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Synthesis of highly substituted 2,3-dihydropyrimido[4,5-d]pyrimidin-4(1H)-ones from 4,6-dichloro-5-formylpyrimidine, amines and aldehydes

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Abstract

A practical strategy was developed for the preparation of highly substituted 2,3-dihydropyrimido[4,5-d]pyrimidin-4(1H)-ones from 4,6-dichloro-5-formylpyrimidine, primary amines, and aldehydes. The key step for this synthesis entails a cyclization reaction involving an intramolecular amide addition to an iminium intermediate formed in situ from 4-amino-pyrimidine-5-carboxamide 2 and aldehydes to form the pyrimido[4,5-d]pyrimidine core with a strategically placed 5-Cl group for further derivatization. The utility of this methodology was demonstrated through the preparation of a 27-membered library of representative 2,3-dihydropyrimido[4,5-d]pyrimidin-4(1H)-ones in moderate to good yields.

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Authors and Affiliations

  1. The Center for Combinatorial Chemistry and Drug Discovery, The School of Pharmaceutical Sciences and The College of Chemistry, Jilin University, 1266 Fujin Road, Changchun, Jilin, 130021, People’s Republic of China

    Jinbao Xiang, Chao Geng, Lang Yi, Qun Dang & Xu Bai

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  1. Jinbao Xiang
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  2. Chao Geng
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  3. Lang Yi
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  4. Qun Dang
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  5. Xu Bai
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Correspondence to Xu Bai.

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Xiang, J., Geng, C., Yi, L. et al. Synthesis of highly substituted 2,3-dihydropyrimido[4,5-d]pyrimidin-4(1H)-ones from 4,6-dichloro-5-formylpyrimidine, amines and aldehydes. Mol Divers 15, 839–847 (2011). https://doi.org/10.1007/s11030-011-9314-5

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  • DOI: https://doi.org/10.1007/s11030-011-9314-5

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