RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2015, 348, 1–12
Benzimidazole Derivatives as Antitumor Agents
Archiv der Pharmazie
NH2, exchangeable D2O); 5.92 (s, 1H, H8a pyrimidine ring);
7.15–7.54 (m, 10H, thiazole, and aromatic rings), 7.71 (m, 2H,
H4, and H7, benzimidazole); 8.05 (m, 2H, H5, H6, benzimid-
azole); 10.17 (s, 1H, NH amid exchangeable D2O); 10.52 (s,
1H, NH pyrimidine exchangeable D2O); 12.112 (s, 1H, NH
benzimidazole exchangeable D2O). MS: m/z 498 (Mþ,
52.32%). IR (KBr, n/cmꢀ1): n (NH2) 3350, 3269, n (NH amid)
3260, n (NH pyrimidine) 3207, n (NH benzimidazole) 3122, n
benzimidazole); 8.79 (m, 2H, H5, H6, benzimidazole); 10.14 (s,
1H, NH amid exchangeable D2O); 10.64 (s, 1H, NH pyrimidine
exchangeable D2O); 12.10 (s, 1H, NH benzimidazole ex-
changeable D2O); MS: m/z 511 (M, 28%), 172 (m1, 100%).
IR (KBr, n/cmꢀ1): n (NH2) 3320, 3263, n (NH amid) 3201, n (NH
–
pyrimidine) 3160, n (NH benzimidazole) 3051, n (C O) 1670,
–
–
n (C N benzimidazole ring) 1605, n (C–S benzimidazole ring)
–
1369. Anal. calcd. for C26H21N7O3S (%) M.W. 511: C, 61.04; H,
4.14; N, 19.17; S, 6.27. Found: C, 61.10; H, 4.15; N, 19.20; S, 6.09.
–
–
(C O) 1673,
n (C N benzimidazole ring) 1603, n (C–S
–
–
benzimidazole ring) 1370. Anal. calcd. for C27H24N6O2S (%)
M.W. 497: C, 65.30; H, 4.87; N, 16.92; S, 6.46. Found: C, 65.31;
H, 4.82; N, 16.91; S, 6.13.
N-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-7-amino-5-(4-
nitrophenyl)-8,8a-dihydro-5H-thiazolo[3,2-a]pyrimidine-
6-carboxamide (6k)
N-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-7-amino-5-(2-
hydroxyphenyl)-8,8a-dihydro-5H-thiazolo[3,2-a]-
pyrimidine-6-carboxamide (6h)
Yield 96%, m.p. 275–277°C. 1H NMR (500 MHz, DMSO-d6): 2.48
(s, 1H, H5 pyrimidine ring); 4.29 (br, 2H, NH2, exchangeable
D2O); 5.78 (s, 1H, H8a pyrimidine ring); 7.08–7.13 (m, 10H,
thiazole, and aromatic rings), 7.72 (m, 2H, H4, and H7,
benzimidazole); 8.06 (m, 2H, H5, H6, benzimidazole); 10.16 (s,
1H, NH amid exchangeable D2O); 10.57 (s, 1H, NH pyrimidine
exchangeable D2O); 12.08 (s, 1H, NH benzimidazole ex-
changeable D2O); MS: m/z 511 (M, 34%). IR (KBr, n/cmꢀ1): n
(NH2) 3319, 3260, n (NH amid) 3192, n (NH pyrimidine) 3163, n
Yield 91%, m.p. 220–222°C. 1H NMR (500 MHz, DMSO-d6): 2.46
(s, 1H, H5 pyrimidine ring); 4.80 (br, 2H, NH2, exchangeable
D2O); 6.02 (s, 1H, H8a pyrimidine ring); 6.80–7.53 (m, 10H,
thiazole, and aromatic rings), 7.71 (m, 2H, H4, and H7,
benzimidazole); 8.07 (m, 2H, H5, H6, benzimidazole); 10.20 (s,
1H, NH amid exchangeable D2O); 10.40 (s, 1H, NH pyrimidine
exchangeable D2O); 10.80 (s, 1H, NH benzimidazole ex-
changeable D2O); 12.00 (br, 1H, OH exchangeable D2O); MS:
m/z 481 (Mꢀ1, 9.08%). IR (KBr, n/cmꢀ1): n (OH) 3520, n (NH2)
3319, 3270, n (NH amid) 3200, n (NH pyrimidine) 3167, n (NH
–
–
(NH benzimidazole) 3052, n (C O) 1670, n (C N benzimidazole
–
–
ring) 1605, n (C–S benzimidazole ring) 1373. Anal. calcd. for
26H21N7O3S (%) M.W. 511: C, 61.04; H, 4.14; N, 19.17; S, 6.27.
C
Found: C, 61.08; H, 4.10; N, 19.18; S, 6.11.
–
–
benzimidazole) 3052, n (C O) 1677, n (C N benzimidazole
–
–
ring) 1604, n (C–S benzimidazole ring) 1374. Anal. calcd. for
26H22N6O2S (%) M.W. 482: C, 64.71; H, 4.60; N, 17.42; S, 6.64.
N-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-7-amino-5-(4-
methylphenyl)-8,8a-dihydro-5H-thiazolo[3,2-a]-
C
Found: C, 64.88; H, 4.62; N, 17.45; S, 6.24.
pyrimidine-6-carboxamide (6l)
Yield 63%, m.p. >300°C. 1H NMR (500 MHz, DMSO-d6): 2.06 (s,
3H, CH3); 2.46(s, 1H, H5 pyrimidine ring); 4.30 (br, 2H, NH2,
exchangeable D2O); 5.84 (s, 1H, H8a pyrimidine ring); 6.81–
7.95 (m, 10H, thiazole, and aromatic rings), 7.78 (m, 2H, H4,
and H7, benzimidazole); 8.06 (m, 2H, H5, H6, benzimidazole);
10.17 (s, 1H, NH amid exchangeable D2O); 10.60 (s, 1H, NH
pyrimidine exchangeable D2O); 12.09 (s, 1H, NH benzimid-
azole exchangeable D2O). MS: m/z (480Mþ1). IR (KBr, n/cmꢀ1):
n (NH2) 3352, 3266, n (NH amid) 3205, n (NH pyrimidine) 3172, n
N-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-7-amino-5-(4-
hydroxyphenyl)-8,8a-dihydro-5H-thiazolo[3,2-a]-
pyrimidine-6-carboxamide (6i)
Yield 90%, m.p. 229–230°C. 1H NMR (500 MHz, DMSO-d6): 2.46
(s, 1H, H5 pyrimidine ring); 4.27 (br, 2H, NH2, exchangeable
D2O); 6.90 (s, 1H, H8a pyrimidine ring); 7.14–7.53 (m, 10H,
thiazole, and aromatic rings), 7.72 (m, 2H, H4, and H7,
benzimidazole); 8.08 (m, 2H, H5, H6, benzimidazole); 10.16 (s,
1H, NH amid exchangeable D2O); 10.40 (s, 1H, NH pyrimidine
exchangeable D2O); 10.60 (s, 1H, NH benzimidazole ex-
changeable D2O); 12.09 (br, 1H, OH exchangeable D2O); MS:
m/z 480 (Mꢀ2, 13.32%). IR (KBr, n/cmꢀ1): n (OH) 3580, n (NH2)
3322, 3250, n (NH amid) 32197, n (NH pyrimidine) 3163, n (NH
–
–
–
(NH benzimidazole) 3050, n (C O) 1698, n (C N benzimidazole
–
ring) 1610, n (C–S benzimidazole ring) 1371. Anal. calcd. for
28H27N6OS (%) M.W. 480: C, 67.48; H, 5.03; N, 17.49; S, 6.69.
C
Found: C, 67.54; H, 5.05; N, 17.52; S, 6.30.
–
–
benzimidazole) 3051, n (C O) 1677, n (C N benzimidazole
N-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-7-amino-5-(4-
(dimethylamino)phenyl)-8,8a-dihydro-5H-thiazolo[3,2-a]-
pyrimidine-6-carboxamide (6m)
–
–
ring) 1605, n (C–S benzimidazole ring) 1374. Anal. calcd. for
26H22N6O2S (%) M.W. 482: C, 64.71; H, 4.60; N, 17.42; S, 6.64.
C
Found: C, 64.77; H, 4.61; N, 17.45; S, 6.27.
Yield 71%, m.p. 295–297°C. 1H NMR (500 MHz, DMSO-d6): 2.06
(s, 6H, 2CH3); 2.46 (s, 1H, H5 pyrimidine ring); 4.30 (br, 2H, NH2,
exchangeable D2O); 5.84 (s, 1H, H8a pyrimidine ring); 6.81–
7.59 (m, 10H, thiazole, and aromatic rings), 7.78 (m, 2H, H4,
and H7, benzimidazole); 8.06 (m, 2H, H5, H6, benzimidazole);
10.17 (s, 1H, NH amid exchangeable D2O); 10.60 (s, 1H, NH
pyrimidine exchangeable D2O); 12.09 (s, 1H, NH benzimid-
azole exchangeable D2O). MS: m/z 511 (Mþ2, 38.46%). IR
(KBr, n/cmꢀ1): n (NH2) 3327, 3258, n (NH amid) 3210, n (NH
N-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-7-amino-5-(2-
nitrophenyl)-8,8a-dihydro-5H-thiazolo[3,2-a]pyrimidine-
6-carboxamide (6j)
Yield 86%, m.p. 215–217°C. 1H NMR (500 MHz, DMSO-d6): 2.46
(s, 1H, H5 pyrimidine ring); 4.31 (br, 2H, NH2, exchangeable
D2O); 5.85 (s, 1H, H8a pyrimidine ring); 7.15–7.93 (m, 10H,
thiazole, and aromatic rings), 8.26 (m, 2H, H4, and H7,
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