Molecules 2021, 26, 3268
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3.1.8. 4-Methyl-4H-pyrido[4,3,2-gh]phenanthridine (8a)
To a solution of 7H-pyrido[4,3,2-gh]phenanthridine (4a) (70.0 mg, 0.32 mmol) in
2 mL acetonitrile, iodomethane (2.0 mL, 32.0 mmol) was added and the resulting mixture
was refluxed for 2 h. The volatiles were then removed under reduced pressure and the
concentrate was evaporated onto celite. Purification by silica gel column chromatography
(CHCl3/MeOH, 95:5 + 0.3% NH3 (aq) v/v) and concentration of the relevant fractions [Rf
= 0.33 (CHCl3/MeOH, 95:5 + 0.3% NH3(aq) v/v)] gave the hydroiodide salt of compound
8a. To obtain the free base, the hydroiodide salt was dissolved in a 20 mL 1:1 mixture of
CH2Cl2 and NH3 (aq) (20%) and stirred at rt for 20 min. The organic layer was separated
and the aqueous layers were extracted with Et2O (2
layers were washed with water (1 10 mL), brine (1
and concentrated in vacuo to give the target compound 8a as dark yellow crystals (52.8 mg,
×
20 mL) and the combined organic
×
×
10 mL), dried (MgSO4), filtered
◦
−1
;
71%), mp 182–183 C; IR (ATR):
ν
max 3485, 3051, 2922, 2851, 2574, 1601, 1327, 820, 748 cm
1H NMR (400 MHz, DMSO-d6): δ 8.29 (dd, J = 8.1 Hz, 1.1 Hz, 1H), 7.97 (d, J = 7.9 Hz, 1H),
7.71 (t, J = 8.1 Hz, 1H), 7.56 (dd, J = 8.2 Hz, 1.2 Hz, 1H), 7.51–7.47 (m, 2H), 7.30–7.26 (m, 1H),
7.05 (d, J = 8.1 Hz, 1H), 6.18 (d, J = 7.6 Hz, 1H), 3.45 (s, 3H) (Figure S4.1, S4.3, and S4.4); 13
C
NMR (100 MHz, DMSO-d6): "δ" 152.9, 145.9, 141.0, 140.9, 133.8, 131.6, 129.2, 127.0, 123.2,
122.9, 121.3, 119.6, 112.2, 108.8, 106.2, 39.6 (Figure S4.2, S4.5, and S4.6); HRMS (ESI): calcd.
for C16H12N2 [M + H+] 233.1073, found 233.1073.
3.1.9. 6-Methoxy-4-methyl-4H-pyrido[4,3,2-gh]phenanthridine (8b)
To a solution of 6-methoxy-7H-pyrido[4,3,2-gh]phenanthridine (4b) (90.0 mg,
0.36 mmol) in 10 mL acetonitrile, iodomethane (2.25 mL, 36.3 mmol) was added and
the resulting mixture refluxed for 2 h. The volatiles were then removed under reduced
pressure and the concentrate was evaporated onto celite. Purification by silica gel column
chromatography (EtOH + 0.1
→
5% NH3 (aq) v/v) and concentration of the relevant frac-
tions [Rf = 0.23 (EtOH)] gave the hydroiodide salt of compound 8b. To obtain the free
base, the hydroiodide salt was dissolved in a 20 mL 1:1 mixture of CH2Cl2 and NH3 (aq)
(20%) and stirred at rt for 20 min. The organic layer was separated and the aqueous layers
were extracted with CH2Cl2 (4
×
20 mL) and the combined organic layers were washed
20 mL), dried (MgSO4), filtered and concentrated in
with water (1 20 mL), brine (1
×
×
vacuo to give the target compound 8b as a dark yellow gel (55.1 mg, 58%). IR (ATR):
1
ν
2918, 2850, 1600, 1255, 1059, 745 cm−1; H NMR (400 MHz, CD2Cl2):
δ
8.19 (dd,
max
J = 8.2 Hz, 1.3 Hz, 1H), 7.79 (dd, J = 8.2 Hz, 1.0 Hz, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.57–7.51
(m, 2H), 7.34–7.30 (m, 1H), 6.74–6.72 (m, 2H), 3.85 (s, 3H), 3.34 (s, 3H) (Figure S5.1, S5.3 and
S5.4); 13C NMR (100 MHz, CD2Cl2):
δ 148.1, 146.3, 140.8, 139.9, 134.8, 130.9, 129.4, 128.6,
124.1, 122.7, 122.5, 119.9, 110.6, 107.7, 57.1, 40.4 (one carbon was obscured or overlapping)
(Figure S5.2, S5.5 and S5.6); HRMS (ESI): calcd. for C17H14N2O 263.1179, found 263.1188.
3.1.10. 4-Methyl-7H-pyrido[2,3-c]carbazolium Iodide (10)
To a solution of 7H-pyrido[2,3-c]carbazole (9a) (40.7 mg, 0.19 mmol) in 5 mL ace-
tonitrile, iodomethane (1.20 mL, 19.6 mmol) was added and the resulting mixture re-
fluxed for 20 h. The volatiles were then removed under reduced pressure and the con-
centrate was evaporated onto celite. Purification by alumina gel column chromatogra-
phy (CHCl3/MeOH, 9:1 v/v + 1% NH3 (aq)) and concentration of the relevant fractions
[Rf = 0.12 (CHCl3/MeOH, 9:1 v/v + 2% NH3 (aq))] gave the target compound 10 as a
bright yellow solid (20.9 mg, 47%), mp 284–286; IR (ATR):
ν
max 3353, 3043, 3006, 2960, 2921,
2853, 1556, 1370, 1326, 741 cm−1; 1H NMR (400 MHz, DMSO-d6):
δ
12.84 (bs, 1H), 9.99 (d,
J = 8.4 Hz, 1H), 9.39 (d, J = 5.6 Hz, 1H), 8.76 (d, J = 8.1 Hz, 1H), 8.50 (d, J = 9.3 Hz, 1H),
8.43 (d, J = 9.4 Hz, 1H), 8.22 (dd, J = 8.5 Hz, 5.7 Hz, 1H), 7.82 (d, J = 8.2 Hz, 1H), 7.64-7.60
(m, 1H), 7.48–7.44 (m, 1H), 4.74 (s, 3H) (Figure S8.1, S8.3, and S8.4); 13C NMR (100 MHz,
DMSO-d6):
δ 145.0, 140.8, 139.8, 137.5, 134.5, 126.6, 125.8, 122.4, 122.1, 121.9, 121.6, 121.1,
116.0, 114.3, 112.8, 46.3 (Figure S8.2, S8.5 and S8.6); HRMS (ESI): calcd. for C16H13N2I [M –
I-] 233.1073, found 233.1073.