2
48 M. Dehamchia and Z. Régaïnia
4
.6.2. 1,3-Dipropyl[1,2,5]thiadiazolo[3,4-b]quinoxaline-2,2-dioxide (6b)
Compound 6b was prepared using 5b (1 equiv., 1 mmol, 0.306 g) and was obtained as a yellowish-
white solid in 48% yield by conventional heating, 70% yield by MWI in ethanol and 81% yield
−
1
by solvent-free MWI. Rf = 0.30 (SiO2, CH2Cl2); IR (KBr, ν cm ): 1332 and 1139 (SO2),
1
1
595 (C=N str); H NMR (300 MHz, CDCl3, ppm): 0.99 (t, 6H, 2CH3), 1.78 (m, 4H, 2CH2),
3
.92 (s, 4H, 2CH2), 7.66–7.69 (dd, 2H, H–Ar, quinoxaline ring protons), 7.85–7.88 (dd, 2H,
+
H–Ar, quinoxaline ring protons); LRMS (CI): 307 [M + H] , 265. Elemental analysis: Calcd for
C14H18N4O2S: C = 54.88; H = 5.92; N = 18.29. Found: C = 54.82; H = 5.95; N = 18.24.
4
.6.3. 1,3-Di-(3-bromopropyl)[1,2,5]thiadiazolo[3,4-b]quinoxaline-2,2-dioxide (6c)
Compound 6c was prepared using 5c (1 equiv., 1 mmol, 0.460 g) and was obtained as a yellowish-
white solid in 42% yield by conventional heating, 64% yield by MWI in ethanol and 79% yield
−
1
by solvent-free MWI. Rf = 0.25 (SiO2, CH2Cl2); IR (KBr, ν cm ): 1334 and 1149 (SO2),
1
1
594 (C=N str); H NMR (300 MHz, CDCl3, ppm): 2.23 (m, 4H, 2CH2), 3.63 (t, 2H, CH2),
4
.10–4.26 (t, 4H, CH2), 7.69–7.72 (dd, 2H, H–Ar, quinoxaline ring protons), 7.88–7.91(dd, 2H,
+
H–Ar, quinoxaline ring protons); LRMS (CI): 465 [M+H] , 386. Elemental analysis: Calcd for
C14H16Br2N4O2S: C = 36.23; H = 3.47; N = 12.07. Found: C = 36.18; H = 3.51; N = 12.09.
Acknowledgements
The authors thank Prof. Wim Dehaen for the opportunity to perform a portion of the reported experiments described in
his laboratory. The authors are also thankful to the head of K. U. Leuven-Belgium and the Algerian Ministry of Research
for financial assistance.
References
(
(
(
1) Bäckbro, K.; Löwgren, S.; Österlund, K.; Atepo, J.; Unge,T.; Hultén, J.; Bonham, N.M.; Schaal, W.; Karlén, A.;
Hallberg, A. J. Med. Chem. 1997, 40, 898–902.
2) Hultén, J.; Bonham, N.M.; Nillroth, U.; Hansson, T.; Zuccarello, G.; Bouzide, A.;Aqvist, J.; Classon, B.; Danielson,
U.H.; Karlèn, A.; Kvarnstom, I.; Samuelsson, B.; Halberg, A. J. Med. Chem. 1997, 40, 885–897.
3) Rockway, T.W.; Zhang, R.; Liu, D.; Betebenner, D.A.; McDaniel, K.F.; Pratt, J.K.; Beno, D.; Montgomery, D.; Jiang,
W.W.; Masse, S.; Kati, W.M.; Middleton, T.; Molla, A.; Maring, C.J.; Kempf, D.J. Bio. Org. Med. Chem. Lett. 2006,
165, 3833–3838.
(4) Lai, Z.; Gan, X.;Wei, L.;Alliston, K.R.;Yu, H.; Li,Y.H.; Groutas, W.C. Arch. Biochem. Biophys. 2004, 429, 191–197.
(5) Groutas,W.C.;Kuang, R.;Ruan, S.;Epp, J.B.;Venkataraman, R.;Truong,T.M. Bioorg. Med. Chem. 1998, 6, 661–671.
(6) Chen, J.J.; Zhang, Y.; Hammond, S.; Dewdney, N.; Ho, T.; Lin, X.; Browner, M.F.; Castelhano, A.L. Bioorg.
Med.Chem. Lett. 1996, 6, 1601–1606.
(
(
(
7) Groutas, W.C.; Kuang, R.Z.; Venkataraman, R. Biochem. Biophys. Res. Commun. 1994, 198, 341–349.
8) Groutas, W.C.; Kuang, R.; Venkataraman, R.; Epp, J.B.; Ruan, S.; Prakash, O. Biochemistry 1997, 36, 4739–4750.
9) Yang, Q.; Li, Y.; Dou, D.; Gan, X.; Mohan, S.; Groutas, C.S.; Stevenson, L.E.; Lai, Z.; Alliston, K.R.; Zhong, J.;
Williams, T.D.; Groutas, W.C. Arch. Biochem. Biophy. 2008, 475, 115–120.
(
10) Sparey, T.; Beher, D.; Best, J.; Biba, M.; Castro, J.L.; Clarke, E.; Hannam, J.; Harrison, T.; Lewis, H.; Madin, A.;
Shearman, M.; Sohal, B.; Tsou, N.; Welch, C.; Wrigley, J. Bioorg. Med. Chem. Lett. 2005, 15, 4212–4216.
11) Gante, J. Angew. Chem. Int. Ed. Engl. 1994, 33, 1699–1720.
(
(
(
12) Boudjabi, S.; Dewynter, G.; Voyer, N.; Toupet, L.; Montero, J.L. Eur. J. Org. Chem. 1999, 9, 2275–2283.
13) Dougherty, J.M.; Probs, D.A.; Robinson, R.E.; Moore, J.D.; Klein, T.A.; Snelgrove, K.A.; Hanson, P.R. Tetrahedron
2
000, 56, 9781–9790.
(
14) Gobec, S.; Urleb, U. Product Class 15: Quinoxalines. In Science of Synthesis: Houben-Weyl Methods of Molecular
Transformations; Yamamoto, Y., Shinkai, I., Eds.; Thieme: Stuttgart, New York, 2004; Vol. 16, pp. 845–912.
15) Yadav, J.S.; Subba Reddy, B.V.; Premalatha, K.; Shankar, K.S. Synthesis 2008, 23, 3787–3792.
16) Romer, D.R.; Aldrich, B.L.; Pews, R.G.; Walter, R.W., Jr. Pestic. Sci. 1995, 43, 263–266.
17) Ortega, M.A.; Montoya, M.E.; Jaso, A.; Zarranz, B.; Tirapu, I.;Aldana, I.; Monge, A. Pharmazie 2001, 56, 205–207.
18) Zarnowski, T.; Kleinrok, Z.; Turski, W.A.; Czuczwar, S.J. Neuropharmacology 1993, 32, 895–900.
19) Metzner, J.; Lippmann, E.; Weber, F.G.; Westphal, G. Pharmazie 1981, 36, 368–370.
(
(
(
(
(