ORIGINAL ARTICLES
8.61 (s, 1H), 8.31 (s, 1H), 8.15 (s, 1H), 7.96 (s, 1H), 7.60-7.51 (m, 2H), 7.43 (s, 1H),
7.42-7.35 (m, 2H), 7.16 (t, J = 7.7 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 3.87 (s, 3H),
3.74 (s, 3H).
3.2.6. 6-Chloro-1-methyl-1H-indole-3-carbohydrazide (3e)
According to the general method, the reaction of 2e with 85% hydrazine hydrate
afforded 3e in 76.0% yield, mp: 211-212 °C. 1H NMR (500 MHz, DMSO-d6) δ 9.21
(s, 1H), 8.12 (d, J = 8.5 Hz, 1H), 7.95 (s, 1H), 7.64 (d, J = 1.9 Hz, 1H), 7.16 (dd, J =
8.5, 1.9 Hz, 1H), 4.33 (s, 2H), 3.81 (s, 3H).
3.3.8. 2-(6-Bromo-1-methyl-1H-indole-3-carbonyl)-N-(1-methyl-1H-in-
dol-3-yl) hydrazine-1-carboxamide (5g)
3.2.7. 5-Bromo-1-methyl-1H-indole-3-carbohydrazide (3f)
According to the general method, the reaction of 3g with 4 afforded 5g in 63.3% yield
as an off-white solid, mp: 225-226 °C.1H NMR (500 MHz, DMSO-d6) δ 9.84 (s, 1H),
8.61 (s, 1H), 8.17-8.11 (m, 2H), 7.95 (s, 1H), 7.69 (d, J = 1.8 Hz, 1H), 7.57 (d, J = 8.0
Hz, 1H), 7.43 (s, 1H), 7.38 (d, J = 8.3 Hz,1H), 7.21 (dd, J = 8.6, 1.9 Hz, 1H), 7.18-7.11
(m, 1H), 7.08-6.99 (m, 1H), 3.86 (s, 3H), 3.74 (s, 3H).
According to the general method, the reaction of 2f with 85% hydrazine hydrate
afforded 3f in 69.0% yield, mp: 231-233 °C. 1H NMR (500 MHz, DMSO-d6) δ 9.23
(s, 1H), 8.29 (d, J = 2.1 Hz, 1H), 7.97 (s, 1H), 7.49 (d, J = 8.7 Hz, 1H), 7.35 (dd, J =
8.7, 2.1 Hz, 1H), 4.33 (s, 2H), 3.82 (s, 3H).
3.2.8. 6-Bromo-1-methyl-1H-indole-3-carbohydrazide (3g)
3.3.9. 2-(5-Methoxy-1-methyl-1H-indole-3-carbonyl)-N-(1-methyl-1H-
According to the general method, the reaction of 2g with 85% hydrazine hydrate
afforded 3g in 72.0% yield, mp: 212-214 °C. 1H NMR (500 MHz, DMSO-d6) δ 9.21
(s, 1H), 8.12 (d, J = 8.5 Hz, 1H), 7.94 (s, 1H), 7.64 (d, J = 1.9 Hz, 1H), 7.17 (dd, J =
8.5, 1.9 Hz, 1H), 4.37 (s, 2H), 3.81 (s, 3H)
indol-3-yl) hydrazine-1-carboxamide (5h)
According to the general method, the reaction of 3h with 4 afforded 5h in 86.9%
yield as an off-white solid, mp: 203-205 °C. 1H NMR (500 MHz, DMSO-d6) δ 9.78
(s, 1H), 8.54 (s, 1H), 8.16 (d, J = 7.9 Hz, 1H), 8.11 (s, 1H), 7.88 (s, 1H), 7.53 (d, J =
8.3 Hz, 1H), 7.37 (s, 1H), 7.30 (d, J = 8.9 Hz, 1H), 7.28 – 7.21 (m, 1H), 7.22 – 7.15
(m, 1H), 7.07 (d, J = 2.5 Hz, 1H), 6.80 (dd, J = 8.9, 2.4 Hz, 1H), 3.87 (s, 3H), 3.78
(s, 3H), 3.70 (s, 3H).
3.2.9. 5-Methoxy-1-methyl-1H-indole-3-carbohydrazide (3h)
According to the general method, the reaction of 2h with 85% hydrazine hydrate
afforded 3h in 71.0% yield, mp: 167-169 °C. 1H NMR (500 MHz, DMSO-d6) δ 9.11
(s, 1H), 7.87 (s, 1H), 7.64 (d, J = 2.5 Hz, 1H), 7.38 (d, J = 8.9 Hz, 1H), 6.85 (dd, J =
8.9, 2.5 Hz, 1H), 4.37 (s, 2H), 3.78 (s, 6H).
3.4. Synthesis of compounds 6a – 6h
3.4.1. General procedure for the preparation of 6a-6h
3.3. Synthesis of compounds 5a – 5h
Trimethylsilyl trifluoromethanesulfonate (3.0 mmol) and dry triethylamine (4.0
mmol) were added to a solution of 5a-h (0.5 mmol) in dry DMF (10 mL). The reaction
mixture was stirred for 4 h at 110 °C. After cooling, the mixture was poured into
water (100 mL) and extracted with ethyl acetate (50 mL × 3). The organic phase was
combined, washed with brine (150 mL × 3), dried over Na2SO4 and concentrated in
vacuo. The residue was purified by flash column chromatography on silica gel using
petroleum ether/ethyl acetate (1:2, v/v) as eluent to afford 6a-h.
3.3.1. General procedure for the preparation of 5a-5h
Compound 4 (0.29 g, 1.7 mmol) in dry THF (5 mL) was added dropwise to a mixture
of 3a-h (1.7 mmol) in dry THF (20 mL) at 0-5 °C. After addition, the mixture was
stirred for 2 h at room temperature. The mixture was then filtered and dried to afford
5a-h.
3.3.2. 2-(1H-indole-3-carbonyl)-N-(1-methyl-1H-indol-3-yl)hydra-
3.4.2. 5-(1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)-2,4-dihydro-3H-
zine-1-carboxamide (5a)
1,2,4-triazol-3-one (6a)
According to the general method, the reaction of 3a with 4 afforded 5a in 85.8% yield
as a off-white solid, mp: 218-220 °C. 1H NMR (500 MHz, DMSO-d6) δ 11.67 (s, 1H),
9.78 (s, 1H), 8.64 (s, 1H), 8.19-8.15 (m, 2H), 7.95 (s, 1H), 7.59 (d, J = 8.0 Hz, 1H),
7.47 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.20-7.13 (m, 3H), 7.04
(t, J = 7.5 Hz, 1H), 3.74 (s, 3H).
According to the general method, the reaction of 5a with trimethylsilyl trifluorometh-
anesulfonate and dry triethylamine provided 6a in 78.6% yield as a white solid, mp:
>250 °C. 1H NMR (500 MHz, Chloroform-d) δ 11.90 (s, 1H), 11.16 (d, J = 1.9 Hz,
1H), 8.19 (d, J = 7.5 Hz, 1H), 7.72 (s, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 7.5
Hz, 1H), 7.33 -7.20 (m, 2H), 7.19-7.10 (m, 2H), 7.07 (t, J = 7.3 Hz, 1H), 6.59 (d, J =
2.8 Hz, 1H), 3.90 (s, 3H).
3.3.3. 2-(5-Fluoro-1-methyl-1H-indole-3-carbonyl)-N-(1-methyl-1H-in-
dol-3-yl) hydrazine-1-carboxamide (5b)
3.4.3. 5-(5-Fluoro-1-methyl-1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)-
According to the general method, the reaction of 3b with 4 afforded 5b in 63.8% yield
as an off-white solid, mp: 224-226 °C.1H NMR (500 MHz, DMSO-d6) δ 9.84 (s, 1H),
8.65 (s, 1H), 8.19 (s, 1H), 8.00-7.89 (m, 2H), 7.72-7.28 (m, 4H), 7.25-6.95 (m, 3H),
3.87 (s, 3H), 3.75 (s, 3H).
2,4-dihydro-3H-1,2,4-triazol-3-one (6b)
According to the general method, the reaction of 5b with trimethylsilyl trifluorometh-
anesulfonate and dry triethylamine provided 6b in 60.4% yield as a white solid, mp:
>250 °C. 1H NMR (500 MHz, DMSO-d6) δ 11.92 (s, 1H), 7.81 (dd, J = 10.1, 2.6 Hz,
1H), 7.70 (s, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.47-7.44 (m, 1H), 7.25 (t, J = 7.7 Hz, 1H),
7.20 (d, J = 7.9 Hz, 1H), 7.11 (dd, J = 9.1, 2.4 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 6.71
(s, 1H), 3.90 (s, 3H), 3.54 (s, 3H). HRMS (ESI) m/z [M + H]+ for C20H17N5OF calcd
362.1412, found 362.1410.
3.3.4. 2-(6-Fluoro-1-methyl-1H-indole-3-carbonyl)-N-(1-methyl-1H-in-
dol-3-yl) hydrazine-1-carboxamide (5c)
According to the general method, the reaction of 3c with 4 afforded 5c in 77.8% yield
as an off-white solid, mp: 215-217 °C.1H NMR (500 MHz, DMSO-d6) δ 9.83 (s, 1H),
8.64 (s, 1H), 8.16-8.09 (m, 2H), 7.96 (s, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.46-7.42 (m,
2H), 7.39 (d, J = 8.3 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.08-7.01 (m, 2H), 3.84 (s,
3H), 3.74 (s, 3H).
3.4.4. 5-(6-Fluoro-1-methyl-1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)-
2,4-dihydro-3H-1,2,4-triazol-3-one (6c)
According to the general method, the reaction of 5c with trimethylsilyl trifluorometh-
anesulfonate and dry triethylamine provided 6c in 67.3% yield as a white solid, mp:
>250 °C. 1H NMR (500 MHz, DMSO-d6) δ 11.93 (s, 1H), 8.15-8.12 (m, 1H), 7.70 (s,
1H), 7.60 (d, J = 8.3 Hz, 1H), 7.33 (dd, J = 10.0, 2.1 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H),
7.20 (d, J = 7.9 Hz, 1H), 7.08-7.00 (m, 2H), 6.65 (s, 1H), 3.90 (s, 3H), 3.50 (s, 3H).
3.3.5. 2-(5-Chloro-1-methyl-1H-indole-3-carbonyl)-N-(1-methyl-1H-in-
dol-3-yl) hydrazine-1-carboxamide (5d)
According to the general method, the reaction of 3d with 4 afforded 5d in 62.2% yield
as an off-white solid, mp: 233-235 °C.1H NMR (500 MHz, DMSO-d6) δ 9.86 (s, 1H),
8.63 (s, 1H), 8.16 (s, 1H), 8.14 (s, 1H), 7.97 (s, 1H), 7.58 (t, J = 7.2 Hz, 2H), 7.43(s,
1H) ,7.39 (d, J = 8.2 Hz 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H), 7.03
(d, J = 7.4 Hz, 1H), 3.87 (s, 3H), 3.74 (s, 3H).
3.4.5. 5-(5-Chloro-1-methyl-1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)-
2,4-dihydro-3H-1,2,4-triazol-3-one (6d)
According to the general method, the reaction of 5d with trimethylsilyl trifluorometh-
anesulfonate and dry triethylamine provided 6d in 63.2% yield as a white solid, mp:
>250 °C. 1H NMR (500 MHz, DMSO-d6) δ 11.94 (s, 1H), 8.13 (d, J = 1.4 Hz, 1H),
7.70 (s, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.29-7.22 (m, 2H),
7.20 (d, J = 7.9 Hz, 1H), 7.05 (t, J = 7.4 Hz, 1H), 6.71 (s, 1H), 3.90 (s, 3H), 3.54 (s,
3H). HRMS (ESI) m/z [M + H]+ for C20H17N5OCl calcd 378.1116, found 378.1104.
3.3.6. 2-(6-Chloro-1-methyl-1H-indole-3-carbonyl)-N-(1-methyl-1H-in-
dol-3-yl) hydrazine-1-carboxamide (5e)
According to the general method, the reaction of 3e with 4 afforded 5e in 54.7% yield
as an off-white solid, mp: 223-224 °C.1H NMR (500 MHz, DMSO-d6) δ 9.83 (s, 1H),
8.61 (s, 1H), 8.17-8.11 (m, 2H), 7.95 (s, 1H), 7.69 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H),
7.43 (s, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.24 -7.12 (m, 2H), 7.03 (t, J = 7.5 Hz, 1H),
3.86 (s, 3H), 3.74 (s, 3H).
3.4.6. 5-(6-Chloro-1-methyl-1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)-
2,4-dihydro-3H-1,2,4-triazol-3-one (6e)
According to the general method, the reaction of 5e with trimethylsilyl trifluorometh-
anesulfonate and dry triethylamine provided 6e in 70.4% yield as a white solid, mp:
>250 °C. 1H NMR (500 MHz, DMSO-d6) δ 11.95 (s, 1H), 8.12 (d, J = 8.6 Hz, 1H),
7.70 (s, 1H), 7.62-7.58 (m, 2H), 7.25 (t, J = 7.7 Hz, 1H), 7.22-7.16 (m, 2H), 7.05 (t, J
= 7.5 Hz, 1H), 6.69 (s, 1H), 3.90 (s, 3H), 3.53 (s, 3H).
3.3.7. 2-(5-Bromo-1-methyl-1H-indole-3-carbonyl)-N-(1-methyl-1H-in-
dol-3-yl) hydrazine-1-carboxamide (5f)
According to the general method, the reaction of 3f with 4 afforded 5f in 77.6% yield
as an off-white solid, mp: 230-232 °C.1H NMR (500 MHz, DMSO-d6) δ 9.85 (s, 1H),
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