; Reagent/catalyst; Temperature;	75%

methanol (67-56-1) + monopotassium salt of 1,2,4-triazole-3,5-dicarboxylic acid (26663-10-5) → dimethyl 1H-1,2,4-triazole-3,5-dicarboxylate (26663-15-0) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5)

Conditions	Yield
With hydrogenchloride at 0℃; for 2h;	A 17% B 15%

methanol (67-56-1) + 1,2,4-triazole-3-carboxamide (3641-08-5) → methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5)

Conditions	Yield
With hydrogenchloride In water at 80℃; for 4h;

methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) + 1,2,3,5-tetraacetylribose (13035-61-5) → 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester (57198-04-6, 39925-10-5)

Conditions	Yield
With toluene-4-sulfonic acid In methanol	95%
With toluene-4-sulfonic acid In ethanol	92%
With toluene-4-sulfonic acid In 2-methyl-propan-1-ol	92%

cyclohexenone (930-68-7) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(3-oxocyclohexyl)-1H-1,2,4-triazole-3-carboxylate

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide In acetonitrile at 23℃; for 1h; Michael Addition;	95%

1,2,3-tri-O-acetyl-α,β-D-ribofuranose-5-[phenylbis(isoamyl-L-aspartyl)]phosphate + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → 1-(methyl 1H-1,2,4-triazole-3-carboxylate-1-yl)-2',3'-di-O-acetyl-β-D-ribofuranose-5-[phenylbis(isoamyl-L-aspartyl)]phosphate

Conditions	Yield
With tin(IV) chloride In 1,2-dichloro-ethane at 20℃; for 24h; Vorbrueggen Nucleoside Synthesis; diastereoselective reaction;	92%

cyclohexylamine (108-91-8) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → N-cyclohexyl-1H-1,2,4-triazole-3-carboxamide

Conditions	Yield
With trimethylaluminum In toluene at 0℃; for 9h; Inert atmosphere; Reflux;	92%

methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → 1H-[1,2,4]triazole-3-carboxylic acid hydrazide (21732-98-9)

Conditions	Yield
With hydrazine hydrate In methanol for 24h; Reflux;	91%

methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) + 1,2,3,5-tetraacetylribose (13035-61-5) → methyl 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylate (38934-69-9)

Conditions	Yield
With methanol; sodium iodide at 65℃; for 1h; Reagent/catalyst;	90%
With trifluorormethanesulfonic acid at 55℃; for 1h; Microwave irradiation;	246.92 g

chloroacetic acid ethyl ester (105-39-5) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2-ethoxy-2-oxoethyl)-1,2,4-triazole-3-carboxylate

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 24h;	89%

4-flourophenylmagnesium bromide (352-13-6) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → bis(4-fluorophenyl)(1H-1,2,4-triazol-3-yl)methanol

Conditions	Yield
In tetrahydrofuran; diethyl ether at 0 - 20℃; Grignard Reaction; Inert atmosphere;	89%

1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (6974-32-9) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxylate (39925-12-7)

Conditions	Yield
With toluene-4-sulfonic acid In methanol	85%

1,2,3,5-tetra-O-acetyl-β-L-ribofuranose (144490-03-9) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-5-carboxylate (263708-15-2) + methyl 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxylate (206269-26-3)

Conditions	Yield
With Bis(p-nitrophenyl) phosphate at 165 - 175℃; for 0.416667h; Condensation;	A 11% B 84%

trityl chloride (76-83-5) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → 1-trityl-1H-[1,2,4]triazole-3-carboxylic acid methyl ester (151607-70-4)

Conditions	Yield
With triethylamine In methanol; N,N-dimethyl-formamide	84%
With triethylamine In N,N-dimethyl-formamide	84%
With triethylamine In DMF (N,N-dimethyl-formamide) at 25℃; for 96h;	84%

4-amino-o-xylene (95-64-7) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → N-(3,4-dimethylphenyl)-1H-1,2,4-triazole-3-carboxamide

Conditions	Yield
With trimethylaluminum In toluene at 0℃; for 9h; Inert atmosphere; Reflux;	83%

1,2,3,5-tetra-O-acetyl-D-ribofuranose (28708-32-9) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester (57198-04-6, 39925-10-5)

Conditions	Yield
With iodine at 100 - 115℃; for 3h; Temperature;	82%
tin(IV) chloride In dichloromethane at 5 - 20℃; for 2h; Heating / reflux;

1,2-di-O-acetyl-5-O-benzoyl-3-deoxy-3-C-methyl-D-ribofuranose (444019-07-2) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → 1-(2-O-acetyl-5-O-benzoyl-3-deoxy-3-C-methyl-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxylic acid methyl ester (1065271-43-3) + 2-(2-O-acetyl-5-O-benzoyl-3-deoxy-3-C-methyl-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxylic acid methyl ester (1065271-44-4)

Conditions	Yield
With Bis(p-nitrophenyl) phosphate at 165℃; for 1.5h;	A 81% B 3%

4-tert-Butylaniline (769-92-6) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → N-(4-(tert-butyl)phenyl)-1H-1,2,4-triazole-3-carboxamide

Conditions	Yield
With trimethylaluminum In toluene at 0℃; for 9h; Inert atmosphere; Reflux;	81%

(2R,3R,4R,5R)-5-(benzoyloxymethyl)-3-methyltetrahydrofuran-2,3,4-triyl tribenzoate + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2-methyl-2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-1,2,4-triazole-3-carboxylate (1254180-64-7)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 60℃; for 3h;	80%

1,2-di-O-acetyl-3,5-di-O-benzoyl-β-L-xylofuranosyle (201287-82-3) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2-O-acetyl-3,5-di-O-benzoyl-β-L-xylofuranosyl)-1,2,4-triazole-3-carboxylate

Conditions	Yield
With Bis(p-nitrophenyl) phosphate at 165 - 175℃; for 0.416667h; Condensation;	79%

Bis(p-nitrophenyl) phosphate (645-15-8) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) + 1,2,3,5-tetraacetylribose (13035-61-5) → 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester (57198-04-6, 39925-10-5)

Conditions	Yield
In cyclohexane; benzene	77.8%

methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) + 1,2,3,5-tetraacetylribose (13035-61-5) → ribavirin (36791-04-5)

Conditions	Yield
With Bis(p-nitrophenyl) phosphate at 80 - 147℃; for 0.833333h; Temperature; Large scale;	77.1%

1,2-di-O-acetyl-5-O-benzoyl-3-deoxy-L-erythro-pentofuranose (170079-20-6) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2-O-acetyl-5-O-benzoyl-3-deoxy-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxylate (263708-28-7)

Conditions	Yield
With Bis(p-nitrophenyl) phosphate at 165 - 175℃; for 0.416667h; Condensation;	77%

1,2,3,5-tetra-O-acetyl-α-L-ribofuranose (659722-55-1) + 1,2,3,5-tetra-O-acetyl-β-L-ribofuranose (144490-03-9) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxylate (206269-26-3)

Conditions	Yield
Stage #1: 1,2,3,5-tetra-O-acetyl-α-L-ribofuranose; 1,2,3,5-tetra-O-acetyl-β-L-ribofuranose; methyl 1H-1,2,4-triazole-3-carboxylate With acetic anhydride In dichloromethane at 90 - 120℃; under 22.5023 Torr; for 1.33333h; Stage #2: With trifluorormethanesulfonic acid at 110 - 120℃; for 4h;	75.1%

4-(chloromethyl)-7-methoxy-2H-chromen-2-one (41295-55-0) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-((7-methoxy-2-oxo-2H-chromen-4-yl)methyl)-1,2,4-triazole-3-carboxylate

