Back
Access and regioselective transformations of 6-substituted 4-aryl-2,8-dichloropyrido[3,2-d]pyrimidine compounds.
Journal article

Access and regioselective transformations of 6-substituted 4-aryl-2,8-dichloropyrido[3,2-d]pyrimidine compounds.

  • 2012-04-17
Published in:
  • The Journal of organic chemistry. - 2012
Catalysis
Cross-Linking Reagents
Models, Molecular
Molecular Structure
Pyridines
Pyrimidines
Stereoisomerism
English We report herein an efficient route for the synthesis of 2,4,8-trichloropyrido[3,2-d]pyrimidines 1 with R(1) substituents at C-6. The potential of such scaffolds was demonstrated by the possibility to displace regioselectively each aromatic chloride to introduce diversity. Sequential sulfur nucleophilic addition followed by Liebeskind-Srogl cross-coupling reaction yielded unprecedented aryl introduction at C-4 on a trichloropyrido[3,2-d]pyrimidine derivative. The reactivity difference of the remaining two chlorides toward S(N)Ar reactions was investigated. Amination yielded high C-2 regioselectivity, while thiolation was influenced by C-6 substituents, resulting in medium to high C-2 versus C-8 regioselectivity. The last chloride was efficiently displaced by S(N)Ar, Suzuki-Miyaura cross-coupling reaction, or reduction. C-2 arylation as a final step was also possible by Liebeskind-Srogl cross-coupling reaction on the previously introduced C-2 thioether. A concise and highly divergent synthetic use of 1 was developed, thereby providing an efficient approach to explore the structure-activity relationship of pyrido[3,2-d]pyrimidine derivatives such as 9, 10, 15, and 16.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/150342
Statistics
Document views: 61 File downloads: