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4.1.2.4. 1,3-Bis(5-chloro-1H-indol-3-yl)propane-1,3-dione (7d). Yel-
low solid; yield: 45%; mp: 220–221 °C; IR 1616 (CO) cmꢁ1 1H
1H NMR (200 MHz, CDCl3) d: 3.21 (2H, s, CH2), 3.75 (, 3H, s, CH3),
3.85 (3H, s, CH3), 6.90 (1H, d, J = 8.8 Hz, H-6), 7.43 (1H, d,
J = 8.8 Hz, H-7), 7.70 (1H, s, H-4), 8.35 (1H, s, H-2); 13C NMR
(50 MHz, CDCl3) d: 33.7 (CH2), 33.7 (CH3), 55.7 (CH3), 103.7 (CH),
110.4 (CH), 113.8 (CH), 115.8 (C), 127.2 (C), 132.4 (C), 135.7 (CH),
156.4 (C) , 194.3 (C). Anal. Calcd for C24H24N2O4: C, 71.27; H, 5.98;
N, 6.93. Found: C, 71.05; H, 5.88; N, 6.76.
;
NMR (200 MHz, CDCl3) d: 3.81 (3H, s, CH3), 4.26 (2H, s, CH2),
7.13–7.26 (2H, m, H-6, H-7), 8.13 (1H, s, H-4), 8.33 (1H, s, H-2);
13C NMR (50 MHz, CDCl3) d: 33.9 (CH3), 56.2 (CH2), 110.7 (CH),
115.4 (C), 122.0 (CH), 123.2 (C), 123.9 (CH), 128.9 (C), 135.8 (C),
139.1 (CH), 187.8 (C). Anal. Calcd for C21H16Cl2N2O2: C, 63.17; H,
4.04; N, 7.02. Found: C, 63.25; H, 3.88; N, 7.12.
4.1.5. General procedure for the preparation of isoxazoles
(3a–e)
4.1.2.5. 1,3-Bis(5-bromo-1H-indol-3-yl)propane-1,3-dione (7e). Yel-
low solid; yield: 48%; mp: 238–240 °C; IR 1626 (CO) cmꢁ1
;
1H
Hydroxylamine hydrochloride (57 mmol) was dissolved in THF
(10 mL) and added dropwise to a stirred solution of 1,3-diketones
7a–e (1 mmol) in THF (10 mL) with a stoikiometric amount of TEA
(1 mL). The reaction was heated at reflux for 72 h. The mixture was
concentrated in vacuo prior to the addition of water (50 mL) and
the reaction products were extracted with DCM (3 ꢂ 50 mL). The
combined organic extracts were dried over sodium sulfate, evapo-
rated and purified by silica gel chromatography using DCM as elu-
ent to give the isoxazoles 3a–e.
NMR (200 MHz, CDCl3) d: 3.84 (3H, s, CH3), 4.28 (2H, s, CH2),
7.15 (1H, d, J = 8.7 Hz, H-6), 7.37 (1H, d, J = 8.7 Hz, H-7), 8.14 (1H,
s, H-2), 8.51 (1H, s, H-4); 13C NMR (50 MHz, CDCl3) d: 33.9 (CH3),
56.6 (CH2), 111.1 (CH), 116.7 (C), 124.5 (C), 125.1 (CH), 126.6
(CH), 128.1 (C), 133.4 (C), 139.0 (CH), 187.8 (C). Anal. Calcd for
C21H16Br2N2O2: C, 51.67; H, 3.30; N, 5.74. Found: C, 51.88; H,
3.56; N, 5.67.
