113712-98-4

Basic information

• Product Name: Tenatoprazole
• Synonyms: 5-Methoxy-2-(((4-methoxy-3,5-dimethylpyridin-2-yl);sulfinyl);TENATOPRAZOLE MONOSODIUM;TENATOPRAZOLE 98+%;3-Methoxy-8-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methyl sulfinyl]-2,7,9-triazabicyclo[4.3.0]nona-2,4,8,10-tetraene;Tenatoprazole;TENATOPRAZOLE/TU-199;5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-imidazo[4,5-β]pyridine
• CAS NO: 113712-98-4
• Molecular Formula: C₁₆H₁₈N₄O₃S
• Molecular Weight: 346.41
• EINECS: 1533716-785-6
• Product Categories: Inhibitors;Heterocyclic Compounds;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;API's
• Mol File: 113712-98-4.mol
• Article Data: 6

Chemical Properties

• Melting Point: 178-180°C
• Boiling Point: 591.5 °C at 760 mmHg
• Flash Point: 311.5 °C
• Appearance: white crystalline powder
• Density: 1.41 g/cm³
• Vapor Pressure: 5.8E-14mmHg at 25°C
• Refractive Index: 1.673
• Storage Temp.: −20°C
• Solubility: DMSO (Slightly, Heated), Methanol (Slightly, Heated)
• PKA: 4.61±0.40(Predicted)
• Stability: Hygroscopic, Temperature Sensitive
• CAS DataBase Reference: Tenatoprazole(CAS DataBase Reference)
• NIST Chemistry Reference: Tenatoprazole(113712-98-4)
• EPA Substance Registry System: Tenatoprazole(113712-98-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26-36/37
• Hazardous Substances Data: 113712-98-4(Hazardous Substances Data)

Usage

Description

Tenatoprazole is a proton pump inhibitor, blocking hog gastric H+/K+-ATPase activity with an IC50 value of 6.2 μM. It is orally bioavailable, blocking induced gastric acid secretion and ulcer formation in rats and humans. Tenatoprazole has a prolonged plasma half-life resulting in persistent effectiveness after withdrawal.

Chemical Properties

White Crystalline Powder

Uses

Different sources of media describe the Uses of 113712-98-4 differently. You can refer to the following data:
1. A proton pump inhibitor for reduction and/or prevention of gastrointestinal disorders
2. A proton pump inhibitor for reduction and/or prevention of gastrointestinal disorders.

InChI:InChI=1/C16H18N4O3S/c1-9-7-17-12(10(2)14(9)23-4)8-24(21)16-18-11-5-6-13(22-3)19-15(11)20-16/h5-7H,8H2,1-4H3,(H,18,19,20)

Synthetic route

5-methoxy-2-[(4-nitro-3,5-dimethyl-2-pyridinyl)methylsulfinyl]imidazo[4,5-b]pyridine + sodium methylate (124-41-4) → tenatoprazole (113712-98-4)

Conditions	Yield
In methanol at -5℃; for 18h;	79.4%

5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylthio)-1H-imidazo[4,5-b]pyridine (113713-24-9) → tenatoprazole (113712-98-4)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In chloroform at -15 - -10℃; Large scale reaction;	74%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 1h;	66.4%
With 3-chloro-benzenecarboperoxoic acid In chloroform

5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylthio)-1H-imidazo[4,5-b]pyridine (113713-24-9) → 5-methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfonyl)-1H-imidazo[4,5-b]pyridine + tenatoprazole (113712-98-4)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In chloroform at 5℃; for 0.0166667h; Product distribution / selectivity;

tenatoprazole (113712-98-4) + methyl iodide (74-88-4) → 5-methoxy-2-(4-methoxy-3,5-dimethylpyridin-2-ylmethanesulfinyl)-1-methyl-1H-imidazo[4,5-b]pyridine (721924-07-8)

Conditions	Yield
With dmap; potassium carbonate In dichloromethane at 25 - 30℃; for 10h;	91.3%

tenatoprazole (113712-98-4) → 5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylthio)-1H-imidazo[4,5-b]pyridine (113713-24-9) + 5'-hydroxyltenatoprazole + 5'-hydroxyltenatoprazole sulfide

Conditions	Yield
With D-glucose-6-; nicotinamide adenine dinucleotide phosphate; yeast glucose-6-phosphate dehydrogenase In aq. phosphate buffer at 37℃; pH=7.4; Catalytic behavior; Kinetics; Reagent/catalyst; Enzymatic reaction; regioselective reaction;	A n/a B 8.2% C 1.3%
With G1T mutant of CYP102A1; NADPH In aq. phosphate buffer; dimethyl sulfoxide at 37℃; for 2h; pH=7.4; Reagent/catalyst; Time; Enzymatic reaction;

(4-chlorosulfonylphenoxy)acetic acid 2-(toluene-4-sulfonyl)ethyl ester (651728-13-1) + tenatoprazole (113712-98-4) → 2-tosylethyl 2-{4-[5-methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-1H-imidazo[4,5-b]pyridine-1-ylsulfonyl]-phenoxy}-acetate (1015067-31-8) + 2-tosylethyl 2-{4-[5-methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-3H-imidazo[4,5-b]pyridine-3-ylsulfonyl]-phenoxy}-acetate (1015067-32-9)

Conditions	Yield
With sodium hydrogencarbonate; triethylamine In dichloromethane at 20℃;

tenatoprazole (113712-98-4) → (-)5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-imidazo[4,5-b]pyridine

Conditions	Yield
Resolution of racemate;
Resolution of racemate;

2-[(chlorocarbonyl)(methyl)amino]ethyl ethyl carbonate (635751-00-7) + tenatoprazole (113712-98-4) → ethyl 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](methyl)amino]ethyl carbonate

Conditions	Yield
With triethylamine; dmap In tetrahydrofuran at 60℃; for 6h;
With dmap; triethylamine In tetrahydrofuran at 60℃; for 6h;	0.721 g

2-[(chlorocarbonyl) (phenyl)amino]ethyl acetate (635751-44-9) + tenatoprazole (113712-98-4) → 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](phenyl)amino]ethyl acetate

Conditions	Yield
With triethylamine; dmap In tetrahydrofuran at 60℃; for 10h;
With dmap; triethylamine In tetrahydrofuran at 60℃; for 10h;	0.311 g

tenatoprazole (113712-98-4) → (+)5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-imidazo[4,5-b]pyridine

Conditions	Yield
Resolution of racemate;

2-(chlorocarbonyl(methyl)amino)ethyl acetate + tenatoprazole (113712-98-4) → 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](methyl)amino]ethyl acetate

Conditions	Yield
With triethylamine; dmap In tetrahydrofuran at 60℃; for 5h;
With dmap; triethylamine In tetrahydrofuran at 60℃; for 5h;	0.173 g

C11H11Cl2NO3 + tenatoprazole (113712-98-4) → 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](methyl)amino]ethyl 3-chlorobenzoate

Conditions	Yield
With triethylamine; dmap In tetrahydrofuran at 60℃; for 14h;
With dmap; triethylamine In tetrahydrofuran at 60℃; for 14h;	0.360 g

bis(trichloromethyl) carbonate (32315-10-9) + 1-acetoxy-2-methylaminoethane hydrochloride (4527-98-4) + tenatoprazole (113712-98-4) → 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](methyl)amino]ethyl acetate

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate With pyridine In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 1-acetoxy-2-methylaminoethane hydrochloride With triethylamine In tetrahydrofuran at 15 - 30℃; for 2h; Stage #3: tenatoprazole With dmap; triethylamine In tetrahydrofuran at 60℃; for 5h;

2-(methylamino)ethyl 3-chlorobenzoate hydrochloride (635750-79-7) + bis(trichloromethyl) carbonate (32315-10-9) + tenatoprazole (113712-98-4) → 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](methyl)amino]ethyl 3-chlorobenzoate

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate With pyridine In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-(methylamino)ethyl 3-chlorobenzoate hydrochloride With triethylamine In tetrahydrofuran at 15 - 30℃; for 2.5h; Stage #3: tenatoprazole With dmap; triethylamine In tetrahydrofuran at 60℃; for 14h;

ethyl 2-(methylamino)ethyl carbonate hydrochloride (635750-86-6) + bis(trichloromethyl) carbonate (32315-10-9) + tenatoprazole (113712-98-4) → ethyl 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](methyl)amino]ethyl carbonate

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate With pyridine In tetrahydrofuran at 0℃; for 0.5h; Stage #2: ethyl 2-(methylamino)ethyl carbonate hydrochloride With triethylamine In tetrahydrofuran at 15 - 30℃; for 2.5h; Stage #3: tenatoprazole With dmap; triethylamine In tetrahydrofuran at 60℃; for 6h;

2-anilinoethyl acetate hydrochloride (30761-89-8) + bis(trichloromethyl) carbonate (32315-10-9) + tenatoprazole (113712-98-4) → 2-[[[5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-3H-imidazo[4,5-b]pyridin-3-yl]carbonyl](phenyl)amino]ethyl acetate

