152628-02-9

Basic information

• Product Name: 2-n-Propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)benzimidazole
• Synonyms: 1,7'-diMethyl-2'-propyl-1H,3'H-;TelMisartan IMpurity A(2-n-propyl-4-Methyl-6-(1-MethylbenziMidazole-2-yl)benziMidazole);TelMisartan IMpurity A;TelMisartan Related CoMpound A;4-Methyl-2-propyl-6-benziMidazolecarboxylic Acid, 97+%;2-Propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole;Telmisartan EP Impurity A;Imp. A:2-n-Propyl-4-methyl-6-(1'-methylbenzimidazole-2-yl)benzimidazole
• CAS NO: 152628-02-9
• Molecular Formula: C₁₉H₂₀N₄
• Molecular Weight: 304.39
• EINECS: 1308068-626-2
• Product Categories: Chemical intermediate for Telmisartan;INTERMEDIATESOF;Imidazol&Benzimidazole;Imidazoles;(intermediate of telmisartan);Intermediates & Fine Chemicals;Pharmaceuticals;pharmaceutical intermediates
• Mol File: 152628-02-9.mol
• Article Data: 22

Chemical Properties

• Melting Point: 130-135 °C(Solv: tetrahydrofuran (109-99-9))
• Boiling Point: 584.802 °C at 760 mmHg
• Flash Point: 307.477 °C
• Appearance: grey powder
• Density: 1.23 g/cm³
• Vapor Pressure: 0-0Pa at 20-25℃
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: soluble in Methanol
• PKA: 11.86±0.30(Predicted)
• CAS DataBase Reference: 2-n-Propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)benzimidazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-n-Propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)benzimidazole(152628-02-9)
• EPA Substance Registry System: 2-n-Propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)benzimidazole(152628-02-9)

Safety Data

• Hazardous Substances Data: 152628-02-9(Hazardous Substances Data)

Usage

Chemical Properties

Grey Powder

Uses

An impurity found in Telmisartan (T017000).

Synthetic route

N-methylbenzene-1,2-diamine dihydrochloride (25148-68-9) + 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid (152628-03-0) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With methanesulfonic acid In i-Amyl alcohol at 130 - 135℃; for 18h; Temperature; Solvent; Reagent/catalyst;	93%
Stage #1: N-methylbenzene-1,2-diamine dihydrochloride; 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid With PPA at 70 - 135℃; for 13.5h; Stage #2: With ammonia In water at 30 - 90℃; for 1h; pH=8.0 - 8.5;	77.4%
With PPA at 150℃; for 20h;	5.86 g
With polyphosphoric acid at 150℃; for 14h;

C19H21IN4 → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With copper(l) iodide; caesium carbonate In dimethyl sulfoxide at 130℃;	93%

C19H21BrN4 → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With copper(l) iodide; caesium carbonate In dimethyl sulfoxide at 130℃;	92%

N-methyl-1,2-phenylenediamine (4760-34-3) + 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid (152628-03-0) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Stage #1: N-methyl-1,2-phenylenediamine; 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid With methanesulfonic acid; phosphorus pentoxide at 75 - 145℃; Stage #2: With sodium hydroxide In water pH=< 3; Product distribution / selectivity;	90%
With polyphosphoric acid at 150 - 155℃; for 4h; Inert atmosphere;	80%
With PPA at 150 - 155℃; Inert atmosphere;
Stage #1: N-methyl-1,2-phenylenediamine; 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid at 70 - 130℃; for 8.5h; Stage #2: With hydrogenchloride In methanol; water at 25℃; for 0.166667h; Stage #3: With ammonium hydroxide In methanol; water at 25℃; for 1h; Reagent/catalyst;

C26H28N4O3S → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With sodium hydroxide In water; acetonitrile at 20℃;	90%

2-n-propyl-4-methyl-6-formylchlorobenzimidazole + N-methyl-o-phenylenediamine hydrochloride → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-formylchlorobenzimidazole; N-methyl-o-phenylenediamine hydrochloride With triethylamine In dichloromethane at 40℃; for 3h; Large scale; Stage #2: With acetic acid In dichloromethane at 60℃; for 5h; Temperature; Reagent/catalyst; Solvent; Large scale;	89.96%

