4-(2-Oxo-2,3-dihydro-1H-benzimidazol-1-yl)butanoic acid supplier

Name
1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO
EINECS
CAS No. 3273-68-5
Article Data8
CAS DataBase
Density 1.316 g/cm³
Solubility
Melting Point 175-176℃
Formula C₁₁H₁₂N₂O₃
Boiling Point 422.74℃[at 101 325 Pa]
Molecular Weight 220.228
Flash Point
Transport Information
Appearance White solid
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms 1-Benzimidazolinebutyricacid, 2-oxo- (7CI,8CI);
PSA 75.09000
LogP 1.19440

Synthetic route

: 52099-78-2
4-(3-isopropenyl-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-butyric acid

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

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;

: 52099-72-6
1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one

: 3153-37-5
methyl 4-chlorobutyrate

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

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%

: 96-48-0
4-butanolide

: 84461-86-9
sodium salt of N-isopropenylbenzimidazolin-2-one

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

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

: 84461-86-9
sodium salt of N-isopropenylbenzimidazolin-2-one

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

Conditions	Yield
With sodium hydroxide In methanol; water

: 52099-72-6
1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

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

: 95-54-5
1,2-diamino-benzene

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

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

: 116199-87-2
ethyl 2,3-dihydro-3-(1-methyl-ethenyl)-2-oxo-1H-benzimidazol-1-butanoate

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

Conditions

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: 92260-81-6
5,6-dihydroimidazo[4,5,1-jk][1]benzazepin-2,7-[1H,4H]-dione

Conditions

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;

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: 1021910-67-7
chloro 2,3-dihydro-2-oxo-1H-benzimidazol-1-butanoate

Conditions

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;

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: 92260-82-7
4,5,6,7-tetrahydro-6-hydroxyimino-imidazo[4,5,1-jk]-[1]-benzazepine-2,7(1H,6H)-dione

Conditions

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: trans-7-amino-6-hydroxy-6,7,8,9-tetrahydro-2H-2,9a-diazabenzo[cd]azulen-1-one potassium salt

Conditions

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: trans-7-[isopropylimino]-6-hydroxy-6,7,8,9-tetrahydro-2H-2,9a-diazabenzo[cd]azulen-1-one

Conditions

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: trans-4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methylethyl)amino]imidazo[4,5,1-jk][1]benzazepin-2(1H)-one acetate

Conditions

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: trans-(+/-)-4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methylethyl)amino]-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: trans-(+/-)-4,5,6,7-tetrahydro-7-hydroxy-6-[(1-methylethyl)amino]-imidazo[4,5,1-jk][1]benzazepin-2(1H)-one hydrochloride

Conditions

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: (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

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: 1019769-22-2
(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

Conditions

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

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

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: 1019768-88-7
(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

B: (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

C: 7-hydroxy-6-{[3-(2-hydroxyphenyl)-1-methylpropyl]amino}-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1]benzazepin-2(1H)-one

Conditions

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

A: (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

B: (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

C: (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

D: (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

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

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

...Expand

: 3273-68-5
4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid

: (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

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

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

4-(2-Oxo-2,3-dihydro-1H-benzimidazol-1-yl)butanoic acid Specification

The CAS register number of 1H-Benzimidazole-1-butanoicacid, 2,3-dihydro-2-oxo- is 3273-68-5. The systematic name about this chemical is 4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)butanoic acid. The molecular formula about this chemical is C₁₁H₁₂N₂O₃ and the molecular weight is 220.22.

Physical properties about 1H-Benzimidazole-1-butanoicacid, 2,3-dihydro-2-oxo- are: (1)ACD/LogP: 1.20; (2)ACD/BCF (pH 5.5): 1; (3)ACD/BCF (pH 7.4): 1; (4)ACD/KOC (pH 5.5): 9; (5)ACD/KOC (pH 7.4): 1; (6)#H bond acceptors: 5; (7)#H bond donors: 2; (8)#Freely Rotating Bonds: 4; (9)Polar Surface Area: 69.64 Å²; (10)Index of Refraction: 1.589; (11)Molar Refractivity: 56.406 cm³; (12)Molar Volume: 167.329 cm³; (13)Polarizability: 22.361x10^-24cm³; (14)Surface Tension: 54.484 dyne/cm.

You can still convert the following datas into molecular structure:
(1)SMILES: OC(=O)CCCN1c2ccccc2NC1=O
(2)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)
(3)InChIKey: PTNUQSFEJXMNOQ-UHFFFAOYAO
(4)Std. InChI: InChI=1S/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)
(5)Std. InChIKey: PTNUQSFEJXMNOQ-UHFFFAOYSA-N

Product Name

1H-BENZIMIDAZOLE-1-BUTANOIC ACID, 2,3-DIHYDRO-2-OXO

Synthetic route

4-(2-Oxo-2,3-dihydro-1H-benzimidazol-1-yl)butanoic acid Specification

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