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7215
Cs2CO3 (2.932 g, 9.000 mmol) were weighed. To this mixture, the
Pd-catalyst was added and the flask was flushed with N2 for
5 min. The resulting mixture was heated at reflux (oil bath temper-
ature: 110 °C) for 24 h under magnetic stirring. After cooling down
to room temperature dichloromethane (25 mL) was added and the
suspension was filtered over a pad of CeliteÒ and rinsed with
CH2Cl2 (125 mL). The solvent was removed under reduced pressure
and the residue was purified by column chromatography on silica
gel using CH2Cl2/MeOH (95:5) as the eluent yielding 24 in 88%
(0.540 g, 2.640 mmol).
White solid; mp 123 °C. dH (CDCl3): 8.35 (d, J = 6.3 Hz, 2H, H-2),
7.45 (dd, J = 8.1, 1.5 Hz, 1H, H-60), 7.44 (dd, J = 8.0, 1.5 Hz, 1H, H-30),
7.25 (ddd, J = 8.1, 7.4, 1.5 Hz, 1H, H-50), 7.03 (ddd, J = 8.0, 7.4,
1.5 Hz, 1H, H-40), 6.88 (d, J = 6.3 Hz, 2H, H-3), 6.37 (br s, 1H, NH);
dC (CDCl3): 150.7, 149.5, 136.8, 130.3, 127.5, 125.6, 124.3, 121.0,
110.5; HRMS (ESI) for C11H10ClN2 [M+H]+: calcd: 205.0533, found:
205.0527.
(CDCl3): 148.8, 145.0, 130.4, 130.0, 129.7, 108.8, 101.2, 40.0; HRMS
(ESI) for C8H9N2 [M+H]+: calcd 133.0760, found 133.0757.
6.1.5.2. 2-Methyl-2H-pyrido[3,4-b]indole (9). b-Carboline (21)
(0.084 g; 0.500 mmol), dry THF (7.5 mL) and CH3I (3.0 mL). Reac-
tion time = 2 h. Eluent: CH2Cl2/MeOH (90:10); yield: 80%
(0.073 g, 0.401 mmol). Bright yellow/orange powder; mp 191–
192 °C (decomp.) (lit. mp 213–215 °C).31 dH (CDCl3): 8.49 (d,
J = 1.4 Hz, 1H, H-1), 8.16 (dt, J = 8.1, 1.0 Hz, 1H, H-5 or H-8), 8.06
(d, J = 6.2 Hz, 1H, H-4), 7.92 (dt, J = 8.5, 0.8 Hz, 1H, H-8 or H-5),
7.57 (ddd, J = 8.5, 6.8, 1.2 Hz, 1H, H-6 or H-7), 7.35 (dd, J = 6.3,
1.7 Hz, 1H, H-3), 7.17 (ddd, J = 8.1, 6.8, 0.9 Hz, 1H, H-7 or H-6),
4.17 (s, 3H, N–CH3); (lit. dH (CDCl3): 8.62 (s, 1H, H-1), 8.16 (t,
J = 7 Hz, 2H, H-3 and H-4), 7.90 (d, J = 8 Hz, 1H, H-8), 7.64 (t,
J = 8 Hz, 1H, H-6 or H-7), 7.50 (d, J = 8 Hz, 1H, H-5), 7.23 (t,
J = 8 Hz, 1H, H-7 or H-6), 4.34 (s, 3H, N–CH3))31; dC (CDCl3):
158.8, 146.0, 132.7, 130.8, 129.0, 122.6, 122.1, 121.3, 119.5,
118.1, 115.2, 46.9; HRMS (ESI) for C12H11N2 [M+H]+: calcd
183.0922, found 183.0914.
