Journal of Medicinal Chemistry
Article
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]-3-
(trifluoromethyl)benzamide (7): white powder (70%); mp 81−83
°C; 1H NMR (500 MHz, CDCl3) δ 8.45 (s, 1H), 8.05 (s, 1H), 7.98 (d,
J = 7.5 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 6.63 (t, J = 8.0 Hz, 1H), 6.55
(br s, 1H), 4.43 (t, J = 6.5 Hz, 2H), 3.58 (m, 2H), 2.32 (quintet, J =
6.5 Hz, 2H); HRESIMS calcd for C13H13F3N5O3 m/z [M + H]+
344.0965, found 344.0969.
5H), 5.47 (dt, J = 19.0, 16.5 Hz, 2H), 4.44 (d, J = 13 Hz, 1H), 3.97 (d,
J = 13.5 Hz, 1H), 3.16 (t, J = 13.5 Hz, 1H), 2.64 (t, J = 13.0 Hz, 1H),
2.60 (d, J = 7.0 Hz, 2H), 1.88 (m, 1H), 1.76 (d, J = 13.0 Hz, 1H), 1.69
(d, J = 13.0 Hz, 1H), 1.36−1.32 (dq, J = 12.5, 4.5 Hz, 1H), 1.16−1.13
(dq, J = 12.0, 4.0 Hz, 1H); HRESIMS calcd for C16H20N5O3 m/z [M +
H]+ 330.1561, found 330.1576. Anal. Calcd for C16H19N5O3: C, 58.35;
H, 5.82; N, 21.26. Found: C, 58.27; H, 5.83; N, 21.30.
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]-3,5-bis-
Data for N-(6-methyl-1,3-benzothiazol-2-yl)-2-(3-nitro-1H-
(trifluoromethyl)benzamide (8): white powder (83%); mp 152−
1,2,4-triazol-1-yl)acetamide (17): off-white powder (59%); mp
1
1
153 °C; H NMR (500 MHz, CD3COCD3) δ 8.72 (s, 1H), 8.52 (s,
230 °C dec; H NMR (500 MHz, CD3COCD3) δ 8.81 (s, 1H), 7.74
2H), 8.46 (br s, 1H), 8.25 (s, 1H), 4.57 (t, J = 7.0 Hz, 2H), 3.59 (q, J =
6.5 Hz, 2H), 2.35 (quintet, J = 7.0 Hz, 2H); HRESIMS calcd for
C14H12F6N5O3 m/z [M + H]+ 412.0839 found 412.0844.
(s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 5.68 (s,
2H), 2.44 (s, 3H); HRESIMS calcd for C12H11N6O3S m/z [M + H]+
319.0608, found 319.0617.
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]-6-
(trifluoromethyl)pyridine-3-carboxamide (9): white powder
(71%); mp 92−94 °C; 1H NMR (500 MHz, CDCl3) δ 9.09 (s,
1H), 8.39 (s, 1H), 8.33 (d, J = 8.5 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H),
6.73 (br s, 1H), 4.43 (t, J = 6.5 Hz, 2H), 3.60 (q, J = 6.5 Hz, 2H), 3.42
(quintet, J = 6.5 Hz, 2H); HRESIMS calcd for C12H12F3N6O3 and
C12H11F3N6NaO3 m/z [M + H]+ and [M + Na]+ 345.0917, 367.0737,
found 345.0929, 367.0745. Anal. Calcd for C12H11F3N6O3: C, 41.87;
H, 3.22; N, 24.41. Found: C, 41.93; H, 3.38; N, 24.17.
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]quinoline-
2-carboxamide (10): off-white powder (70%); mp 135−137 °C; 1H
NMR (500 MHz, CD3OD) δ 8.68 (s, 1H), 8.46 (d, J = 8.5 Hz, 1H),
8.17 (t, J = 9.0 Hz, 2H), 8.0 (d, J = 8.5 Hz, 1H), 7.83 (t, J = 8.5 Hz,
1H), 7.69 (t, J = 8.0 Hz, 1H), 4.46 (t, J = 8.0 Hz, 2H), 3.58 (t, J = 6.5
Hz, 2H), 2.34 (quintet, J = 6.5 Hz, 2H); HRESIMS calcd for
C15H15N6O3 and C15H14N6NaO3 m/z [M + H]+ and [M + Na]+
327.1200, 349.1020, found 327.1209, 349.1026.