C19H22N4O → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With p-toluenesulfonyl chloride In water; acetonitrile at 0 - 20℃;	88%
Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 0 - 20 °C 2: sodium hydroxide / acetonitrile; water / 20 °C View Scheme

2-methyl-4-(1-methyl-1H-benzimidazol-2-yl)-6-nitrobenzenamine (1345840-05-2) + butyraldehyde (123-72-8) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With sodium dithionite In methanol; water for 12h; Reflux;	85%

C19H21N3O*ClH → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Stage #1: C19H21N3O*ClH With bis(trichloromethyl) carbonate; N,N-dimethyl-formamide In acetonitrile at 80 - 85℃; for 2h; Stage #2: With hydroxylamine In acetonitrile at 20℃; for 1h; Stage #3: With triethylamine; p-toluenesulfonyl chloride at 0 - 20℃;	85%
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide; bis(trichloromethyl) carbonate / acetonitrile / 2 h / 80 - 85 °C 2: p-toluenesulfonyl chloride / acetonitrile; water / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide; bis(trichloromethyl) carbonate / acetonitrile / 2 h / 80 - 85 °C 2: triethylamine / acetonitrile / 0 - 20 °C 3: sodium hydroxide / acetonitrile; water / 20 °C View Scheme

N1-methylbenzene-1,2-diamine hydrochloride (81684-80-2) + 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid (152628-03-0) → desmethyl dibenzimidazole (884330-09-0) + 7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid(2-methylaminophenyl)amide (884330-18-1) + 3-amino-4-butyrylamino-5-methyl-N-(2-methylaminophenyl)benzamide (884330-17-0) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With polyphosphoric acid at 150 - 155℃;	A n/a B n/a C n/a D 84%

N-[2-methyl-4-(1-methylbenzimidazole)-2-yl-6-nitrophenyl]-butanamide (1083158-66-0) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen In isopropyl alcohol at 100℃; under 6000.6 Torr; for 12h; Temperature; Solvent; Reagent/catalyst; Autoclave;	82.3%

N1-methylbenzene-1,2-diamine hydrochloride (81684-80-2) + 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid (152628-03-0) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Stage #1: N1-methylbenzene-1,2-diamine hydrochloride; 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid With phosphorus pentoxide; phosphoric acid at 70 - 130℃; Stage #2: With ammonia In water; ethyl acetate for 3h; pH=9 - 10; Product distribution / selectivity; Cooling with ice;	82%
Stage #1: N1-methylbenzene-1,2-diamine hydrochloride; 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid With PPA; Polyphosphoric acid (PPA) In water at 90 - 155℃; for 5.75 - 7h; Stage #2: With sodium hydroxide In water pH=5.5 - 6; Product distribution / selectivity;

N-methyl-1,2-phenylenediamine (4760-34-3) + 4-methyl-2-propyl-1H-benzimidazole-6-carboxylic acid methyl ester (152628-00-7) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With polyphosphoric acid at 150℃; for 12h;	62%

C19H21BrN4 → C15H14BrN3 + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With caesium carbonate; copper(II) oxide In dimethyl sulfoxide at 130℃; for 8h;	A 19.9% B 61.3%

3-methyl-5-(1-methyl-1H-benzoimidazol-2-yl)-benzene-1,2-diamine + butyric acid (107-92-6) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With polyphosporic acid at 120℃; for 4h;	47%

C19H21ClN4 → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
With copper(l) iodide; caesium carbonate In dimethyl sulfoxide at 130℃;	13%

methyl 4-amino-3-methylbenzoate (18595-14-7) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 6 steps 1: chlorobenzene / 100 °C 2: fuming HNO3, 60percent H2SO4 / 0 °C 3: H2 / 10percent Pd/C / methanol / 50 °C / 3750.3 Torr 4: glacial CH3COOH / 1.5 h / Heating 5: 5.46 g / aq. NaOH / methanol / 2 h / Heating 6: 5.86 g / polyphosphoric acid / 20 h / 150 °C View Scheme
Multi-step reaction with 6 steps 1: triethylamine / dichloromethane / 0 °C 2: sulfuric acid; nitric acid 3: hydrogen / methanol / 100 °C / 3750.38 Torr 4: acetic acid / 1 h / Reflux 5: sodium hydroxide / water; methanol / 2 h / Reflux 6: polyphosphoric acid / 14 h / 150 °C View Scheme

