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M. Raghu Prasad et al. / European Journal of Medicinal Chemistry 43 (2008) 614e620
ymax: 3190, 3320 (NH2), 2910 (alk) cmꢀ1; 1H NMR (CDCl3) d:
1.0e1.1 (t, 3H, J ¼ 10.9 Hz, CH3CH2CH2e), 1.7e2.0 (m, 4H,
CH2 at 6 and 7), 2.45e2.55 (m, 2H, eCH2CH2CH3),
2.75e2.80 (m, 2H, CH2 at 5 and 8), 3.85e4.05 (m, 2H, e
CH2CH2CH3), 4.20e4.30 (d. 2H, J ¼ 5.5 Hz, eNHNH2, D2O
exchangeable), 6.6e6.8 (t, 1H, J ¼ 5.6 Hz, NHNH2, D2O ex-
changeable) ppm; EI-MS [m/z, %]: 262 [Mþ 100]. Anal. Calcd
for C13H18N4S: C, 59.54; H, 6.87; N, 21.37. Found: C, 59.85; H,
7.05; N, 21.60.
C13H14N4S2: C, 53.79; H, 7.3; N, 19.3. Found: C, 54.04; H,
7.26; N, 19.12.
4.1.2.5. 5-Propyl-8,9-dimethylthieno[3,2-e][1,2,4]triazolo[4,3-c]
pyrimidine-3(2H)-thione (4e). M.p. 198e200 ꢁC; yield 65%; IR
(KBr) ymax: 3190 (NH), 2910 (CH3), 1200 (C]S), 1290 (CeN)
1
cmꢀ1; H NMR (DMSO-d6) d: 1.10e1.13 (t, 3H, J ¼ 10.9 Hz,
CH3CH2CH2e), 2.28 (s, 6H, CH3), 2.45e2.55 (m, 2H,
CH3CH2CH2e), 3.05e3.15 (m, 2H, CH3CH2CH2e), 11.2 (s,
1H, NH, D2O exchangeable) ppm; EI-MS [m/z, %]: 278 [Mþ
100]. Anal. Calcd for C12H14N4S2: C, 51.79; H, 5.03; N, 20.14.
Found: C, 52.05; H, 5.25; N, 20.35.
4.1.2. General procedure for the preparation of 5-alkyl/aryl-
8,9-dimethyl/8,9,10,11-tetrahydro[1]benzothieno[3,2-e]
[1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thiones (4aek)
2-Alkyl/aryl-4-hydrazino-5,6-dimethyl/5,6,7,8-tetrahydro-
benzo[b]thieno[2,3-d]pyrimidines (3aek) [10 mmol] and car-
bon disulphide [7.6 g, 10 ml, 100 mmol] in 10% alcoholic
potassium hydroxide (20 ml) solution was heated under reflux
for 5 h. The reaction mixture was cooled and added onto
crushed ice. The solid product thus obtained was filtered, dried
and recrystallized from chloroformeethanol (1:1) mixture.
4.1.2.6. 5-Propyl-8,9,10,11-tetrahydro[1]benzothieno[3,2-e]
[1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (4f). M.p. > 300 ꢁC;
yield 74%; IR (KBr) ymax: 3190 (NH), 2910 (CH3), 1200
1
(C]S), 1290 (CeN) cmꢀ1; H NMR (DMSO-d6) d: 1.0e
1.1 (t, 3H, J ¼ 11.1 Hz, CH3CH2CH2), 1.7e2.0 (m, 4H, CH2
at 9 and 10), 2.45e2.55 (m, 2H, CH3CH2CH2), 2.75e2.80
(t, 2H, J ¼ 8.3 Hz, CH2 at 5), 2.85e3.05 (t, 2H, J ¼ 8.3 Hz,
CH2 at 8), 3.85e4.0 (m, 2H, CH3CH2CH2), 14.0 (s, 1H,
NH, D2O exchangeable) ppm; EI-MS [m/z, %]: 304 [Mþ
50]. Anal. Calcd for C14H16N4S2: C, 55.26; H, 5.26; N,
18.42. Found: C, 55.50; H, 5.55; N, 18.65.
4.1.2.1. 5-Methyl-8,9-dimethylthieno[3,2-e][1,2,4]triazolo[4,3-
c]pyrimidine-3(2H)-thione (4a). M.p. 275e276 ꢁC; yield 69%;
IR (KBr) ymax: 3190 (NH), 2910 (CH3), 1200 (C]S), 1290
1
(CeN) cmꢀ1; H NMR (CDCl3) d: 1.2 (s, 3H, CH3 at 5), 2.45
(s, 6H CH3 at 8 and 9), 11.4 (s, 1H, NH, D2O exchangeable)
ppm; EI-MS [m/z, %]: 250 [Mþ 100]. Anal. Calcd for
C10H10N4S2: C, 48.00; H, 4.00; N, 22.40. Found: C, 48.25; H,
4.30; N, 22.75.