4.1.3. Synthesis of N,N,N0,N0-tetramethylsuccinamide
5.3 mL (0.05 mol) of succinyl chloride at 0 °C was added drop-
wise to a solution of dimethylamine (40% in water, 2 mmol). The
mixture was stirred for 30 min and then extracted with DCM, dried
and evaporated to afford the pure N,N,N0,N0-tetramethylsuccina-
4.1.5.1. 3-30-Isoxazole-3,5-diylbis(1-methyl-1H-indole) (3a). Yel-
low solid; yield: 42%; mp: 214–215 °C; 1H NMR (200 MHz,
DMSO-d6) d: 3.90 (s, 3H, CH3), 3.91 (s, 3H, CH3), 7.19 (s, 1H, H-
40), 7.22–8.20 (m, 10H, ArH); 13C NMR (50 MHz, DMSO-d6) d:
33.8 (CH3), 32.9 (CH3), 95.2 (CH), 102.7 (C), 104.0 (C), 110.2 (CH),
110.7 (CH), 119.6 (CH), 120.4 (CH), 120.8 (CH), 121.3 (CH), 122.2
(CH), 122.4 (CH), 124.1 (C), 124.9 (C), 129.6 (CH), 131.0 (CH),
136.9 (C), 137.1 (C), 158.3 (C), 164.7 (C). Anal. Calcd for
C21H17N3O: C, 77.04; H, 5.23; N, 12.84. Found: C, 77.24; H, 5.13;
N, 13.09.
mide: white solid; yield: 100%; mp: 68–69 °C; IR 1633 (CO) cmꢁ1
;
1H NMR (200 MHz, CDCl3) d: 2.63 (2H, s, CH2), 2.91 (3H, s, CH3),
3.04 (3H, s, CH3); 13C NMR (50 MHz, CDCl3) d: 28.0 (CH2), 35.5
(CH3), 37.2 (CH3), 172.3 (C). Anal. Calcd for C8H16N2O2: C, 55.79;
H, 9.36; N, 16.27. Found: C, 55.62; H, 9.50; N, 16.01.
4.1.4. General procedure for the preparation of 1,4-bis(indol-3-
yl)butane-1,4-diones (8a–e)
4.1.5.2. 3-30-Isoxazole-3,5-diylbis(1,5-dimethyl-1H-indole)
(3b). Yellow solid; yield: 50%; mp: 214–215 °C; 1H NMR (200 MHz,
DMSO-d6) d: 2.47 (s, 3H, CH3), 2.51 (s, 3H, CH3), 3.86 (s, 3H, CH3),
3.87 (s, 3H, CH3) 7.09–8.08 (m, 9H, Ar) ; 13C NMR (50 MHz,
DMSO-d6) d: 21.2 (CH3), 21.3 (CH3), 32.8 (CH3), 32.9 (CH3), 95.0
(CH), 102.2 (C), 103.6 (C), 109.9 (CH), 110.3 (CH), 119.3 (CH),
121.0 (CH), 123.7 (CH), 123.9 (CH), 124.3 (C), 125.1 (C), 129.1 (C),
124.5 (CH), 129.8 (C), 131.0 (CH), 135.4 (C), 135.6 (C), 158.4 (C),
164.8 (C). Anal. Calcd for C23H21N3O: C, 77.72; H, 5.96; N, 11.82.
Found: C, 77.57; H, 6.09; N, 12.00.
Phosphorus oxychloride (5.3 mL, 57 mmol) was slowly added to
N,N,N0,N0-tetramethylsuccinamide (2.58 g, 15 mmol) at 10–20 °C
and the mixture was stirred for 24 h. Then N-methylindoles 6a–e
(30 mmol) were slowly added keeping the temperature below
45 °C. After the addition was complete the mixture was heated
for 8 h to 55–60 °C (for derivative 8a) or stirred at rt for 20 h (for
derivatives 8b–e). The solution was poured onto crushed ice, made
basic with sodium hydroxide 10 M and filtered. The solid was
washed with water, dried and purified by chromatography using
(DCM/ethyl acetate 9/1) as eluent to afford the pure derivatives
8a–c; whereas derivatives 8d,e were used for next step without
purification.
4.1.5.3. 3-30-Isoxazole-3,5-diylbis(5-methoxy-1-methyl-1H-indole)