methyl 4-(n-butyrylamino)-3-methylbenzoate (301533-59-5) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: fuming HNO3, 60percent H2SO4 / 0 °C 2: H2 / 10percent Pd/C / methanol / 50 °C / 3750.3 Torr 3: glacial CH3COOH / 1.5 h / Heating 4: 5.46 g / aq. NaOH / methanol / 2 h / Heating 5: 5.86 g / polyphosphoric acid / 20 h / 150 °C View Scheme
Multi-step reaction with 5 steps 1: sulfuric acid; nitric acid 2: hydrogen / methanol / 100 °C / 3750.38 Torr 3: acetic acid / 1 h / Reflux 4: sodium hydroxide / water; methanol / 2 h / Reflux 5: polyphosphoric acid / 14 h / 150 °C View Scheme

4-methyl-2-propyl-1H-benzimidazole-6-carboxylic acid methyl ester (152628-00-7) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 5.46 g / aq. NaOH / methanol / 2 h / Heating 2: 5.86 g / polyphosphoric acid / 20 h / 150 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydroxide; water / methanol / 80 °C 2.1: phosphorus pentoxide; phosphoric acid / 70 - 130 °C 2.2: 3 h / pH 9 - 10 / Cooling with ice View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 2 h / Reflux 2: polyphosphoric acid / 14 h / 150 °C View Scheme

methyl 4-(n-butyrylamino)-3-methyl-5-aminobenzoate (675882-71-0) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: glacial CH3COOH / 1.5 h / Heating 2: 5.46 g / aq. NaOH / methanol / 2 h / Heating 3: 5.86 g / polyphosphoric acid / 20 h / 150 °C View Scheme
Multi-step reaction with 3 steps 1: acetic acid / 1 h / Reflux 2: sodium hydroxide / water; methanol / 2 h / Reflux 3: polyphosphoric acid / 14 h / 150 °C View Scheme

4-butyrylamino-3-methyl-5-nitro-benzoic acid methyl ester (152628-01-8) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: H2 / 10percent Pd/C / methanol / 50 °C / 3750.3 Torr 2: glacial CH3COOH / 1.5 h / Heating 3: 5.46 g / aq. NaOH / methanol / 2 h / Heating 4: 5.86 g / polyphosphoric acid / 20 h / 150 °C View Scheme
Multi-step reaction with 2 steps 1.1: water; sodium dithionite / 70 - 100 °C 2.1: phosphorus pentoxide; phosphoric acid / 70 - 130 °C 2.2: 3 h / pH 9 - 10 / Cooling with ice View Scheme
Multi-step reaction with 3 steps 1.1: sodium dithionite / water / 70 - 100 °C 2.1: sodium hydroxide; water / methanol / 80 °C 3.1: phosphorus pentoxide; phosphoric acid / 70 - 130 °C 3.2: 3 h / pH 9 - 10 / Cooling with ice View Scheme
Multi-step reaction with 4 steps 1: hydrogen / methanol / 100 °C / 3750.38 Torr 2: acetic acid / 1 h / Reflux 3: sodium hydroxide / water; methanol / 2 h / Reflux 4: polyphosphoric acid / 14 h / 150 °C View Scheme

3-amino-4-butyrylamino-5-methyl-N-(2-methylaminophenyl)benzamide (884330-17-0) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Stage #1: 3-amino-4-butyrylamino-5-methyl-N-(2-methylaminophenyl)benzamide With PPA at 150 - 155℃; Stage #2: With sodium hydroxide In water at 70 - 80℃; for 0.5 - 0.75h; pH=5 - 6; Product distribution / selectivity;

7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid(2-methylaminophenyl)amide (884330-18-1) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Stage #1: 7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid(2-methylaminophenyl)amide With PPA at 150 - 155℃; Stage #2: With sodium hydroxide In water at 70 - 80℃; for 0.5 - 0.75h; pH=5 - 6; Product distribution / selectivity;

C15H13N3O3 (1345840-14-3) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h 1.2: 3.5 h / 5 - 20 °C 2.1: ammonia / ethanol; water / 6 h / 90 °C / Autoclave 3.1: sodium dithionite / methanol; water / 12 h / Reflux View Scheme

2-(4-methoxy-3-methyl-5-nitrophenyl)-1-methyl-1H-benzimidazole (1345840-21-2) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonia / ethanol; water / 6 h / 90 °C / Autoclave 2: sodium dithionite / methanol; water / 12 h / Reflux View Scheme

4-hydroxy-3-methyl-benzaldehyde (15174-69-3) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: nitric acid / 1.67 h / -15 °C 2.1: sodium hydroxide / water / 0.5 h 2.2: 6.25 h / 0 - 70 °C 3.1: dihydrogen peroxide / methanol; water / 4 h / 5 - 10 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h 4.2: 3.5 h / 5 - 20 °C 5.1: ammonia / ethanol; water / 6 h / 90 °C / Autoclave 6.1: sodium dithionite / methanol; water / 12 h / Reflux View Scheme

4-hydroxy-3-methyl-5-nitrobenzaldehyde (54674-91-8) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium hydroxide / water / 0.5 h 1.2: 6.25 h / 0 - 70 °C 2.1: dihydrogen peroxide / methanol; water / 4 h / 5 - 10 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h 3.2: 3.5 h / 5 - 20 °C 4.1: ammonia / ethanol; water / 6 h / 90 °C / Autoclave 5.1: sodium dithionite / methanol; water / 12 h / Reflux View Scheme

4-methoxy-3-methyl-5-nitrobenzaldehyde (861792-67-8) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: dihydrogen peroxide / methanol; water / 4 h / 5 - 10 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h 2.2: 3.5 h / 5 - 20 °C 3.1: ammonia / ethanol; water / 6 h / 90 °C / Autoclave 4.1: sodium dithionite / methanol; water / 12 h / Reflux View Scheme

ortho-cresol (95-48-7) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium hydroxide / water / 6.5 h / 60 °C 2.1: nitric acid / 1.67 h / -15 °C 3.1: sodium hydroxide / water / 0.5 h 3.2: 6.25 h / 0 - 70 °C 4.1: dihydrogen peroxide / methanol; water / 4 h / 5 - 10 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h 5.2: 3.5 h / 5 - 20 °C 6.1: ammonia / ethanol; water / 6 h / 90 °C / Autoclave 7.1: sodium dithionite / methanol; water / 12 h / Reflux View Scheme

methyl 3,4-diamino-5-methylbenzoate (668276-43-5) → 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: polyphosphoric acid / 0.17 h / 150 °C / 1551.49 Torr / Irradiation 2: polyphosphoric acid / 12 h / 150 °C View Scheme

Methyl 4'-(bromomethyl)biphenyl-2-carboxylate (114772-38-2) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 4'-[[4-methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazol-1-yl]methyl]biphenyl-2-carboxylic acid methyl ester (528560-93-2)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium tert-butylate In dimethyl sulfoxide; isopropyl alcohol Inert atmosphere; Stage #2: Methyl 4'-(bromomethyl)biphenyl-2-carboxylate In dimethyl sulfoxide; isopropyl alcohol at 30 - 35℃; for 6h; Inert atmosphere;	95.1%
With potassium tert-butylate In 1-methyl-pyrrolidin-2-one at 0 - 10℃; for 3.416h; Solvent; Reagent/catalyst; Temperature;	95%
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium tert-butylate In dimethyl sulfoxide; isopropyl alcohol at 45℃; for 1h; Stage #2: Methyl 4'-(bromomethyl)biphenyl-2-carboxylate In dimethyl sulfoxide; isopropyl alcohol at 30℃; for 6h;	94.8%

2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) + 4'-bromomethylbiphenyl-2-carboxylic acid (150766-86-2) → telmisatran (144701-48-4)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With sodium hydride In N,N-dimethyl-formamide at 0 - 5℃; for 1h; Stage #2: 4'-bromomethylbiphenyl-2-carboxylic acid In N,N-dimethyl-formamide at 10℃; Solvent; Reagent/catalyst; Temperature;	95%

4'-chloromethylbiphenyl-2-carboxylic acid methyl ester + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 4'-[[4-methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazol-1-yl]methyl]biphenyl-2-carboxylic acid methyl ester (528560-93-2)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium hydroxide In acetonitrile for 0.166667h; Stage #2: 4'-chloromethylbiphenyl-2-carboxylic acid methyl ester In acetonitrile	92%