4.1.2.7. 5-Phenyl-8,9-dimethylthieno[3,2-e][1,2,4]triazolo[4,3-c]
pyrimidine-3(2H)-thione (4g). M.p. > 300 ꢁC; yield 80%; IR
(KBr) ymax: 3190 (NH), 2910 (CH3), 1200 (C]S), 1290 (Ce
1
N) cmꢀ1; H NMR (DMSO-d6) d: 2.4 (s, 6H, CH3 at 8 and
9), 7.2e7.6 (m, 5H, C6H5), 14.2 (s, 1H, NH, D2O exchangeable)
ppm; EI-MS [m/z, %]: 312 [Mþ 100]. Anal. Calcd for
C15H12N4S2: C, 57.69; H, 3.84; N, 17.9. Found: C, 57.84; H,
4.12; N, 18.15.
4.1.2.2.
5-Methyl-8,9,10,11-tetrahydro[1]benzothieno[3,2-e]
[1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (4b). M.p. 280e
281 ꢁC; yield 76%; IR (KBr) ymax: 3190 (NH), 2910 (CH3),
1200 (C]S), 1290 (CeN) cmꢀ1; H NMR (CDCl3) d: 1.9
1
(m, 4H, CH2 at 9 and 10), 2.35 (s, 1H CH3), 2.7e3.0 (m, 4H,
CH2 at 8 and 11), 11.1 (s, 1H, NH, D2O exchangeable) ppm;
EI-MS [m/z, %]: 276 [Mþ 100]. Anal. Calcd for C12H12N4S2:
C, 52.17; H, 4.34; N, 20.28. Found: C, 52.45; H, 4.66; N, 20.50.
4.1.2.8. 5-Phenyl-8,9,10,11-tetrahydro[1]benzothieno[3,2-e]
[1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (4h). M.p. >
300 ꢁC; yield 80%; IR (KBr) ymax: 3190 (NH), 2910 (CH3),
1
1200 (C]S), 1290 (CeN) cmꢀ1; H NMR (DMSO-d6) d:
1.5e1.7 (m, 4H, CH2 at 9 and 10), 2.5e2.7 (m, 4H, CH2 at
8 and 11), 7.2e7.6 (m, 5H, ArH ), 14.3 (s, 1H, NH, D2O ex-
changeable) ppm; EI-MS [m/z, %]: 339 [Mþ100]. Anal. Calcd
for C15H12N4S2: C, 60.35; H, 4.14; N, 16.56. Found: C, 60.60;
H, 4.45; N, 16.95.
4.1.2.3. 5-Ethyl-8,9-dimethylthieno[3,2-e][1,2,4]triazolo[4,3-c]
pyrimidine-3(2H)-thione (4c). M.p. 180e181 ꢁC; yield 68%; IR
(KBr) ymax: 3190 (NH), 2910 (CH3), 1200 (C]S), 1290 (CeN)
1
cmꢀ1; H NMR (DMSO-d6) d: 1.2e1.4 (t, 3H, J ¼ 8.69 Hz,
CH2CH3), 2.35 (s, 6H CH3 at 8 and 9), 3.4 (t, 2H,
J ¼ 8.69 Hz, CH2CH3), 11.1 (s, 1H, NH, D2O exchangeable)
ppm; EI-MS [m/z, %]: 264 [Mþ 100]. Anal. Calcd for
C11H12N4S2: C, 50.76; H, 4.61; N, 21.53. Found: C, 50.95;
H, 4.75; N, 21.65.
4.1.2.9. 5-Benzyl-8,9-dimethylthieno[3,2-e][1,2,4]triazolo[4,3-
c]pyrimidine-3(2H)-thione (4i). M.p. 165e167 ꢁC; yield 73%;
IR (KBr) ymax: 3190 (NH), 2910 (CH3), 1200 (C]S), 1290 (Ce
N) cmꢀ1; 1H NMR (DMSO-d6) d: 2.5 (s, 6H, CH3), 3.2 (S, 2H,
CH2Ph), 7.28e7.67 (m, 5H, C6H5), 14.1 (s, 1H, NH, D2O ex-
changeable) ppm; EI-MS [m/z, %] (70 eV): 326 [Mþ 25], 294
[MþꢀSH, 100]. Anal. Calcd for C16H14N4S2: C, 58.89; H,
4.29; N, 17.17. Found: C, 59.16; H, 4.55; N, 17.35.
4.1.2.4. 5-Ethyl-8,9,10,11-tetrahydro[1]benzothieno[3,2-e]
[1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (4d). M.p. 244e
245 ꢁC; yield 72%; IR (KBr) ymax: 3190 (NH), 2910 (CH3),
;
1200 (C]S), 1290 (CeN) cmꢀ1 1H NMR (DMSO-d6) d:
1.1 (t, 3H J ¼ 4.4 Hz, CH3), 1.7e2.0 (m, 4H, CH2 at 9 and
10), 2.8e3.0 (m, 4H, CH2 at 8 and 11), 3.9e4.0 (q, 2H,
J ¼ 4.24 Hz, eCH2CH3), 14.0 (s, 1H, NH, D2O exchangeable)
ppm; EI-MS [m/z, %]: 290 [Mþ 100]. Anal. Calcd for
4.1.2.10. 5-Benzyl-8,9,10,11-tetrahydro[1]benzothieno[3,2-e]
[1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (4j). M.p. 232e
234 ꢁC; yield 75%; IR (KBr) ymax: 3190 (NH), 2910 (CH3),
;
1200 (C]S), 1290 (CeN) cmꢀ1 1H NMR (DMSO-d6) d: