53786-28-0

Basic information

• Product Name: 5-Chloro-1-(4-piperidyl)-2-benzimidazolinone
• Synonyms: 1-(4-PIPERIDINYL)-1,3-DIHYDRO-5-CHLOROBENZIMIDAZOLONE;5-Chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one;5-CHLORO-1-(4-PIPERIDINYL)-1,3-DIHYDRO-2H-BENZIMIDAZOL-2-ONE;5-CHLORO-1-(4-PIPERIDINYL)-2-BENZIMIDAZOLIDINONE;5-CHLORO-1-(4-PIPERIDINYL)-2-BENZIMIDAZOLINONE;5-CHLORO-1-(4-PIPERIDYL)-2-BENZIMIDAZOLINONE;5-CHLORO-1-DIHYDRO-1-(4-PIPERIDINYL)-2H-BENZOMIDEZOLE-2-ONE;5-CHLORO-1-PIPERIDIN-4-YL-1,3-DIHYDRO-BENZOIMIDAZOL-2-ONE
• CAS NO: 53786-28-0
• Molecular Formula: C₁₂H₁₄ClN₃O
• Molecular Weight: 251.71
• EINECS: 258-771-6
• Product Categories: Benzimidazoles;BenzimidazolesHeterocyclic Building Blocks;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Aromatics, Heterocycles, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 53786-28-0.mol
• Article Data: 7

Chemical Properties

• Melting Point: 228-231 °C(lit.)
• Appearance: /
• Density: 1.323 g/cm³
• Vapor Pressure: 0Pa at 20℃
• Refractive Index: 1.605
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 11.12±0.30(Predicted)
• Water Solubility: 549mg/L at 20℃
• CAS DataBase Reference: 5-Chloro-1-(4-piperidyl)-2-benzimidazolinone(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Chloro-1-(4-piperidyl)-2-benzimidazolinone(53786-28-0)
• EPA Substance Registry System: 5-Chloro-1-(4-piperidyl)-2-benzimidazolinone(53786-28-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 53786-28-0(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 53786-28-0 differently. You can refer to the following data:
1. 5-Chloro-1-(4-piperidyl)-2-benzimidazolinone is a metabolite of the gastrokinetic and antinauseant drug Domperidone (D531100).
2. 5-Chloro-1-(4-piperidinyl)-2-benzimidazolidinone (Domperidone EP Impurity A) is a metabolite of the gastrokinetic and antinauseant drug Domperidone (D531100).

General Description

5-Chloro-1-(4-piperidyl)-2-benzimidazolinone is a 2-benzimidazolone derivative. It exhibits anti-nauseant properties.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C12H14ClN3O/c13-8-1-2-11-10(7-8)15-12(17)16(11)9-3-5-14-6-4-9/h1-2,7,9,14H,3-6H2,(H,15,17)

Synthetic route

4-(5-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester (53786-46-2) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
With sodium hydroxide for 8h; Heating;	96%
With sodium hydroxide at 100℃;
With ammonium chloride In water

ethyl 4-aminopiperidine-1-carboxylate (58859-46-4) + 2-phenylethyl halide → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: Na2CO3; KI / cyclohexanol / 0.17 h / 180 °C / microwave irradiation 2: Zn; aq. HCl / methanol / 50 °C 3: acetonitrile 4: aq. NaOH / 100 °C View Scheme

ethyl 4-[(2-amino-4-chlorophenyl)amino]piperidine-1-carboxylate (53786-45-1) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile 2: aq. NaOH / 100 °C View Scheme
Multi-step reaction with 2 steps 1: 90 percent / Et3N / CH2Cl2 / 0.5 h / 0 °C 2: 96 percent / 10percent NaOH / 8 h / Heating View Scheme

4-(4-chloro-2-nitro-anilino)-piperidine-1-carboxylic acid ethyl ester (53786-44-0) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: Zn; aq. HCl / methanol / 50 °C 2: acetonitrile 3: aq. NaOH / 100 °C View Scheme
Multi-step reaction with 3 steps 1: 93 percent / H2 / Raney Ni / ethanol; tetrahydrofuran / 1 h / Ambient temperature 2: 90 percent / Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 96 percent / 10percent NaOH / 8 h / Heating View Scheme

ethyl 4-aminopiperidine-1-carboxylate (58859-46-4) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 65 percent / Na2CO3, KI / various solvent(s) / 28 h / 160 °C 2: 93 percent / H2 / Raney Ni / ethanol; tetrahydrofuran / 1 h / Ambient temperature 3: 90 percent / Et3N / CH2Cl2 / 0.5 h / 0 °C 4: 96 percent / 10percent NaOH / 8 h / Heating View Scheme

