G. Karabanovich et al. / European Journal of Medicinal Chemistry 82 (2014) 324e340
337
solvent was evaporated under reduced pressure, and the crude
product was purified by column chromatography (Hexane/EtOAc).
d
7.55e7.44 (m, 5H), 7.42e7.36 (m, 2H), 7.33e7.24 (m, 3H), 4.68 (s,
2H); 13C NMR (75 MHz, CDCl3)
d
147.18, 136.24, 133.94, 130.20,
129.75, 129.11, 128.80, 127.91, 123.88, 32.56. IR (KBr): 3030, 2922,
1595, 1497, 1374, 1233, 1089, 1014, 973, 765, 693 cmꢂ1. Anal. Calcd
for C14H12N4Se: C, 53.34; H, 3.84; N, 17.77. Found: C, 53.25; H, 3.98;
N, 17.53.
4.7.2. 5-Benzylselanyl-1-cyclohexyl-1H-tetrazole (13e)
The reaction was carried out in THF. The product was purified by
column chromatography (Mobile phase: Hexane/EtOAc, 6:1). Yield:
76% (white solid); mp 62 ꢀC. 1H NMR (300 MHz, CDCl3)
d 7.32e7.20
(m, 5H), 4.53 (s, 2H), 4.08e3.97 (m, 1H), 1.90e1.79 (m, 6H),
4.7.8. 1-Cyclohexyl-5-[(2,4-dinitrobenzyl)selanyl]-1H-tetrazole
(14e)
1.71e1.67 (m, 1H), 1.37e1.20 (m, 3H); 13C NMR (75 MHz, CDCl3)
d
144.91, 136.79, 128.91, 128.77, 127.83, 58.81, 32.77, 32.23, 25.08,
Cyclohexylisoselenocyanate (12e) (1 mmol) and sodium azide
(1.2 mmol) in water (5 mL) were stirred at rt overnight. The
aqueous solution was filtered and washed with EtOAc (2 ꢁ 7 mL).
2,4-Dinitrobenzyl chloride (1 mmol) and TBAB (0.1 mmol) in CH2Cl2
(7 mL) were added to the aqueous solution. The reaction mixture
was stirred at rt overnight. The organic layer was separated and
dried over anhydrous sodium sulfate; the solvent was evaporated
under reduced pressure. The product was purified by column
chromatography (Mobile phase: Hexane/EtOAc, 10:1). Yield: 50%
24.73. IR (KBr): 2935, 2857, 1494, 1452, 1421, 1365, 1272, 1185, 1083,
1001, 894, 817, 753, 696 cmꢂ1. Anal. Calcd for C14H18N4Se: C, 52.34;
H, 5.65; N, 17.44. Found: C, 52.27; H, 5.98; N, 17.36. MS (ESI): m/z
322.97 [M þ H]þ.
4.7.3. 5-[(3,5-Dinitrobenzyl)selanyl]-1-hexyl-1H-tetrazole (15c)
The reaction was carried out in CH3CN. The product was purified
by column chromatography (Mobile phase: Hexane/EtOAc, 10:1).
Yield: 45% (white solid); mp 57e58 ꢀC. 1H NMR (500 MHz, Acetone)
(yellowish solid); mp 98e99 ꢀC. 1H NMR (500 MHz, CDCl3)
d 8.98 (d,
d
8.82e8.79 (m, 3H), 4.89 (s, 2H), 4.29 (t, J ¼ 7.1 Hz, 2H), 1.81e1.76
J ¼ 2.3 Hz, 1H), 8.41 (dd, J ¼ 8.6, 2.3 Hz, 1H), 8.18 (d, J ¼ 8.6 Hz, 1H),
(m, 2H), 1.25e1.20 (m, 6H), 0.82 (t, J ¼ 7.0 Hz, 3H); 13C NMR
4.94 (s, 2H), 4.07e3.98 (m, 1H), 2.01e1.85 (m, 6H), 1.78e1.71 (m,
(125 MHz, Acetone)
d
149.28, 146.43, 144.77, 130.30, 118.25, 48.66,
1H), 1.46e1.20 (m, 3H); 13C NMR (125 MHz, CDCl3)
d 147.44, 146.94,
31.67, 30.55, 30.32, 26.52, 22.96, 14.10. IR (KBr): 3111, 2933, 2859,
145.12, 141.32, 134.33, 128.21, 121.08, 59.20, 32.22, 28.08, 25.04,
24.68. IR (KBr): 3089, 2955, 2853, 1611, 1537, 1455, 1426, 1340, 1277,
1193, 1175, 1083, 997, 913, 817, 802, 744, 712, 684 cmꢂ1. Calcd for
C14H16N6O4Se: C, 40.89; H, 3.92; N, 20.43. Found: C, 40.57; H, 4.17;
N, 20.06.
