3273-68-5

Usage

Uses

Used in Organic Synthesis:
1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO is used as a synthetic building block for the creation of various organic compounds. Its application in organic synthesis is due to its unique chemical structure, which allows for the formation of new molecules with potential applications in different industries.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO is used as a key intermediate in the synthesis of drugs targeting specific medical conditions. Its role in drug development is attributed to its ability to form complex molecular structures that can interact with biological targets, potentially leading to the development of new therapeutic agents.
Used in Chemical Research:
1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO is also utilized in chemical research to study the properties and reactivity of benzimidazole-based compounds. This research can contribute to the understanding of their potential applications in various fields, including materials science, agrochemistry, and environmental science.

InChI:InChI=1/C11H12N2O3/c14-10(15)6-3-7-13-9-5-2-1-4-8(9)12-11(13)16/h1-2,4-5H,3,6-7H2,(H,12,16)(H,14,15)

Synthetic route

4-(3-isopropenyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-butyric acid (52099-78-2) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
With hydrogenchloride In water at 100℃; for 6h;	100%
With hydrogenchloride In 1,2-dimethoxyethane	96%
With hydrogenchloride In tetrahydrofuran; water for 2h;
With hydrogenchloride; water In tetrahydrofuran for 2h;

1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one (52099-72-6) + methyl 4-chlorobutyrate (3153-37-5) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
Stage #1: 1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one; methyl 4-chlorobutyrate With tetrabutylammomium bromide; potassium carbonate; potassium iodide In dimethyl sulfoxide at 110 - 115℃; Stage #2: With water; sodium hydroxide at 95 - 100℃; for 6h; Stage #3: With hydrogenchloride In water at 80 - 85℃;	95%

4-butanolide (96-48-0) + sodium salt of N-isopropenylbenzimidazolin-2-one (84461-86-9) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
In N,N-dimethyl-formamide at 160 - 170℃; for 2h;	30%

sodium salt of N-isopropenylbenzimidazolin-2-one (84461-86-9) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2) 4 N hydrochloric acid / 1) DMF, 150 deg C to 160 deg C, 2 h, 2) water 2: 100 percent / 4 N HCl / H2O / 6 h / 100 °C View Scheme

ethyl 2,3-dihydro-2-oxo-1H-benzimidazol-1-butanoate → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
With sodium hydroxide In methanol; water

1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one (52099-72-6) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium carbonate / acetone / 18 h / Heating / reflux 2.1: sodium hydroxide; water / tetrahydrofuran / 20 °C / Heating / reflux 2.2: 0.5 h / 2 °C 3.1: hydrogenchloride; water / tetrahydrofuran / 2 h View Scheme

1,2-diamino-benzene (95-54-5) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / xylene / 60.5 h / 120 - 150 °C 2.1: potassium carbonate / acetone / 18 h / Heating / reflux 3.1: sodium hydroxide; water / tetrahydrofuran / 20 °C / Heating / reflux 3.2: 0.5 h / 2 °C 4.1: hydrogenchloride; water / tetrahydrofuran / 2 h View Scheme

ethyl 2,3-dihydro-3-(1-methyl-ethenyl)-2-oxo-1H-benzimidazol-1-butanoate (116199-87-2) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide; water / tetrahydrofuran / 20 °C / Heating / reflux 1.2: 0.5 h / 2 °C 2.1: hydrogenchloride; water / tetrahydrofuran / 2 h View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → 5,6-dihydroimidazo[4,5,1-jk][1]benzazepin-2,7-[1H,4H]-dione (92260-81-6)

Conditions	Yield
With aluminium trichloride; thionyl chloride 2.) 1,2-dichloroethane; Yield given. Multistep reaction;
Multi-step reaction with 2 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 10 - 20 °C / Industry scale; Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 58 - 60 °C / 2025.2 Torr / Industry scale 2.2: 5 - 20 °C / Industry scale View Scheme
Stage #1: 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid With thionyl chloride In dichloromethane at 20℃; for 2h; Stage #2: With aluminum (III) chloride In dichloromethane at 20℃; Heating / reflux;

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → chloro 2,3-dihydro-2-oxo-1H-benzimidazol-1-butanoate (1021910-67-7)

Conditions	Yield
With thionyl chloride In dichloromethane at 20 - 25℃; for 2h;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 10 - 20℃; for 2 - 6h; Product distribution / selectivity;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 10 - 20℃; Industry scale; Inert atmosphere;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 10 - 20℃; Industry scale; Inert atmosphere;

