Chemistry of Heterocyclic Compounds 2016, 52(9), 743–749
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1
29.3 (C Ar); 132.3 (C Ar); 133.5 (C Ar); 148.5 (C-5');
the Ministry of Education and Science of the Russian
Federation (State assignment 4.1626.2014 / K).
50.3 (C-4'); 159.4 (C-3'); 160.1 (C=O); 162.2 (C-5).
Found, %: C 53.92; H 2.45; N 17.89. C14
H
8
N
4
O S.
3
Calculated, %: C 53.84; H 2.58; N 17.94.
References
Methyl 5-[3-(2-chloro-6-fluorophenyl)isoxazol-4-yl]-
,2,3-thiadiazole-4-carboxylate (8e) was obtained analo-
1
2
. Giomi, D.; Cordero, F. M.; Machetti, F. In Comprehensive
Heterocyclic Chemistry III; Katritzky, A. R.; Rees, C. W.;
Scriven, E. F. V. Pergamon Press: Oxford, 2008, Vol. 4,
p. 365.
. Gehling, V. S.; Hewitt, M. C.; Vaswani, R. G.; Leblanc, Y.;
Côté, A.; Nasveschuk, C. G.; Taylor, A. M.; Harmange, J.-C.;
Audia, J. E.; Pardo, E.; Joshi, S.; Sandy, P.; Mertz, J. A.;
Sims, R. J.; Bergeron, L.; Bryant, B. M.; Bellon, S.; Poy, F.;
Jayaram, H.; Sankaranarayanan, R.; Yellapantula, S.;
Srinivasamurthy, N. B.; Birudukota, S.; Albrecht, B. K. ACS
Med. Chem. Lett. 2013, 4, 835.
1
gously to compound 8a. Yield 322 mg (95%), mp 236–
–
1
2
38°C. IR spectrum, ν, cm : 1723, 1421, 1328, 1128.
1
H NMR spectrum (DMSO-d
OCH ); 7.44–7.58 (2H, m, H Ar); 7.72–7.78 (1H, m,
H Ar); 9.85 (1H, s, H-5'). C NMR spectrum (DMSO-d
δ, ppm: 52.9 (OCH ); 107.6 (C-4); 114.2; 115.4; 126.3;
6
), δ, ppm: 3.84 (3H, s,
3
1
3
6
),
3
1
33.9; 134.3; 147.4; 149.0; 156.4; 160.0; 161.4; 161.9.
Found, %: C 45.82; H 2.22; N 12.14. C13
H
7
ClFN
3
O S.
3
Calculated, %: C 45.96; H 2.08; N 12.37.
3
4
. Di Nunno, L.; Vitale, P.; Scilimati, A.; Tacconelli, S.;
Patrignani, P. J. Med. Chem. 2004, 47, 4881.
. Galenko, A. V.; Khlebnikov, A. F.; Novikov, M. S.;
Pakalnis, V. V.; Rostovskii, N. V. Russ. Chem. Rev. 2015, 84, 335.
Methyl 5-[3-(pyridin-2-yl)isoxazol-4-yl]-1,2,3-thiadia-
zole-4-carboxylate (8f) was obtained analogously to
compound 8a. Yield 158 mg (55%), mp 148–149°C. IR
–1
1
spectrum, ν, cm : 1718, 1470, 1330, 1205. H NMR
5. Girardin, M.; Dolman, S. J.; Lauzon, S.; Ouellet, S. G.;
Hughes, G.; Fernandez, P.; Zhou, G.; O'Shea, P. D. Org.
Process Res. Dev. 2011, 15, 1073.
spectrum (DMSO-d
6
), δ, ppm: 3.64 (3H, s, OCH
3
); 7.44–
7
.47 (1H, m, H Ar); 7.93–8.04 (1H, m, H Ar); 8.43–8.50
1
3
6. Brodney, M. A.; Beck, E. M.; Butler, C. R.; Barreiro, G.;
Johnson, E. F.; Riddell, D.; Parris, K.; Nolan, C. E.; Fan, Y.;
Atchison, K.; Gonzales, C.; Robshaw, A. E.; Doran, S. D.;
Bundesmann, M. W.; Buzon, L.; Dutra, J.; Henegar, K.;
La Chapelle, E.; Hou, X.; Rogers, B. N.; Pandit, J.; Lira, R.;
Martinez-Alsina, L.; Mikochik, P.; Murray, J. C.; Ogilvie, K.;
Price, L.; Sakya, S. M.; Yu, A.; Zhang, Y.; O'Neill, T. J. Med.
Chem. 2015, 58, 3223.
(
(
1H, m, H Ar); 9.44 (1H, s, H-5'). C NMR spectrum
DMSO-d ), δ, ppm: 52.3 (OCH ); 105.7 (C-4); 122.6;
25.2; 137.8; 147.1; 148.8; 149.2; 150.6; 158.2 (C-3'); 160.1
C=О); 161.9 (C-5). Found, %: C 50.13; H 2.63; N 19.55.
