Solid Phase Synthesis of Aminopropenones and Aminopropenoates; Efficient and Versatile Synthons for Combinatorial Synthesis of Heterocycles

Abstract

Simple and fast solid phase methods for the synthesis of heterocycles will be described. Two different three-step methods are presented. The first method includes esterifications of N-protected glycine derivatives to a solid support (Merrifield resin), formation of aminopropenoates and subsequent reaction with dinucleophiles. The second method includes methylamination of a Merrifield resin, formation of aminopropenones via in-situ formation of an active intermediate in a three-component reaction and finally treatment with dinucleophiles to form heterocycles. These procedures lead not only to the formation of heterocycles but also to simultaneous intramolecular cleavage of the products from the resin giving the product in pure form in the solution. In addition, the use of microwave dielectric heating enhanced the velocity of all reaction steps and was found to be a very efficient complement to the solid phase synthesis.

Key words

solid-phase synthesis - microwave irradiation - combinatorial chemistry - heterocycles

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10

In this project SmithSynthesizer^TM available from Personal Chemistry AB was used. This instrument is fully automated equipped with temperature and pressure control and can run up to 120 unattended reactions sequentially the process vial is cooled actively by pressurized air after the irradiation.

12

Results not shown.

16

To our surprise we could not form the solid supported benzylmethylamine from methylamine in MeOH under the same conditions.