106669-71-0

Basic information

• Product Name: arpromidine
• Synonyms: arpromidine;1-[3-(4-Fluorophenyl)-3-(2-pyridyl)propyl]-2-[3-(1H-imidazol-4-yl)propyl]guanidine;BU-E-50;HE-90371
• CAS NO: 106669-71-0
• Molecular Formula: C₂₁H₂₅FN₆
• Molecular Weight: 380.469
• Mol File: 106669-71-0.mol

Chemical Properties

• Boiling Point: 619.9°Cat760mmHg
• Flash Point: 328.7°C
• Appearance: /
• Density: 1.23g/cm³
• Vapor Pressure: 2.7E-15mmHg at 25°C
• Refractive Index: 1.623
• CAS DataBase Reference: arpromidine(CAS DataBase Reference)
• NIST Chemistry Reference: arpromidine(106669-71-0)
• EPA Substance Registry System: arpromidine(106669-71-0)

Safety Data

• Hazardous Substances Data: 106669-71-0(Hazardous Substances Data)

Usage

Originator

Arpromidine,Onbio Inc.

Manufacturing Process

42.4 g (0.2 mol) of (4-fluorophenyl)-pyrid-2-yl-acetonitrile are dissolved in 50 ml of dimethylformamide and introduced dropwise into a suspension, cooled with ice, of 5.0 g of sodium hydride (put into the process as a dispersion in mineral oil) in 150 ml of dimethylformamide. The reaction mixture is then stirred at room temperature for 15 min and thereafter heated under reflux for 5 h after the addition of 53.4 g (0.21 mol) of N-(2-bromoethyl)phthalimide. When the resulting reaction mixture has cooled down, it is diluted with 500 ml of ether and the organic phase is washed with water until neutral, dehydrated over sodium sulfate and then concentrated by evaporation under vacuum. The N-[3-(cyano-3-(4-fluorophenyl)-3-(pyrid-2-yl)propyl]phthalimide, oily residue, melting point 154°C (crystallizing from methanol), yield: 48.5 g (63%). 46.25 g (0.12 mol) of N-[3-cyano-3-(4-fluorophenyl)-3-(pyrid-2- yl)propyl]phthalimide in 100 ml of 75% sulfuric acid are heated to 150°C for 5 h. When the reaction mixture is cold, it is poured out on ice, filtered through a glass filter, alkalized with sodium hydroxide solution and extracted with ether. The combined extracts are washed with water, dehydrated over sodium sulfate and concentrated by evaporation under vacuum, and the product obtained is isolated by distillation at 150°-155°C/0.8 mm Hg. 19.1 g (yield: 69%) of the 3-(4-fluorophenyl)-3-(pyrid-2-yl) propylamine are obtained. 1.15 g (5 mmol) of 3-(4-fluorophenyl)-3-(pyrid-2-yl)-propylamine and 1.59 g (5 mmol) of N-benzoyl-diphenylimidocarbonate are stirred together in 20 ml of methylene chloride for 15 min at room temperature. The solvent is distilled off under vacuum and the residue is taken up with 30 ml of pyridine and then heated under reflux for 60 min after the addition of 0.69 g (5.5 mmol) of 3- (imidazol-4-yl)-propylamine. The reaction mixture is concentrated by evaporation under vacuum and the residue is dissolved in dilute acid and extracted with ether to remove the phenol formed in the reaction. Alkalization of the aqueous phase with ammonia is followed by extraction with methylene chloride, and the organic phase is washed with water, dehydrated over sodium sulfate and concentrated by evaporation under vacuum. The crude product is purified by preparative layer chromatography (silica gel 60 PF254, containing gypsum, solvent: chloroform/methanol 99+1, ammoniacal atmosphere). 1.4 g (yield 58%) of N-benzoyl-N'-[3-(4-fluorophenyl)-3-(pyrid-2-yl)propyl]-N"-[3- (imidazol-4-yl)propyl]-guanidine a non-crystalline solid (foam) are obtained (crystallisation from ethyl acetate). 0.97 g (2 mmol) of N-benzoyl-N'-[3-(4-fluorophenyl)-3-(pyrid-2-yl)propyl]-N"- [3-(imidazol-4-yl)propyl]-guanidine are heated under reflux in 45 ml of 18% hydrochloric acid for 6 h. When the reaction mixture has cooled down, the benzoic acid formed is removed by extraction with ether, the aqueous phase is evaporated to dryness under vacuum and the residue is dehydrated in a high vacuum: 0.9 g (yield 92%) of a hygroscopic, non-crystalline N-[3-(4-fluorophenyl)-3-(pyrid-2-yl)propyl]-N'-[3-(imidazol-4-yl)propyl]-guanidine is obtained.

Therapeutic Function

Histamine H2-receptor agonist

InChI:InChI=1/C21H25FN6/c22-17-8-6-16(7-9-17)19(20-5-1-2-11-25-20)10-13-27-21(23)26-12-3-4-18-14-24-15-28-18/h1-2,5-9,11,14-15,19H,3-4,10,12-13H2,(H,24,28)(H3,23,26,27)

Upstream product

• 106669-70-9 N-Benzoyl-N'-[3-(4-fluorophenyl)-3-(pyrid-2-yl)propyl]N-[3-(imidazol-4-yl)propyl]-guanidine 

Related news

Synthesis and histamine H2 agonistic activity of arpromidine (cas 106669-71-0) analogues: replacement of the pheniramine-like moiety by non-heterocyclic groups08/02/2019

Analogues of the potent histamine H2 agonist arpromidine, characterized by non-heterocyclic groups (phenyl, cyclohexyl, alkyl) instead of the pheniramine-like portion, were prepared and tested for their H2 agonistic and H1 antagonistic activity in the isolated guinea pig right atrium and ileum, ...detailed

Relevant articles and documents

IMIDAZOLYL ALKYL GUANIDINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL PREPARATIONS CONTAINING THESE COMPOUNDS

New imidazolylalkyl-guanidine derivatives are described, which by virtue of their agonistic action on histamine-H 2 receptors and in part also due to their additional H 1-antagonistic receptor activity can be used in the treatment of cardiac diseases, certain forms of hypertension and diseases of arterial occlusion.These imidazolylalkyl-guanidine derivatives correspond to the general formula I: STR1