Microwave‐Assisted Synthesis of Substituted Pyrrolo[2,3‐d]pyrimidines

Abstract

A new synthetic route to triaryl pyrrolo[2,3‐d]pyrimidines from common 4,6‐dichloropyrimidine has been developed. The triarylated compounds are synthesized by three cross‐coupling reactions using three different catalysts. The introduction of a C‐6 aryl group was achieved in a two‐step process under Sonogashira conditions [Pd(dba)2/CuI] followed by intramolecular cyclization, and application of Suzuki–Miyaura conditions [Pd(PPh3)4; PdCl2(PPh3)2] led to C‐4 and C‐5 diarylation. This sequence allows a flexible synthetic approach to highly arylated pyrrolopyrimidines containing different aryl groups.

Two‐Step Regioselective Synthesis of 3‐(Sulfonylamino)imidazo[1,2‐a]pyrimidines from 2‐Aminopyrimidines and N‐(2,2‐Dichloro‐2‐phenylethylidene)arensulfonamides

“…In this work related to Suzuki–Miyaura and Liebeskind–Srogl couplings as well as in previous studies,12,13 we have used microwave irradiation. The use of microwave irradiation as opposed to conventional heating significantly increases the yield and accelerates the rate of a reaction.…”

Modification of Pyrrolo[2,3‐d]pyrimidines by C–H Borylation Followed by Cross‐Coupling or Other Transformations: Synthesis of 6,8‐Disubstituted 7‐Deazapurine Bases

“…Regioselective cross‐coupling reactions were used in the synthesis of 2,4‐disubstituted pyrrolo[2,3‐ d ]pyrimidines8 and, in combination with C–H arylation, for the synthesis of 2,4,6‐triarylpyrrolo[2,3‐ d ]pyrimidines 9. A combination of palladium‐ and copper‐assisted heterocyclization, followed by halogenation at the 5‐position and Suzuki coupling was used for 4,5,6‐trisubstituted derivatives 10. We have recently reported11 a chemoselective synthesis of 4,5‐diarylpyrrolo[2,3‐ d ]pyrimidines by using a combination of the Liebeskind–Srogl and Suzuki coupling reactions.…”

A Strategy for the Triarylation of Pyrrolo­pyrimidines by Using Microwave‐Promoted Cross‐Coupling Reactions

“…In previous reports related to the synthesis of pyrrolopyrimidines, we employed stepwise arylations at the C‐4 and C‐5 positions of 6‐aryl‐4,6‐dihalopyrrolo[2,3‐ d ]pyrimidines,12 and more recently, we reported details of a one‐pot synthesis of 4,6‐disubstituted pyrrolopyrimidines 13. The substitution of pyrrolopyrimidines is often difficult to control, and selectivity plays an special role when different substituents need to be introduced 14…”