1541, 1460, 1426, 1385, 1343 (NO2), 1179, 1074, 809, 729, 675 cmꢂ1
.
Anal. Calcd for C14H18N6O4Se: C, 40.69; H, 4.39; N, 20.33. Found: C,
41.01; H, 4.61; N, 20.14. MS (ESI): m/z 415.0 [M þ H]þ.
4.7.4. 1-Benzyl-5-[(3,5-dinitrobenzyl)selanyl]-1H-tetrazole (15d)
The reaction was carried out in CH3CN. The product was purified
by column chromatography (Mobile phase: Hexane/EtOAc, 5:1).
Yield: 33% (light brown solid); mp 152e154 ꢀC. 1H NMR (500 MHz,
4.7.9. 5-[(3,5-Dinitrobenzyl)selanyl]-1-phenyl-1H-tetrazole (15g)
The reaction was carried out in CH3CN. The product was purified
by column chromatography (Mobile phase: Hexane/EtOAc, 10:1).
Yield: 28% (light beige solid); mp 141e143 ꢀC (with decomposition).
Acetone)
(m, 3H), 7.22e7.19 (m, 2H), 5.57 (s, 2H), 4.81 (s, 2H); 13C NMR
(126 MHz, Acetone) 149.21, 146.86, 144.55, 134.90, 130.16, 129.72,
d
8.75 (t, J ¼ 2.2 Hz, 1H), 8.68 (d, J ¼ 2.2 Hz, 2H), 7.33e7.29
Rf (Hexane/EtOAc, 3:1) 0.18. 1H NMR (300 MHz, Acetone)
d
8.85 (d,
J ¼ 2.1 Hz, 2H), 8.80 (t, J ¼ 2.1 Hz, 1H), 7.78e7.39 (m, 5H), 4.95 (s,
2H); 13C NMR (75 MHz, Acetone)
149.29, 147.59, 144.56, 134.88,
131.44, 130.88, 130.46, 125.20, 118.29, 30.39. IR (KBr): 3098, 1536,
1499, 1342, 1232, 1093, 1036, 914, 809, 771, 734, 692, 672 cmꢂ1
d
129.45, 128.81, 118.26, 52.09, 30.51. Anal. Calcd for C15H12N6O4Se: C,
42.97; H, 2.88; N, 20.05. Found: C, 43.19; H, 2.88; N, 19.75.
d
.
4.7.5. 1-Cyclohexyl-[(3,5-dinitrobenzyl)selanyl]-1H-tetrazole (15e)
The reaction was carried out in CH3CN. The product was purified
by column chromatography (Mobile phase: Hexane/EtOAc, 5:1).
Yield: 68% (yellowish solid); mp 103 ꢀC. 1H NMR (500 MHz, CDCl3)
Anal. Calcd for C14H10N6O4Se: C, 41.50; H, 2.49; N, 20.74. Found: C,
41.32; H, 2.71; N, 20.47.