2,5-dichloronitrobenzene (89-61-2) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 65 percent / Na2CO3, KI / various solvent(s) / 28 h / 160 °C 2: 93 percent / H2 / Raney Ni / ethanol; tetrahydrofuran / 1 h / Ambient temperature 3: 90 percent / Et3N / CH2Cl2 / 0.5 h / 0 °C 4: 96 percent / 10percent NaOH / 8 h / Heating View Scheme

1-(tert-butoxycarbonyl)-4-aminopiperidine (87120-72-7) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium carbonate / dimethyl sulfoxide / 20 °C / Inert atmosphere 2: hydrazine hydrate / water; ethanol / 0.17 h / 45 °C 3: tetrahydrofuran / 20 °C / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

2-fluoro-5-chloronitrobenzene (345-18-6) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium carbonate / dimethyl sulfoxide / 20 °C / Inert atmosphere 2: hydrazine hydrate / water; ethanol / 0.17 h / 45 °C 3: tetrahydrofuran / 20 °C / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

tert-butyl 4-((4-chloro-2-nitrophenyl)amino)piperidine-1-carboxylate (460047-89-6) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrazine hydrate / water; ethanol / 0.17 h / 45 °C 2: tetrahydrofuran / 20 °C / Inert atmosphere 3: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

tert-butyl 4-((2-amino-4-chlorophenyl)amino)piperidine-1-carboxylate (1429415-80-4) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

tert-butyl 4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)piperidine-1-carboxylate (460047-90-9) → 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃;

5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 5-chloro-6-nitro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

Conditions	Yield
With nitric acid In o-xylene at 60℃;	95%
With nitric acid In 1,2-dichloro-benzene at 60℃; for 2h;	64%
With nitric acid In 1,2-dichloro-benzene at 20 - 60℃; for 2h;	64%
With nitric acid In o-xylene at 60℃; for 2h;

7-chloro-1-(2,4-difluorophenyl)-1,4-dihydro-8-methyl-6-nitro-4-oxoquinolone-3-carboxylic acid (1146300-32-4) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 7-(4-(6-chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)piperidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid (1146300-60-8)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide Microwave irradiation;	91%

1-tert-butyl-7-chloro-1-1,4-dihydro-8-methyl-6-nitro-4-oxoquinolone-3-carboxylic acid (1146300-33-5) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 1-tert-butyl-7-(4-(6-chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)piperidin-1-yl)-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid (1146300-77-7)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide Microwave irradiation;	89%

2-thiophenylcarboxylic acid (527-72-0) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 5-chloro-1-(1-(thiophene-2-carbonyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one

Conditions	Yield
With pyridine; 1,3,5-trichloro-2,4,6-triazine In acetonitrile at 140℃; for 0.0833333h; Microwave irradiation;	89%

5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxylic acid (40133-08-2) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 5-chloro-1-(1-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carbonyl) piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one

Conditions	Yield
With pyridine; 1,3,5-trichloro-2,4,6-triazine In acetonitrile at 140℃; for 0.0833333h; Microwave irradiation;	85%

7-chloro-1-cyclopropyl-1,4-dihydro-8-methyl-6-nitro-4-oxoquinolone-3-carboxylic acid (1146300-31-3) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 7-(4-(6-chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)piperidin-1-yl)-1-cyclopropyl-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid (1146300-43-7)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide Microwave irradiation;	82%

1-(4-fluorophenyl)-1,4-dihydro-7-methoxy-6-nitro-4-oxo-1,8-naphthyridine-3-carboxylic acid (960313-86-4) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C27H20ClFN6O6

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide microwave irradiation;	78%

(S)-9,10-difluoro-3-methyl-8-nitro-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid (236743-93-4) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C25H21ClFN5O7

Conditions	Yield
In dimethyl sulfoxide microwave irradiation;	78%

1-cyclopropyl-6,7-difluoro-1,4-dihydro-5-nitro-8-methoxy-4-oxoquinoline-3-carboxylic acid (112811-77-5) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C26H23ClFN5O7 (1018937-91-1)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide for 0.0333333h; microwave irradiation;	78%

7-chloro-1-(4-fluorophenyl)-1,4-dihydro-6-nitro-4-oxoquinoline-3-carboxylic acid (368839-20-7) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 7-(4-(6-chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)piperidin-1-yl)-1-(4-fluorophenyl)-1,4-dihydro-6-nitro-4-oxoquinoline-3-carboxylic acid (1119087-61-4)

Conditions	Yield
In dimethyl sulfoxide Microwave irradiation;	78%

5-chloro-2,2-diphenylpentanenitrile (1585-11-1) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 5-[4-(5-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidin-1-yl]-2,2-diphenyl-pentanenitrile

