Synthesis of cyclopentaquinazolines

摘要

A method of producing 6-amino-cyclopenta[g]quinazolines, in enantiomerically enriched form, is provided. In particular, the method may be applicable to the synthesis of N—{N-{4-[N-((6S)-2 -hydroxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclo-penta[g]quinazolin-6-yl)-N-(prop-2 -ynyl)amino]benzoyl}-L-γ-glutamyl}-D-glutamic acid (ONX-0801).;

主权项

1. A process for producing a cyclopentaquinazoline from a 5-amino-6-haloindanone comprising the steps of:
(a) acylation of the 5-amino group; (b) cyanide displacement of the 6-halo group; (c) hydrolysis of the nitrile group produced in step (b); and (d) cyclisation of a 5-(N-acylamino)-6-amidoindanone to form a cyclopentaquinazoline ring system; and (e) reduction of the indanone keto group to produce an indanol.