New findings in the alkylation and N-deprotection of (4S)-4-methyl-2- benzyl-2,4-dihydro-1H-pyrazino [2,1-b] quinazoline-3,6-diones

Article abstract of DOI:10.1016/S0957-4166(97)00629-0

Alkyl halides behave differently to benzyl halides in C-1 alkylation of the title compounds. The syn and anti 1,4-disubstituted diastereomers thus obtained show different regioselectivity by further alkylation leading to the 1,4,4-and 1,1,4-trisubstituted compounds, respectively. Alkylation is always directed anti with respect to the bulkier substituent at C-l or C-4. Debenzylation attempts on 2-benzyl-derivatives lb by treatment with HCOOH and C/Pd or H²/C-Pd/MeOH/H⁺ led to C-1 oxidised or 7,8,9,10-tetrahydro- derivatives. Deprotection of 2-p-methoxybenzyland 2-(2,4-dimethoxybenzyl)- derivatives with CAN and with TFA/anisole, respectively, was successful, but in the latter case epimerization at C-1 occurred.