4.7.10. 5-[(3,5-Dinitrobenzyl)selanyl]-1-(4-methoxyphenyl)-1H-
tetrazole (15j)
d
8.94e8.90 (m, 1H), 8.72e8.69 (m, 2H), 4.77 (s, 2H), 4.13e4.04 (m,
1H), 2.02e1.86 (m, 6H), 1.77e1.74 (m, 1H), 1.46e1.22 (m, 3H); 13C
NMR (125 MHz, CDCl3) 148.51,143.93,142.17,129.44,118.07, 59.27,
The reaction was carried out in THF. The product was purified by
column chromatography (Mobile phase: Hexane/EtOAc, 7:1). Yield:
33% (brownish solid); mp 131e132 ꢀC (with decomposition). Rf
d
32.29, 29.48, 25.05, 24.67. IR (KBr): 3095, 2941, 2859, 1538, 1452,
1424, 1383, 1361, 1342, 1276, 1198, 1083, 1005, 922, 817, 808, 731,
671 cmꢂ1. Anal. Calcd for C14H16N6O4Se: C, 40.89; H, 3.92; N, 20.43.
Found: C, 40.93; H, 4.21; N, 20.74.
(Hexane/EtOAc, 3:1) 0.12. 1H NMR (500 MHz, Acetone)
d 8.83 (d,
J ¼ 2.1 Hz, 2H), 8.80 (t, J ¼ 2.1 Hz,1H), 7.48 (d, J ¼ 9.0 Hz, 2H), 7.14 (d,
J ¼ 9.0 Hz, 2H), 4.91 (s, 2H), 3.89 (s, 3H); 13C NMR (125 MHz,
Acetone)
d 162.07, 149.27, 147.77, 144.63, 130.42, 127.39, 126.94,
4.7.6. Method D
118.26, 115.81, 56.11, 30.26. IR (KBr): 3089, 2923, 1608, 1591, 1537,
1511, 1446, 1342, 1257, 1173, 1020, 913, 839, 730, 672 cmꢂ1. Anal.
Calcd for C15H12N6O5Se: C, 41.39; H, 2.78; N, 19.31. Found: C, 41.59;
H, 2.41; N, 19.0.
A saturated solution of sodium azide (1.2 mmol) in water
(0.5 mL) was added to the solution of arylisoselenocyanate 12g, 12j
or 12n (1 mmol) and alkyl halide (0.7 mmol) in 10 mL of organic
solvent (THF or CH3CN). The reaction proceeded with the release of
nitrogen and the precipitation of elemental selenium and was
completed in 15e30 min. Upon completion, selenium powder was
filtered off. The solvent was evaporated and the residue was
adsorbed onto silica gel and purified by column chromatography or
reverse phase column chromatography.
4.7.11. 1-(4-Bromophenyl)-5-[(3,5-dinitrobenzyl)selanyl]-1H-
tetrazole (15n)
The reaction was carried out in THF, 3,5-dinitrobenzyl iodide
was used as an alkylating agent. The product was purified by col-
umn chromatography (Mobile phase: Hexane/EtOAc, 8:1). Yield:
34% (white solid); mp 154e155 ꢀC (with decomposition). Rf (Hex-
4.7.7. 5-Benzylselanyl-1-phenyl-1H-tetrazole (13g)
ane/EtOAc, 3:1) 0.12. 1H NMR (500 MHz, Acetone)
d 8.84 (d,
The reaction was carried out in THF. The product was purified by
reverse phase column chromatography (Mobile phase: CH3CN/H2O,
2:1) Yield: 17% (beige solid); mp 71 ꢀC. Rf (Hexane/EtOAc, 3:1) 0.72,
Rf (RP-18; CH3CN/H2O, 2:1) 0.27. 1H NMR (300 MHz, CDCl3)
J ¼ 2.1 Hz, 2H), 8.80 (t, J ¼ 2.1 Hz,1H), 7.84 (d, J ¼ 8.8 Hz, 2H), 7.58 (d,
J ¼ 8.8 Hz, 2H), 4.95 (s, 2H); 13C NMR (125 MHz, Acetone)
d 148.38,
146.76,143.59, 133.19, 133.11, 129.57, 126.28, 123.99, 117.40, 29.71. IR
(KBr): 3104, 2923, 1530, 1496, 1361, 1340, 1176, 1073, 1007, 841, 731,