Conditions	Yield
With sodium carbonate; sodium iodide In acetonitrile at 160℃; under 12901 Torr; for 0.25h; microwave irradiation;	76%

1-cyclopropyl-1,4-dihydro-7-methoxy-6-nitro-4-oxo-1,8-naphthyridine-3-carboxylic acid (960313-85-3) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C24H21ClN6O6

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide microwave irradiation;	76%

5‑bromo‑7‑methylindole (15936-81-9) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 5-chloro-1-(1-(7-methyl-1H-indol-5-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (1248590-98-8)

Conditions	Yield
With RuPhos palladacycle; lithium hexamethyldisilazane; ruphos In tetrahydrofuran at 65℃; for 4h; Inert atmosphere; Sealed vial;	76%

2-(4-bromobutyl)isoindoline-1,3-dione (5394-18-3) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 2-(4-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)butyl)isoindoline-1,3-dione

Conditions	Yield
With potassium carbonate; sodium iodide In acetonitrile Reflux;	75.2%

2-chloro-3-fluoro-5,12-dihydro-5-oxobenzothiazolo<3,2-a>quinoline-6-carboxylic acid (102614-43-7) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C28H20ClFN4O4S (1028203-07-7)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide microwave irradiation;	75%

2-chloro-3-nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid (1028202-77-8) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C28H20ClN5O6S (1028203-08-8)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide microwave irradiation;	74%

1-tert-butyl-1,4-dihydro-7-methoxy-6-nitro-4-oxo-1,8-naphthyridine-3-carboxylic acid (960313-87-5) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C25H25ClN6O6

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide microwave irradiation;	72%

1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid (112811-72-0) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C26H24ClFN4O5 (1018937-88-6)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide for 0.0333333h; microwave irradiation;	70%

7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone (129722-34-5) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 7-(4-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one (1314032-14-8)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile Reflux; Inert atmosphere;	70%

1-tert-butyl-7-chloro-1,4-dihydro-6-nitro-4-oxoquinoline-3-carboxylic acid (494204-73-8) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 1-tert-butyl-7-(4-(6-chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)piperidin-1-yl)-1,4-dihydro-6-nitro-4-oxoquinoline-3-carboxylic acid (1119088-12-8)

Conditions	Yield
In dimethyl sulfoxide Microwave irradiation;	69%

levofloxacin Q-acid (100986-89-8) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → C25H22ClFN4O5

Conditions	Yield
In dimethyl sulfoxide microwave irradiation;	67%

1-cyclopropyl-6-nitro-4-oxo-7-chloro-1,4-dihydroquinoline-3-carboxylic acid (93107-29-0) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 7-(4-(6-chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)piperidin-1-yl)-1-cyclopropyl-1,4-dihydro-6-nitro-4-oxoquinoline-3-carboxylic acid (1119087-10-3)

Conditions	Yield
In dimethyl sulfoxide Microwave irradiation;	67%

1-(3-iodopropyl)-2,3-dihydro(4,5,6,7-D4)-1H-1,3-benzodiazol-2-one + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 1-{3-[4-(5-chloro-2-oxo-2,3-dihydro-1 H-1,3-benzodiazol-1-yl)piperidin-1-yl]propyl}-2,3-dihydro(4,5,6,7-D4)-1H-1,3-benzodiazol-2-one

Conditions	Yield
Stage #1: 1-(3-iodopropyl)-2,3-dihydro(4,5,6,7-D4)-1H-1,3-benzodiazol-2-one; 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one In tetrahydrofuran; N,N-dimethyl-formamide for 2.16667h; Inert atmosphere; Stage #2: With potassium carbonate In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 48h;	64%

4-bromo-2-fluorobenzaldehyde (57848-46-1) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 1-(1-(4-bromo-2-fluorobenzyl)piperidin-4-yl)-5-chloro-1H-benzo[d]imidazol-2(3H)-one

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 20℃; Inert atmosphere;	63%

2-(bromomethyl)-2,3-dihydrobenzo[1,4]dioxine (2164-34-3) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 5-Chloro-1-[1-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-4-yl]-1,3-dihydro-benzoimidazol-2-one (85076-06-8)

Conditions	Yield
With triethylamine; sodium iodide In N,N-dimethyl-formamide for 60h; Ambient temperature;	60%

2,3-dihydro-2,2-dimethyl-5-chloro-7-(oxiranyl-methoxy)-benzofuran (1089210-20-7) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 1-((2,3-dihydro-2,2-dimethyl-5-chloro-benzofuran-7-yl)-oxy)-3-(4-(2,3-dihydro-2-oxo-5-chloro-benzoimidazol-1-yl)-piperidin-1-yl)-propan-2-ol (1089209-50-6)

