N.B. Patel et al. / European Journal of Medicinal Chemistry 62 (2013) 677e687
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6.1.4.1. 2-[5-(2-Benzylsulfanyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-
ylsulfanyl]-N-(5-methyl-thiazol-2-yl)-acetamide (6a). A mixture of 5
(2 g, 0.006 mol), dimethylformamide (25 ml), potassium carbonate
(1.6 g, 0.012 mol) and 2-chloro-N-(5-methyl-thiazol-2-yl)-aceta-
mide 1a (1.5 g, 0.006 mol) was heated to 90 ꢂC for 8 h. Completion
of reaction was periodically observed by thin layer chromatography
using mobile phase toluene:methanol (8:2). After completion of
reaction, filtered the inorganics, the filtrate obtained was quenched
with ice water and stirred for 1 h and the solid separated was fil-
tered and dried through pump to afford title compound 6a as off
white solid (72%); m.p. 200e202 ꢂC; IR (KBr) cmꢀ1: 3363 (eNH str.),
0.006 mol), dimethylformamide (25 ml), potassium carbonate
(1.6 g, 0.012 mol) and 2-chloro-N-[1,2,4]triazol-4-yl-acetamide 1d
(0.96 g, 0.006 mol) was heated to 90 ꢂC for 10 h. Completion of
reaction was periodically observed by thin layer chromatography
using mobile phase toluene:methanol (8:2). After completion of
reaction, filtered the inorganics, the filtrate obtained was quenched
with ice water and stirred for 1 h and the solid separated was fil-
tered and dried through pump to afford title compound 6d as
golden brown solid (69%); m.p. 210e212 ꢂC; IR (KBr) cmꢀ1: 3264 (e
NH str.), 1682 (C]O str.); 1H NMR (DMSO, 400 MHz)
d: 4.26 (s, 2H,
SCH2), 4.39 (s, 2H, SCH2), 7.20e7.48 (m, 6H, AreHbn/py), 8.08 (s, 2H,
triazoleeH), 8.16e8.18 (dd, 1H, AreHpy), 8.27e8.28 (dd, 1H, Are
Hpy), 10.88 (s, 1H, CONH disappeared on D2O exchange); 13C NMR
1679 (C]O str.); 1H NMR (DMSO, 400 MHz)
d: 2.33 (s, 3H, CH3),
4.40 (s, 2H, SCH2), 4.47 (s, 2H, SCH2), 7.162 (s, 1H, thiazoleeH),
7.165e7.426 (m, 6H, AreHbn/py), 8.19e8.21 (dd, 1H, AreHpy),
8.68e8.69 (dd, 1H, AreHpy), 12.34 (s, 1H, CONH disappeared on
(DMSO-d6, 400 MHz) d: 33.49, 39.23, 117.23, 118.34, 127.10, 128.11,
129.07, 136.29, 137.43, 146.35, 151.16, 157.93 161.62, 163.20, 174.35
Anal. found (calc.) for C18H15N7O2S2 (%): C, 50.69 (50.81); H, 3.42
(3.55); N, 22.96 (23.04); mass m/z (Mþ) 425.
D2O exchange); 13C NMR (DMSO-d6, 400 MHz)
d: 13.07, 33.78,
34.16, 117.50, 118.79, 122.70, 126.19, 128.32, 128.89, 136.62, 137.67,
138.14, 150.56, 157.42 162.68, 163.80, 169.27, 172.20; Anal. found
(calc.) for C20H17N5O2S3 (%): C, 52.61 (52.73); H, 3.55 (3.76); N,15.26
(15.37); mass m/z (Mþ) 455.
6.1.4.5. 2-[5-(2-Benzylsulfanyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-
ylsulfanyl]-1-(4-methyl-piperazin-1-yl)-ethanone (6e). A mixture of
5 (2 g, 0.006 mol), dimethylformamide (25 ml), potassium car-
bonate (1.6 g, 0.012 mol) and 2-chloro-1-(4-methyl-piperazin-1-
yl)-ethanone 1e (1.05 g, 0.006 mol) was heated to 90 ꢂC for 8 h.
