The synthesis of a tricyclic pyrrolopyrimidine related to N 6-hydroxyadenine

Abstract

The synthesis of 9-methylpyrrolo[4,3,2-de]pyrimido [4,5-c]dihydrooxazepine 34, a tricyclic pyrrolo[2,3-d]pyrimidine analogue of the mutagenic purine N⁶-hydroxyadenine, and several novel pyrrolo[2,3-d]pyrimidines is described. The presence of the third ring constrains the amino substituent of 34 to an anti orientation and is expected to improve dramatically the base-pairing characteristics of the analogue with both cytosine and thymine when present in DNA. An intramolecular cyclisation reaction of 5-(aminooxyethyl)-4-chloro-7-methyl-2-methylsulfonyl-7H -pyrrolo[2,3-d]pyrimidine 30 gave 33, which was converted into the target molecule 34 via the displacement of the methylsulfonyl group with hydrazine followed by oxidation of the hydrazino group with mercuric oxide. An analogous cyclisation with 5-(aminooxyethyl)-4-chloro-7-methyl-7H-pyrrolo [2,3-d]pyrimidine 31 was less effective, whilst the corresponding 2-amino derivative 32 failed to cyclise.