1258306-01-2

Upstream product

• 2417-72-3 Methyl 4-(bromomethyl)benzoate 
• 768-35-4 3-fluorophenylboronic acid 
• 456-41-7 1-(Bromomethyl)-3-fluorobenzene 
• 99768-12-4 4-methoxycarbonylphenylboronic acid 

Downstream Products

• 1258306-03-4 N,N-diethyl 4-[(N-tert-butoxycarbonyl-4-hydroxypiperidin-4-yl)-3-fluorobenzyl]benzamide 
• 1258306-02-3 N,N-diethyl 4-(3-fluorobenzyl)benzamide 
• 1382991-51-6 N-(2-(5-bromo-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide 
• 1382991-52-7 4-(3-fluorobenzyl)-N-(4-(triethylsilyl)but-3-ynyl)benzamide 
• 1382991-55-0 N-(2-(5-cyano-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide 
• 1382991-56-1 N-(2-(5-acetyl-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide 
• 1382991-57-2 4-(3-fluorobenzyl)-N-(2-(4,5,6-trifluoro-2-(triethylsilyl)-1H-indol-3-yl)ethyl)benzamide 
• 1382991-58-3 N-(2-(5-chloro-7-fluoro-2-(triethylsilyl)-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide 
• 1382992-55-3 4-(3-fluorobenzyl)-N-(2-(5-phenyl-1H-indol-3-yl)ethyl)benzamide 
• 1382992-56-4 4-(3-fluorobenzyl)-N-(2-(5-morpholino-1H-indol-3-yl)ethyl)benzamide 
• 1382992-57-5 N-(2-(5-cyano-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide 
• 1382992-58-6 N-(2-(5-acetyl-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide 
• 1382992-59-7 4-(3-fluorobenzyl)-N-(2-(4,5,6-trifluoro-1H-indol-3-yl)ethyl)benzamide 
• 1382992-60-0 N-(2-(5-chloro-7-fluoro-1H-indol-3-yl)ethyl)-4-(3-fluorobenzyl)benzamide 

Relevant academic research and scientific papers

NEW COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1) wherein R1, R2, R4, R6, E, n, Y1, Y2, Y3, Y4, Y5, L, B, R8, and m are as defined in the claims.

NEW COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds. The compounds have the formula (A1) wherein R1, R2, R4, R6, E, n, Y1, Y2, Y3, Y4, Y5, L, B, R8, and m are as defined in the claims.

A continuous flow process using a sequence of microreactors with in-line IR analysis for the preparation of N,N-diethyl-4-(3-fluorophenylpiperidin-4- ylidenemethyl)benzamide as a potent and highly selective δ-opioid receptor agonist

This article describes the design, optimisation and development of a continuous flow synthesis of N,N-diethyl-4-(3-fluorophenylpiperidin-4- ylidenemethyl)benzamide, a potent δ-opioid receptor agonist developed by AstraZeneca. The process employs a sequence of flow-based microreactors, with integrated purification employing solid-supported reagents and in-line IR analytical protocols using a newly developed ReactIR flow cell. With this monitoring device, initiation of the fourth input flow stream can be precisely controlled during the synthesis. A four-step flow synthesis of a potent δ-opioid receptor agonist was developed (see scheme), using a continuation of pumping devices in combination with cartridges packed with appropriate scavengers to effect clean delivery of the product. We have also reported the use of in-line ReactIR monitoring to synchronise pumping of a late input stream to coordinate reactive components.