1273546-86-3

Upstream product

• 174265-12-4 2-bromo-5-chlorobenzaldehyde 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1379974-95-4 2-(2-bromo-5-chlorophenyl)ethan-1-amine 
• 127792-49-8 2-(2-bromo-5-chlorophenyl)acetonitrile 
• 60666-70-8 2-bromo-5-chlorobenzyl alcohol 

Downstream Products

• 1273547-07-1 (3S)-(E)-N-Boc-N-[2-[5-chloro-2-(3-hydroxybut-1-enyl)-phenyl]ethyl]amine 
• 1273546-98-7 (3S)-(E)-N-Boc-N-[2-[2-(3-tert-butyldimethylsilyloxy-1-butenyl)-5-chlorophenyl]ethyl]amine 

Relevant academic research and scientific papers

Phenethyl nicotinamides, a novel class of NaV1.7 channel blockers: Structure and activity relationship

The NaV1.7 ion channel is an attractive target for development of potential analgesic drugs based on strong genetic links between mutations in the gene coding for the channel protein and inheritable pain conditions. The (S)-N-chroman-3-ylcarboxamide series, exemplified by 1, was used as a starting point for development of new channel blockers, resulting in the phenethyl nicotinamide series. The structure and activity relationship for this series was established and the metabolic issues of early analogues were addressed by appropriate substitutions. Compound 33 displayed acceptable overall in vitro properties and in vivo rat PK profile.

Synthesis of chiral 1-substituted tetrahydroisoquinolines by the intramolecular 1,3-chirality transfer reaction catalyzed by Bi(OTf)3

The intramolecular 1,3-chirality transfer reaction of chiral amino alcohols 1 with 99% ee was developed to construct chiral 1-substituted tetrahydroisoquinoline 2. Bi(OTf)3 (10 mol %)-catalyzed cyclization of 1 (R = H) afforded (S)-1-(E)-propenyl tetrahydroisoquinoline 2 (R = H) in 83% yield with a ratio of 98:2. The stereochemistry at the newly formed chiral center was produced by a syn SN2′-type process. In this reaction, the substituent on the benzene ring of 1 significantly affected the reactivities and selectivities. A plausible reaction mechanism was proposed.