A.R. Bhat et al. / European Journal of Medicinal Chemistry 46 (2011) 3158e3166
3165
N 13.03; IR
(C]N); 1H NMR (DMSO)
1H, SCHN), 2.63 (s, 6H, CH3), 2.32e2.41 (m, 1H, NCH), 1.99e2.13 (m,
10H, CH2); 13C NMR (DMSO)
/ppm: 169.35 (C]O), 166.92 (C]O),
158.39 (C]N), 153.24 (C]N), 139.22, 136.95, 132.10,130.29, 129.13,
123.12 (Ar-C), 65.87 (SCN), 37.02, 29.95, 27.36, 26.95, 22.01, 21.23,
19.89 (aliphatic); ESI-MS m/z: [Mþ þ H] 431.6
n
(cmꢁ1): 2918 (CH3), 2876 (CH2), 1651, 1640 (CO), 1430
(ppm): 7.39e7.353 (m, 5H, Ar-H), 5.37 (s,
12.96; IR
n
(cmꢁ1): 2918 (CH3), 2851 (CH2), 1661, 1649 (CO), 1440
(ppm): 1.92e2.16 (m, 8H, CH2), 2.38 (s,
d
(C]N); 1H NMR (CDCl3)
d
6H, CH3), 2.64 (s, 3H, CH3), 2.81e2.94 (m, 1H, NeCH), 5.34 (s, 1H,
N]CH), 7.73e7.56 (m, 3H, Ar-H), 8.24 (s, 1H, Ar-H); ESI-MS m/z:
[Mþ þ H] 431.6
d
4.3.19. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-
dihydro-1,3,4-thiadiazole-2-yl)-N-cyclohexylacetamide (19B)
Light black; yield 63%; mp 188 ꢀC; Anal. Calc. for C22H25Cl N4O2S:
4.3.12. N-4-acetyl-5-(2-chloroquinolin-3-yl)-4,5-dihydro-1,3,4-
thiadiazole-2-yl)-N-cyclooctylacetamide (12B)
C 59.38, H 5.66, N 12.59 found C 59.42, H 5.63, N 12.56; IR
2933 (CH3), 2867 (CH2), 1660, 1651 (CO), 1430 (C]N); 1H NMR
(DMSO) (ppm): 8.36 (s, 1H, Ar-H), 7.49e7.61 (m. 3H, Ar-H), 6.23 (s,
n
(cmꢁ1):
Brownish; yield 69%; mp 208 ꢀC; Anal. Calc. for C23H27ClN4O2S:
C 60.20, H 4.36, N 12.76, found : C 60.24, H 4.33, N 12.79; IR
2937 (CH3), 2861 (CH2), 1672, 1651 (CO), 1492 (C]N); 1H NMR
(CDCl3) (ppm): 10.89 (s, 1H, NNH), 7.45e7.69 (m, 5H, A-H), 5.39 (s,
1H, SCHN), 2.56e2.61 (m, 1H, NCH), 2.43 (s, 6H, CH3), 1.72e1.81 (m,
4H, CH2), 1.49e1.65 (m, 10H, CH2); 13C NMR (CDCl3)
(ppm): 175.52
n
(cmꢁ1):
d
1H, CNH), 5.26 (s, 1H, SCHN), 2.92e3.01 (m, 1H, NCH), 2.59 (s, 6H,
CH3), 2.51 (s. 3H, CH3), 1.73e1.93 (m, 10H, CH2); ESI-MS m/z:
[Mþ þ H] 445.1
d
d
(C]O), 165.32 (C]O), 153.95 (C]N), 147.86 (C]N), 137.32, 135.20,
129.01, 128.24, 127.35 (Ar-C), 53.11 (SCN), 38.96, 33.25, 29.94, 27.27,
24.95, 21.43 (aliphatic); ESI-MS m/z: [Mþ þ H] 460.2
4.3.20. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-
dihydro-1,3,4-thiadiazole-2-yl)-N-cyclooctylacetamide (20B)
Brownish; yield 54%; mp 219 ꢀC; Anal. Calc. for C24H29ClN4O2S:
C 60.94, H 6.18, N 11.84 found : C 60.92, H 6.21, N 11.80; IR
2937 (CH3), 2891 (CH2), 1670, 1640 (CO), 1492 (C]N); 1H NMR