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate With pyridine In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-anilinoethyl acetate hydrochloride With triethylamine In tetrahydrofuran at 15 - 30℃; for 3h; Stage #3: tenatoprazole With dmap; triethylamine In tetrahydrofuran at 60℃; for 10h;

tenatoprazole (113712-98-4) → 5-methoxy 2-[[(4-methoxy-3,5-dimethyl)-2-pyridyl methyl]sulfinyl]1H imidazo[4,5-b]pyridine, potassium salt

Conditions	Yield
With potassium hydroxide In water at 0℃; for 12h; Product distribution / selectivity;

tenatoprazole (113712-98-4) → 5'-hydroxyltenatoprazole + 5'-hydroxyltenatoprazole sulfide

Conditions	Yield
With G1T mutant of CYP102A1 for 0.5h; Kinetics; Reagent/catalyst; Enzymatic reaction;

Upstream product

• 113713-24-9 5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylthio)-1H-imidazo[4,5-b]pyridine 
• 124-41-4 sodium methylate 

Downstream Products

• 113713-24-9 5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylthio)-1H-imidazo[4,5-b]pyridine 
• 1015067-31-8 2-tosylethyl 2-{4-[5-methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-1H-imidazo[4,5-b]pyridine-1-ylsulfonyl]-phenoxy}-acetate 
• 1015067-32-9 2-tosylethyl 2-{4-[5-methoxy-2-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethanesulfinyl)-3H-imidazo[4,5-b]pyridine-3-ylsulfonyl]-phenoxy}-acetate 

Related news

Structural studies of several solvated potassium salts of Tenatoprazole (cas 113712-98-4) crystallizing as conglomerates08/22/2019

Despite the weak acidic character of tenatoprazole it is possible to crystallize, in strong alkaline media, different solvated salts of this active pharmaceutical ingredient. Among these solid phases, some potassium salts exhibiting non congruent solubilities, form stable conglomerates in equili...detailed

Characterization of the inhibitory activity of Tenatoprazole (cas 113712-98-4) on the gastric H+,K+-ATPase in vitro and in vivo08/21/2019

Tenatoprazole is a prodrug of the proton pump inhibitor (PPI) class, which is converted to the active sulfenamide or sulfenic acid by acid in the secretory canaliculus of the stimulated parietal cell of the stomach. This active species binds to luminally accessible cysteines of the gastric H+,K+...detailed

Relevant articles and documents

Continuous flow multipoint dosing approach for selectivity engineering in sulfoxidation

A continuous synthesis approach with multipoint dosing of one of the reagents is demonstrated for the synthesis of sulfoxide compounds such as proton pump inhibitors. Use of multipoint dosing of the oxidizing agent helped to minimize the possibility of over-oxidation leading to sulfone. Different oxidizing agents were used, and the effect of various parameters (viz. mole ratio of sulfide to oxidizing agent, temperature, residence time, concentration of oxidizing agent, etc.) on the yield of the desired sulfoxide compound was studied. Single-point and multipoint dosing approaches of the oxidizing agent were used for the most promising set of parameters. The performance was compared in terms of conversion of sulfide and the selectivity of the desired sulfoxide. Numbering up approach was used to produce the sulfoxide in a relatively large quantity at laboratory scale with complete conversion and over 99% selectivity for the sulfoxide.

Improved synthetic approach to tenatoprazole

An improved synthetic approach to tenatoprazole 1 is described. It started from 2,3,5-trimethyl-4-nitropyridine-N-oxide 2 with acetic anhydride via rearrangement and hydrolysis to give 3, Chlorination with SOCl2 yielded 2-chloromethyl-3,5-dimethyl-4-nitropyridine hydrochloride 4, then 4 condensed with 2-mercapto-5-methoxy imidazole [4,5-b]pyridine 5 to give 5-methoxy-2-[(4-nitro-3,5-dimethyl-2-pyridinyl)methylthio]imidazole[4,5-b] pyridine 6. At last the title compound 1 was produced by two methods: 6 was oxidized with MCPBA and then methoxylated with CH3ONa to give 1 and 6 was first methoxylated with CH3ONa and then oxidized with MCPBA to give 1. The overall yield is around 26% for both five-step syntheses. Copyright Taylor & Francis Group, LLC.

CONTINUOUS FLOW PROCESS FOR THE PREPARATION OF SULPHOXIDE COMPOUNDS

A continuous micromixer based process for the synthesis of sulphoxide compounds with a reaction time of less than or equal one minute is disclosed. The process shows selectivity of > 95% towards the sulphoxide compounds.