6.1.4. 5H-Pyrido[4,3-b]indole (25)
A
10-mL microwave vial was charged with N-(2-chloro-
phenyl)pyridin-4-amine (24) (0.123 g, 0.600 mmol), DBU
(0.137 g, 0.900 mmol) and 1.0 mL of a stock solution of catalyst*
(5 mol % Pd, 10 mol % ligand, solvent = dioxane) and the mixture
was stirred and flushed with argon for 1 min. Next, the vial was
sealed with an Al crimp cap with a septum and heated at 180 °C
in a CEM Discover microwave apparatus. The set power was
300 W and the total heating time was 10 min. After the reaction
vial had cooled down to room temperature using a propelled air
flow, it was opened and the reaction mixture transferred into a
round-bottomed flask using CH2Cl2 (50 mL). The solvent was evap-
orated and the crude product purified via flash column chromatog-
raphy on silica gel using CH2Cl2/7 N ammonia in MeOH (98:2) as
the eluent yielding 25 in 99% (0.100 g, 0.594 mmol).
6.1.5.3. 2-Methyl-2H-pyrido[4,3-b]indole (11). 5H-Pyrido[4,3-
b]indole (25) (0.084 g; 0.500 mmol), dry THF (2.5 mL) and CH3I
(0.25 mL). Reaction time = 4 h. Eluent: CH2Cl2/MeOH (90:10);
yield: 94% (0.086 g, 0.472 mmol). White-yellowish solid, mp
205–206 °C (lit. mp 172–173 °C).32 The characterization data are
identical to those reported in the literature.32 For comparison, we
report here our 1H NMR data: dH (DMSO-d6): 9.05 (d, J = 1.7 Hz,
1H, H-1), 8.10 (dd, J = 7.8, 1.3 Hz, 1H, H-9), 7.92 (dd, J = 7.2,
1.7 Hz, 1H, H-3), 7.63 (dd, J = 8.2, 0.9 Hz, 1H, H-6), 7.40 (ddd,
J = 8.2, 7.0, 1.3 Hz, 1H, H-7), 7.39 (d, J = 7.2 Hz, 1H, H-4), 7.13
(ddd, J = 7.8, 7.0, 0.9 Hz, 1H, H-8), 4.11 (s, 3H, N–CH3).
6.1.5.4. 1-Methyl-1H-pyrido[3,2-b]indole (13). 5H-Pyrido[3,2-
b]indole (26) (0.084 g; 0.500 mmol), dry THF (2.5 mL) and CH3I
(0.25 mL). Reaction time = 4 h. Eluent: CH2Cl2/MeOH (90:10);
yield: 92% (0.084 g, 0.461 mmol). Orange solid, mp 202–204 °C
(lit. mp 202–206 °C).10 The characterization data are identical to
those reported in the literature.10 For comparison, we report here
our 1H NMR data: dH (DMSO-d6): 8.33–8.27 (m, 3H, H-2, H-4 and
H-9), 7.67 (dd, J = 8.5, 1.0 Hz, 1H, H-6), 7.53 (dd, J = 8.3, 5.8 Hz,
1H, H-3), 7.45 (ddd, J = 8.5, 6.8, 1.2 Hz, 1H, H-7), 7.07 (ddd,
J = 8.2, 6.8, 1.0 Hz, 1H, H-8), 4.71 (s, 3H, N–CH3).
White solid; mp 224 °C (lit. mp 225 °C).29 The characterization
data are identical to those reported in the literature.30 For compar-
ison, we report here our 1H NMR data: dH (DMSO-d6): 11.72 (br s,
1H, NH), 9.36 (s, 1H, H-1), 8.45 (d, J = 5.7 Hz, 1H, H-3), 8.24 (ddd,
J = 7.8, 1.2, 0.8 Hz, 1H, H-9), 7.59 (ddd, J = 8.2, 1.0, 0.8 Hz, 1H, H-
6), 7.49 (dd, J = 5.7, 1.0 Hz, 1H, H-4), 7.48 (ddd, J = 8.2, 7.1, 1.2 Hz,
1H, H-7), 7.28 (ddd, J = 7.8, 7.1, 1.0 Hz, 1H, H-8).
*The stock solution of catalyst (5 mol % Pd/1 mL dry dioxane)
was prepared by charging
a flask with Pd2(dba)3 (0.137 g,
0.150 mmol) followed by adding dry, freshly distilled dioxane
(9.4 mL) and P(t-Bu)3 (1 M in toluene) (0.6 mL, 0.6 mmol). The
solution was subsequently stirred for 15 min under argon
atmosphere.
6.1.6. General methylation procedure for the preparation of 10
and 14
6.1.6.1. 6-Methyl-1H-pyrrolo[2,3-c]pyridin-6-ium iodide (10). In
a round-bottomed flask 1H-pyrrolo[2,3-c]pyridine (28) (0.132 g,
1.000 mmol), toluene (15.0 mL) and CH3I (6.0 mL) were heated at re-
flux under N2 atmosphere (oil bath temperature: 120 °C) for 6 h with
magnetic stirring. Then the precipitated material was filtered off. The
crude product was mixed with silica gel and purified via column
chromatography on silica gel using CHCl3/MeOH/TEA (80:19:1) as
the eluent yielding 6-methyl-1H-pyrrolo[2,3-c]pyridin-6-ium iodide
(10) in 60% (0.156 g, 0.600 mmol).
Yellow solid, mp 135–138 °C. dH (CDCl3): 9.74 (s, 1H, H-7), 8.02
(d, J = 2.8 Hz, 1H, H-2), 8.00 (dd, J = 6.8, 1.4 Hz, 1H, H-5), 7.92 (dd,
J = 6.8, 0.7 Hz, 1H, H-4), 6.78 (dd, J = 2.8, 0.7 Hz, 1H, H-3), 4.47 (s,
3H, N–CH3); dC (CDCl3): 138.7, 136.1, 132.2, 131.9, 131.6, 118.0,
103.9, 47.9; Anal. Calcd for C8H9IN2 (260.07): C, 36.95; H, 3.49;
N, 10.77. Found: C, 36.67; H, 3.35; N, 10.86.
6.1.5. General methylation procedure for the synthesis of 8, 9,
11, 13
6.1.5.1. 7-Methyl-7H-pyrrolo[2,3-b]pyridine (8). In a round-bot-
tomed flask 1H-pyrrolo[2,3-b]pyridine (27) (0.059 g, 0.500 mmol),
dry THF (5.0 mL) and CH3I (0.5 mL) were heated at reflux under N2
atmosphere (oil bath temperature: 80 °C) for 1 h with magnetic stir-
ring. Then the solvent was evaporated to dryness under reduced
pressure and the crude product was mixed with silica gel and puri-
fied via flash column chromatography on silica gel using CH2Cl2/
MeOH (90:10) as the eluent yielding 7-methyl-1H-pyrrolo[2,3-b]pyr-
idine-7-ium iodide (8ꢀHI). To obtain the free base, 8ꢀHI was brought
in a mixture of CH2Cl2 (100 mL) and 28–30% ammonia in water
(100 mL). The organic phase was separated and the aqueous phase
was subsequently extracted with CH2Cl2 (4 ꢂ 50 mL). The combined
organic phase was dried over MgSO4, filtered and evaporated to dry-
ness to yield 8 in 95% (0.063 g, 0.477 mmol).
6.1.6.2. 4-Methyl-4H-pyrrolo[3,2-b]pyridine (14). 1H-Pyrrolo-
[3,2-b]pyridine (30) (0.132 g, 1.000 mmol), toluene (15 mL) and
CH3I (6.0 mL). Reaction time = 6 h. Eluent: CHCl3/MeOH/TEA (80/
19/1); yield: 75% (0.099 g, 0.749 mmol). Brown oil, dH (CDCl3):
8.28 (d, J = 1.8 Hz, 1H, H-2), 8.18 (dd J = 7.8 Hz, 1H, H-7), 7.58 (d,
Yellow liquid, dH (CDCl3): 8.05 (d, J = 7.4 Hz, 1H, H-4), 7.89 (d,
J = 2.6 Hz, 1H, H-2), 7.47 (d, J = 6.2 Hz, 1H, H-6), 6.76 (dd, J = 7.4,
6.2 Hz, 1H, H-5), 6.66 (d, J = 2.6 Hz, 1H, H-3), 4.21 (s, 3H, CH3); dC