Toward pyrrolo[2,3-d]pyrimidine scaffolds.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Pyrrolo[2,3-d]pyrimidines are a crucial scaffold in medicinal chemistry.
• Existing synthetic routes often lack efficiency or versatility for creating diverse substitutions.

Purpose of the Study:

• To establish a new, efficient synthetic pathway for highly substituted pyrrolo[2,3-d]pyrimidines.
• To explore the formation of aromatic fused systems within this class of compounds.

Main Methods:

• Utilizing a Ugi-Smiles reaction followed by a Sonogashira coupling (cascade).
• Employing a base-catalyzed intramolecular cyclization for ring formation.
• Investigating the use of formaldehyde as a specific input for aromatic system generation.

Main Results:

• A novel cascade reaction sequence was successfully developed.
• The method allows for the synthesis of diverse, highly substituted pyrrolo[2,3-d]pyrimidines.
• Aromatic fused systems were obtained via isomerization of an exo-alkylidene intermediate when using formaldehyde.

Conclusions:

• The presented Ugi-Smiles/Sonogashira cascade offers an efficient route to pyrrolo[2,3-d]pyrimidines.
• This methodology provides access to valuable aromatic fused systems, expanding synthetic possibilities.