172152-35-1

Basic information

• Product Name: 2-[[(4-Methoxy-3-methyl-2-pyridinyl)methyl]thio]-6-(1H-pyrrol-1-yl)-1H-benzimidazole
• Synonyms: 2-[[(4-Methoxy-3-methyl-2-pyridinyl)methyl]thio]-6-(1H-pyrrol-1-yl)-1H-benzimidazole;5-(1H-pyrrol-1-yl)-2-[(4-methoxy-3-methyl-2-pyridyl)-methylthio]-1-hydro-benzimidazole
• CAS NO: 172152-35-1
• Molecular Formula: C₁₉H₁₈N₄OS
• Molecular Weight: 350.43742
• Mol File: 172152-35-1.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 590.4±60.0 °C(Predicted)
• Appearance: /
• Density: 1.30±0.1 g/cm3(Predicted)
• PKA: 9.26±0.10(Predicted)
• CAS DataBase Reference: 2-[[(4-Methoxy-3-methyl-2-pyridinyl)methyl]thio]-6-(1H-pyrrol-1-yl)-1H-benzimidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[[(4-Methoxy-3-methyl-2-pyridinyl)methyl]thio]-6-(1H-pyrrol-1-yl)-1H-benzimidazole(172152-35-1)
• EPA Substance Registry System: 2-[[(4-Methoxy-3-methyl-2-pyridinyl)methyl]thio]-6-(1H-pyrrol-1-yl)-1H-benzimidazole(172152-35-1)

Safety Data

• Hazardous Substances Data: 172152-35-1(Hazardous Substances Data)

Usage

Uses

Desoxy Ilaprazole is an intermediate in the synthesis of Ilaprazole (I266400), a proton pump inhibitor (PPI) used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD) and duodenal ulcer.

Synthetic route

5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole-2-thiol (172152-53-3) + 2-chloromethyl-4-methoxy-3-methylpyridine hydrochloride (86604-74-2) → 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1)

Conditions	Yield
With sodium hydroxide at 40℃; Solvent; Reagent/catalyst;	89.7%
With sodium hydroxide In methanol at 50℃; for 1.5h;	81.2%

cis,trans-2,5-dimethoxytetrahydrofuran (696-59-3) + 5-amino-2-[(4-methoxy-3-methyl-2-pyridyl)-methylthio]-1-hydro-benzimidazole (910664-00-5) → 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1)

Conditions	Yield
With acetic acid at 120℃; for 0.0833333h;	38.1%
With acetic acid for 0.0833333h; Product distribution / selectivity; Heating / reflux;

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)sulfinyl)-5-(1H-pyrrol-1-yl)benzimidazol-1-ide sodium salt

Conditions	Yield
With sodium hypochlorite; sodium hydroxide In tetrahydrofuran; water at 0 - 5℃; for 1.5h; Solvent;	94.7%

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → ilaprazole (834897-64-2)

Conditions	Yield
With peracetic acid; sodium tungstate; C94H124N6 In water at 0℃; for 8h; Inert atmosphere;	90%

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → ilaprazole (910664-01-6)

Conditions	Yield
With sodium molybdate; C78H60Cl8N6; dihydrogen peroxide In water at 0℃; for 8h; Inert atmosphere;	90%

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → ilaprazole

Conditions	Yield
With tert.-butylnitrite; dihydrogen peroxide In tert-butyl alcohol at 0 - 25℃; for 10h;	83%
Stage #1: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole With triethylamine In ethanol at 30℃; for 0.166667h; pH=8-9; Stage #2: With dihydrogen peroxide In ethanol for 6h; Reagent/catalyst;	75%
With 3-chloro-benzenecarboperoxoic acid In chloroform at -40℃; for 0.333333h;	64%
With 3-chloro-benzenecarboperoxoic acid In chloroform at 20℃;	45.5%
With NADPH; cytochrome P450 In aq. phosphate buffer at 37℃; for 0.75h; pH=7.4; Enzymatic reaction;

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → (-)-5-(1H-pyrrol-1-yl)-2-[[(4-methoxy-3-methyl-2-pyridyl)-methyl]sulfinyl]-1-hydro-benzimidazole

Conditions	Yield
With titanium(IV) isopropylate; tert.-butylhydroperoxide; water; (R)-1,1'-Bi-2-naphthol; N-ethyl-N,N-diisopropylamine In toluene at 25℃; for 16h; Product distribution / selectivity;	60.9%
With titanium(IV) isopropylate; L-(+)-diisopropyl tartrate; Cumene hydroperoxide; water; N-ethyl-N,N-diisopropylamine In toluene at 25 - 30℃; for 3.5 - 5.5h; Product distribution / selectivity;	55.3%
With titanium(IV) isopropylate; Cumene hydroperoxide; water; (R)-1,1'-Bi-2-naphthol; N-ethyl-N,N-diisopropylamine In toluene at 25℃; for 13h; Product distribution / selectivity;	53.2%

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → (-)-5-(1H-pyrrol-1-yl)-2-[[(4-methoxy-3-methyl-2-pyridyl)-methyl]sulfinyl]-1-hydro-benzimidazole

