Optimised synthesis of diamino-triazinylmethyl benzoates as inhibitors of Rad6B ubiquitin conjugating enzyme

Recently, we have identified the first inhibitors of Rad6B, an E2 enzyme essential for post-replication DNA repair and a potential new drug target for the treatment of breast cancer. We report two newly optimised synthetic routes to our [4-amino-6-(phenylamino)-1,3,5-triazin-2-yl]methyl 4-nitrobenzoate target compounds TZ8 and TZ9 with general applicability for further structure activity relationship studies around this pharmacophore. The key step involved the condensation/cyclisation between phenylbiguanide and either ethyl bromoacetate or dimethyloxalate in good yield. (C) 2014 Elsevier Ltd. All rights reserved.