Completion of reaction was periodically observed by thin layer
chromatography using mobile phase toluene:methanol (8:2). After
completion of reaction, filtered the inorganics, the filtrate obtained
was quenched with ice water and stirred for 1 h and the solid
separated was filtered and dried through pump to afford title
compound 6e as light brown solid (41%); m.p. 158e160 ꢂC; IR (KBr)
cmꢀ1: 1664 (C]O str.), 1337 (CeN str.); 1H NMR (DMSO, 400 MHz)
6.1.4.2. 2-[5-(2-Benzylsulfanyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-
ylsulfanyl]-N-(4,6-dimethoxy-pyrimidin-2-yl)-acetamide
(6b). A
mixture of 5 (2 g, 0.006 mol), dimethylformamide (25 ml), potas-
sium carbonate (1.6 g, 0.012 mol) and 2-chloro-N-(4,6-dimethoxy-
pyrimidin-2-yl)-acetamide 1b (1.39 g, 0.006 mol) was heated to
95e100 ꢂC for 14 h. Completion of reaction was periodically
observed by thin layer chromatography using mobile phase tolue-
ne:methanol (7:3). After completion of reaction, filtered the in-
organics, the filtrate obtained was quenched with ice water and
stirred for 1 h and the solid separated was filtered and dried
through pump to afford title compound 6b as off white solid (65%);
m.p. 232e234 ꢂC; IR (KBr) cmꢀ1: 3309 (eNH str.), 1655 (C]O str.),
d: 2.25 (s, 3H, CH3), 2.44 (t, 4H, piperazineeNeCH2), 3.32 (t, 4H,
piperazineeNeCH2), 4.37 (s, 2H, SCH2), 4.50 (s, 2H, SCH2), 7.20e
7.45 (m, 6H, AreHbn/py), 8.01e8.03 (dd, 1H, AreHpy), 8.48e8.49
1267, 1082 (CeOeC str.); 1H NMR (DMSO, 400 MHz)
d
: 3.73 (s, 3H,
(dd, 1H, AreHpy); 13C NMR (DMSO-d6, 400 MHz)
d: 28.13, 33.19,
OCH3), 3.92 (s, 3H, OCH3), 4.39 (s, 2H, SCH2), 4.52 (s, 2H, SCH2), 7.11
(s, 1H, pyrimidineeH), 7.12e7.40 (m, 6H, AreHbn/py), 8.09e8.11
(dd, 1H, AreHpy), 8.52e8.53 (dd, 1H, AreHpy), 11.12 (s, 1H, CONH
37.34, 44.35, 54.67, 61.53, 116.63, 118.29, 126.17, 128.02, 128.66,
136.89, 137.53, 150.76, 158.19 161.85, 163.20, 171.27; Anal. found
(calc.) for C21H23N5O2S2 (%): C, 57.01 (57.12); H, 5.45 (5.25); N, 15.71
(15.86); mass m/z (Mþ) 441.
disappeared on D2O exchange); 13C NMR (DMSO-d6, 400 MHz)
d:
37.29, 39.32, 55.78 116.29, 119.54, 126.27, 128.13, 128.79, 136.68,
137.88, 150.25, 157.12, 157.84, 162.32, 163.79, 170.57, 171.35; Anal.
found (calc.) for C22H20N6O4S2 (%): C, 53.06 (53.21); H, 4.15 (4.06);
N, 16.86 (16.92); mass m/z (Mþ) 496.