Conditions	Yield
Stage #1: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole With titanium(IV) isopropylate; diethyl (2S,3S)-tartrate In chloroform at 20 - 31℃; for 1h; Stage #2: With Cumene hydroperoxide; N-ethyl-N,N-diisopropylamine In chloroform at 31℃; for 18h; Product distribution / selectivity;	49.7%
Stage #1: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole With titanium(IV) isopropylate; diethyl (2S,3S)-tartrate In chloroform at 20 - 31℃; for 1h; Stage #2: With Cumene hydroperoxide; N-ethyl-N,N-diisopropylamine In chloroform at 31℃; for 18h; Product distribution / selectivity;	49.7%
Stage #1: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole With titanium(IV) isopropylate; diethyl (2S,3S)-tartrate In chloroform at 20 - 80℃; for 0.0833333h; Molecular sieve; Stage #2: With water In chloroform at 20 - 80℃; for 1h; Molecular sieve; Stage #3: With Cumene hydroperoxide; N-ethyl-N,N-diisopropylamine In chloroform at 20 - 80℃; for 16 - 18h; Product distribution / selectivity; Molecular sieve;	35.5%

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → (-)-5-(1H-pyrrol-1-yl)-2-[[(4-methoxy-3-methyl-2-pyridyl)-methyl]sulfinyl]-1-hydro-benzimidazole + (-)-5-(1H-pyrrol-1-yl)-2-[[(4-methoxy-3-methyl-2-pyridyl)-methyl]sulfinyl]-1-hydro-benzimidazole

Conditions	Yield
Stage #1: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole With titanium(IV) isopropylate; diethyl (2S,3S)-tartrate In dichloromethane for 0.0833333h; Stage #2: With Cumene hydroperoxide; N-ethyl-N,N-diisopropylamine In dichloromethane; water at 20℃; for 22h; Product distribution / selectivity;	A n/a B 37.7%
Stage #1: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole With titanium(IV) isopropylate; diethyl (2S,3S)-tartrate In chloroform for 0.0833333h; Stage #2: With Cumene hydroperoxide; N-ethyl-N,N-diisopropylamine In chloroform; water at 20 - 30℃; for 1 - 18h; Product distribution / selectivity;	A n/a B 32.7%
Stage #1: 2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole With titanium(IV) isopropylate; diethyl (2S,3S)-tartrate; 4 A molecular sieve In toluene Stage #2: With Cumene hydroperoxide; N-ethyl-N,N-diisopropylamine In water; toluene Stage #3: With Cumene hydroperoxide; N-ethyl-N,N-diisopropylamine In chloroform at 20 - 30℃; for 1 - 18h; Product distribution / selectivity;	A n/a B 32.7%

2-(((4-methoxy-3-methylpyridin-2-yl)methyl)thio)-5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole (172152-35-1) → 5-(1H-pyrrol-1-yl)-2-[[(4-methoxy-3-methyl)-2-pyridyl-1-oxide]methyl]sulfinyl-1H-benzimidazole

Conditions	Yield
With dihydrogen peroxide; acetic acid In methanol at 45℃;	3.58 g

Upstream product

• 172152-53-3 5-(1H-pyrrol-1-yl)-1H-benzo[d]imidazole-2-thiol 
• 86604-74-2 2-chloromethyl-4-methoxy-3-methylpyridine hydrochloride 
• 696-59-3 cis,trans-2,5-dimethoxytetrahydrofuran 
• 910664-00-5 5-amino-2-[(4-methoxy-3-methyl-2-pyridyl)-methylthio]-1-hydro-benzimidazole 

Relevant articles and documents

Preparation method of thioether

The preparation method comprises the following steps: (a) reacting a halogenated alkyl pyridine derivative or a salt thereof with 2 -mercaptobenzimidazole derivative in a water-soluble organic solvent under basic conditions. (b) The reaction solution obtained in step (a) was subjected to first devitrification step and second devitrification step, and purified. The prepared thioether is low in water content, uniform in water content and high in thioether purity, facilitates control of the water content of a reaction system in a subsequent thioether asymmetric oxidation reaction, and ensures high selectivity and reproducibility of asymmetric oxidation reaction. In addition, the preparation method of the thioether provided by the invention is simple in process and good in repeatability, and is more conducive to large-scale production.

Method for synthesizing intermediate of Ilaprazole sodium salt

The invention provides a method for synthesizing an intermediate of an Ilaprazole sodium salt. The method comprises the following steps: (1) adding a starting raw material, i.e., 5-(1H-pyrrol-1-yl)-2-mercaptobenzimidazole into a reaction bottle containing a sodium hydroxide solution and deionized water, and carrying out stirring with heating; and (2) adding a mixture solution of 2-chloromethoxy-4-methoxy-3-methylpyridine hydrochloride and deionized water into the reaction bottle, and carrying out a reaction until the reaction ends, thereby obtaining 5-(1H-pyrrol-1-yl)-2-[(4-methoxy-3-methyl-2-pyridyl)-methylthio]-1-H-benzimidazole. According to the method, the yield reaches 86% and is far higher than that of the existing technologies, and the used solvent is environmentally friendly and is pollution-free to environment; and the reaction operation is simple, the reaction conditions are easily controlled, and the obtained product is high in purity.

Substituted sulfoxide compounds, methods for preparing the same and use thereof

Disclosed are an optically pure compound having formula I, its pharmaceutically acceptable salt and its pharmaceutically acceptable solvate, and a use thereof in manufacturing medicaments and pharmaceutical compositions. A process for preparing the compound defined therein is also provided.