A. B. S. Maya et al. / Bioorg. Med. Chem. 13 (2005) 2097–2107
2105
idue dissolved in CHCl3. The organic layer was washed
with saturated NaCl, dried over Na2SO4 and the solvent
evaporated to yield a residue that was purified by col-
umn chromatography (hexane–ethyl acetate 2:1),
obtaining 23 mg (75%) of 19 as an oil. 1H NMR d
3.54 (6H, s, 3-OCH3 and 5-OCH3), 3.70 (3H, s, N–
CH3), 3.82 (3H, s, 4-OCH3), 3.88 (3H, s, indole–
OCH3), 6.53 (2H, s, Ar–H), 6.99 (1H, dd, J1 = 8.8 Hz,
J2 = 2.2 Hz, indole–H), 7.32 (1H, d, J = 2.2 Hz, in-
dole–H), 7.41 (1H, d, J = 8.8 Hz, indole–H), 7.49–7.54
(3H, m, Ar–H), 7.81 (1 H. d, J = 8.8 Hz, Ar–H), 7.83–
7.87 (2H, m, Ar–H), 7.87 (1H, br s, Ar–H). 13C NMR
d 31.2 (CH3), 55.7 (· 2) (CH3), 56.0 (CH3), 60.9
(CH3), 101.4 (CH), 106.7 (· 2) (CH), 110.5 (CH),
112.5 (CH), 114.2 (C), 115.0 (C), 126.4 (CH), 126.6
(CH), 127.0 (C), 127.7 (CH), 127.9 (CH), 128.1 (CH),
128.6 (CH), 129.5 (C), 130.3 (CH), 132.7 (C), 133.1
(C), 135.8 (C), 138.3 (C), 152.9 (· 2) (C), 154.8 (C).
HRMS m/z found 453.1897; calcd for C29H27NO4 m/z
453.1940.
(CH), 112.6 (CH), 115.4 (C), 125.3 (CH), 125.7 (CH),
126.6 (C), 127.6 (· 3) (CH), 127.6 (C), 127.7 (CH),
128.4 (CH), 132.5 (C), 132.7 (C), 133.6 (· 2) (C), 137.9
(C), 138.6 (C), 153.0 (· 2) (C), 155.1 (C). HRMS m/z
found 495.2063; calcd for C31H29NO5 m/z 495.2046.
Anal. Calcd for C31H29NO5: C, 68.95; H, 5.79; N,
3.22. Found: C, 68.90; H, 5.82; N, 3.04.
4.1.20.
3-[5-Methoxy-3-(naphth-2-yl)-2-(3,4,5-trimeth-
oxyphenyl)-1H-indol-1-yl]-1-dimethylamino-propan-2-ol
(22). Compound 21 (12 mg, 0.03 mmol) was added to a
30% solution of dimethylamine in ethanol. The reaction
mixture was stirred at room temperature for 24 h and
the solvent was removed, yielding 14 mg (90%) of 22
1
as a solid. H NMR d 1.5–1.9 (2H, m, Me2N–CH2),
2.20 (6H, s, N(CH3)2, 3.5–3.6 (1H, m, CHOH), 3.66
(6H, s, 3-OCH3 and 5-OCH3), 3.83 (3H, s, 4-OCH3),
3.88 (3H, s, indole–OCH3), 4.0–4.4 (2H, m, indole–
CH2), 6.64 (2H, s, Ar–H), 6.97 (1H, dd, J1 = 8.4 Hz,
J2 = 2.2 Hz, indole–H), 7.28–7.47 (3H, m, Ar–H), 7.32
(1H, d, J = 8.4 Hz, indole–H), 7.45 (1H, d, J = 2.2 Hz,
indole–H), 7.72 (1H, d, J = 8.4 Hz, Ar–H), 7.74–7.82
(2H, m, Ar–H), 7.87 (1H, br s, Ar–H). 13C NMR d
45.2 (· 2) (CH3), 48.3 (CH2), 56.1 (· 2) (CH3), 60.9
(· 2) (CH3) 62.9 (CH2), 66.6 (CH), 101.5 (CH), 108.8
(· 2) (CH), 111.3 (CH), 112.5 (CH), 115.4 (C), 125.2
(CH), 125.8 (CH), 127.1 (C), 127.5 (· 3) (CH), 127.7
(CH), 128.5 (CH), 131.5 (C), 131.7 (C), 132.4 (C),
132.8 (C), 133.6 (C), 138.3 (C), 138.5 (C), 153.0 (· 2)
(C), 154.9 (C). MS m/z 541. Anal. Calcd for
C33H36N2O5: C, 73.31; H, 6.71; N, 5.18. Found: C,
73.24; H, 6.69; N, 5.00.
4.1.18. 5-Methoxy-2-(3,4,5-trimethoxyphenyl)-3-(naphth-
2-yl)-1H-indole (20). From ketone
6
(250 mg,
0.74 mmol), compound 20 (172 mg, 53%) was obtained
by the previously described procedure, isolated as a solid
after chromatography (hexane–ethyl acetate 3:2) and
purified by crystallization from hexane–ethyl acetate.
