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C. Le Sann et al. / Tetrahedron 63 (2007) 12903–12911
1.2 mmol, 5 equiv) and ethanol (2 mL) were then added. The
reaction mixture was heated at reflux for 18 h then cooled to
room temperature. Ethyl acetate (50 mL) was added and the
organic layer was washed with water (2ꢂ100 mL), sepa-
rated and dried. The solvent was evaporated yielding a yel-
low solid, which was purified by column chromatography
(DCM/MeOH/TEA, 50:50:1) to give 6a as a yellow solid
(86 mg, 57%). Mp 237–238 ꢀC (decomp.); IR (KBr disk)
n: 3436 (N–H), 2936 (–CH2–), 1607 (CH aromatic) 1477
(–CH2–), 1244 (C–O); 1H NMR (500 MHz, CDCl3):
d 1.82–1.84 (8H, m, H-b), 2.04–2.10 (4H, m, H-200), 2.61–
2.62 (8H, m, H-a), 2.70–2.72 (4H, m, H-300), 4.07–4.08
indolo[3,2-b]quinoline 1 (0.2 g, 0.48 mmol) was added to
DME (6 mL) together with tetrakis(triphenylphosphine)-
palladium(0) (0.034 g, 0.0288 mmol, 0.06 equiv) and
4-(30-morpholinyl-propoxy)phenyl-boronic acid 7c (0.38 g,
1.44 mmol, 3 equiv). Aqueous sodium carbonate solution
(2 M, 1.2 mL, 2.4 mmol, 5 equiv) and ethanol (4 mL) were
then added. The reaction mixture was heated at reflux for
18 h then cooled to room temperature. Ethyl acetate
(50 mL) was added and the organic layer was washed with
water (2ꢂ100 mL), separated and dried. The solvent was
evaporated to a yellow solid, which was purified by column
chromatography (DCM/MeOH, 50:50) to give 6c as a yellow
solid (0.18 g, 57%). Mp 180–182 ꢀC (decomp.); IR (KBr
disk) n: 3408 (N–H), 2927 and 2852 (–CH2–), 1606 (CH
aromatic), 1242 (C–O); 1H NMR (500 MHz, CDCl3): d 2.06–
2.08 (4H, m, H-200), 2.60 (8H, br s, H-a), 2.64–2.65 (4H, m,
H-300), 3.79–3.81 (8H, m, H-b), 4.07–4.08 (4H, m, H-100),
(4H, m, H-100), 6.97–7.01 (4H, m, J3 –2 8.5, H-30), 7.46
0
0
(1H, d, J9–8 8.5, H-9), 7.63–7.67 (4H, m, J2 –3 8.5, H-20),
7.77 (1H, dd, J8–9 8.5, J8–6 1.5, H-8), 7.90 (1H, dd, J3–4 9,
J3–1 2, H-3), 8.02 (2H, br s, H-1 and H-11), 8.36 (1H, d,
J4–3 9, H-4), 8.57 (1H, s, N–H), 8.71 (1H, d, J6–8 1.5, H-
6); 13C NMR (125 MHz, CDCl3): d 23.5 (4C, C-a), 28.7
(2C, C-200), 53.2 (2C, C-300), 54.2 (4C, C-a), 66.4 (2C, C-
10), 111.2 (C-9), 113.3 (C-1 or C-11), 115.0 (4C, C-30),
119.8 (C-6), 122.8, 124.0 (C-1 or C-11), 126.3 (C-3),
127.4, 128.4 (4C, C-20), 129.5 (C-4), 133.3, 133.5 (2C, C-
10), 133.8, 137.6, 142.7, 143.6, 146.4, 158.2 (2C, C-40); m/z
(CI): 625.4 (M+1, 100%), 554 (2), 441 (3), 338 (5), 222 (7).
HRMS (CI) found: 625.3520 (C41H44N4O2 requires:
625.3543).
0
0
6.97–7.02 (4H, m, J3 –2 8.5, H-30), 7.48 (1H, d, J9–8 9, H-
0
0
9), 7.64–7.69 (4H, m, J2 –3 8.5, H-20), 7.78 (1H, dd, J8–9 9,
J8–6 2, H-8), 7.92 (1H, dd, J3–4 9, J3–1 2, H-3), 8.02 (1H,
d, J1–3 2, H-1), 8.05 (1H, s, H-11), 8.38 (1H, d, J4–3 9, H-
4), 8.46 (1H, s, N–H), 8.71 (1H, d, J6–8 2, H-6); 13C NMR
(125 MHz, CDCl3): d 26.5 (2C, C-200), 53.9 (4C, C-a), 56.1
(2C, C-300), 66.4 (2C, C-100), 67.0 (4C, C-b), 111.7 (C-9),
113.9 (C-11), 115.3 (2C, C-30), 120.3 (C-6), 124.4 (C-1),
126.9 (C-3), 127.7, 128.1, 128.6 (2C, C-20), 129.3 (C-8),
129.8 (C-4), 133.7 (2C, C-10), 138.0, 143.0, 143.9, 146.7,
158.5 (2C, C-40), 159.1; m/z (CI): 657.4 (M+1, 100%), 540
(27), 442 (61), 295 (12), 238 (10), 222 (5). HRMS (CI)
found: 657.3437 (C41H44N4O4 requires: 657.3441).
0
0
4.1.21. 2,7-Bis[40-(300-N-piperidinyl-propoxy)phenyl]-
10H-indolo[3,2-b]quinoline 6b. 10-Acetyl-2,7-bis-(bro-
mo)-indolo[3,2-b]quinoline 1 (0.1 g, 0.24 mmol) was added
to DME (3 mL) together with tetrakis(triphenylphosphine)-
palladium(0) (17 mg, 14.4 mmol, 0.06 equiv) and 4-(30-piper-
idinyl-propoxy)phenyl-boronic acid 7b (0.19 g, 0.72 mmol,
3 equiv). Aqueous sodium carbonate solution (2 M,
0.6 mL, 1.2 mmol, 5 equiv) and ethanol (2 mL) were then
added. The reaction mixture was heated at reflux for 18 h
then cooled to room temperature. Ethyl acetate (50 mL)
was added and the organic layer was washed with water
(2ꢂ100 mL), separated and dried. The solvent was evapo-
rated to yield a yellow solid, which was purified by column
chromatography (DCM/MeOH/TEA, 50:50:1) to give 6b as
a yellow solid (94.2 mg, 60%). Mp 210–212 ꢀC (decomp.);
IR (KBr disk) n: 3430 (N–H), 2932 (–CH2–), 1608 (CH ar-
4.1.23. 2,7-Bis{40-[300-N-(4000-methyl-piperazinyl)-pro-
poxy]-phenyl}-10H-indolo[3,2-b]quinoline 6d. 10-Acetyl-
2,7-bis-(bromo)-indolo[3,2-b]quinoline 1 (100 mg, 0.24 mmol)
was added to DME (3 mL) together with tetrakis(triphenyl-
phosphine)palladium(0) (17 mg, 14.4 mmol, 0.06 equiv) and
4-[30-(400-methyl-piperazinyl)-propoxy]phenyl-boronic acid
7d (200 g, 0.72 mmol, 3 equiv). Aqueous sodium carbonate
solution (2 M, 0.6 mL, 1.2 mmol, 5 equiv) and ethanol
(2 mL) were then added. The reaction mixture was heated
at reflux for 18 h then cooled to room temperature. Ethyl
acetate (50 mL) was added and the organic layer was washed
with water (2ꢂ100 mL), separated and dried. The solvent
was evaporated to yield a yellow solid, which was purified
by column chromatography (DCM/MeOH, 50:50) to give
6d as a yellow solid (85 mg, 52%). Mp 238–240 ꢀC
(decomp.); IR (KBr disk) n: 3430 (N–H), 2932 and 2797
(–CH2–), 1606 (CH aromatic), 1242 (C–O); 1H NMR
(500 MHz, CDCl3): d 2.01–2.04 (4H, m, H-200), 2.31 (6H,
s, N–CH3), 2.56–2.59 (20H, m, H-300, H-2000 and H-3000),
1
omatic), 1477(–CH2–), 1244 (C–O); H NMR (500 MHz,
CDCl3): d 1.50 (4H, br s, H-c), 1.69–1.70 (8H, m, H-b),
2.10 (4H, m, H-200), 2.54–2.63 (12H, m, H-a and H-300),
4.07–4.10 (4H, m, H-100), 6.99–7.04 (4H, m, J3 –2 8.5, H-
0
0
30), 7.51 (1H, d, J9–8 8.5, H-9), 7.66–7.69 (4H, m, J2 –3
0
0
8.5, H-20), 7.81 (1H, dd, J8–9 8.5, J8–6 1.5, H-8), 7.92 (1H,
dd, J3–4 9, J3–1 2, H-3), 8.06 (1H, d, J1–3 2, H-1), 8.07
(1H, s, H-11), 8.22 (1H, s, N–H), 8.37 (1H, d, J4–3 9, H-4),
8.72 (1H, s, H-6); 13C NMR (125 MHz, CDCl3): d 24.5
(2C, C-c), 26.0 (4C, C-b), 26.9 (2C, C-200), 54.7 (4C, C-a),
56.0 (2C, C-300), 66.7 (2C, C-100), 111.2 (C-9), 113.3 (C-11),
114.9 (4C, C-30), 119.8 (C-6), 124.0 (C-1), 126.4 (C-3),
127.4, 127.7, 128.3 (4C, C-30), 128.8 (C-8), 129.6 (C-4),
133.4 (2C, C-10), 133.8, 137.6, 142.6, 143.7, 146.5, 158.3
(2C, C-40), 158.9; m/z (CI): 653.5 (M+1, 100%), 467 (9),
438 (11), 338 (17), 279 (6), 236 (9). HRMS (CI) found:
653.3856 (C43H48N4O2 requires: 653.3856).
4.08–4.10 (4H, m, H-100), 6.99–7.04 (4H, m, J3 –2 9, H-30),
0
0
0
0
7.48 (1H, d, J9–8 8.5, H-9), 7.65–7.70 (4H, m, J2 –3 9, H-
20), 7.79–7.81 (1H, d, J8–9 8.5, H-8), 7.92 (1H, J3–4 8.5, H-
3), 8.04 (1H, s, H-11), 8.05 (1H, br s, H-1), 8.31 (1H, s,
N–H), 8.37 (1H, d, J4–3 8.5, H-4), 8.72 (1H, br s, H-6);
13C NMR (125 MHz, CDCl3): d 25.3 (2C, C-200), 44.5 (2C,
NCH3), 51.7 (8C, C-2000 and C-3000), 53.6 (2C, C-300), 64.8
(2C, C-100), 109.5 (C-9), 111.6 (C-11), 113.4 (4C, C-30),
118.2 (C-6), 122.4 (C-1), 124.8 (C-3), 125.8, 126.1, 126.9
(4C, C-20), 127.2 (C-8), 128.0 (C-4), 131.7 (2C, C-10),
132.2, 136.1, 140.1, 142.1, 144.9, 156.7 (2C, C-40), 157.2;
m/z (CI): 683.5 (M+1, 56%), 468 (100). HRMS (CI) found:
683.4055 (C43H50N6O2 requires: 683.40734).
4.1.22. 2,7-Bis[40-(300-N-morpholinyl-propoxy)phenyl]-
10H-indolo[3,2-b]quinoline 6c. 10-Acetyl-2,7-bis-(bromo)-