Conditions	Yield
Stage #1: methyl 1H-1,2,4-triazole-3-carboxylate With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: 4-(chloromethyl)-7-methoxy-2H-chromen-2-one In N,N-dimethyl-formamide at 80℃;	75%

methylamine (74-89-5) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → N-methyl-1H-1,2,4-triazole-3-carboxamide

Conditions	Yield
In methanol for 1h; Reflux;	73%

α-D-1,3,5-tri-O-benzoyl-2-O-[3-(trifluoromethyl)benzoyl]ribofuranose (145828-13-3) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-((2R,3R,4R,5R)-4-(benzoyloxy)-5-((benzoyloxy)methyl)-3-((3-(trifluoromethyl)benzoyl)oxy)tetrahydrofuran-2-yl)-1H-1,2,4-triazole-3-carboxylate (1384470-92-1)

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile at 120℃; for 15h; Microwave irradiation; regioselective reaction;	72%

1,2,3,5-tetra-O-acetyl-α-L-ribofuranose (659722-55-1) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxylate (206269-26-3)

Conditions	Yield
Stage #1: 1,2,3,5-tetra-O-acetyl-α-L-ribofuranose; methyl 1H-1,2,4-triazole-3-carboxylate In acetic acid methyl ester at 90℃; Stage #2: With trifluorormethanesulfonic acid In acetic acid methyl ester at 115℃; under 22.5023 Torr; for 4h;	70%
With trifluorormethanesulfonic acid In acetic acid methyl ester at 90 - 115℃; under 22.5023 Torr; for 4h;	70%

(3aR,3bR,4aS,5S,5aS)-3b-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-ol (915694-38-1) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-((3aR,3bR,4aS,5R,5aS)-3b-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-yl)-1H-1,2,4-triazole-3-carboxylate

Conditions	Yield
Stage #1: methyl 1H-1,2,4-triazole-3-carboxylate With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Stage #2: (3aR,3bR,4aS,5S,5aS)-3b-(((tert-butyldiphenylsilyl)oxy)methyl)-2,2-dimethylhexahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxol-5-ol In tetrahydrofuran at 20℃;	68%

1,2,3,5-tetra-O-acetyl-β-L-ribofuranose (144490-03-9) + methyl 1H-1,2,4-triazole-3-carboxylate (4928-88-5) → methyl 1-(2,3,5-tri-O-acetyl-β-L-ribofuranosyl)-1,2,4-triazole-3-carboxylate (206269-26-3)

Conditions	Yield
With Bis(p-nitrophenyl) phosphate at 160 - 165℃; for 0.416667h;	66%

Upstream product

• 67-56-1 methanol 
• 124-41-4 sodium methylate 
• 3641-08-5 1,2,4-triazole-3-carboxamide 
• 3641-14-3 5-amino-1H-[1,2,4]-triazole-3-carboxylic acid methyl ester 
• 4928-87-4 1,2,4-triazole-3-carboxylic acid 
• 26663-10-5 monopotassium salt of 1,2,4-triazole-3,5-dicarboxylic acid 

