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2.3 Hz, 1H), 7.95 (d, J=8.6 Hz, 1H), 7.78 (s, 1H), 7.77 (d, J=8.9 Hz,
1H), 7.58 (d, J=8.6 Hz, 1H), 7.54 (dd, J=8.8, 2.3 Hz, 1H), 7.31 (dd,
J=8.9, 7.5 Hz, 1H), 7.27 (dd, J=8.8, 7.5 Hz, 1H), 3.82 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=154.5, 152.1, 135.2, 133.7, 131.9,
126.8, 126.6, 125.1, 121.9, 120.8, 119.3, 119.0, 118.8, 117.6, 117.3,
42.4 ppm.
5-Methyl-2-{[3-(piperidin-1-yl)propyl]amino}-11H-indolo[3,2-
c]quinolin-5-ium chloride (2e).
A solution of 2a (50.0 mg,
0.16 mmol), CyJohnPhos (11.2 mg, 0.032 mmol), Pd(OAc)2 (7.2 mg,
0.032 mmol), NaOtBu (61.5 mg, 0.64 mmol) and 3-(piperidin-1-yl)-
propan-1-amine (91.4 mg, 102.1 mL, 0.64 mmol) in tBuOH/DME (1:1,
2 mL) was reacted and purified according to General Procedure D
to give 2e as
a
dark-yellow solid (28.8 mg, 48%). 1H NMR
General
Procedure D.
2-{[2-(Diethylamino)ethyl]amino}-5-
(400 MHz, CDCl3): d=8.31 (s, 1H), 7.77 (d, J=9.1 Hz, 1H), 7.75 (d,
J=8.3 Hz, 1H), 7.53 (s, 1H), 7.37 (dd, J=9.1, 7.6 Hz, 1H), 7.29 (d,
J=8.5 Hz, 1H), 7.16 (dd, J=8.3, 7.6 Hz, 1H), 6.82 (d, J=8.5 Hz, 1H),
4.03 (s, 3H), 3.26 (m, 2H), 2.50 (t, J=6.4 Hz, 2H), 2.50–2.42 (m, 4H),
1.92–1.80 (t, J=6.0 Hz, 2H), 1.70–1.62 (m, 4H), 1.57–1.45 ppm (m,
2H); 13C NMR (100 MHz, CDCl3): d=147.3, 134.8, 127.8, 126.4,
123.3, 120.9, 120.5, 119.6, 119.3, 117.6, 115.9, 114.1, 101.1, 58.2,
54.8, 43.6, 43.3, 26.4, 25.4, 24.6 ppm.
methyl-11H-indolo[3,2-c]quinolin-5-ium chloride (2b). A solution
of 2a (50.0 mg, 0.16 mmol), 2-(dicyclohexylphosphino)biphenyl
(CyJohnPhos, 11.2 mg, 0.032 mmol), Pd(OAc)2 (7.2 mg, 0.032 mmol),
NaOtBu (61.5 mg, 0.64 mmol) and N1,N1-diethylethane-1,2-diamine
(74.4 mg, 89.9 mL, 0.64 mmol) in tBuOH/DME (1:1, 2 mL) was stirred
in a closed vessel, under microwave radiation (Pmax =300 W) at
1708C for 2 h. After cooling to room temperature, the crude mix-
ture was filtered over Celite 545, the solid washed with CH2Cl2/
MeOH (9:1) and the filtrate evaporated under reduced pressure.
The residue was then suspended in Na2CO3 5% aqueous solution
(50 mL) and extracted with CH2Cl2 (3ꢂ50 mL). The combined or-
ganic extracts were dried with brine, anhydrous Na2SO4 and con-
centrated under reduced pressure. Purification by preparative TLC
on neutral aluminum oxide, using CH2Cl2/MeOH (9:1) as eluent and
desorbent from the aluminum oxide, gave 2b as a dark-yellow
solid (29.3 mg, 56%). After NMR characterization, 2b was precipi-
tated in its salt form, from CH2Cl2 (2 mL) with HCl in Et2O, filtered
and dried under reduced pressure. 1H NMR (400 MHz, CDCl3): d=
7.99 (s, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.74 (s, 1H), 7.73 (d, J=8.2 Hz,
1H), 7.42 (dd, J=8.0, 7.5 Hz, 1H), 7.22 (d, J=8.8 Hz, 1H), 7.17 (dd,
J=8.2, 7.5 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 3.82 (s, 3H), 3.28–3.20
(m, 2H), 2.73 (t, J=5.0 Hz, 2H), 2.59 (q, J=7.0 Hz, 4H), 1.06 ppm (t,
J=7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=147.1, 134.6, 130.2,
128.6, 126.4, 125.2, 122.6, 120.7, 119.6, 119.3, 118.2, 117.9, 115.6,
103.1, 51.9, 47.2, 43.4, 41.7, 12.4 ppm.
5-Methyl-2-[(3-morpholinopropyl)amino]-11H-indolo[3,2-c]quino-
lin-5-ium chloride (2 f). Reaction of 2a (50.0 mg, 0.16 mmol), Cy-
JohnPhos (11.2 mg, 0.032 mmol), Pd(OAc)2 (7.2 mg, 0.032 mmol),
NaOtBu (61.5 mg, 0.64 mmol) and 3-morpholinopropan-1-amine
(92.2 mg, 93.5 mL, 0.64 mmol) in tBuOH/DME (1:1, 2 mL), followed
by purification according to General Procedure D gave 2 f as
1
a dark-yellow solid (29.5 mg, 49%). H NMR (400 MHz, CDCl3): d=
7.97 (s, 1H), 7.96 (d, J=7.7 Hz, 1H), 7.80 (d, J=1.9 Hz, 1H), 7.78 (d,
J=8.1 Hz, 1H), 7.47 (dd, J=7.7, 7.6 Hz, 1H), 7.26 (d, J=8.7 Hz, 1H),
7.23 (dd, J=8.1, 7.6 Hz, 1H), 6.87 (dd, J=8.7, 1.9 Hz, 1H), 3.81 (s,
3H), 3.84–3.68 (m, 4H), 3.33 (t, J=6.0 Hz, 2H), 2.52 (t, J=6.5 Hz,
2H), 2.55–2.45 (m, 4H), 1.86 ppm (2t, J=6.5, 6.0 Hz 2H).13C NMR
(100 MHz, CDCl3): d=154.1, 153.0, 146.9, 134.2, 128.7, 126.2, 125.9,
123.4, 120.5, 119.5, 119.0, 118.9, 117.8, 116.2, 102.9, 67.7, 58.2, 54.5,
44.1, 43.1, 26.0 ppm.
2-{[5-(Diethylamino)pentan-2-yl]amino}-5-methyl-11H-indolo[3,2-
c]quinolin-5-ium chloride (2g).
A solution of 2a (50.0 mg,
2-{[3-(Isopropylamino)propyl]amino}-5-methyl-11H-indolo[3,2-
c]quinolin-5-ium chloride (2c). Reaction of 2a (50.0 mg,
0.16 mmol), CyJohnPhos (11.2 mg, 0.032 mmol), Pd(OAc)2 (7.2 mg,
0.032 mmol), NaOtBu (61.5 mg, 0.64 mmol) and N1-isopropylpro-
pane-1,3-diamine (74.4 mg, 89.6 mL, 0.64 mmol) in tBuOH/DME (1:1,
2 mL), followed by purification according to General Procedure D
0.16 mmol), CyJohnPhos (11.2 mg, 0.032 mmol), Pd(OAc)2 (7.2 mg,
0.032 mmol), NaOtBu (61.5 mg, 0.64 mmol) and N1,N1-diethylpen-
tane-1,4-diamine (101.3 mg, 124.0 mL, 0.64 mmol) in tBuOH/DME
(1:1, 2 mL) was reacted and purified according to General Proced-
ure D to give 2g as a dark-yellow solid (30.1 mg, 48%). 1H NMR
(400 MHz, CDCl3): d=8.15 (s, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.86 (s,
1H), 7.79 (d, J=7.6 Hz, 1H), 7.42 (dd, J=7.9, 7.4 Hz, 1H), 7.30 (d,
J=9.2 Hz, 1H), 7.18 (dd, J=7.6, 7.4 Hz, 1H), 6.86 (d, J=9.2 Hz, 1H),
3.90 (s, 3H), 3.72 (m, Hz, 1H), 2.53 (q, J=7.1 Hz, 4H), 2.42 (t, J=
6.5 Hz, 2H), 1.66–1.52 (m, 4H), 1.25 (d, J=6.8 Hz, 3H), 1.02 ppm (t,
J=7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=152.0, 151.0, 145.8,
134.1, 127.9, 125.8, 124.9, 122.4, 120.1, 119.1, 118.4, 117.8, 117.5,
115.3, 103.0, 52.8, 48.5, 46.7, 42.6, 35.0, 23.7, 20.6, 11.5 ppm.
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gave 2c as a dark-yellow solid (23.0 mg, 41%). H NMR (400 MHz,
CDCl3): d=7.95 (s, 1H), 7.93 (d, J=7.5 Hz, 1H), 7.76 (d, J=7.7 Hz,
1H), 7.72 (s, 1H), 7.45 (dd, J=7.7, 7.5 Hz, 1H), 7.21 (d, J=8.1 Hz,
1H), 7.19 (dd, J=7.7, 7.2 Hz, 1H), 6.83 (d, J=8.1 Hz, 1H), 3.80 (s,
3H), 3.30 (t, J=6.6 Hz, 2H), 2.83 (dd, J=12.5, 6.2 Hz, 1H), 2.77 (t,
J=6.5 Hz, 2H), 1.86 (m, 2H), 1.10 ppm (t, J=6.2 Hz, 6H); 13C NMR
(100 MHz, CDCl3): d=152.2, 151.7, 146.4, 133.7, 127.9, 125.7, 124.9,
122.4, 119.9, 118.9, 118.4, 118.0, 117.2, 115.3, 102.1, 48.9, 45.8, 43.1,
42.5, 29.5, 22.9 ppm.
5-Methyl-2,8-dibromo-5H-indolo[3,2-c]quinoline (3a). Reaction of
1b (0.5 g, 1.3 mmol) and MeI (1.88 g, 0.828 mL, 13.0 mmol) in
CH3CN (5 mL) according to General Procedure C, gave 3b as
2-{[3-(Diethylamino)propyl]amino}-5-methyl-11H-indolo[3,2-
1
c]quinolin-5-ium chloride (2d).
A solution of 2a (50.0 mg,
a dark-yellow solid (0.332 g, 62%). H NMR (400 MHz, DMSO): d=
0.16 mmol), CyJohnPhos (11.2 mg, 0.032 mmol), Pd(OAc)2 (7.2 mg,
0.032 mmol), NaOtBu (61.5 mg, 0.64 mmol) and N1,N1-diethylpro-
pane-1,3-diamine (83.3 mg, 100.9 mL, 0.64 mmol) in tBuOH/DME
(1:1, 2 mL) was reacted and purified according to General Proced-
ure D to give 2d as a dark-yellow solid (16.2 mg, 28%). 1H NMR
(400 MHz, CDCl3): d=8.02 (s, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.78 (s,
1H), 7.77 (d, J=7.4, 1H), 7.45 (dd, J=7.6, 7.4 Hz, 1H), 7.26 (d, J=
9.1 Hz, 1H), 7.20 (dd, J=7.4, 7.1 Hz, 1H), 6.85 (d, J=9.1 Hz, 1H),
3.83 (s, 3H), 3.32 (t, J=6.0 Hz, 2H), 2.64–2.54 (m, 6H), 1.85 (q, J=
6.7 Hz, 2H)„ 1.08 ppm (t, J=7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d=152.4, 151.7, 146.7, 133.8, 127.9, 125.7, 125.0, 122.5, 119.9,
118.9, 118.3, 118.0, 117.2, 115.3, 102.2, 52.2, 46.9, 43.9, 42.6, 25.9,
11.8 ppm; FTIRC-MS: predicted: 361.24, found: 361.23829.
9.53 (s, 1H), 8.86 (d, J=2.2 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.08 (d,
J=9.2 Hz, 1H), 8.03 (dd, J=9.2, 2.2 Hz, 1H), 7.74 (d, J=8.6 Hz, 1H),
7.58 (dd, J=8.6, 2.0 Hz, 1H), 4.28 ppm (s, 3H); 13C NMR (100 MHz,
DMSO): d=152.2, 150.6, 140.9, 134.9, 132.9, 128.9, 127.4, 126.4,
122.9, 122.3, 121.0, 120.1, 119.3, 115.8, 113.2, 43.4 ppm.
5-Methyl-2,9-dibromo-5H-indolo[3,2-c]quinoline (3b). Reaction of
1c (0.5 g, 1.3 mmol) and MeI (1.88 g, 0.828 mL, 13.0 mmol) in
CH3CN (5 mL) according to General Procedure C, gave 3b as
1
a dark-orange solid (0.352 g, 68%). H NMR (400 MHz, DMSO): d=
9.39 (s, 1H), 8.81 (s, 1H), 8.05 (d, J=8.3 Hz, 1H), 8.01 (d, J=9.0 Hz,
1H), 7.98 (d, J=9.0 Hz, 1H), 7.95 (s, 1H), 7.39 (d, J=8.3 Hz, 1H),
4.23 ppm (s, 3H); 13C NMR (100 MHz, DMSO): d=156.2, 152.8,
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