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → 4,5,6,7-tetrahydro-6-hydroxyimino-imidazo[4,5,1-jk]-[1]-benzazepine-2,7(1H,6H)-dione (92260-82-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 10 - 20 °C / Industry scale; Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 58 - 60 °C / 2025.2 Torr / Industry scale 2.2: 5 - 20 °C / Industry scale 3.1: hydrogenchloride; sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 48 - 65 °C / Industry scale View Scheme
Multi-step reaction with 2 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → trans-7-amino-6-hydroxy-6,7,8,9-tetrahydro-2H-2,9a-diazabenzo[cd]azulen-1-one potassium salt

Conditions

Yield

Multi-step reaction with 4 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 10 - 20 °C / Industry scale; Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 58 - 60 °C / 2025.2 Torr / Industry scale 2.2: 5 - 20 °C / Industry scale 3.1: hydrogenchloride; sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 48 - 65 °C / Industry scale 4.1: potassium hydroxide / water / 40 °C / Industry scale; Inert atmosphere 4.2: 40 °C / 6000.6 Torr / Industry scale View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → trans-7-[isopropylimino]-6-hydroxy-6,7,8,9-tetrahydro-2H-2,9a-diazabenzo[cd]azulen-1-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 10 - 20 °C / Industry scale; Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 58 - 60 °C / 2025.2 Torr / Industry scale 2.2: 5 - 20 °C / Industry scale 3.1: hydrogenchloride; sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 48 - 65 °C / Industry scale 4.1: potassium hydroxide / water / 40 °C / Industry scale; Inert atmosphere 4.2: 40 °C / 6000.6 Torr / Industry scale 5.1: acetic acid / water / 15 - 30 °C / pH 7.5 / Industry scale View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → trans-4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methylethyl)amino]imidazo[4,5,1-jk][1]benzazepin-2(1H)-one acetate

Conditions

Yield

Multi-step reaction with 6 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 10 - 20 °C / Industry scale; Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 58 - 60 °C / 2025.2 Torr / Industry scale 2.2: 5 - 20 °C / Industry scale 3.1: hydrogenchloride; sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 48 - 65 °C / Industry scale 4.1: potassium hydroxide / water / 40 °C / Industry scale; Inert atmosphere 4.2: 40 °C / 6000.6 Torr / Industry scale 5.1: acetic acid / water / 15 - 30 °C / pH 7.5 / Industry scale 6.1: hydrogen / 5%-palladium/activated carbon / water / 2.5 h / 15 - 70 °C / 6000.6 Torr / Industry scale 6.2: 30 - 70 °C / pH 6.8 / Industry scale View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → trans-(+/-)-4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methylethyl)amino]-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 7 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 10 - 20 °C / Industry scale; Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 58 - 60 °C / 2025.2 Torr / Industry scale 2.2: 5 - 20 °C / Industry scale 3.1: hydrogenchloride; sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 48 - 65 °C / Industry scale 4.1: potassium hydroxide / water / 40 °C / Industry scale; Inert atmosphere 4.2: 40 °C / 6000.6 Torr / Industry scale 5.1: acetic acid / water / 15 - 30 °C / pH 7.5 / Industry scale 6.1: hydrogen / 5%-palladium/activated carbon / water / 2.5 h / 15 - 70 °C / 6000.6 Torr / Industry scale 6.2: 30 - 70 °C / pH 6.8 / Industry scale 7.1: sodium hydroxide / water / 50 °C / pH 11 / Industry scale; Inert atmosphere View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → trans-(+/-)-4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methylethyl)amino]-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one hydrochloride