Downstream Products

• 143702-93-6 methyl 1-(2-nitrobenzyl)-1,2,4-triazole-3-carboxylate 
• 143702-92-5 methyl 1-(2-nitrobenzyl)-1,2,4-triazole-5-carboxylate 
• 3641-08-5 1,2,4-triazole-3-carboxamide 
• 57198-04-6 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester 
• 870562-61-1 1-(2-cyano-5-fluoro-phenyl)-J H-1,2,4-triazole-3-carboxylic acid methyl ester 
• 36791-04-5 ribavirin 
• 151607-70-4 1-trityl-1H-[1,2,4]triazole-3-carboxylic acid methyl ester 
• 1001057-66-4 1-[(2R,3R,5R)-3-benzoyloxy-5-(diethoxy-phosphorylmethoxy)-tetrahydrofuran-2-yl]-1H-[1,2,4]triazole-3-carboxylic acid methyl ester 
• 908005-19-6 1-(2,2-dimethyl-6-trityloxymethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl)-1H-[1,2,4]triazole-3-carboxylic acid methyl ester 
• 39030-43-8 1-β-D-ribofuranosyl-1H-1,2,4-triazole-5-carboxamide 
• 878479-16-4 1-(2,2-dimethyl-6-trityloxymethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yl)-1H-1,2,4-triazole-3-carboxylic acid methyl ester 
• 594860-63-6 methyl 1-[2-O-acetyl-3-O-benzyl-5,6-dideoxy-6-(diethoxyphosphinyl)-6,6-difluoro-β-D-ribofuranosyl]-1,2,4-triazole-3-carboxylate 
• 871578-72-2 (2'R,3'S,4'R)-1-(2',3'-di-benzyloxymethyl-tetrahydrofuran-4'-yl)-3-methoxycarbonyl-1,2,4-triazole 
• 871578-63-1 (2'R,3'S,4'R)-1-(2'-benzyloxymethyl-3'-hydroxytetrahydrofuran-4'-yl)-3-methoxycarbonyl-1,2,4-triazole 

Relevant articles and documents

Method for synthesizing 1, 2, 4-triazole-3-carboxylic acid methyl ester

The invention discloses a method for synthesizing 1, 2, 4-triazole-3-carboxylic acid methyl ester, and belongs to the field of organic chemistry. The method comprises the following reaction steps: reacting trichloroacetonitrile 1 with formylhydrazine 2 to generate an intermediate 3, then carrying out cyclization reaction to obtain an intermediate 4, and finally carrying out alcoholysis reaction togenerate 1, 2, 4-triazole-3-carboxylic acid methyl ester 5. According to the method, only three steps of reaction are needed, the overall yield is high, dangerous diazotization deamination reaction in a traditional synthesis process is avoided, the safety risk in the reaction process is reduced, and meanwhile the production cost can be reduced.

Structure Kinetics Relationships and Molecular Dynamics Show Crucial Role for Heterocycle Leaving Group in Irreversible Diacylglycerol Lipase Inhibitors

Drug discovery programs of covalent irreversible, mechanism-based enzyme inhibitors often focus on optimization of potency as determined by IC50-values in biochemical assays. These assays do not allow the characterization of the binding activity (Ki) and reactivity (kinact) as individual kinetic parameters of the covalent inhibitors. Here, we report the development of a kinetic substrate assay to study the influence of the acidity (pKa) of heterocyclic leaving group of triazole urea derivatives as diacylglycerol lipase (DAGL)-α inhibitors. Surprisingly, we found that the reactivity of the inhibitors did not correlate with the pKa of the leaving group, whereas the position of the nitrogen atoms in the heterocyclic core determined to a large extent the binding activity of the inhibitor. This finding was confirmed and clarified by molecular dynamics simulations on the covalently bound Michaelis-Menten complex. A deeper understanding of the binding properties of covalent serine hydrolase inhibitors is expected to aid in the discovery and development of more selective covalent inhibitors.

Chemoenzymatic method of 1,2,4-triazole nucleoside synthesis: Possibilities and limitations

Possibilities and limitations of chemoenzymatic synthesis of novel structural analogues of an antiviral preparation of Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) were established. A synthesis of various amides of 1H-1,2,4-triazole-3-carboxylic acid and its 5-substituted analogues - potential substrates of purine nucleoside phosphorylase - has been described. Comparative efficiency of preparation methods of these amides, as well as the methods of introduction of functional groups to the C5 position of heterocyclic system, were investigated. Novel analogues of Ribavirin containing various substitutes in the carboxamide group were synthesized. A biotechnological method was developed for the preparation of 1-β-D-ribofuranozyl-1,2,4-triazole-3-carbonitryl, an intermediate in the synthesis of Viramidine, the modern analogue of Ribavirin.