Solid‐Phase Synthesis of Aryl‐Alkylamine Derivatives Using Protected Aminoalcohol Building Blocks on SynPhase^TM Lanterns

Abstract

A series of aryl-alkylamine carboxamide and sulfonamide derivatives were synthesized on a BAL linker using SynPhase TM Lanterns. All the reaction steps were performed on a solid support. The key stage was on-resin substitution of TBDPSi-protected aminoalcohols with various amines, which circumvented the multistep solution-phase synthesis of alkylamine building blocks. The chemistry applied allows building up focused libraries targeted on CNS receptors.

Solid-Phase Synthetic Route to Multiple Derivatives of a Fundamental Peptide Unit

“…The acylating agent (R 2 = 4-NC-Ph), nucleophile R 3 and chain length were kept constant. In addition these initial studies, which focused on the compatibility of the protected silyl alcohol with alkylation chemistry, utilized the alcohol activation and amine incorporation procedures ( via mesylate 27a ) employed in the earlier lantern-based work [ 11 ]. Products for this 11-step synthesis were obtained in moderate overall yields ( Table 1 ).…”

“…The solid-phase synthesis of 3 utilizes BAL-type linkers, “lantern” technology, and either of two synthetic routes ( Scheme 2 , Path A or B). While Path A provides a direct route to product, Path B (through intermediate 17 ) permits greater flexibility by incorporation of many amines after attachment of the amino acid onto the BAL resin [ 11 ].…”