(3c). Yellow solid; yield: 52%; mp: 201–202 °C; 1H NMR (200 MHz,
DMSO-d6) d: 3.84 (s, 3H, CH3), 3.86 (s, 1H, CH3), 3.87 (s, 1H, CH3),
3.90 (s, 1H, CH3), 6.90–8.07 (m, 9H, Ar) ; 13C NMR (50 MHz,
DMSO-d6) d: 33.8 (CH3), 33.9 (CH3), 55.3 (CH3), 55.6 (CH3), 94.7
(CH), 101.7 (CH), 102.4 (C), 102.9 (CH), 103.7 (C), 111.1 (CH),
111.5 (CH), 112.2 (CH), 112.3 (CH), 124.6 (C), 125.3 (C), 129.9
(CH), 131.3 (CH), 132.1 (C), 132.3 (C), 154.5 (C), 154.9 (C), 158.4
(C), 164.8 (C). Anal. Calcd for C23H21N3O3: C, 71.30; H, 5.46; N,
10.85. Found: C, 71.45; H, 5.67; N, 10.64.
4.1.4.1. 1,4-Bis(1-methyl-1H-indol-3-yl)butane-1,4-dione (8a). Yel-
low solid; yield: 80%; mp: 224–226 °C; IR 1631 (CO) cmꢁ1 1H
;
NMR (200 MHz, CDCl3) d: 3.35 (2H, s, CH2), 3.78 (3H, s, CH3), 7.25–
7.29 (3H, m, H-5, H-6, H-7), 7.83 (1H, s, H-2), 8.37 (1H, d, J = 1.6,
7.3 Hz, H-4); 13C NMR (50 MHz, CDCl3) d: 33.4 (CH3), 34.0 (CH2),
109.5 (CH), 116.2 (C), 122.4 (CH), 122.5 (CH), 123.2 (CH), 126.3 (C),
135.7 (CH), 137.4 (C), 194.3 (C). Anal. Calcd for C22H20N2O2: C,
76.72; H, 5.85; N, 8.13. Found: C, 76.80; H, 6.02; N, 8.30.
4.1.5.4. 3-30-Isoxazole-3,5-diylbis(5-chloro-1-methyl-1H-indole)
(3d). Yellow solid; yield: 40%; mp: 246–247 °C; 1H NMR (200 MHz,
DMSO-d6) d: 3.90 (s, 3H, CH3), 3.91 (s, 3H, CH3), 7.28–8.24 (m, 9H,
Ar); 13C NMR (50 MHz, DMSO-d6) d: 33.1 (CH3), 33.2 (CH3), 95.5
(CH), 102.3 (C), 103.7 (C), 112.1 (CH), 112.5 (CH), 118.7 (CH),
120.3 (CH), 122.2 (CH), 122.4 (CH), 124.9 (C), 125.2 (C), 125.7 (C),
125.9 (C), 131.1 (CH), 132.7 (CH), 135.5 (C), 135.7 (C), 158.1 (C),
164.1 (C). Anal. Calcd for C21H15Cl2N3O: C, 63.65; H, 3.82; N,
10.60. Found: C, 63.38; H, 4.03; N, 10.81.
4.1.4.2. 1,4-Bis(1,5-methyl-1H-indol-3-yl)butane-1,4-dione (8b). Yel-
low solid; yield: 56%; mp: 300–302 °C; IR 1620 (CO) cmꢁ1 1H
;
NMR (200 MHz, CDCl3) d: 2.40 (3H, s, CH3), 3.21 (2H, s, CH2),
3.85 (3H, s, CH3), 7.10 (1H, d, J = 8.7 Hz, H-6), 7.42 (1H, d ,
J = 8.7 Hz, H-7), 7.98 (1H, s, H-4), 8.36 (1H, s, H-2); 13C NMR
(50 MHz, CDCl3) d: 21.5 (CH3), 33.5 (CH2), 34.1 (CH3), 109.2 (CH),
114.8 (C), 122.3 (CH), 124.8 (CH), 125.5 (C), 132.2 (C), 135.7 (CH),
136.5 (C), 194.7 (C). Anal. Calcd for C24H24N2O2: C, 77.39; H,
6.49; N, 7.52. Found: C, 77.62; H, 6.35; N, 7.76.
4.1.5.5. 3-30-Isoxazole-3,5-diylbis(5-bromo-1-methyl-1H-indole)
(3e). Yellow solid; yield: 42%; mp: 246–247 °C; 1H NMR (200 MHz,
4.1.4.3. 1,4-Bis(5-methoxy-1H-indol-3-yl)butane-1,4-dione
(8c). White solid; yield: 67%; mp: 213–214 °C; IR 1631 (CO) cmꢁ1
;