3-Aminopyrroles and their application in the synthesis of pyrrolo[3,2-d]pyrimidine (9-deazapurine) derivatives

Abstract

3-Aminopyrrole derivatives have been synthesized from 3-anilino-2-cyanoacrylonitrile using Thorpe-Ziegler cyclization. These substituted pyrroles are readily converted into 5H-pyrrolo[3,2-d]pyrimidine (9-deazapurines).

Synthetic Entries to and Biological Activity of Pyrrolopyrimidines

“…However, when the starting material was 369b, the Dimroth rearrangement was not possible and N 3 -phenylpyrimidinones 371 were obtained. 143 A final example of the versatility of the pyrimidine condensation approach is found in the search for neuropeptide Y5 antagonists (refer to section 3.1.2 for SAR). As direct cyclization of α-cyanoketones 373 with amino diethyl malonate failed, the ketones were transformed into their corresponding enolic tosylates 374 and were then condensed in the presence methylated, after which the phenolic OH was activated by mesylation and finally substituted by piperidine, affording compound 378d.…”

“…Using aniline instead of ammonia, the Dimroth rearrangement could be performed from 369a , affording 4-phenylaminopyrimidines 372 in good yields. However, when the starting material was 369b , the Dimroth rearrangement was not possible and N 3 -phenylpyrimidinones 371 were obtained …”

I2-catalyzed synthesis of 3-aminopyrrole with homopropargylic amines and nitrosoarenes

“…10 Nevertheless, as crucial structural components in various bioactive natural products (Scheme 1A), 11 3-aminopyrroles are still rather limited in terms of synthetic approaches. 12 There are two main traditional methods for synthesizing 3-aminopyrrole compounds (Scheme 1C): one involves the structural modification of pyrrole derivatives; 13 while the other method constructs a pyrrole ring unit with multi compounds as precursors. 14 These methods are unable to meet the demand of synthesizing 3-aminopyrroles.…”