Conditions

Yield

Multi-step reaction with 8 steps 1.1: oxalyl dichloride / N,N-dimethyl-formamide / dichloromethane / 10 - 20 °C / Industry scale; Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 58 - 60 °C / 2025.2 Torr / Industry scale 2.2: 5 - 20 °C / Industry scale 3.1: hydrogenchloride; sodium nitrite / N,N-dimethyl-formamide / 1.5 h / 48 - 65 °C / Industry scale 4.1: potassium hydroxide / water / 40 °C / Industry scale; Inert atmosphere 4.2: 40 °C / 6000.6 Torr / Industry scale 5.1: acetic acid / water / 15 - 30 °C / pH 7.5 / Industry scale 6.1: hydrogen / 5%-palladium/activated carbon / water / 2.5 h / 15 - 70 °C / 6000.6 Torr / Industry scale 6.2: 30 - 70 °C / pH 6.8 / Industry scale 7.1: sodium hydroxide / water / 50 °C / pH 11 / Industry scale; Inert atmosphere 8.1: hydrogenchloride / water / 10 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-7-hydroxy-6-[((S)-1-methyl-3-phenylpropyl)amino]-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-7-hydroxy-6-[((R)-1-methyl-3-phenylpropyl)amino]-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: methanol / 20 - 80 °C / Microwave irradiation 5.3: Amberlyst.(R). 15 ion-exchange resin View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (E)-(6R,7R)-6-{[(R)-3-(2-fluorophenyl)-1-methylprop-2-en-1-yl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-(E)-6-{[(S)-3-(2-fluorophenyl)-1-methylprop-2-en-1-yl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (E)-(6S,7S)-6-{[(R)-3-(2-fluorophenyl)-1-methylprop-2-en-1-yl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (E)-(6S,7S)-6-{[(S)-3-(2-fluorophenyl)-1-methylprop-2-en-1-yl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h / 20 °C 5.2: 72 h View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6S,7S)-7-hydroxy-6-{[(R)-3-(4-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-7-hydroxy-6-{[(S)-3-(4-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-7-hydroxy-6-{[(R)-3-(4-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-7-hydroxy-6-{[(S)-3-(4-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 60 h / 20 °C 5.2: 18 h / 0 - 20 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-6-{[(R)-3-(4-aminophenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions	Yield
Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogen / di-μ-chlorobis(norbornadiene)dirhodium(I) / methanol; water / 16 h / 80 °C / 15001.5 Torr 4.1: triethylamine / methanol / 0.33 h 4.2: 120 h / 60 °C 5.1: hydrogen / palladium 10% on activated carbon / methanol / 55 °C / 760.05 Torr View Scheme
Multi-step reaction with 9 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h 6.1: diethylamine / isopropyl alcohol / Heating / reflux; Sonication 7.1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C 8.1: triethylamine / methanol / 0.33 h 8.2: 120 h / 60 °C 9.1: hydrogen / palladium 10% on activated carbon / methanol / 55 °C / 760.05 Torr View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6S,7S)-7-hydroxy-6-{[(S)-3-(2-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one (1019769-22-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 0.33 h 5.2: 40 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: potassium hydroxide / methanol / 0.33 h 5.2: 60 h / 60 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-7-hydroxy-6-{[(R)-3-(2-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one (1019768-88-7) + (6R,7R)-7-hydroxy-6-{[(S)-3-(2-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + 7-hydroxy-6-{[3-(2-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions	Yield
Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 0.33 h 5.2: 40 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: potassium hydroxide / methanol / 0.33 h 5.2: 60 h / 60 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-7-hydroxy-6-{[(R)-3-(2-hydroxyphenyl)-1,3-dimethylbutyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-7-hydroxy-6-{[(S)-3-(2-hydroxyphenyl)-1,3-dimethylbutyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-7-hydroxy-6-{[(R)-3-(2-hydroxyphenyl)-1,3-dimethylbutyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-7-hydroxy-6-{[(S)-3-(2-hydroxyphenyl)-1,3-dimethylbutyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h / 20 °C 5.2: 108 h / 20 - 60 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6S,7S)-7-hydroxy-6-({(R)-3-[3-(hydroxymethyl)phenyl]-1-methylpropyl}amino)-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-7-hydroxy-6-({(S)-3-[3-(hydroxymethyl)phenyl]-1-methylpropyl}amino)-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-7-hydroxy-6-({(R)-3-[3-(hydroxymethyl)phenyl]-1-methylpropyl}amino)-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-7-hydroxy-6-({(S)-3-[3-(hydroxymethyl)phenyl]-1-methylpropyl}amino)-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 6 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 18 h / 20 °C 5.2: 1 h / 20 °C 5.3: Amberlyst.(R). 15 ion-exchange resin 6.1: hydrogen / platinum(IV) oxide / water; isopropyl alcohol / 0.5 h / 3102.97 Torr View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-6-{[(R)-3-(5-fluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-{[(S)-3-(5-fluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(R)-3-(5-fluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(S)-3-(5-fluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 0.5 h / 50 °C 5.2: 18 h / 50 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-7-hydroxy-6-{[(R)-3-(2-hydroxy-3-methoxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-7-hydroxy-6-{[(S)-3-(2-hydroxy-3-methoxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-7-hydroxy-6-{[(R)-3-(2-hydroxy-3-methoxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-7-hydroxy-6-{[(S)-3-(2-hydroxy-3-methoxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h 5.2: 18 h / 20 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6S,7S)-6-{[(R)-3-(3-chloro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(S)-3-(3-chloro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-{[3-(3-chloro-2-hydroxyphenyl)-(1R)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-{[(S)-3-(3-chloro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h / 20 °C 5.2: 120 h / 20 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6S,7S)-6-{[(R)-3-(2,3-dihydro-1-benzofuran-5-yl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(S)-3-(2,3-dihydro-1-benzofuran-5-yl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-{[(R)-3-(2,3-dihydro-1-benzofuran-5-yl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-{[(S)-3-(2,3-dihydro-1-benzofuran-5-yl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h / 20 °C 5.2: 60 h / 20 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6S,7S)-6-({(R)-3-[4-(cyclopropylmethoxy)phenyl]-1-methylpropyl}amino)-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-({(S)-3-[4-(cyclopropylmethoxy)phenyl]-1-methylpropyl}amino)-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-({(R)-3-[4-(cyclopropylmethoxy)phenyl]-1-methylpropyl}amino)-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-({(S)-3-[4-(cyclopropylmethoxy)phenyl]-1-methylpropyl}amino)-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: potassium hydroxide / methanol 5.2: 48.5 h / 0 - 20 °C 5.3: Amberlyst.(R). 15 ion-exchange resin View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-6-{[(R)-3-(3,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-{[(S)-3-(3,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(R)-3-(3,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(S)-3-(3,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 0.42 h 5.2: 80 h / 50 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-6-{[(R)-3-(4,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6R,7R)-6-{[(S)-3-(4,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(R)-3-(4,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one + (6S,7S)-6-{[(S)-3-(4,5-difluoro-2-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

