Solid Phase Synthesis of Tertiary Amines on Amide REM Resins:  Grignard and Metal Hydride Compatible Resins

Abstract

Four new amide REM resins (AM REM 2-5) are described, and their use is illustrated for the synthesis of tertiary amines 6-9 and 13-16. Amide REM resins 4 and 5, which have a phenyl ring attached to the amide nitrogen, are found to give superior product yields and purities, and the resins are stable to a wider range of reagents and conditions compared to REM resin 1.

Ligand- and structure-basedin silicostudies to identify kinesin spindle protein (KSP) inhibitors as potential anticancer agents

“…Subsequently, thesescaffoldswere subjected to moleculardocking and molecular dynamics followed by the calculations of binding free energies. Finally, two ligands (MB-41570 and CB-10358) wereidentified as potentialand easily obtainable or synthesizable (Nankervis et al, 2011;Plater, Murdoch, Morphy, Rankovic, & Rees, 2000)KSP inhibitors. Since the two identified hits (MB41570 and CB10358) demonstrated similar interactions as compared to SB-743921 and exhibited higher binding energies, we synthesized these and evaluated them against the basal and the MT-stimulated KSP ATPase activities.…”

Solid‐supported well‐defined synthesis of telechelic polyester by acid‐promoted ring‐opening polymerization of ϵ‐caprolactone

“…The designed system is depicted in Scheme , which involves immobilization of alcohol on crosslinked polystyrene (PS) resin by 1,4‐addition of amino alcohol to an immobilized acryloyl moiety ( 1 → 2 ), acid‐promoted ring‐opening polymerization of ϵ‐caprolactone initiated from the immobilized alcohol ( 2 → 3 ), and isolation of the formed polyester from the resin via cleavage of the β‐amino ester linker ( 3 → 5 ). The β‐amino ester linker has been developed for solid‐supported synthesis of functionalized amine 7, 8. This linker can be cleaved by quaternization of the amino group with alkyl halide and successive treatment of the corresponding ammonium salt with tertiary amine, resulting in Hoffman degradation to release the functionalized amine from the resin with regeneration of the original acryloyl moiety.…”

“…The resin 1 having acryloyl moiety was easily obtained by esterification of a hydroxymethylated crosslinked PS resin with acryloyl chloride in the presence of N , N ‐diisopropylethylamine (DIPEA) 7, 8. Thus, 1 was shaken with an excess amount of 2‐( N ‐methylamino)‐ethanol in a mixed solvent of dichloromethane and N , N ‐dimethylformamide (DMF) to immobilize the corresponding alcohol moiety by 1,4‐addition of the amino group to the acryloyl moiety.…”

Solid-phase Synthesis of Tertiary N-Methyl Amines Including Tropanes

“…Solid-phase methods for synthesis of tertiary amines including N -methyl amines have been reported by Andersson . Others ,− reported solid-phase alkylation and cleavage of tertiary amines by Hofmann type elimination from REM-type resins. An interesting method for debenzylating cleavage of quaternized amines from the Merrifield support based on nucleophilic displacement was reported by Cai .…”