March 2018
1H-1,2,3-Triazole-tethered Isatin–coumarin Hybrids: Design, Synthesis and In
Vitro Anti-mycobacterial Evaluation
779
1-(2-(4-(((4-Methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-1H-
1,2,3-triazol-1-yl)ethyl)indoline-2,3-dione (7a). Yield: 53%.
(1H, d, Ar─H), 8.35 (1H, s, Ar─H). ESI-MS m/z: 460
[M + H]+. Elemental Anal. Calcd (%) for C24H21N5O5: C,
62.74; H, 4.61; N, 15.24; Found: C, 62.63; H, 4.45; N, 15.07.
3-(Methoxyimino)-5-methyl-1-(2-(4-(((4-methyl-2-oxo-2H-
chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)ethyl)indolin-2-
one (7f). Yield: 54%. 1H NMR (400 MHz, CDCl3) δ 2.23
(3H, s, ─CH3), 2.40 (3H, s, ─CH3), 4.10–4.19 (5H, m,
NOCH3 and ─CH2 of linker), 4.66 (2H, t, ─CH2 of
linker), 5.20 (2H, s, ─CH2O─), 6.25 (1H, s, Ar─H), 6.74
(1H, d, Ar─H), 6.98 (1H, d, Ar─H), 7.09–7.11 (2H, m,
Ar─H), 7.67–7.69 (2H, m, Ar─H), 8.34 (1H, s, Ar─H).
ESI-MS m/z: 474 [M + H]+. Elemental Anal. Calcd (%)
for C25H23N5O5: C, 63.42; H, 4.90; N, 14.79; Found: C,
1H NMR (400 MHz, CDCl3) δ 2.40 (3H, s, ─CH3), 4.14
(2H, t, ─CH2 of linker), 4.68 (2H, t, ─CH2 of linker), 5.20
(2H, s, ─CH2O─), 6.22 (1H, s, Ar─H), 6.88 (1H, d,
Ar─H), 6.98 (1H, d, Ar─H), 7.05–7.08 (2H, m, Ar─H),
7.51–7.52 (2H, m, Ar─H), 7.67 (1H, d, Ar─H), 8.35 (1H,
s, Ar─H). ESI-MS m/z: 431 [M + H]+. Elemental
Anal. Calcd (%) for C23H18N4O5: C, 64.18; H, 4.22; N,
13.02; Found: C, 64.05; H, 4.01; N, 12.87.
5-Methyl-1-(2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-
1H-1,2,3-triazol-1-yl)ethyl)indoline-2,3-dione (7b).
Yield:
1
56%. H NMR (400 MHz, CDCl3) δ 2.28 (3H, s, ─CH3),
2.40 (3H, s, ─CH3), 4.16 (2H, t, ─CH2 of linker), 4.70
(2H, t, ─CH2 of linker), 5.25 (2H, s, ─CH2O─), 6.27 (1H,
s, Ar─H), 6.80 (1H, d, Ar─H), 7.03 (1H, d, Ar─H), 7.13
(1H, s, Ar─H), 7.35–7.38 (2H, m, Ar─H), 7.72 (1H, d,
Ar─H), 8.38 (1H, s, Ar─H). ESI-MS m/z: 445 [M + H]+.
C24H20N4O5: C, 64.86; H, 4.54; N, 12.61; Found: C,
63.28; H, 4.65; N, 14.71.
5-Chloro-1-(2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)
methyl)-1H-1,2,3-triazol-1-yl)ethyl)indoline-2,3-dione (7g). Yield:
1
57%. H NMR (400 MHz, CDCl3) δ 2.40 (3H, s, ─CH3),
4.22–4.28 (5H, m, NOCH3 and ─CH2 of linker), 4.66 (2H, t,
─CH2 of linker), 5.20 (2H, s, ─CH2O─), 6.22 (1H, s,
Ar─H), 6.83 (1H, d, Ar─H), 6.98 (1H, d, Ar─H), 7.08
(1H, s, Ar─H), 7.33 (1H, d, Ar─H), 7.68 (1H, d, Ar─H),
7.80 (1H, s, Ar─H), 8.30 (1H, s, Ar─H). ESI-MS m/z: 494
[M + H]+, 496 [M + 2 + H]+. Elemental Anal. Calcd (%) for
C24H20ClN5O5: C, 58.36; H, 4.08; N, 14.18; Found:
64.71; H, 4.39; N, 12.55.
5-Chloro-1-(2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-
1H-1,2,3-triazol-1-yl)ethyl)indoline-2,3-dione (7c). Yield: 51%.
1H NMR (400 MHz, CDCl3) δ 2.41 (3H, s, ─CH3), 4.23
(2H, t, ─CH2 of linker), 4.34 (2H, t, ─CH2 of linker), 5.21
(2H, s, ─CH2O─), 6.27 (1H, s, Ar─H), 6.81 (1H, d, Ar─H),
6.98 (1H, d, Ar─H), 7.10 (1H, s, Ar─H), 7.32 (1H, d,
Ar─H), 7.67 (1H, d, Ar─H), 7.80 (1H, s, Ar─H), 8.30 (1H,
s, Ar─H). ESI-MS m/z: 465 [M + H]+, 467 [M + 2 + H]+.
