205701-85-5

Basic information

• Product Name: 5-(Ethoxymethyl)-7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide
• Synonyms: RWJ-51204
• CAS NO: 205701-85-5
• Molecular Formula: C₂₁H₁₉F₂N₃O₃
• Molecular Weight: 399.3907
• Mol File: 205701-85-5.mol

Chemical Properties

• Boiling Point: 532.95°C at 760 mmHg
• Flash Point: 276.118°C
• Density: 1.418g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.645
• PKA: 10.81±0.70(Predicted)
• CAS DataBase Reference: 5-(Ethoxymethyl)-7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(Ethoxymethyl)-7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide(205701-85-5)
• EPA Substance Registry System: 5-(Ethoxymethyl)-7-fluoro-N-(2-fluorophenyl)-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxamide(205701-85-5)

Safety Data

• Hazardous Substances Data: 205701-85-5(Hazardous Substances Data)

Upstream product

• 155202-16-7 7-fluoro-N-(2-fluorophenyl)-1,2,3,5-tetrahydro-3-oxopyrido[1,2-a]benzimidazole-4-carboxamide 
• 3188-13-4 ethyl chloromethyl ether 
• 328546-72-1 3-[(4-fluoro-2-nitrophenyl)amino]propanenitrile 
• 364-78-3 2-nitro-4-fluoroaniline 
• 348-54-9 2-Fluoroaniline 

Relevant articles and documents

5-HETEROATOM-CONTAINING ALKYL SUBSTITUTED-3-OXO-PYRIDO(1,2-a) BENZIMIDAZOLE-4-CARBOXAMIDE DERIVATIVES USEFUL IN TREATING CENTRAL NERVOUS SYSTEM DISORDERS

A compound of the general formula 1; (1) is disclosed as useful in treating disorders of the central nervous system. Pharmaceutical compositions and methods of treatment are also disclosed.

Potential anxiolytic agents. Part 4: Novel orally-active N5-substituted pyrido[1,2-a]benzimidazoles with high GABA-A receptor affinity

A series of pyrido[1,2-a]benzimidazoles (PBIs) with substitution on the N5-nitrogen has been synthesized and found to possess high affinity for the benzodiazepine (BZD) site on the GABA-A receptor. The compounds evaluated include those bearing a heteroalkyl group and heterocyclic rings. The most promising of these compounds is ethoxymethyl analogue 24, which has an IC50 of 0.1 nM for the BZD site on the GABA-A receptor and has been advanced to human clinical trials.

Process research for the synthesis of RWJ-51204, a novel anxiolytic agent

RWJ-51204, the lead compound in our pyrido [1,2-α] benzimidazole (PBI) series, was shown to exhibit anxiolytic efficacy in animal models at doses which did not cause central nervous system side effects commonly observed with other anxiolytic agents. To prepare supplies of drug substance for early toxicological and clinical studies, we needed to develop a safe and scaleable synthesis. Our main focus was to improve the last two steps of the process which involved formation of the penultimate carboxamide intermediate followed by alkylation using potentially toxic chloromethyl ethyl ether. Due to safety issues concerning storage and handling of this reagent during the large scale synthesis, we investigated alternate routes to minimize potential exposure risks. The process research carried out for the final steps that led to the safe and cost-effective multi-kilogram synthesis of RWJ-51204 is described herein.