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Gaponenko et al.
J = 7.9 Hz); 7.01 (m, 1 H, Ar); 7.13 (m, 2 H, Ar); 7.22 (m, 3 H,
C6H4NO2ꢀ4, Ar); 7.55 (m, 2 H, N(4)H, Ar); 8.02 (d, 2 H,
C6H4NO2ꢀ4, J = 8.9 Hz); 10.66 (s, 1 H, N(1)H).
0.39 g (71%), colorless crystals, m.p. 235—236 °C. Found (%):
C, 63.88; H, 3.93; N, 18.33. C29H21N7O3S. Calculated (%):
C, 63.61; H, 3.87; N, 17.90. 1H NMR (DMSOꢀd6), δ: 4.61, 4.92
(both d, 1 H each, NCH2Ph, J = 15.5 Hz); 5.54 (s, 1 H, H(7´));
5ꢀFluoroꢀ2´ꢀ(4ꢀnitrophenyl)spiro[indoleꢀ3,3´ꢀ[1,3,4]thiadiꢀ
azino[3,2ꢀa]benzimidazol]ꢀ2(1H)ꢀone (5c). Yield 0.224 g (50%),
white crystals, m.p. 315—320 °C (MeOH). Found (%): C, 59.06;
H, 3.15; F, 4.25; N, 15.65. C22H14FN5O3S. Calculated (%):
C, 59.15; H, 3.19; F, 4.37; N, 15.54. 1H NMR (DMSOꢀd6), δ: 5.57
(s, 1 H, H(2)); 6.25 (dd, 1 H, Hindole, J = 2.5 Hz, J = 2.5 Hz);
6.76 (m, 1 H, Hindole); 7.09—7.36 (m, 6 H, Ar, C6H4NO2ꢀ4);
7.60 (d, 1 H, Ar, J = 7.4 Hz); 7.76 (s, 1 H, N(4)H); 8.09 (d, 2 H,
C6H4NO2ꢀ4, J = 8.8 Hz); 10.87 (s, 1 H, N(1)H).
5,7ꢀDimethylꢀ2´ꢀ(4ꢀnitrophenyl)spiro[indoleꢀ3,3´ꢀ[1,3,4]ꢀ
thiadiazino[3,2ꢀa]benzimidazol]ꢀ2(1H)ꢀone (5d). Yield 0.32 g
(70%), light yellow crystals, m.p. 306—309 °C (MeOH). Found (%):
C, 63.01; H, 4.19; N, 15.31. C24H19N5O3S. Calculated (%):
C, 63.15; H, 4.14; N, 15.39. 1H NMR (DMSOꢀd6), δ: 1.97, 2.01
(both s, 3 H each, C(5)Me, C(7)Me); 5.52 (s, 1 H, H(2´)); 6.27,
6.88 (both s, 1 H each, H(4), H(6)); 7.09—7.30 (m, 5 H,
Ar, C6H4NO2ꢀ4); 7.58 (m, 2 H, Ar, N(4´)H); 8.06 (d, 2 H,
C6H4NO2ꢀ4, J = 8.8 Hz); 10.75 (s, 1 H, N(1)H).
6.69—6.80 (m, 3 H, Hindole, CH2Ph); 6.91 (d, 1 H, Hindole
,
J = 6.8 Hz); 7.05—7.13 (m, 4 H, Hindole, CH2Ph); 7.22 (d, 2 H,
4ꢀNO2C6H4, J = 8.4 Hz); 7.33 (m, 1 H, Hindole); 7.80 (d, 2 H,
Py, J = 6.2 Hz); 7.98 (d, 2 H, 4ꢀNO2C6H4, J = 8.4 Hz); 8.32
(s, 1 H, N(5´)H); 8.68 (d, 2 H, Py, J = 6.2 Hz). MS (EI, 70 eV),
m/z (Irel (%)): 370 (5), 312 (1), 236 (3), 208 (4), 190 (3), 178 (6),
145 (7), 133 (3), 104 (9), 91 (100), 76 (10).
B. Synthesis of 1ꢀbenzylꢀ7´ꢀ(4ꢀnitrophenyl)ꢀ3´ꢀ(4ꢀpyridyl)ꢀ
spiro[indoleꢀ3,6´ꢀ[1,2,4]triazolo[3,4ꢀb][1,3,4]thiadiazin]ꢀ2(1H)ꢀ
one (7b). Compound 8 (1 mmol) was added to a solution of
NaOH (1 mmol) in EtOH (10 mL). After the mixture became
homogeneous, 4ꢀnitrobenzyl bromide (1 mmol) was added. After
homogenization was completed, the reaction mixture was heatꢀ
ed for 5 min, whereupon an additional amount of NaOH
(1 mmol) was added. The reaction mixture was refluxed for 2 h,
cooled, diluted with water, and neutralized with dilute HCl. The
precipitate that formed was filtered off and recrystallized from
MeCN. The yield was 0.36 g (66%).
5ꢀMethoxyꢀ1ꢀmethylꢀ2´ꢀ(4ꢀnitrophenyl)spiro[indoleꢀ3,3´ꢀ
[1,3,4]thiadiazino[3,2ꢀa]benzimidazol]ꢀ2(1H)ꢀone (5e). Yield
0.25 g (53%), beige crystals, m.p. 267—269 °C (MeOH). Found (%):
C, 60.88; H, 4.04; N, 14.79. C24H19N5O4S. Calculated (%):
C, 60.80; H, 3.98; N, 14.83. 1H NMR (DMSOꢀd6), δ: 2.86, 3.51
(both s, 3 H each, NMe, OMe); 5.59 (s, 1 H, H(2´)); 6.06 (d, 1 H,
Ar, J = 2.2 Hz); 6.83 (d, 1 H, Ar, J = 8.6 Hz); 6.91 (m, 1 H, Ar);
7.09—7.30 (m, 5 H, Ar, C6H4NO2ꢀ4); 7.60 (d, 1 H, Ar, J = 7.7 Hz);
7.79 (s, 1 H, NH); 8.06 (d, 2 H, C6H4NO2ꢀ4, J = 8.7 Hz).
1ꢀBenzylꢀ2´ꢀ(4ꢀnitrophenyl)spiro[indoleꢀ3,3´ꢀ[1,3,4]thiaꢀ
diazino[3,2ꢀa]benzimidazol]ꢀ2(1H)ꢀone (5f). Yield 0.19 g (91%),
light yellow crystals, decomp. 280—285 °C (MeOH). Found (%):
C, 67.04; H, 4.07; N, 13.48. C29H21N5O3S. Calculated (%):
C, 67.22; H, 4.11; N, 13.42. 1H NMR (DMSOꢀd6), δ: 4.55, 4.91
(both d, 1 H each, CH2Ph, J = 15.8 Hz); 5.62 (s, 1 H, H(2´));
6.64 (m, 3 H, Ar); 6.83 (d, 1 H, Ar, J = 7.9 Hz); 6.89—7.20 (m, 8 H,
Ar); 7.24 (m, 2 H, Ar); 7.55 (d, 1 H, Ar, J = 7.4 Hz); 7.81 (s, 1 H,
NH); 7.94 (d, 2 H, C6H4NO2ꢀ4, J = 8.6 Hz).
Synthesis of spirocyclic 1,2,4ꢀtriazolo[3,4ꢀb][1,3,4]thiaꢀ
diazines 7 (general procedure). A. NꢀAlkylisatin (1 mmol) was
added to a solution of 4ꢀaminoꢀ3ꢀ(4ꢀnitrobenzyl)thioꢀ4Hꢀ1,2,4ꢀ
triazole 6 (1 mmol) in EtOH. After the mixture became homoꢀ
geneous, NaOH (1 mmol) was added. The reaction mixture was
refluxed for 2 h, cooled, diluted with water, and neutralized with
dilute HCl. The precipitate that formed was filtered off and reꢀ
crystallized from MeCN.
1ꢀBenzylꢀ7´ꢀ(4ꢀnitrophenyl)ꢀ3´ꢀphenylspiro[indoleꢀ3,6´ꢀ
[1,2,4]triazolo[3,4ꢀb][1,3,4]thiadiazin]ꢀ2(1H)ꢀone (7a). Yield
0.40 g (75%), colorless crystals, m.p. 278 °C. Found (%): C, 66.21;
H, 4.12; N, 15.79. C30H22N6O3S. Calculated (%): C, 65.92;
H, 4.06; N, 15.37. 1H NMR (DMSOꢀd6), δ: 4.59, 4.91 (both d, 1 H
each, NCH2Ph, J = 15.9 Hz); 5.51 (s, 1 H, H(7)); 6.65—6.81
(m, 3 H, Hindole, CH2Ph); 6.88 (d, 1 H, Hindole, J = 7.8 Hz);
7.02—7.12 (m, 4 H, Hindole, CH2Ph); 7.21 (d, 2 H, 4ꢀNO2C6H4,
J = 9.1 Hz); 7.32 (m, 1 H, Hindole); 7.45 (m, 3 H, Ph); 7.75 (m, 2 H,
Ph); 7.95 (d, 2 H, 4ꢀNO2C6H4, J = 9.1 Hz); 8.14 (s, 1 H,
N(5´)H). MS (EI, 70 eV), m/z (Irel (%)): 370 (5), 293 (2), 263 (1),
208 (2), 190 (3), 179 (4), 149 (8), 133 (4), 103 (18), 91 (100), 77 (12).
1ꢀBenzylꢀ7´ꢀ(4ꢀnitrophenyl)ꢀ3´ꢀ(4ꢀpyridyl)spiro[indoleꢀ3,6´ꢀ
[1,2,4]triazolo[3,4ꢀb][1,3,4]thiadiazin]ꢀ2(1H)ꢀone (7b). Yield
1ꢀBenzylꢀ7´ꢀ(4ꢀnitrophenyl)ꢀ3´ꢀ(3ꢀpyridyl)spiro[indoleꢀ3,6´ꢀ
[1,2,4]triazolo[3,4ꢀb][1,3,4]thiadiazin]ꢀ2(1H)ꢀone (7c). Yield
0.393 g (72%), colorless crystals, m.p. 166—168 °C. Found (%):
C, 63.87; H, 3.94; N, 18.35. C29H21N7O3S. Calculated (%):
C, 63.61; H, 3.87; N, 17.90. 1H NMR (DMSOꢀd6), δ: 4.59, 4.91
(both d, 1 H each, NCH2Ph, J = 15.9 Hz); 5.53 (s, 1 H, H(7´));
6.69—6.80 (m, 3 H, Hindole, CH2Ph); 6.89 (d, 1 H, Hindole
,
J = 6.8 Hz); 7.00—7.15 (m, 4 H, Hindole, CH2Ph); 7.21 (d, 2 H,
4ꢀNO2C6H4, J = 8.4 Hz); 7.40—7.53 (m, 2 H, Hindole, Py); 8.01
(d, 2 H, 4ꢀNO2C6H4, J = 8.4 Hz); 8.13 (s, 1 H, N(5´)H); 8.35
(d, 1 H, Py, J = 8.1 Hz); 8.62 (d, 1 H, Py, J = 5.0 Hz); 8.88
(s, 1 H, Py). MS (EI, 70 eV), m/z (Irel (%)): 370 (2), 369 (2), 280
(2), 236 (2), 193 (4), 178 (6), 150 (7), 133 (3), 104 (17), 91 (100),
78 (18), 77 (18).
1ꢀBenzylꢀ3´ꢀ(2ꢀfuryl)ꢀ7´ꢀ(4ꢀnitrophenyl)spiro[indoleꢀ3,6´ꢀ
[1,2,4]triazolo[3,4ꢀb][1,3,4]thiadiazin]ꢀ2(1H)ꢀone (7d). Yield
0.42 g (78%), colorless crystals, m.p. 267—269 °C. Found (%):
C, 62.73; H, 3.83; N, 15.99. C28H20N6O4S. Calculated (%):
C, 62.68; H, 3.76; N, 16.66. 1H NMR (DMSOꢀd6), δ: 4.60, 4.91
(both d, 1 H each, NCH2Ph, J = 15.9 Hz); 5.51 (s, 1 H, H(7´));
6.61 (m, 1 H, Hfuran(4)); 6.70—6.80 (m, 3 H, Hindole, CH2Ph);
6.88 (m, 2 H, Hindole, Hfuran); 7.02—7.14 (m, 4 H, Hindole
,
CH2Ph); 7.20 (d, 2 H, 4ꢀNO2C6H4, J = 8.7 Hz); 7.33 (m, 1 H,
Hindole); 7.85 (s, 1 H, Hfuran); 7.95 (d, 2 H, 4ꢀNO2C6H4, J = 8.7 Hz);
8.08 (s, 1 H, N(5´)H). MS (EI, 70 eV), m/z (Irel (%)): 370 (8),
301 (1), 283 (5), 253 (4), 190 (3), 179 (5), 149 (10), 133 (4),
109 (4), 91 (100), 76 (9).
1ꢀMethylꢀ7´ꢀ(4ꢀnitrophenyl)ꢀ3´ꢀphenylspiro[indoleꢀ3,6´ꢀ
[1,2,4]triazolo[3,4ꢀb][1,3,4]thiadiazin]ꢀ2(1H)ꢀone (7e). Yield
0.32 g (68%), colorless crystals, m.p. 168—170 °C. Found (%):
C, 61.22; H, 3.92; N, 18.41. C24H18N6O3S. Calculated (%):
C, 61.27; H, 3.86; N, 17.86. 1H NMR (DMSOꢀd6), δ: 2.82 (s, 3 H,
Me); 5.41 (s, 1 H, H(7´)); 6.65 (d, 1 H, Hindole, J = 6.8 Hz); 6.89
(d, 1 H, Hindole, J = 7.4 Hz); 7.05 (m, 1 H, Hindole); 7.18 (d, 2 H,
4ꢀNO2C6H4, J = 8.4 Hz); 7.35 (m, 1 H, Hindole); 7.43 (m, 3 H,
Ph); 7.75 (m, 2 H, Ph); 8.01 (d, 2 H, 4ꢀNO2C6H4, J = 8.4 Hz);
8.11 (s, 1 H, N(5´)H). MS (EI, 70 eV), m/z (Irel (%)): 293 (14),
280 (8), 262 (7), 205 (5), 190 (5), 177 (15), 159 (27), 150 (53),
131 (22), 104 (100), 89 (46), 77 (92), 50 (50).