Arkivoc 2018, vii, 0-0
Parmar, T. H. et al.
chromatography on silica gel (eluent: 0-70% n-Hexane/EtOAc) to afford the product 4-(4-(2-(furan-2-yl)-1H-
benzo[d]imidazol-1-yl)piperidine-1-carbonyl)benzenesulfonamide as yellow solid (140 mg, 65.71%); mp 248-
o
1
251 C; H NMR (400 MHz, DMSO-d6): δ 1.83-1.90 (m, 2H), 1.92-2.05 (m, 3H), 2.51 (m,1H), 2.90-3.01 (m, 2H),
3.64 (m, 1H), 4.73 (m, 1H), 5.06 (s, br, 1H), 6.79 (s, br, 1H), 7.17-7.29 (m, 3H), 7.48 (m, 2H), 7.73 (m, 2H), 7.93
(m, 4H); LC-MS, RT: 1.463 min, 100%, λmax: 254 nm; MS: m/z [M+1] 451.3; Anal. Calc. for C23H22N4O4S: C,
61.32; H, 4.92; N, 12.44; Found: C, 61.26; H, 4.85; N, 12.38%.
[1,1'-Biphenyl]-4-yl(4-(2-(furan-2-yl)-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methanone
(7e).
[1,1'-
biphenyl]-4-carboxylicacid (107.6 mg, 0.543 mmol) was added in DMF (3 mL) cool to 0 oC, HATU (281 mg, 0.74
o
mmol) was added and stirred for 30 min at 0 C. 2-(furan-2-yl)-1-(piperidin-4-yl)-1H-benzo[d]imidazole
o
hydrochloride 6 (150 mg, 0.493 mmol) was added portion wise and stirred for 30 min at 0 C. DIPEA (0.27 mL,
o
0.156 mmol) was added dropwise at 0 C and stirred for 16 h. Extracted with ethyl acetate (3 × 15 mL) and
dried over anhydrous Na2SO4 and concentrated in vacuum. The crude product was purified by column
chromatography on silica gel (eluent: 0-50% n-Hexane/EtOAc) to afford the product [1,1'-biphenyl]-4-yl(4-(2-
(furan-2-yl)-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methanone as yellow solid (170 mg, 79.79%); mp 128-131
oC; 1H NMR (400 MHz, DMSO-d6): δ 1.24-1.34 (m, 3H), 1.97 (s, br, 2H), 3.01 (m, 1H), 3.85 (m, 1H), 4.74 (m, 1H),
5.08 (s, br, 1H), 6.80 (s, br, 1H), 7.18 (s, br, 1H), 7.29 (s, br, 2H), 7.41-7.50 (m, 3H), 7.64 (s, 2H), 7.72-7.77 (m,
5H),7.92 (s, 1H), 8.03 (s, 1H); 13C-NMR (101 MHz, DMSO-d6): δ 169.51, 145.52, 144.88, 144.06, 143.66, 141.69,
139.86, 135.54, 134.16, 129.53, 128.36, 128.12, 127.29, 127.19, 123.28, 122.75, 120.11, 113.94, 113.49,
112.60, 55.08, 54.05, 47.16, 41.65, 30.63, 29.89, 29.51, 18.55, 17.19; LC-MS, RT: 1.788 min, 99%, λmax: 254
nm; MS: m/z [M+1] 448.4; Anal. Calc. for C29H25N3O2: C, 77.83; H, 5.63; N, 9.39; Found: C, 77.76; H, 5.59; N,
9.33%.
(2,5-Dimethylphenyl) (4-(2-(furan-2-yl)-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)methanone (7f). 2,5-
o
dimethylbenzoic acid (82 mg, 0.543 mmol) was added in DMF (3 mL) cool to 0 C, HATU (281 mg, 0.74 mmol)
o
was added and stirred for 30 min at 0 C. 2-(furan-2-yl)-1-(piperidin-4-yl)-1H-benzo[d]imidazole hydrochloride
o
6 (150 mg, 0.493 mmol) was added portion wise and stirred for 30 min at 0 C. DIPEA (0.27 mL, 0.156 mmol)
o
was added dropwise at 0 C and stirred for 16 h. Extracted with ethyl acetate (3 × 15 mL) and dried over
anhydrous Na2SO4 and concentrated in vacuum. The crude product was purified by column chromatography
on silica gel (eluent: 0-70% n-Hexane/EtOAc) to afford the product (2,5-dimethylphenyl)(4-(2-(furan-2-yl)-1H-
o
1
benzo[d]imidazol-1-yl)piperidin-1-yl)methanone as yellow solid (155 mg, 72.75%); mp 150-154 C; H NMR
(400 MHz, DMSO-d6): δ 1.25 (m, 6H), 1.86 (s, br, 1H), 2.09 (s, br, 1H), 2.32 (m, 2H), 2.96-3.02 (m, 1H), 3.23-3.29
(m, 1H), 3.63 (s, br, 1H), 4.77 (s, br, 1H), 5.049 (s, 1H), 6.68 (d, J 7.2 Hz, 1H), 6.99 (s, 1H), 7.14-7.29 (m, 5H),
7.68-7.70 (m, 1H), 7.89-8.03 (m, 2H); LC-MS, RT: 1.675 min, 95.43%, λmax: 202 nm, MS: m/z [M+1] 400.4;
Anal. Calc. for C25H25N3O2: C, 75.16; H, 6.31; N, 10.52; Found: C, 75.10; H, 6.25; N, 10.47%.
(4-(2-(Furan-2-yl)-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)(thiophen-3-yl)methanone (7g). 3-acetylbenzoic
o
acid (89 mg, 0.543 mmol) was added in DMF (3 mL) cool to 0 C, HATU (281 mg, 0.74 mmol) was added and
o
stirred for 30 min at 0 C. 2-(furan-2-yl)-1-(piperidin-4-yl)-1H-benzo[d]imidazole hydrochloride 6 (150 mg,
o
0.493 mmol) was added portion wise and stirred for 30 min at 0 C. DIPEA (0.27 mL, 0.156 mmol) was added
o
dropwise at 0 C and stirred for 16 h. Extracted with ethyl acetate (3 × 15 mL) and dried over anhydrous
Na2SO4 and concentrated in vacuum. The crude product was purified by column chromatography on silica gel
(eluent: 0-60% n-Hexane/EtoAc) to afford the product (4-(2-(furan-2-yl)-1H-benzo[d]imidazol-1-yl)piperidin-1-
o
1
yl)(thiophen-3-yl)methanone as yellow solid (145 mg, 68%); mp 155-158 C; H NMR (400 MHz, DMSO-d6): δ
1.91-2.06 (m, 4H), 2.64 (s, 3H), 3.02 (m, 2H), 3.71 (m, 1H), 4.75 (m, 1H), 5.07 (S, 1H), 6.80 (S, 1H), 7.19 (d, J 2.8
Hz, 1H), 7.25-7.32 (m, 2H), 7.64-7.70 (m, 2H), 7.81 (d, J 7.2 Hz, 1H), 7.95 (d, J 7.2 Hz, 1H), 8.03-8.07 (m, 3H); LC-
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