Conditions	Yield
In ethanol at 20℃; for 72h;	58%

7-fluoro-2-<(tosyloxy)methyl>-1,4-benzodioxan (107617-97-0) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 5-Chloro-1-[1-(7-fluoro-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-4-yl]-1,3-dihydro-benzoimidazol-2-one (107617-74-3)

Conditions	Yield
With triethylamine; potassium iodide In dimethyl sulfoxide at 80℃; for 20h;	57%

5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) + 4-bromo-2-fluoroacetophenone (625446-22-2) → 1-(1-(1-(4-bromo-2-fluorophenyl)ethyl)piperidin-4-yl)-5-chloro-1H-benzo[d]imidazol-2(3H)-one

Conditions	Yield
Stage #1: 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one; 4-bromo-2-fluoroacetophenone With titanium(IV) isopropylate at 60℃; for 2h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In tetrahydrofuran at 20℃; Inert atmosphere;	56%

6,7-dimethyl-2-(toluene-4-sulfonyloxymethyl)-2,3-dihydro-benzo[1,4]dioxine (3635-70-9) + 5-chloro-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (53786-28-0) → 1-[(6,7-Dimethyl-benzo-1,4-dioxan-2-yl)-methyl]-4-(5-chlorobenzimidazol-2-on-1-yl)-piperidine (85076-21-7)

Conditions	Yield
With triethylamine; potassium iodide In dimethyl sulfoxide at 80℃; for 20h;	55%

Upstream product

• 53786-46-2 4-(5-chloro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester 
• 58859-46-4 ethyl 4-aminopiperidine-1-carboxylate 
• 460047-90-9 tert-butyl 4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)piperidine-1-carboxylate 
• 1429415-80-4 tert-butyl 4-[(2-amino-4-chlorophenyl)amino]piperidine-1-carboxylate 
• 460047-89-6 tert-butyl 4-[(4-chloro-2-nitrophenyl)amino]piperidine-1-carboxylate 
• 345-18-6 2-fluoro-5-chloronitrobenzene 
• 87120-72-7 1-(tert-butoxycarbonyl)-4-aminopiperidine 
• 89-61-2 2,5-dichloronitrobenzene 
• 53786-44-0 4-(4-chloro-2-nitro-anilino)-piperidine-1-carboxylic acid ethyl ester 
• 53786-45-1 ethyl 4-[(2-amino-4-chlorophenyl)amino]piperidine-1-carboxylate 

Downstream Products

• 95017-57-5 1-(1-{3-[Bis-(4-fluoro-phenyl)-amino]-propyl}-piperidin-4-yl)-5-chloro-1,3-dihydro-benzoimidazol-2-one 
• 85494-56-0 1-[1-(4-(4-fluorophenyl)-tetrahydro-2-furylmethyl)-4-piperidyl]-5-chloro-benzimidazolin-2-one maleate 
• 58859-90-8 5-chloro-1-{1-[4-(4-fluoro-phenyl)-4-phenyl-butyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one 
• 57808-66-9 domperidone 
• 1074762-24-5 C₂₅H₂₈ClF₃N₄O 
• 1074762-29-0 C₂₅H₂₈ClN₅O 
• 1074762-23-4 C₂₄H₂₉ClN₄O 
• 1074762-25-6 C₂₄H₂₈Cl₂N₄O 
• 1074762-22-3 C₂₅H₃₁ClN₄O 
• 1074762-27-8 C₂₄H₂₈ClN₅O₃ 
• 1116118-84-3 (S)-5-chloro-1-(1-(2-fluoro-3-phenylpropyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one 
• 1116118-89-8 (R)-5-chloro-1-(1-(2-fluoro-3-phenylpropyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one 
• 1116118-95-6 (S)-5-chloro-1-(1-(2-cyclohexyl-2-fluoroethyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one 
• 1116119-02-8 5-chloro-1-(1-(2-cyclohexyl-2,2-difluoroethyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one 

Relevant articles and documents

Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias

While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/βarr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

NOVEL PIPERIDINYL-1,3-DIHYDRO-BENZOIMIDAZOL-2-ONES AS M1 AGONISTS

The present invention relates to novel M1 agonistic compounds of the present invention and their use in the treatment of cognitive impairment associated i.a. with schizophrenia and in the treatment of other diseases mediated by the muscarinic M1 receptor.

Dipeptides which promote release of growth hormone

Compounds of formula (I) are growth hormone releasing peptide mimetics which are useful for the treatment and prevention of osteoporosis. STR1