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Synthesis 2013; 45(24): 3404-3412
DOI: 10.1055/s-0033-1339977
DOI: 10.1055/s-0033-1339977
paper
A Novel Synthesis of Tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones
Authors
Further Information
Publication History
Received: 19 July 2013
Accepted after revision: 18 September 2013
Publication Date:
18 October 2013 (online)
Abstract
A novel simple five-step synthesis of 1,6-disubstituted tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones has been developed. The synthetic protocol starts with ‘ring switching’ transformation of commercially available 5,6-dihydro-2H-pyran-2-one into the 5-(2-hydroxyethyl)pyrazolidin-3-one, followed by addition of the latter to isocyanates, Appel bromination, cyclization, and N(1)-alkylation with alkyl halides to give the title compounds. In comparison to a 12-step synthesis reported recently, the present method is clearly superior with respect to the number of synthetic steps and versatility of substituents at position 6.
Key words
pyrazolo[1,5-c]pyrimidines - ring-switching - cyclization - saturated heterocycles - 3-pyrazolidinonesSupporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
Included are 1H and 13C NMR spectra of compounds 4, 6, and 8–10, as well as ORTEP views and diffraction data for compounds 8b, 10d, and 4f.
- Supporting Information (PDF) (opens in new window)
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