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Synthesis 2012(6): 895-902  
DOI: 10.1055/s-0031-1289733
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Reactions of Ethyl (4,5-Dihydrofuran-3-yl)-2-oxoacetate and Ethyl 2-(3,4-Dihydro-2H-pyran-6-yl)-2-oxoacetate with 1-Unsubstituted Aminoazoles

Oleksandr O. Stepaniuka,b, Vitalii O. Matvienkoa,b, Ivan S. Kondratov*b,c, Oleg V. Shishkind, Dmitriy M. Volochnyukb,e, Pavel K. Mykhailiuka,b, Andrei A. Tolmacheva,b
a Kyiv National Taras Shevchenko University, 64 Volodymirska st., 01033 Kiev-33, Ukraine
b Enamine Ltd., 23 A. Matrosova st., 01103 Kiev, Ukraine
Fax: +380(44)5373253; e-Mail: vanya_ko@mail.ru;
c Institute of Bioorganic Chemistry and Petrochemistry, National Ukrainian Academy of Science, Murmanska 1, 02660 Kiev-94, Ukraine
d STC Institute for Single Crystals, NAS of Ukraine, 60 Lenina ave., 61001 Kharkiv, Ukraine
e Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, 02094 Kiev-94, Ukraine
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Publication History

Received 9 December 2011
Publication Date:
01 March 2012 (online)

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Abstract

The reactions of ethyl (4,5-dihydrofuran-3-yl)-2-oxo­acetate and ethyl 2-(3,4-dihydro-2H-pyran-6-yl)-2-oxoacetate, as 1,3-bielectrophiles, with N-unsubstituted 5-aminoazoles, as N-C-N-binucleophiles, are the subject of this work. Regioselective heterocyclizations of ethyl 2-(3,4-dihydro-2H-pyran-6-yl)-2-oxoacetate lead to 3-hydroxypropyl-7-ethoxycarbonyl substituted pyrazolo[1,5-a]pyrimidines and triazolo[1,5-a]pyrimidines whilst the corresponding reactions of ethyl (4,5-dihydrofuran-3-yl)-2-oxoacetate result in the formation of oxodihydropyrano[4,3-e] annulated products.

Key words

lactones - aminoazoles - heterocyclization - pyrazolo[1,5-a]pyrimidines - triazolo[1,5-a]pyrimidines

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22

Crystal data for 13d: colorless crystals, C15H19N3O5, M = 321.33, triclinic, space group = P 1. At 293 K, a = 4.922(1) Å, b = 13.569(2) Å, c = 23.370(4) Å, α = 90.12(1)˚, β = 94.30(2)˚, γ = 92.94(2)˚, V = 1554.3(5) ų, Z = 4, d calcd = 1.373 g/cm³, µ(MoKα) = 0.104 mm-¹, F(000) = 680. Intensities of 18299 reflections (9005 independent, R int = 0.024) were measured on an Xcalibur-3 diffractometer (graphite monochromated MoKα radiation, CCD detector, ω-scaning, 2θmax = 60˚). Crystal data for 13f: colorless crystals, C13H16N4O5, M = 308.30, monoclinic, space group = P21/c. At 293 K, a = 9.0325(4) Å, b = 18.6803(6) Å, c = 9.5238(4) Å, α = 109.879(5)˚, V = 1511.2(1) ų, Z = 4, d calcd = 1.355 g/cm³, µ(MoKα) = 0.106 mm-¹, F(000) = 648. Intensities of 17049 reflections (4400 independent, R int = 0.027) were measured on an Xcalibur-3 diffractometer (graphite monochromated MoKα radiation, CCD detector, ω-scanning, 2θmax = 60˚). The structures were solved by direct methods using the SHELXTL package.²³ Restrictions on the bond lengths C(sp³)-C(sp³) (1.54 Å) were applied during the refinement of structure 13d. The positions of the hydrogen atoms were located from electron density difference maps and refined using the riding model with Uiso = nUeq of the carrier atom (n = 1.5 for methyl and hydroxy groups and n = 1.2 for other hydrogen atoms). The hydrogen atom involved in formation of the intermolecular hydrogen bond in structure 13f was refined within isotropic approximation. Full-matrix least-squares refinement of the structures against F ² in anisotropic approximation for non-hydrogen atoms using 8831 (13d) and 4364 (13f) reflections was converged to wR2 = 0.262 (R1 = 0.076 for 4111 reflections with F>4s(F), S = 0.957) for structure 13d, and wR2 = 0.122 (R1 = 0.045 for 2326 reflections with F>4s(F), S = 0.910) for structure 13f. The final atomic coordinates, and crystallographic data for molecules 13d and 13f have been deposited at the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: +44(1223)336033, e-mail: deposit@ccdc.cam.ac.uk] and are available on request quoting the deposition numbers CCDC 843315 for 13d and CCDC 843316 for 13f.