Yield

Multi-step reaction with 5 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h / 45 °C 5.2: 120 h / 45 °C View Scheme

4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5) → (6R,7R)-6-{[3-(2-chloro-3-hydroxyphenyl)-1-methylpropyl]amino}-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogen / di-μ-chlorobis(norbornadiene)dirhodium(I) / methanol; water / 16 h / 80 °C / 15001.5 Torr 4.1: triethylamine / methanol / 0.33 h 4.2: 18 h / 60 °C View Scheme
Multi-step reaction with 8 steps 1.1: thionyl chloride / dichloromethane / 2 h / 20 °C 1.2: 20 °C / Heating / reflux 2.1: hydrogenchloride; t-butylnitrite; acetic acid / 1,4-dioxane / 3 h / 20 °C 3.1: hydrogenchloride; hydrogen / palladium 10% on activated carbon / methanol / 3 h / 20 °C / 1137.76 Torr 4.1: sodium tetrahydroborate / methanol / 18.5 h / 0 - 20 °C 5.1: triethylamine / methanol / 1 h 6.1: diethylamine / isopropyl alcohol / Heating / reflux; Sonication 7.1: hydrogenchloride / 1,4-dioxane / 1 h / 20 °C 8.1: triethylamine / methanol / 0.33 h 8.2: 18 h / 60 °C View Scheme

Upstream product

• 96-48-0 4-butanolide 
• 84461-86-9 sodium salt of N-isopropenylbenzimidazolin-2-one 
• 52099-78-2 4-(3-isopropenyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-butyric acid 
• 95-54-5 1,2-diamino-benzene 
• 116199-87-2 ethyl 2,3-dihydro-3-(1-methyl-ethenyl)-2-oxo-1H-benzimidazol-1-butanoate 
• 52099-72-6 1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one 
• 3153-37-5 methyl 4-chlorobutyrate 

Downstream Products

• 92260-81-6 5,6-dihydroimidazo[4,5,1-jk][1]benzazepin-2,7-[1H,4H]-dione 
• 92260-82-7 4,5,6,7-tetrahydro-6-hydroxyimino-imidazo[4,5,1-jk]-[1]-benzazepine-2,7(1H,6H)-dione 
• 119520-06-8 trans-(+/-)-4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methylethyl)amino]-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one hydrochloride 
• 1021910-71-3 6-amino-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one hydrochloride 

Relevant academic research and scientific papers

A SEARCH FOR PESTICIDES IN THE N,N'-DI(CARBOXYPROPYL)-BENZIMIDAZOLIN-2-ONE SERIES

The reaction of benzimidazolin-2-ones with γ-butyrolactone has given N-mono- and N,N'-dicarboxypropylbenzimidazolin-2-ones.It has been shown that the yields and structures of the compounds synthesized depend on the nature of the substituent in the benzene nucleus of the benzimidazolin-2-ones.