S. Calculated, %: C 50.00; H 2.80; N 19.43.
6
3
1
(
C
12
H
8
N
4
O
3
Methyl 5-(3-cyclohexylisoxazol-4-yl)-1,2,3-thiadiazole-
4
-carboxylate (8g) was obtained analogously to compound
8
a. Yield 200 mg (68%), colorless crystals, mp 76–78°C.
7. Amegadzie, A. K.; Gardinier, K. M.; Hembre, E. J. Hong, J. E.;
Jungheim, L. N.; Muehl, B. S.; Remick, D. M.; Robertson, M. A.;
Savin, K. A. WO Patent 2003091226.
1
H NMR spectrum (CDCl
3
), δ, ppm: 1.11–1.41 (4H, m,
H сyclo-Нех); 1.41–1.63 (2H, m, H сyclo-Нех); 1.63–1.91
8
9
1
. Leban, J.; Tasler, S.; Saeb, W.; Chevrier, C. WO Patent
2012101263; Chem. Abstr. 2012, 158, 17532d.
. Bakulev, V. A.; Tarasov, E. V.; Morzherin, Y. Y.; Luyten, I.;
Toppet, S.; Dehaen, W. Tetrahedron 1998, 54, 850
0. Lebedev, A. T.; Dankova, E. F.; Mokrushin, V. S.; Petrosyan, V. S.
Tetrahedrоn 1989, 45, 7329.
(
(
(
4H, m, H сyclo-Нех); 2.57–2.70 (1H, m, H сyclo-Нех); 3.95
13
3H, s, OCH
3
); 9.19 (1H, s, H-5'). C NMR spectrum
CDCl ), δ, ppm: 25.7; 26.2; 31.7; 35.9; 53.3; 65.0; 105.6;
3
+
1
49.2; 149.5; 159.4; 160.9. Mass spectrum, m/z: 293 [M] .
Found, %: C 53.17; H 5.23; N 14.25. C13
H
15
N
3
O S.
3
Calculated, %: C 53.23; H 5.15; N 14.32.
11. Bakulev, V. A.; Mokrushin, V. S. Chem. Heterocycl. Compd.
1986, 22, 811. [Khim. Geterotsikl. Soedin. 1986, 1011.]
1
X-ray structural analysis of compound 6g. Single
2. Buettelmann, B.; Han, B.; Knust, H.; Thomas, A. WO Patent
crystals for compound 6g (C14
were obtained from ethanol. X-ray structural analysis was
performed on an Xcalibur automatic 4-circle
diffractometer with a CCD-detector according to the
standard procedure (ω-scanning in 1° steps with a
monochromatic МоKα beam). Diffraction data for the
compound were obtained at 295(2) K, an empirical cor-
rection for the absorption was introduced. The structure
was solved and refined using Olex2 software package.2
The structures were solved by the direct statistical method
using the ShelXS software and refined against F by the
least-squares technique in the full-matrix anisotropic
approximation for all non-hydrogen atoms using ShelXL
software.30 Hydrogen atoms of C–H bonds were placed in
geometrically calculated positions and refined in the
isotropic approximation. The full set of X-ray structural
data was deposited at the Cambridge Crystallographic Data
Center (deposit CCDC 1508884).
H
10Cl
2
N
4
O
2
, М 337.161)
2
007074078; Chem. Abstr. 2007, 147, 143428.
1
3. Thorarensen, A.; Ruble, C. J.; Fisher, J. F.; Romero, D. L.;
Beauchamp, T. J.; Northuis, J. M. WO Patent 2004018428;
Chem. Abstr., 2004, 140, 235498.
3
1
1
4. Eiden, F.; Patzelt, G. Arch. Pharm. 1986, 319, 242.
5. Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.;
Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem.
Soc. 2005, 127, 210.
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1
6. Bakulev, V. A.; Efimov, I. V.; Belyaev, N. A.; Rozin, Yu. A.;
Volkova, N. N.; El'tsov, O. S. Chem. Heterocycl. Compd.
2012, 47, 1593. [Khim. Geterotsikl. Soedin. 2011, 1900.]
7. Al-Shiekh, M. A.; Salah El-Din, A. M.; Hafez, E. A.;
Elnagdi, M. H. J. Chem. Res., Synop. 2004, 174.
2
7
2
1
1
1
2
8. Jones, R. C. F.; Dawson, C. E.; O'Mahony, M. J. Synlett 1999, 873.
9. Jones, R. C. F.; Pillainayagam, T. A. Synlett 2004, 2815.
0. Bakulev, V. A.; Efimov, I. V.; Belyaev, N. A.; Zhidovinov, S. S.;
Rozin, Yu. A.; Volkova, N. N.; Khabarova, A. A.; El'tsov, O. S.
Chem. Heterocycl. Compd. 2013, 48, 1880. [Khim.
Geterotsikl. Soedin. 2012, 2002.]
2
2
1. Harjinder, S; Jayant, S; Jitender, K. RSC Adv. 2013, 3, 22360.
2. Krompiec, S.; Bujak, P.; Szczepankiewicz, W. Tetrahedron
Lett. 2008, 49, 6071.
This work was supported financially by the Russian
Foundation for Basic Research (grant 14-03-01033) and
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