3273-68-5

Basic information

• Product Name: 1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO
• Synonyms: Buzolic acid, >=95%;1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO;4-(2-OXO-2,3-DIHYDROBENZOIMIDAZOL-1-YL)BUTYRIC ACID;4-(2-oxo-2,3-dihydro-1H-1,3-benzimidazol-1-yl)butanoic acid;4-2-oxo-2,3-hihydro-1H-benzimidazol-1-yl)butanoic acid;2-Oxo-1-benzimidazolinebutyric Acid;2-Oxo-;(2-Oxo-3H-benziMidazol-1-...
• CAS NO: 3273-68-5
• Molecular Formula: C₁₁H₁₂N₂O₃
• Molecular Weight: 220.22
• Product Categories: Aliphatics;Aromatics;Heterocycles
• Mol File: 3273-68-5.mol
• Article Data: 8

Chemical Properties

• Melting Point: 175-176℃
• Boiling Point: 422.74℃[at 101 325 Pa]
• Appearance: White solid
• Density: 1.316
• Refractive Index: 1.589
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Ethyl Acetate (Very Slightly, Heated), Methanol (Slightly)
• PKA: 4.75±0.10(Predicted)
• CAS DataBase Reference: 1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO(CAS DataBase Reference)
• NIST Chemistry Reference: 1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO(3273-68-5)
• EPA Substance Registry System: 1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO(3273-68-5)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 3273-68-5(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 3273-68-5 differently. You can refer to the following data:
1. 2-Oxo-1-benzimidazolinebutyric Acid is a compound useful in organic synthesis.
2. 2-Oxo-1-benzimidazolinebutyric Acid (cas# 3273-68-5) is a compound useful in organic synthesis.

Chemical Properties

White Solid

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 
• 52099-72-6 1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one 
• 3153-37-5 methyl 4-chlorobutyrate 
• 116199-87-2 ethyl 2,3-dihydro-3-(1-methyl-ethenyl)-2-oxo-1H-benzimidazol-1-butanoate 
• 95-54-5 1,2-diamino-benzene 
• 52099-78-2 4-(3-isopropenyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-butyric acid 

Downstream Products

• 1021910-71-3 6-amino-7-hydroxy-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one hydrochloride 

Relevant articles and documents

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.

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.