Method for preparing 2, 3-dihydro-2-oxo-1H-benzimidazole-1-butyric acid

The invention relates to a method for preparing 2, 3-dihydro-2-oxo-1H-benzimidazole-1-butyric acid, which comprises the following steps of: dehydrating 1, 3-dihydro-1-(1-methylvinyl)-2H-benzimidazole-2-one in an organic solvent at 100-120 DEG C under the action of an acid-binding agent, adding ethyl 4-bromobutyrate for reaction after dehydration, cooling the reaction liquid to 70-90 DEG C after the reaction is finished, adding water preheated to 40-60 DEG C, stirring and splitting phases at proper time; and adding alkali into an organic phase, carrying out saponification reaction under the environment of 45-80 DEG C and 150-200 mbar, slowly adding hydrochloric acid at the temperature of 40-60 DEG C after the saponification reaction is finished, then reacting for 2-4 hours at the temperature of 90-110 DEG C, cooling, filtering, washing a filter cake with water, and drying the filter cake to constant weight at 50-70 DEG C and 100-180 mbar. Potassium carbonate is used to replace sodium hydride, so that the problems of high potential safety hazard, serious three-waste pollution and the like in the traditional process are fundamentally eliminated, the production process is simpler and more convenient by frying in one pot, and the production cost is reduced; and meanwhile, the method is simple, convenient and safe to operate, reasonable in process condition, high in reaction yield and relatively high in implementation value.

ONE POT SYNTHESIS OF 4-(1,2-DIHYDRO-2-OXOBENZO[D]IMIDAZOL-3-YL)BUTANOIC ACID, A KEY INTERMEDIATE OF ZILPATEROL

The present invention relates to one pot process for the preparation of 4-(1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)butanoic acid of Formula- I, which is a key intermediate and its use in the preparation of Zilpaterol, which comprises condensation of methyl-4-chloro butyrate with 1-(prop-1-en-2-yl)-1H-benzo[d]imidazol-2(3H)-one in presence of a base and suitable solvent to give corresponding ester derivative, further hydrolyzation and acidification in presence of inorganic solvent to obtain Formula- I.

BENZAZEPIN-2(1H)-ONE DERIVATIVES

Compounds of formula (I) and pharmaceutically acceptable salts thereof are agonists at the beta-2 adrenoceptor. They are useful as feed additives for livestock animals.

HETEROCYCLIC COMPOUNDS USEFUL AS ANABOLIC AGENTS FOR LIVESTOCK ANIMALS

Compounds of formula (I) and pharmaceutically acceptable salts thereof are agonists at the beta-2 adrenoceptor. They are useful as feed additives for livestock animals.

Synthesis of imidazobenzazepinthiones: A new series of HIV-1 reverse transcriptase inhibitors

A general route to a series of novel imidazobenzazepines that are 'carba' analogs of the TIBO class of non-nucleoside HIV-1 reverse transcriptase inhibitors has been developed. A pair of allyl side-chain containing compounds were found to have significant HIV-1 inhibitory activity.

Novel 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-j-k][1]-benzazepin-2-(1H)-one

Novel 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][1]-benzazepin-2-(1H)-one derivatives of the formula STR1 wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms optionally substituted with a hydroxyl, aryl and aryloxy of 6 to 10 carbon atoms, cycloalkyl of 3 to 7 carbon atoms optionally interrupted with a heteroatom optionally substituted with alkyl of 1 to 4 carbon atoms and the wavy lines indicates that the 7-OH and 6-amino have the trans configuration and their non-toxic, pharmaceutically acceptable acid addition salts having remarkable anti-hypertensive and hypotensive activity and vasodilatatory activity and their preparation.

SYNTHESIS OF N-CARBOXYALKYLBENZIMIDAZOLIN-2-ONES

The corresponding N-mono and N,N'-dicarboxyalkylbenzimidazolin-2-ones were prepared by the reaction of the sodium salts of benzimidazolin-2-one and its 1,5,6-substituted derivatives with chloroacetic acid, acrylonitrile. and γ-butyrolactone.