A Novel Synthesis of Tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones

Jona Mirnik; Uroš Grošelj; Ana Novak; Georg Dahmann; Amalija Golobič; Marta Kasunič; Branko Stanovnik; Jurij Svete

doi:10.1055/s-0033-1339977

Synthesis, Inhaltsverzeichnis

Synthesis 2013; 45(24): 3404-3412
DOI: 10.1055/s-0033-1339977

paper

A Novel Synthesis of Tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones

Jona Mirnik

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia Fax: +386(1)2419360 eMail: Jurij.svete@fkkt.uni-lj.si

,

Uroš Grošelj*

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia Fax: +386(1)2419360 eMail: Jurij.svete@fkkt.uni-lj.si

,

Ana Novak

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia Fax: +386(1)2419360 eMail: Jurij.svete@fkkt.uni-lj.si

,

Georg Dahmann

^bBoehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, 88397 Biberach, Germany

,

Amalija Golobič

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia Fax: +386(1)2419360 eMail: Jurij.svete@fkkt.uni-lj.si

,

Marta Kasunič

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia Fax: +386(1)2419360 eMail: Jurij.svete@fkkt.uni-lj.si

,

Branko Stanovnik

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia Fax: +386(1)2419360 eMail: Jurij.svete@fkkt.uni-lj.si

,

Jurij Svete*

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia Fax: +386(1)2419360 eMail: Jurij.svete@fkkt.uni-lj.si

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

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-pyrazolidinones

Volltext

Referenzen

References

1a Joule JA, Mills K. Heterocyclic Chemistry . 5th ed. Wiley-Blackwell; New York: 2010
1b Patrick GL. An Introduction to Medicinal Chemistry . 4th ed. Oxford University Press; Oxford: 2009
1c Pernerstorfer J. Molecular Design and Combinatorial Compound Libraries. In Handbook of Combinatorial Chemistry. Drugs, Catalysts, Materials. Vol. 2. Nicolaou KC, Hanko R, Hartwig W. Wiley-VCH; Weinheim: 2002: 725
1d Dolle RE. Solid-phase Synthesis of Heterocyclic Systems (Heterocycles Containing One Heteroatom). In Handbook of Combinatorial Chemistry. Drugs, Catalysts, Materials. Vol. 2. Nicolaou KC, Hanko R, Hartwig W. Wiley-VCH; Weinheim: 2002: 643

2a Hajos G, Riedl Z. Aza Analogues of Pyrazolo[1,5-a]pyridines Containing Additional Nitrogen Atoms in the Six-Membered Ring. In Science of Synthesis. Vol. 12. Neier R. Thieme; Stuttgart: 2006: 667
2b Regan AC. Pyrazolo[1,5-c]pyrimidine . In Comprehensive Heterocyclic Chemistry III . Vol. 11. Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Cossy, J.; Elsevier Science Ltd; Oxford: 2008: 577
2c Sliskovic DR. Pyrazolo[1,5-c]pyrimidine . In Comprehensive Heterocyclic Chemistry III . Vol. 8. Katritzky AR, Rees CV, Scriven EF. V. Elsevier Science Ltd; Oxford: 1996: 362 ; and references cited therein

3a Maier T, Baer T, Lindenmaier A, Vennemann M, Braunger J, Boehm M, Gekeler V, Zimmermann A. PCT Int. Appl WO 2007144384, 2007 ; Chem. Abstr. 2007, 148, 79077.
3b Mallams AK, Madison V, Paruch K. PCT Int. Appl WO 2007032936, 2007 ; Chem. Abstr. 2007, 146, 358880.
3c Maier T, Zuelch A, Ciossek T, Baer T, Beckers T. PCT Int. Appl WO 2006027346, 2006 ; Chem. Abstr. 2006, 144, 350709.

4a Gudmundsson K, Johns BA. PCT Int. Appl WO 2003076441, 2003 ; Chem. Abstr. 2003, 139, 261327.
4b Gudmundsson KS, Johns BA, Waterhead J. Bioorg. Med. Chem. Lett. 2009; 19: 5689

5 Casebier D. PCT Int. Appl WO 2010091303, 2010 ; Chem. Abstr. 2010, 153, 260549.

6a Kahraman M, Smith ND, Bonnefous C, Noble SA, Payne JE. PCT Int. Appl WO 2010088518, 2010 ; Chem. Abstr. 2010, 153, 260364.
6b Smith ND, Bonnefous C, Kahraman M, Noble SA, Payne JE, Govek SP. PCT Int. Appl WO 2010048149, 2010 ; Chem. Abstr. 2010, 152, 501397.

7a Atta KF. M, Farahat OO. M, Ghobashy M, Marei MG. Molecules 2011; 16: 10387
7b Atta KF. M, Marei MG, Abd El-MagiadS. M, El-Nashar FH. A. Heterocycles 2011; 83: 1873

8 Lee W.-C, Carter MB, Sun L, Lyne P, Chuaqui C, Zheng Z, Singh J, Boriack-Sjodin P. PCT Int. Appl WO 2004022054, 2004 ; Chem. Abstr. 2004, 140, 270867.

9a Kaneko Y, Kita H, Ikesu S. Jpn. Kokai Tokkyo Koho JP 04283272, 1992 ; Chem. Abstr. 1992, 119, 74607.
9b Kaneko Y, Kita H, Ikesu S. Jpn. Kokai Tokkyo Koho JP 04204441, 1992 ; Chem. Abstr. 1992, 118, 90726.
9c Yamakawa K, Ishii Y. Jpn. Kokai Tokkyo Koho JP 04191736, 1992 ; Chem. Abstr. 1992, 117, 261569.
9d Kaneko Y. Jpn. Kokai Tokkyo Koho JP 02236545, 1990 ; Chem. Abstr. 1990, 115, 18490.

10 Mahgoub FM, Abdel-Nabey BA, El-Samadisy YA. Mater Chem. Phys. 2010; 120: 104
11 Grošelj U, Podlogar A, Novak A, Dahmann G, Golobič A, Stanovnik B, Svete J. Synthesis 2013; 45: 639

12a Svete J. (4R*,5R*)-4-Benzoylamino-5-phenyl-3-pyrazolidinone – A Useful Building Block in the Synthesis of Functionalized Pyrazoles. Horvat MA, Golob JH. Nova Science Publishers; New York: 2008: 129 ; (open-access item, the pdf is available at https://www.novapublishers.com/catalog/product_info.php?products_id=16416); and references cited therein
12b Novak A, Testen A, Bezenšek J, Grošelj U, Hrast M, Kasunič M, Gobec S, Stanovnik B, Svete J. Tetrahedron 2013; 69: 6648 ; and references cited therein

13a Grošelj U, Kralj D, Wagger J, Dahmann G, Stanovnik B, Svete J. ARKIVOC 2012; (iii): 49 ; and references cited therein
13b Perdih P, Baškovč J, Dahmann G, Grošelj U, Kočar D, Stanovnik B, Svete J. Synthesis 2011; 2822
13c Žerovnik D, Grošelj U, Kralj D, Malavašič Č, Bezenšek J, Dahmann G, Stare K, Meden A, Stanovnik B, Svete J. Synthesis 2010; 3363

14 Farrugia LJ. J. Appl. Crystallogr. 1997; 30: 565
15 Structural and other crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 941194–941199 for compounds 4b, 4f, 8a, 8b, 10a, and 10d, respectively. A copy of the data can be obtained, free of charge, by applying to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: +44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].

Zusatzmaterial

Supporting Information