6.1.4.6. Preparation of 2-[5-(2-benzylsulfanyl-pyridin-3-yl)-[1,3,4]
oxadiazol-2-ylsulfanyl]-N-[4-(5-methyl-benzothiazol-2-yl)-phenyl]-
acetamide (6f). A mixture of 5 (2 g, 0.006 mol), dimethylformamide
(25 ml), potassium carbonate (1.6 g, 0.012 mol) and 2-chloro-N-[4-
(5-methyl-benzothiazol-2-yl)-phenyl]-acetamide 1f (1.86 g,
0.006 mol) was heated to 115e120 ꢂC for 15 h. Completion of re-
action was periodically observed by thin layer chromatography
using mobile phase toluene:methanol:ethyl acetate (7:2:1). After
completion of reaction, filtered the inorganics, the filtrate obtained
was quenched with ice water and stirred for 1 h and the solid
separated was filtered and dried through pump to afford title
compound 6f as buff yellowish solid (52%); m.p. 204e206 ꢂC; IR
(KBr) cmꢀ1: 3263 (eNH str.), 1661 (C]O str.); 1H NMR (DMSO,
6.1.4.3. 2-[5-(2-Benzylsulfanyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-
ylsulfanyl]-N-(4,6-dichloro-pyrimidin-2-yl)-acetamide (6c). A mix-
ture of 5 (2 g, 0.006 mol), dimethylformamide (25 ml), potassium
carbonate (1.6 g, 0.012 mol) and 2-chloro-N-(4,6-dichloro-pyrimidin-
2-yl)-acetamide 1c (1.45 g, 0.006 mol) was heated to 95e100 ꢂC for
14 h. Completion of reaction was periodically observed by thin layer
chromatography using mobile phase toluene:methanol (7:3). After
completion of reaction, filtered the inorganics, the filtrate obtained
was quenched with icewaterand stirred for 1 h and the solid separated
was filtered and dried through pump to afford title compound 6c as
grayish brown solid (61%); m.p. 228e230 ꢂC; IR (KBr) cmꢀ1: 3289 (e
400 MHz) d: 2.45 (s, 3H, CH3), 4.06 (s, 2H, SCH2), 4.50 (s, 2H, SCH2),
6.79e8.05 (m, 13H, AreH), 8.58e8.59 (dd, 1H, AreHpy), 8.69e8.70
(dd, 1H, AreHpy), 10.35 (s, 1H, CONH disappeared on D2O ex-
NH str.), 1662 (C]O str.); 1H NMR (DMSO, 400 MHz)
d: 4.22 (s, 2H,
SCH2), 4.43 (s, 2H, SCH2), 7.21 (s,1H, pyrimidineeH), 7.22e7.49 (m, 6H,
AreHbn/py), 8.18e8.19 (dd,1H, AreHpy), 8.46e8.47 (dd,1H, AreHpy),
11.98 (s,1H, CONH disappeared on D2Oexchange);13C NMR (DMSO-d6,
change); 13C NMR (DMSO-d6, 400 MHz)
d: 19.27, 33.92, 40.26,
117.88, 119.31, 121.86, 123.45, 126.65, 126.98, 127.13, 128.49, 129.11,
132.54, 135.87, 136.14, 137.56, 141.14, 151.19, 155.87, 158.21 163.02,
163.20, 170.42, 172.69; Anal. found (calc.) for C30H23N5O2S3 (%): C,
61.81 (61.94); H, 3.45 (3.99); N, 12.01 (12.04); mass m/z (Mþ) 581.
400 MHz) d: 33.13, 36.55, 117.39, 118.94, 119.46, 127.14, 128.19, 128.82,
135.21, 136.22, 151.36, 158.04 161.98, 162.9, 163.84, 169.23 Anal. found
(calc.) for C20H14Cl2N6O2S2 (%): C, 47.39 (47.53); H, 2.65 (2.79); N,16.56
(16.63); mass m/z (Mþ) 505.
6.1.4.7. Preparation of 2-[5-(2-benzylsulfanyl-pyridin-3-yl)-[1,3,4]
oxadiazol-2-ylsulfanyl]-N-(6-thiocyanato-benzothiazol-2-yl)-aceta-
mide (6g). A mixture of 5 (2 g, 0.006 mol), dimethylformamide
(25 ml), potassium carbonate (1.6 g, 0.012 mol) and 2-chloro-N-(6-
6.1.4.4. 2-[5-(2-Benzylsulfanyl-pyridin-3-yl)-[1,3,4]oxadiazol-2-
ylsulfanyl]-N-[1,2,4]triazol-4-yl-acetamide (6d). A mixture of 5 (2 g,