Data for N-[4-(3-nitro-1H-1,2,4-triazol-1-yl)butyl]quinoline-
2-carboxamide (11): off-white powder (67%); mp 124−126 °C; 1H
NMR (500 MHz, CD3COCD3) δ 8.75 (br s, 1H), 8.70 (s, 1H), 8.52
(d, J = 8.5 Hz, 1H), 8.24 (d, J = 8.5 Hz, 1H), 8.06 (t, J = 9.5 Hz, 2H),
7.84 (t, J = 7.0 Hz, 1H), 7.70 (t, J = 7.0 Hz, 1H), 4.52 (t, J = 7.0 Hz,
2H), 3.58 (q, J = 6.5 Hz, 2H), 2.09 (m, 2H),1.76 (quintet, J = 7.0 Hz,
2H); HRESIMS calcd for C16H17N6O3 m/z [M + H]+ 341.1357, found
341.1369.
Data for N-(6-chloro-1,3-benzothiazol-2-yl)-2-(3-nitro-1H-
1,2,4-triazol-1-yl)acetamide (18): off-white powder (58%); mp
1
245−248 °C dec; H NMR (500 MHz, CD3COCD3) δ 8.81 (s, 1H),
8.06 (s, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.04 (dd, J = 8.5, 2.0 Hz, 1H),
5.71 (s, 2H); HRESIMS calcd for C11H8ClN6O3S m/z [M + H]+
339.0062, 341.0034, found 339.0072, 341.0045.
Data for N-(5-chloro-1,3-benzoxazol-2-yl)-2-(3-nitro-1H-
1,2,4-triazol-1-yl)acetamide (19): off-white powder (45%); mp
1
208−210 °C dec; H NMR (500 MHz, CD3COCD3) δ 8.76 (s, 1H),
7.60 (s, 1H), 7.59 (d, J = 9.0 Hz, 1H), 7.34 (dd, J = 8.5, 2.0 Hz, 1H),
5.80 (s, 1H); HRESIMS calcd for C11H6ClN6O4 m/z [M − H]−
321.0145, 323.0119, found 321.0147, 323.0143.
Data for 1-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(3-nitro-1H-
1,2,4-triazol-1-yl)propyl]urea (20): white powder (95%); mp 151−
152 °C; 1H NMR (500 MHz, CD3COCD3) δ 8.71 (s, 1H), 8.68 (br s,
1H), 8.15 (s, 2H), 7.54 (s, 1H), 6.31 (br s, 1H), 4.51 (t, J = 6.5 Hz,
2H), 3.35 (m, 2H), 2.21 (quintet, J = 6.5 Hz, 2H); HRESIMS calcd for
C14H13F6N6O3 m/z [M + H]+ 427.0948, found 427.0954.
Data for N-[3-(2-nitro-1H-imidazol-1-yl)propyl]-4-
(trifluoromethyl)benzene-1-sulfonamide (21): white powder
1
(56%); mp 129−131 °C; H NMR (500 MHz, CDCl3) δ 7.99 (d, J
= 8.0 Hz, 2H), 7.82 (d, J = 8.5 Hz, 2H), 7.24 (s, 1H), 7.19 (s, 1H),
4.77 (br t, 1H), 4.57 (t, J = 7.0 Hz, 2H), 3.06 (q, J = 6.5 Hz, 2H), 2.12
(quintet, J = 6.5 Hz, 2H); HRESIMS calcd for C13H14F3N4O4S and
C13H13F3N4NaO4S m/z [M + H]+ and [M + Na]+ 379.0682, 401.0502
found 379.0685, 401.0506.
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]-
quinoxaline-2-carboxamide (12): off-white powder (66%); mp
Data for N-[2-(3-nitro-1H-1,2,4-triazol-1-yl)ethyl]-4-
(trifluoromethyl)benzene-1-sulfonamide (22): white powder
(35%); mp 155−156 °C; 1H NMR (500 MHz, CDCl3 + several
drops of CD3COCD3) δ 8.51 (s, 1H), 7.99 (d, J = 8.5 Hz, 2H), 7.82
(d, J = 8.5 Hz, 2H), 7.04 (br s, 1H), 4.56 (t, J = 6.0 Hz, 2H), 3.56 (m,
2H); HRESIMS calcd for C11H11F3N5O4S m/z [M + H]+ 366.0478,
found 366.0481.
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]-4-
(trifluoromethyl)benzene-1-sulfonamide (23): white powder
(88%); mp 67−68 °C; 1H NMR (500 MHz, CDCl3) δ 8.36 (s,
1H), 7.97 (d, J = 8.5 Hz, 2H), 7.81 (d, J = 8.5 Hz, 2H), 5.01 (br t,
1H), 4.51 (t, J = 6.5 Hz, 2H), 3.03 (q, J = 6.5 Hz, 2H), 2.23 (quintet, J
= 6.0 Hz, 2H); HRESIMS calcd for C12H13F3N5O4S m/z [M + H]+
380.0635, found 380.0635.
1
143−144 °C; H NMR (500 MHz, CDCl3) δ 9.67 (s, 1H), 8.47 (s,
1H), 8.22 (d, J = 8.0 Hz, 1H), 8.21 (br s, 1H), 8.12 (d, J = 7.5 Hz,
1H), 7.90 (m, 2H), 4.45 (t, J = 6.5 Hz, 2H), 3.66 (q, J = 6.5 Hz, 2H),
2.39 (quintet, J = 6.5 Hz, 2H); HRESIMS calcd for C14H14N7O3 m/z
[M + H]+ 328.1153, found 328.1166. Calculated analysis for
C14H13N7O3: C, 51.38; H, 4.0; N, 29.96. Found: C, 51.29; H, 4.17;
N, 29.68.
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]-4-phenyl-
1
benzamide (13): white powder (96%); mp 177−179 °C; H NMR
(500 MHz, CDCl3) δ 8.48 (s, 1H), 7.85 (d, J = 8.5 Hz, 2H), 7.69 (d, J
= 7.0 Hz, 2H), 7.48 (t, J = 7.5 Hz, 2H), 7.40 (t, J = 7.5 Hz, 1H), 6.49
(br t, 1H), 4.43 (t, J = 6.5 Hz, 2H), 3.57 (q, J = 6.5 Hz, 2H), 2.30
(quintet, J = 6.5 Hz, 2H); HRESIMS calcd for C18H18N5O3 and
C18H17N5NaO3 m/z [M + H]+ and [M + Na]+ 352.1404, 374.1224,
found 352.1406, 374.1222. Anal. Calcd for C18H17N5O3: C, 61.53; H,
4.88; N, 19.93. Found: C, 61.79; H, 4.96; N, 19.58.
Data for N-[4-(3-nitro-1H-1,2,4-triazol-1-yl)butyl]-4-
(trifluoromethyl)benzene-1-sulfonamide (24): white powder
1
(49%); mp 83−85 °C; H NMR (500 MHz, CD3OD) δ 8.59 (s,
1H), 8.03 (d, J = 8.0 Hz, 2H), 7.89 (d, J = 8.0 Hz, 2H), 4.32 (t, J = 7.0
Hz, 2H), 2.94 (t, J = 6.5 Hz, 2H), 1.96 (quintet, J = 7.5 Hz, 2H), 1.51
(quintet, J = 7.5 Hz, 2H); HRESIMS calcd for C13H15F3N5O4S m/z
[M + H]+ 394.0791, found 394.0796.
Data for N-benzyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)acetamide
(14): off-white powder (40%); mp 103−106 °C; 1H NMR (500 MHz,
CDCl3) δ 8.39 (s, 1H), 7.38−7.28 (m, 5H), 6.26 (br s, 1H), 4.98 (s,
2H), 4.50 (d, J = 5.5 Hz, 2H); HRESIMS calcd for C11H12N5O3 m/z
[M + H]+ 262.0935, found 262.0935.
Data for 2-(3-nitro-1H-1,2,4-triazol-1-yl)-N-{[4-
(trifluoromethyl)phenyl]methyl}acetamide (15): white micro-
crystal (78%); mp 168−170 °C; 1H NMR (500 MHz, CDCl3) δ
8.37 (s, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 6.35
(br s, 1H), 4.99 (s, 2H), 4.56 (d, J = 6.0 Hz, 2H); HRESIMS calcd for
C12H11F3N5O3 and C12H10F3N5NaO3 m/z [M + H]+ and [M + Na]+
330.0809, 352.0628, found 330.0814, 352.0632.
Data for N-[3-(3-nitro-1H-1,2,4-triazol-1-yl)propyl]-2,5-bis-
(trifluoromethyl)benzene-1-sulfonamide (25): white powder
1
(85%); mp 131−133 °C; H NMR (500 MHz, CDCl3) δ 8.42 (s,
1H), 8.31 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 8.0 Hz, 2H),
5.10 (br s, 1H), 4.49 (t, J = 6.5 Hz, 2H), 3.07 (m, 2H), 2.25 (quintet, J
= 6.5 Hz, 2H); HRESIMS calcd for C13H12F6N5O4S and
C13H11F6N5NaO4S m/z [M + H]+ and [M + Na]+ 448.0509,
470.0328, found 448.0496, 470.0310.
Data for 1-(4-benzylpiperidin-1-yl)-2-(3-nitro-1H-1,2,4-tria-
zol-1-yl)ethan-1-one (16): white powder (84%); mp 129−131 °C;
1H NMR (500 MHz, CD3COCD3) δ 8.57 (s, 1H), 7.31−7.18 (m,
Data for N-[2-(3-nitro-1H-1,2,4-triazol-1-yl)ethyl]-3,5-bis-
(trifluoromethyl)benzene-1-sulfonamide (26): white powder
1
(40%); mp 164−165 °C; H NMR (500 MHz, CD3COCD3) δ 8.67
5562
dx.doi.org/10.1021/jm300508n | J. Med. Chem. 2012, 55, 5554−5565