![Regioselective synthesis of 2,8-disubstituted 4-aminopyrido[3,2-d]pyrimidine-6-carboxylic acid methyl ester compounds.](/static/images/no-image.png)
Journal article
Regioselective synthesis of 2,8-disubstituted 4-aminopyrido[3,2-d]pyrimidine-6-carboxylic acid methyl ester compounds.
- Bouscary-Desforges G Merck Serono S.A., 9, Chemin des Mines, 1202 Geneva, Switzerland.
- Bombrun A
- Augustine JK
- Bernardinelli G
- Quattropani A
- 2011-11-29
Published in:
- The Journal of organic chemistry. - 2012
English
We report herein the synthesis of 4-amino-2,8-dichloropyrido[3,2-d]pyrimidine derivatives 2 and their regioselective diversification through S(N)Ar and metal-catalyzed cross-coupling reactions. While amination of 2 took place selectively at C-2, the regioselectivity of thiol or thiolate addition depended on the reaction conditions. Selective C-8 addition was obtained in DMF with Hünig's base and C-2 addition in (i)PrOH. These C-2 or C-8 regioselective thiolations provided an opportunistic way to selectively activate either of the two positions toward the metal-catalyzed cross-coupling reaction. The chloride could be efficiently substituted by Suzuki-Miyaura reaction and the sulfanyl group by Liebeskind-Srogl cross-coupling reaction, demonstrating the orthogonality of both reactive centers. The development of regioselective conditions for these different transformations yielded the synthesis of 4-amino-2,6,8-trisubstituted pyrido[3,2-d]pyrimidine derivatives, with various substituents.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1021/jo201834d
- PMID 22118529
- Persistent URL
- https://sonar.rero.ch/global/documents/148953
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