(4-(bromomethyl)-1H-indol-1-yl)(phenyl)methanone (1241048-04-3) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → [4-[[2-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole-1-yl]methyl]-1H-indol-1-yl](phenyl)methanone

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With sodium hydride In tetrahydrofuran; mineral oil at 50℃; for 0.5h; Stage #2: (4-(bromomethyl)-1H-indol-1-yl)(phenyl)methanone In tetrahydrofuran; mineral oil at 50℃; for 3h;	91.9%

2-mesitylenesulphonyl chloride (773-64-8) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 3-(mesitylsulfonyl)-1,7-dimethyl-2-propyl-1H,3H-2,5-bibenzo[d]imidazole

Conditions	Yield
With tetrabutylammomium bromide; sodium hydroxide In benzene at 0 - 20℃;	90%

Methyl 4'-(bromomethyl)biphenyl-2-carboxylate (114772-38-2) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → telmisatran (144701-48-4)

Conditions	Yield
Stage #1: Methyl 4'-(bromomethyl)biphenyl-2-carboxylate; 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium hydroxide In dimethyl sulfoxide at 25 - 50℃; for 4h; Stage #2: With water; acetic acid In water; dimethyl sulfoxide at 20℃; pH=3.8 - 4; Product distribution / selectivity;	88%
Stage #1: Methyl 4'-(bromomethyl)biphenyl-2-carboxylate; 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With sodium hydroxide In dimethyl sulfoxide at 25 - 50℃; for 4h; Stage #2: With water; acetic acid In water; dimethyl sulfoxide pH=4.2; Product distribution / selectivity;	80%

4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile (114772-54-2) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 4'-[[2-n-propyl-4-methyl-6-(1-methyl-benzimidazol-2-yl)-1H-benzimidazol-1-yl]-methyl]-2-cyano-biphenyl (144702-27-2)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium tert-butylate In ISOPROPYLAMIDE at 20℃; for 1h; Stage #2: 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile In ISOPROPYLAMIDE at 5 - 10℃; for 2h;	87.5%
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium tert-butylate In ISOPROPYLAMIDE at 20℃; for 1h; Stage #2: 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile In ISOPROPYLAMIDE at 5 - 10℃; for 2h;	87.5%
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium hydroxide In acetone at 20 - 25℃; Stage #2: 4'-(bromomethyl)-1,1'-biphenyl-2-carbonitrile In acetone at 20 - 25℃; Product distribution / selectivity;	87.73%

2,5-dichlorobenzenesulphonyl chloride (5402-73-3) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 3-(2,5-dichlorophenylsulfonyl)-1,7-dimethyl-2-propyl-1H,3H-2,5-bibenzo[d]imidazole

Conditions	Yield
With tetrabutylammomium bromide; sodium hydroxide In benzene at 0 - 20℃;	87%

4'-bromomethyl-biphenyl-2-carboxylic acid tert-butyl ester (114772-40-6) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → tert-butyl 4'-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylate (144702-26-1)

Conditions	Yield
With potassium tert-butylate In 1-methyl-pyrrolidin-2-one at 10℃; for 4h;	86%
With sodium In methanol at 70℃; Reagent/catalyst; Temperature; Solvent;	71%
With potassium tert-butylate In N,N-dimethyl acetamide at 75 - 80℃; for 3h; Inert atmosphere;	70%
With potassium tert-butylate 1.) DMSO, RT, 30 min, 2.) DMSO, 14 h; Multistep reaction;
With potassium tert-butylate In dimethyl sulfoxide at 25 - 30℃; for 3.5h; Product distribution / selectivity;

2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) + (5-(bromomethyl)-1H-indol-1-yl)(phenyl)methanone (145303-52-2) → [5-[[2-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole-1-yl]methyl]-1H-indol-1-yl](phenyl)methanone

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With sodium hydride In tetrahydrofuran; mineral oil at 50℃; for 0.5h; Stage #2: (5-(bromomethyl)-1H-indol-1-yl)(phenyl)methanone In tetrahydrofuran; mineral oil at 50℃; for 3h;	85.6%

2-(4'-chloromethyl-biphenyl-2-yl)-4,4-dimethyl-4,5-dihydrooxazole (158144-51-5) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 3'-([2'-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)biphenyl-4-yl]methyl)-1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzimidazole (1191259-51-4)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With sodium hydride In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: 2-(4'-chloromethyl-biphenyl-2-yl)-4,4-dimethyl-4,5-dihydrooxazole In tetrahydrofuran; N,N-dimethyl acetamide at 20℃; Reflux; Inert atmosphere;	85%

4,4-dimethyl-2-(4'-methanesulfonyloxymethylbiphenyl-2-yl)oxazoline (158144-52-6) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 3'-([2'-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)biphenyl-4-yl]methyl)-1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzimidazole (1191259-51-4)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With sodium hydride In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: 4,4-dimethyl-2-(4'-methanesulfonyloxymethylbiphenyl-2-yl)oxazoline In tetrahydrofuran; N,N-dimethyl acetamide at 20℃; Inert atmosphere; Reflux;	85%

2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) + 4-bromobenzenesulfonyl chloride (98-58-8) → 3-(4-bromophenylsulfonyl)-1,7-dimethyl-2-propyl-1H,3H-2,5-bibenzo[d]imidazole

Conditions	Yield
With tetrabutylammomium bromide; sodium hydroxide In benzene at 0 - 20℃;	84%

4-(chloromethyl)biphenyl-2'-carboxylic acid (667457-41-2) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → telmisatran (144701-48-4)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Cooling with ice; Stage #2: 4-(chloromethyl)biphenyl-2'-carboxylic acid In N,N-dimethyl-formamide at 20 - 50℃; for 5h; Reagent/catalyst; Temperature;	84%

p-toluenesulfonyl chloride (98-59-9) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 1,7-dimethyl-2-propyl-3-tosyl-1H,3H-2,5-bibenzo[d]imidazole

Conditions	Yield
With tetrabutylammomium bromide; sodium hydroxide In benzene at 0 - 20℃;	83%

1-bromomethyl-4-bromobenzene (589-15-1) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 3'-(4-bromobenzyl)-1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzo[d]imidazole

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at 25 - 35℃; Inert atmosphere;	80%
With potassium carbonate In ISOPROPYLAMIDE at 20℃; for 8h;

2-Bromo-4'-(bromomethyl)biphenyl (1187523-96-1) + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → 3'-((2'-bromobiphenyl-4-yl)methyl)-1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzo[d]imidazole (1206701-77-0)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium tert-butylate In ISOPROPYLAMIDE at 20 - 30℃; Stage #2: 2-Bromo-4'-(bromomethyl)biphenyl In ISOPROPYLAMIDE at 5 - 10℃;	75.4%

4'-chloromethylbiphenyl-2-carboxylic acid methyl ester + 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole (152628-02-9) → telmisatran (144701-48-4)

Conditions	Yield
Stage #1: 2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole With potassium hydroxide In acetonitrile for 0.166667h; Stage #2: 4'-chloromethylbiphenyl-2-carboxylic acid methyl ester In acetonitrile Stage #3: With hydrogenchloride In water	75.1%

Upstream product

• 25148-68-9 N-methylbenzene-1,2-diamine dihydrochloride 
• 152628-03-0 4-methyl-2-n-propyl-1H-benzimidazole-6-carboxylic acid 
• 18595-14-7 methyl 4-amino-3-methylbenzoate 
• 81684-80-2 N¹-methylbenzene-1,2-diamine hydrochloride 
• 1345840-21-2 2-(4-methoxy-3-methyl-5-nitrophenyl)-1-methyl-1H-benzimidazole 
• 1345840-05-2 2-methyl-4-(1-methyl-1H-benzimidazol-2-yl)-6-nitrobenzenamine 
• 123-72-8 butyraldehyde 
• 15174-69-3 4-hydroxy-3-methyl-benzaldehyde 
• 54674-91-8 4-hydroxy-3-methyl-5-nitrobenzaldehyde 
• 861792-67-8 4-methoxy-3-methyl-5-nitrobenzaldehyde 
• 95-48-7 ortho-cresol 
• 95-53-4 o-toluidine 
• 61495-04-3 2,2-dimethyl-N-(2-methylphenyl)propanamide 
• 301533-59-5 methyl 4-(n-butyrylamino)-3-methylbenzoate 

Downstream Products

• 144702-26-1 tert-butyl 4'-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylate 
• 144701-48-4 telmisatran 
• 528560-93-2 4'-[[4-methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazol-1-yl]methyl]biphenyl-2-carboxylic acid methyl ester 
• 1187523-95-0 3'-(2'-iodo-biphenyl-4-ylmethyl)-1,7'-dimethyl-2'-propyl-1H,3'H-[2,5']bibenzoimidazolyl 
• 1197049-17-4 C₂₈H₂₇BrN₄ 
• 1191259-51-4 3'-([2'-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)biphenyl-4-yl]methyl)-1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzimidazole 
• 884330-05-6 4'-(1,4'-dimethyl-2'-propyl-1H-[2,5']dibenzimidazolyl-3'-ylmethyl)biphenyl-2-carboxylic acid methyl ester hydrochloride 
• 144702-27-2 4'-[[2-n-propyl-4-methyl-6-(1-methyl-benzimidazol-2-yl)-1H-benzimidazol-1-yl]-methyl]-2-cyano-biphenyl 
• 960356-44-9 4'-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylic acid ammonium salt 
• 172525-90-5 4'-[(2-n-propyl-4-methyl-6-(1-methyl-benzimidazol-2-yl)-benzimidazol-1-yl)methyl]-biphenyl-2-carboxaldehyde 

Relevant articles and documents

Novel synthetic approach, spectroscopic characterization and theoretical studies on global and local reactive properties of a bibenzimidazolyl derivative

Benzimidazole derivatives are of interest because they can exhibit multi-drug like properties and thus finds wide applications in biomedicine. Present work describes a novel route for the synthesis of a benzimidazole derivative, 1,7′-Dimethyl-2′-propyl-1H,3′H-[2,5′]bibenzoimidazolyl (R4) by using dibutyltin dilaurate (DBTDL) as catalyst. The catalyst, DBTDL is commercial and environmentally benign. The molecular structure of R4 was confirmed by FT-IR, 1H, 13C NMR, and mass spectrometry techniques. The detailed reactivity study of R4 encompasses spectroscopic characterization and computational investigations of global and local reactive properties based on the density functional theory (DFT) and time dependent density functional theory (TD-DFT) calculations, and molecular dynamics (MD) and molecular docking (MDoc) simulations. Global reactive properties of the title compound have been investigated by the analysis of frontier molecular orbitals. Local reactive properties have been investigated by the analysis of quantum-molecular descriptors such as molecular electrostatic potential (MEP), average local ionization energy (ALIE) surfaces, and Fukui functions. Bond dissociation energies (BDE) have been calculated in order to determine molecule sites that could be sensitive towards the autoxidation mechanism, while the radial distribution functions have been calculated in order to determine atoms with the significant interactions with water molecules.

Compound based on benzimidazole substituted halogenated phenyl n-butylamidine and preparation method of compound

The invention relates to a compound based on benzimidazole substituted halogenated phenyl n-butylamidine as shown in a formula II and a preparation method thereof. According to the method disclosed by the invention, nitrification and polyphosphoric acid cyclization reactions are avoided, and the generation of a large amount of waste acid reaction liquid is avoided from the source.

Synthetic method 2 - n-propyl -4 - methyl -6 - (1 -methylbenzimidazole -2 -yl) benzimidazole (by machine translation)

The invention relates to the technical field of synthesis of medical intermediates, and discloses a synthesis method of 2 - n-propyl -4 - methyl -6 - (1 -methylbenzimidazole -2 -yl) benzimidazole; S1: a condensation closed loop is obtained; and the reaction temperature is controlled to 3 - and the intermediate IV is N - [-4 - methyl -5 - (40 - 110 °C-methylbenzimidazole) 2 -nitrophenyl]-butylamide; S2: a reduction ring; and the preparation method comprises the following steps: S3: condensation ring-ring synthesis and intermediate IV of -4 -propyl -4 - 1 -6 - methyl 1 - S4 -2 - (-6 -methylbenzimidazol 2 -yl) benzimidazole -2 . 2 - N-propyl -4 - methyl -6 - (1 -methylbenzimidazole -2 -yl) benzimidazole is higher in purity, reduced in impurities and high in yield. (by machine translation)