(CDCl3) (ppm): 5.12 (s, 1H, SCHN), 7.63e7.82 (m, 4H, Ar-H),
n
(cmꢁ1):
4.3.13. N-4-acetyl-5-(2-chloroquinolin-3-yl)-4,5-dihydro-1,3,4-
thiadiazole-2-yl)-N-o-tolylacetamide (13B)
d
Creamy white; yield 64%; mp 192 ꢀC; Anal. Calc. for:
C22H19ClN4O2S: C 60.20, H 4.36, N 12.78, found: C 60.23, H 4.34,
2.51e2.62 (m, 1H, NCH), 2.48 (s, 6H, CH3), 2.37 (s, 3H, CH3),
1.65e1.73 (m, 4H, CH2), 1.31e1.56 (m, 10H, CH2); ESI-MS m/z:
[Mþ þ H] 438.2
N 12.75; IR n
(cmꢁ1): 3064 (Ar,CeH), 2926 (CH3),1655,1642 (CO),1435
(C]N); 1H NMR (CDCl3)
d(ppm): 7.16e7.69 (m, 9H, Ar-H), 5.59 (s, 1H,
SCHN), 2.51(s,3H, CH3), 2.43(s, 6H, CH3); ESI-MS m/z:[Mþ þ Na] 461.7
4.3.21. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-
dihydro-1,3,4-thiadiazole-2-yl)-N-o-tolylacetamide (21B)
Creamy white; yield 56%; mp 203 ꢀC; Anal. Calc. for:
C23H21ClN4O2S: C 60.99, H 4.67, N 12.37, found: C 60.95, H 4.71, N
4.3.14. N-4-acetyl-5-(2-chloroquinolin-3-yl)-4,5-dihydro-1,3,4-
thiadiazole-2-yl)-N-(2,5-difluorophenyl)acetamide (14B)
Blue black; yield 71%; mp 204 ꢀC; Anal. Calc. for C21H15ClN4O2S:
12.34; IR n
(cmꢁ1): 3095 (Ar,CeH), 2964 (CH3),1655,1642 (CO),1435
C 54.73, H 3.28, N 12.61, found C 54.69, H 3.31, N 12.58; IR
n
(cmꢁ1):
(C]N); 1H NMR (CDCl3)
d(ppm): 2.68 (s, 6H, CH3), 2.73 (s, 6H, CH3),
3072 (Ar,CeH), 2909 (CH3), 1678, 1664 (CO), 1435 (C]N); 1H NMR
5.37 (s, 1H, SCHN), 7.12e7.44 (m, 8H, Ar-H); ESI-MS m/z: [Mþ þ Na]
(DMSO)
d
(ppm): 2.58 (s, 6H, CH3), 5.43 (s, 1H, SCHN), 7.89e8.61 (m,
475.7
8H, Ar-H); ESI-MS m/z: [Mþ þ H] 461.5
4.3.22. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-
dihydro-1,3,4-thiadiazole-2-yl)-N-(2,5-difluorophenyl)acetamide
(22B)
4.3.15. N-4-acetyl-5-(2-chloroquidnolin-3-yl)-4,5-dihydro-1,3,4-
thiadiazole-2-yl)-N-p-tolylacetamide (15B)
Light pink; yield 68%; mp 207 ꢀC; Anal. Calc. for C22H19ClN4O2S:
Blackish; yield 58%; mp 198 ꢀC; Anal. Calc. for C22H17ClF2N4O2S:
C 60.20, H 4.36 N 12.76, found C 60.23, H 4.33, N 12.79; IR
n
(cmꢁ1):
C 55.64, H 3.61, N 11.80, found C 55.69, H 3.59, N 11.82; IR
n
(cmꢁ1):
3056 (Ar,CeH), 2926 (CH3), 1678,1640 (CO), 1445 (C]N); 1H NMR
3075 (Ar,CeH), 2934 (CH3), 1664, 1640 (CO), 1435 (C]N); 1H NMR
(CDCl3)
d
(ppm): 7.29e7.64 (m, 9H, Ar-H), 5.19 (s, 1H, SCHN), 2.36 (s,
(DMSO) d(ppm): 11.71(s, 1H, NNH), 7.76e7.98 (m, 7H, Ar-H), 7.17 (s,
3H, CH3), 2.19 (s, 6H, CH3),; ESI-MS m/z: [Mþ þ H] 484.7
1H, CH]N), 2.64 (s, 3H, CH3); ESI-MS m/z: [Mþ þ H] 475.8
4.3.16. N-4-acetyl-5-(2-chloroquinolin-3-yl)-4,5-dihydro-1,3,4-
thiadiazole-2-yl)-N-(4-nitophenyl)aceamide (16B)
4.3.23. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-
dihydro-1,3,4-thiadiazole-2-yl)-N-p-phenylacetamide (23B)
White; yield 64%; mp 201 ꢀC; Anal. Calc. for C23H21ClN4O2S:
C 60.99, H 4.67, N 12.37, found C 61.02, H 4.65 N 12.41; IR
Blackish; yield 65%; mp 204 ꢀC.; Anal. Calc. for C22H16ClN5O4S:
C 60.20, H 4.36, N 12.76, found C 60.16, H 4.39, N 12.71; IR
n
(cmꢁ1):
3027 (Ar,CeH), 2952 (CH3), 1671,1658 (CO), 1449 (C]N); 1H NMR
n
(cmꢁ1): 3062 (Ar,CeH), 2911 (CH3), 1678, 1610 (CO), 1445 (C]
(DMSO)
d
(ppm): 7.51e8.09 (m, 9H, Ar-H), 5.12 (s, 1H, SCHN), 2.49 (s,
N); 1H NMR (CDCl3)
d(ppm): 7.23e7.61 (m, 8H, Ar-H), 5.61 (s, 1H,
6H, CH3); ESI-MS m/z: [Mþ þ Na] 492.5
SCHN), 2.69 (s, 6H, CH3), 2.34 (s, 6H, CH3); 13C NMR (CDCl3)
d/
ppm: 174.36 (C]O), 168.95 (C]O), 153.48 (C]N), 149.95 (C]N),
141.49, 139.10,135.08, 130.65, 128.76, 125.91, 124.34, 122.11
(Ar-C), 49.02 (SCN), 24.03, 22.01, 21.24 (aliphatic); ESI-MS m/z:
[Mþ þ H] 453.8
4.3.17. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-dihydro-
1,3,4-thiadiazole-2-yl)acetamide (17B)
Yellowish; yield 63%; mp 213 ꢀC Anal. Calc. for C16H15ClN4O2S:
C 52.96, H 4.17, N 15.44, found C 53.01, H 4.13, N 15.48; IR
3194 (NH), 2961 (CH3), 1658, 1645 (CO), 1479 (C]N); 1H NMR
(CDCl3) (ppm): 8.13 (s, 1H, Ar-H), 7.39e7.69 (m, 3H, Ar-H), 5.28 (s,
n
(cmꢁ1):
4.3.24. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-
dihydro-1,3,4-thiadiazole-2-yl)-N-(4-nitrophenyl)acetamide (24B)
Creamy white; yield 55%; mp 207 ꢀC; Anal. Calc. for
C22H18ClN5O2S: C 54.80, H 3.75, N 14.47, found C 54.74, H 3.78,
d
1H, N]CH), 2.65 (s, 6H, CH3), 2.48 (s, 3H, CH3), 2.19 (s, 1H, NH2);
ESI-MS m/z: [Mþ þ H] 363.5
N 14.51; IR
1449 (C]N); 1H NMR (DMSO)
4.93 (s, 1H, SCHN), 2.51 (s, 3H, CH3), 2.24 (s, 6H, CH3); 13C NMR
(DMSO) /ppm: 172.36 (C]O), 175.39 (C]O), 156.64 (C]N), 151.37
(C]N), 140.19, 139.74, 136.38, 133.27, 131.24, 129.84, 128.68, 124.84,
n
(cmꢁ1): 3054 (Ar,CeH), 2952 (CH3), 1640, 1604 (CO),
4.3.18. N-4-acetyl-5-(2-chloro-8-methylquinolin-3-yl)-4,5-
dihydro-1,3,4-thiadiazole-2-yl)-N-cyclpentylacetamide (18B)
Dark brown; yield 58%; mp 209 ꢀC; Anal. Calc. for
C21H23ClN4O2S: C 58.53, H 5.38, N 13.00, found C 58.56, H 5.34, N
d(ppm): 7.19e7.39 (m, 8H, Ar-H),
d