Elemental Anal. Calcd (%) for C23H17ClN4O5: C, 59.43;
C, 58.17; H, 3.88; N, 14.03.
5-Fluoro-3-(methoxyimino)-1-(2-(4-(((4-methyl-2-oxo-2H-
chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)ethyl)indolin-2-
1
one (7h). Yield: 68%. H NMR (400 MHz, CDCl3) δ
2.42 (3H, s, ─CH3), 4.18–4.24 (5H, m, NOCH3 and
─CH2 of linker), 4.69 (2H, t, ─CH2 of linker), 5.22 (2H,
s, ─CH2O─), 6.24 (1H, s, Ar─H), 6.85 (1H, d, Ar─H),
6.99 (1H, d, Ar─H), 7.08 (1H, s, Ar─H), 7.17 (1H, d,
Ar─H), 7.68 (1H, d, Ar─H), 7.70 (1H, s, Ar─H), 8.32
(1H, s, Ar─H). ESI-MS m/z: 478 [M + H]+. Elemental
Anal. Calcd (%) for C24H20FN5O5: C, 60.37; H, 4.22; N,
H, 3.69; N, 12.05; Found: C, 58.22; H, 3.51; N, 11.88.
5-Fluoro-1-(2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-
1H-1,2,3-triazol-1-yl)ethyl)indoline-2,3-dione (7d).
Yield:
1
42%. H NMR (400 MHz, CDCl3) δ 2.42 (3H, s, ─CH3),
4.20 (2H, t, ─CH2 of linker), 4.71 (2H, t, ─CH2 of
linker), 5.20 (2H, s, ─CH2O─), 6.26 (1H, s, Ar─H), 6.86
(1H, d, Ar─H), 7.00 (1H, d, Ar─H), 7.07 (1H, s, Ar─H),
7.18 (1H, d, Ar─H), 7.64 (1H, d, Ar─H), 7.69 (1H, s,
Ar─H), 8.33 (1H, s, Ar─H). ESI-MS m/z: 449 [M + H]+.
Elemental Anal. Calcd (%) for C23H17FN4O5: C, 61.61;
H, 3.82; N, 12.49; Found: C, 61.47; H, 3.68; N, 12.31.
14.67; Found: C, 60.19; H, 4.08; N, 14.42.
3-(Ethoxyimino)-1-(2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)
methyl)-1H-1,2,3-triazol-1-yl)ethyl)indolin-2-one (7i). Yield:
1
59%. H NMR (400 MHz, CDCl3) δ 1.36–1.41 (3H, m,
OCH2CH3), 2.42 (3H, s, ─CH3), 4.19 (2H, s, ─CH2 of
linker), 4.41–4.49 (2H, m, OCH2CH3), 4.70 (2H, t, ─CH2
of linker), 5.22 (2H, s, ─CH2O─), 6.25 (1H, s, Ar─H),
6.88 (1H, d, Ar─H), 7.00–7.06 (2H, m, Ar─H), 7.11 (1H,
s, Ar─H), 7.33–7.35 (1H, m, Ar─H), 7.70 (1H, d, Ar─H),
7.88 (1H, d, Ar─H), 8.33 (1H, s, Ar─H). ESI-MS m/z:
The general procedure for preparing targets 7e–l.
A
mixture of the corresponding amine hydrochloride. After
cooling to room temperature, the mixture was extracted
with EA (10 mL * 3). The combined organic layers were
concentrated under reduced pressure, and the residue was
purified by column chromatography (silica gel) eluted with
PE to v(PE) : v(EA) = 1:1 to give the title compounds
474 [M
+
H]+. Elemental Anal. Calcd (%) for
C25H23N5O5: C, 63.42; H, 4.90; N, 14.79; Found: C,
63.33; H, 4.74; N, 14.61.
3-(Ethoxyimino)-5-methyl-1-(2-(4-(((4-methyl-2-oxo-2H-
chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)ethyl)indolin-2-
one (7j). Yield: 47%. 1H NMR (400 MHz, CDCl3) δ 1.38
(3H, t, OCH2CH3), 2.27 (3H, s, ─CH3), 2.42 (3H, s,
─CH3), 4.17 (2H, t, ─CH2 of linker), 4.45 (2H, q,
OCH2CH3), 4.72 (2H, t, ─CH2 of linker), 5.21 (2H, s,
─CH2O─), 6.26 (1H, s, Ar─H), 6.84 (1H, d, Ar─H),
7.00 (1H, d, Ar─H), 7.16 (1H, s, Ar─H), 7.31–7.34 (2H,
7e–l (47–68%).
3-(Methoxyimino)-1-(2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)
oxy)methyl)-1H-1,2,3-triazol-1-yl)ethyl)indolin-2-one (7e). Yield:
1
62%. H NMR (400 MHz, CDCl3) δ 2.46 (3H, s, ─CH3),
4.17–4.26 (5H, m, NOCH3, ─CH2 of linker), 4.72 (2H, t,
─CH2 of linker), 5.25 (2H, s, ─CH2O─), 6.28 (1H, s,
Ar─H), 6.93 (1H, d, Ar─H), 7.05–7.14 (3H, m, Ar─H),
7.30–7.37 (1H, m, Ar─H), 7.72–7.74 (1H, m, Ar─H), 7.89
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet