208110-64-9

Basic information

• Product Name: befiradol
• Synonyms: befiradol;1-(3-Chloro-4-fluorobenzoyl)-4-fluoro-N-[(5-methyl-2-pyridinyl)methyl]-4-piperidinemethanamine;Unii-rat9oha1yh;F 13640;(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[(5-methylpyridin-2-yl)methylamino]methyl]piperidin-1-yl]methanone
• CAS NO: 208110-64-9
• Molecular Formula: C₂₀H₂₂ClF₂N₃O
• Molecular Weight: 393.863
• Mol File: 208110-64-9.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 536.9±50.0 °C(Predicted)
• Appearance: /
• Density: 1.30
• PKA: 8.01±0.20(Predicted)
• CAS DataBase Reference: befiradol(CAS DataBase Reference)
• NIST Chemistry Reference: befiradol(208110-64-9)
• EPA Substance Registry System: befiradol(208110-64-9)

Safety Data

• Hazardous Substances Data: 208110-64-9(Hazardous Substances Data)

Upstream product

• 448920-98-7 2-[1-[(3-chloro-4-fluorophenyl)carbonyl]-4-fluoropiperidin-4-yl]-2-hydroxyacetonitrile 
• 45715-08-0 ((5-methyl-pyridin-2-yl)-methyl)-amine 
• 403-16-7 3-chloro-4-fluorobenzoic acid 
• 161647-06-9 [5-methylpyridin-2-yl]methanamine hydrochloride 
• 161647-06-9 (5-methylpyridin-2-yl)methylamine (dihydrochloride) 
• 280-57-9 1,4-diaza-bicyclo[2.2.2]octane 
• 208111-39-1 N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-aminomethylpiperidine 
• 208111-36-8 N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-hydroxymethylpiperidine 
• 208111-51-7 N-(3-chloro-4-fluorobenzoyl)-1-oxa-6-azaspiro<2,5>octane 
• 223632-64-2 1-[(3-chloro-4-fluorophenyl)carbonyl]piperidin-4-one 
• 65055-17-6 3-chloro-4-fluorobenzoyl chloride 
• 177-11-7 4,4-ethylenedioxy-piperidine 
• 448920-97-6 6-[(3-chloro-4-fluorophenyl)carbonyl]-1-oxa-6-azaspiro[2.5]octane-2-carbonitrile 
• 208111-37-9 N-(3-chloro-4-fluorobenzoyl)-4-fluoro-4-(4-methylphenylsulonuloxymethyl)-piperidine 

Downstream Products

• 1256167-79-9 N-[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl]methyl-N-methyl-N-(5-methylpyridin-2-yl)methylamine 

Relevant articles and documents

Conformational analysis and crystal structure of {[1-(3-chloro-4- fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt

{[1-(3-Chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl} [(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt (C20H 22ClF2N3O, C4H4O 4) (1) was synthesized and characterized by the complete 1H, 13C and 19F NMR analyses. The conformation of the piperidin ring, in the solution state, was particularly studied from the coupling constants determined by recording a double-quantum filtered COSY experiment in phase-sensitive mode. 1H NMR line-shape analysis was used, at temperatures varying between -5 and +60 °C, to determine the enthalpy of activation of the rotational barrier around the CN bond. Compound 1 crystallizes in the triclinic space group P1 with a = 8.517(3) A, b = 12.384(2) A, c = 12.472(3) A, α = 70.88(2)°, β = 82.04(2)°, γ = 83.58(2)°. The results strongly indicate that the solid and solution conformations are similar. Thermal stability and phases transitions were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore polymorphism screening was studied from recrystallization of 1 performed in seven solvents and by slurry conversion in water. The X-ray powder diffraction (XRPD) and differential scanning calorimetry results suggested that 1 crystallizes into one crystalline form which melts at 157 °C (ΔH = 132 J g-1).

Novel pyridylmethylamines as highly selective 5-HT1A superagonists

To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, α1, and α2-adrenergic as well as D1-D4 dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT1A superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT1A recognition with a Ki value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

Pyridylmethylamines polypyridine-2-yl-synthesis of the intermediate body,

The invention concerns a novel method for preparing pyridin-2-yl-methylamine derivatives by reducing amination of cyanohydrins.