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Synthesis 2003(11): 1739-1743
DOI: 10.1055/s-2003-40891
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Solid-Phase Synthesis of Pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones

Nadège Graveleau, Thierry Masquelin*
Combinatorial & Parallel Chemistry, Basilea Pharmaceutica Ltd, Grenzacherstrasse 487, 4002 Basel, Switzerland
Fax: thierry.masquelin@basileapharma.com;
Further Information

Publication History

Received 7 April 2003
Publication Date:
25 July 2003 (online)

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Abstract

We report a novel, and versatile solid-phase synthesis of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones starting from the polymer-bound pyrimidine 3. The key step is based on the reaction of the support-bound pyrimidine 3 with isocyanates 4, involving formation of a carbamate intermediate, followed by a base-catalysed intramolecular ring closure, to give polymer-bound 3-monosubstituted 1H-pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones 5. At this stage, subsequent treatment with alkyl halides 6 lead to 1,3-disubstituted 2H-pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione intermediates 7, which after oxidation and cleavage with various amines 8 gave 1,3-disubstituted 7-amino-2H-pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones 9 in moderate yields and high purity.

Key words

solid-phase - pyrimidine - base-catalysed ring clo­sure - intramolecular cyclisation - pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones