Synthesis of Antimalarial Agents from 2,3-Dihydro-1,6-Diazaphenalene Derivatives.
Abstract
In agreement with our original synthetic plan 7-nitro-2,5-dichloro-1,6-diazaphenalene (41) was converted in one step to 7-amino-1,6-diazaphenalene dihydrochloride (1); however conversion of this stable salt into the free base 2 resulted in decomposition of 2 prohibiting attachment of the alkylamino side chains to this molecule. Consequently, a variety of experiments were carried out on 1,6-diazphenalene (4) to define of 4 with electrophiles (+NO2, +Br, +I, +C1, PhN2+), acylating agents and alkylhalides. In addition, 4 was reacted with oxidizing agents such as singlet oxygen and peracids. It was found that 4 reacted with many of these agents in similar fashion to that previously reported for imidazole. Use of the LDA/alkylation technology developed during this study resulted in the synthesis of the target 54, moreover, syntheses of other key compounds 20, 46, 50, and 55 have been accomplished. These bases should be more useful for preparation of antimalarial agents for they provide entry into 1-alkyl-7-aminoalkyl-1-1,6-diazaphenalenes which would appear to be much more stable than 2.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1982
- Accession Number
- ADA134268
Entities
People
- James M Cook
Organizations
- University of Wisconsin–Milwaukee