John Paul Kilburn

Solid-phase synthesis of substituted 2-aminomethylbenzimidazoles

Abstract Resin-bound 4-fluoro-3-nitrobenzoic acid is converted by reaction with a range of amines and reduction, to substituted 1,2-diaminobenzenes, whose reaction with activated amino acids followed by acid-catalyzed cyclisation gave resin-bound benzimidazoles; Fmoc-deprotection, acylation and TFA-mediated cleavage gave substituted 2-aminomethylbenzimidazoles via a new solid support strategy.

1,3,4-Oxadiazole formation; a novel solid support strategy

Abstract A new approach to the synthesis of 1,3,4-oxadiazoles on solid support is described. Resin bound 1-acyl thiosemicarbazides were treated with a variety of dehydrating agents at different temperatures, which revealed that thiosemicarbazides were effectively cyclised by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl); mild acidic cleavage from the solid support released the substituted 1,3,4-oxadiazoles in excellent purity.

A novel facile solid-phase strategy for the synthesis of N,N′,N″-substituted guanidines

Abstract A new facile solid-phase synthesis of N,N′,N″-substituted guanidines from an immobilised amine component is described. The resin-bound amine was reacted with di-(2-pyridyl)thionocarbonate to generate the isothiocyanate which was treated with aryl/alkyl amines to yield the corresponding resin-bound thiourea. Desulfurisation of the thiourea was readily achieved by treatment with triphenylphosphine dichloride, and further reaction with aryl/alkyl amines followed by acidic cleavage with trifluoroacetic acid yielded N,N′,N″-substituted guanidines of excellent purity and in good yield.

A convenient large-scale chiral synthesis of protected 2-substituted 4-oxo-piperidine derivatives

Abstract A convenient large-scale chiral synthesis of protected 2-substituted-4-oxo-piperidine derivatives is described. Hetero Diels–Alder reaction between trifluoroacetic acid–boron trifluoride activated (1-phenyl-ethylimino)acetic acid ethyl ester and 2-trimethylsilyloxy-1,3-butadiene gave rise to a mixture of two diastereomers of 4-oxo-1-(1-phenyl-ethyl)-piperidine-2-carboxylic acid ethyl ester. Starting from (S)-1-phenyl-ethylamine pure adduct can be obtained by crystallization of the diastereomeric mixture. Reduction of the ester group gave rise to the corresponding hydroxymethyl analogue, which was subjected to further functional group transformations to yield the desired protected 2-aminomethyl-4-oxo-piperidine derivative without any racemization being observed.

Substituted 2-amino-1,3,4-thiadiazines: a novel solid-phase approach

A novel and facile strategy for synthesis of substituted 2-amino-1,3,4-thiadiazines on solid support is described. Resin bound isothiocyanate prepared from an immobilised primary amine and di-(2-pyridyl)thionocarbonate was reacted with hydrazine hydrate to form the intermediate thiosemicarbazide. Further reaction with a range of α-bromoketones followed by mild acidic cleavage from the solid support released the substituted 2-amino-1,3,4-thiadiazines in respectable yields and excellent purity.