THE DEVELOPMENT OF PYRROLOPYRIMIDINE LIBRARIES

This thesis describes the development of protocols for the preparation of both pyrrolo[1,2-c]pyrimidine and pyrrolo[1,2-c]pyrimidin-5(4aH)-one libraries. These sequences were used to synthesise analogs, which will be examined for their kinase inhibitory levels. In Chapter One, a brief overview of how these scaffolds emerged as potent kinase inhibitors and an overview of previous strategies used for their synthesis is described. Chapter Two covers investigations into the synthesis of the pyrrolo[1,2-c]pyrimidin-5(4aH)-one core using previously established methodology, where the key step is a metal-catalysed cycloisomerisation reaction. However, it was established that compounds containing thiomethyl groups at the C1 position could not be used for the substitution with amino groups. Efforts to prepare the chloro-substituted scaffold are described. In Chapter Three, previously established methodology using ionic hydrogenation was applied to prepare the pyrrolo[1,2-c]pyrimidine core. This process proved to be low-yielding. A reliable and more efficient procedure was developed, which involves cyclisation of vinyl-substituted derivatives. With access to the scaffold, substitution of the thiomethyl group at C1 with amines was investigated. A brief summary of the work described in this thesis and potential future studies is given in Chapter 4. Full experimental procedures are included in Chapter 5.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2012

Author dc:creator

• Da Rocha, Joana

• Pyrrolopyrimidine libraries
• Kinase inhibitors
• Metal-catalysed cycloisomerisation
• Ionic hydrogenation
• Vinyl-substituted derivatives

Statement dc:rights

• open access
• CC BY-NC-ND 3.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by-nc-nd/3.0/au/

Language dc:language

EN

Identifier

https://doi.org/10.26190/unsworks/16046

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/52515