Mp: 104 ꢂC (hexane–ethyl acetate). 1H NMR d 3.51
(6H, s, 3-OCH3 and 5-OCH3), 3.79 (3H, s, 4-OCH3),
3.84 (3H, s, indole–OCH3), 6.63 (2H, s, Ar–H), 6.91
(1H, dd, J1 = 8.8 Hz, J2 = 2.2 Hz, indole–H), 7.14 (1H,
d, J = 2.2 Hz, indole–H), 7.32 (1H, d, J = 8.8 Hz, in-
dole–H), 7.52 (1H, d, J = 8.4 Hz, Ar–H), 7.54–7.64
(3H, m, Ar–H), 7.75–7.95 (2H, m, Ar–H), 8.00 (1H, br
s, Ar–H), 8.68 (1H, br s, NH). 13C NMR d 55.8 (· 3)
(CH3), 60.8 (CH3), 101.0 (CH), 105.1 (· 2) (CH), 111.8
(CH), 112.9 (CH), 114.6 (C), 125.5 (CH), 125.9 (CH),
127.6 (· 2) (CH), 127.7 (CH), 127.8 (C), 128.4 (CH),
129.0 (CH), 129.3 (C), 131.0 (C), 132.0 (C), 132.1 (C),
133.7 (C), 135.0 (C), 137.4 (C), 153.1 (· 2) (C), 154.7
(C). HRMS m/z found 439.1726; calcd for C28H25NO4
m/z 439.1784. Anal. Calcd for C28H25NO4: C, 76.52;
H, 5.73; N, 3.19. Found: C, 76.46; H, 5.68; N, 2.97.
4.1.21. 2-(3,4,5-Trimethoxyphenyl)-3-(naphth-2-yl)qui-
noxaline (23). Glacial AcOH (500 lL) and o-phenylendi-
amine (100 lL, 0.15 mmol) were added to a solution of
diketone 11 (25 mg, 0.07 mmol) in dry EtOH (2 mL).
The reaction mixture was refluxed for 24 h. Next, EtOH
was removed under vacuum. Water was added and the
mixture extracted with ethyl acetate (· 3). The combined
organic layers were sequentially washed with 2 N HCl,
saturated NaHCO3 and saturated NaCl, dried over
anhydrous Na2SO4 and the solvent evaporated to obtain
29 mg (98%) of the quinoxaline derivative 23 as a thick
oil. 1H NMR d 3.55 (6H, s, 3-OCH3 and 5-OCH3), 3.84
(3H, s, 4-OCH3), 6.79 (2H, s, Ar–H), 7.45–7.56 (3H, m,
Ar–H), 7.77–7.87 (3H, m, Ar–H), 7.78 (1H, d,
J = 8.4 Hz, Ar–H), 8.17–8.23 (2H, m, Ar–H), 8.22
(1H, br s, Ar–H). 13C NMR d 56.1 (· 2) (CH3), 61.1
(CH3), 107.7 (· 2) (CH), 126.6 (CH), 127.1 (CH),
127.8 (· 2) (CH), 127.9 (CH), 128.7 (CH), 129.4 (· 2)
(CH), 129.6 (CH), 130.2 (CH), 131.1 (CH), 132.2 (C),
133.4 (· 2) (C), 136.9 (C), 137.0 (C), 139.2 (C), 141.4
(C), 141.5 (C), 153.2 (· 2) (C), 153.6 (C). HRMS m/z
found 422.1668; calcd for C27H22N2O3 m/z 422.1630.
4.1.19. 5-Methoxy-3-(naphth-2-yl)-2-(3,4,5-trimethoxy-
phenyl)-1-(oxiran-2-ylmethyl)-1H-indole (21). Com-
pound 21 (16 mg, 46%) was prepared from indole 20
(30 mg, 0.07 mmol), according to the previously de-
scribed procedure, and obtained as a solid which was
purified by crystallization from hexane–ethyl acetate.
Mp: 142 ꢂC (hexane–ethyl acetate). 1H NMR d 2.37
(1H, dd, J1 = 4.4 Hz, J2 = 2.6 Hz, oxirane), 2.72 (1H, t,
J = 4.4 Hz, oxirane), 3.10–3.15 (1H, m, oxirane), 3.54
(6H, s, 3-OCH3 and 5-OCH3), 3.82 (3H, s, 4-OCH3),
3.88 (3H, s, indole–OCH3), 4.01–4.24 (1H, m, N–CH
H), 4.35 (1H, dd, J1 = 15.4 Hz, J2 = 4.4 Hz, N–CHH),
6.53 (2H, s, Ar–H), 7.00 (1H, dd, J1 = 8.8 Hz,
J2 = 2.6 Hz, indole–H), 7.33 (1H, d, J = 2.6 Hz, in-
dole–H), 7.41–7.55 (3H, m, Ar–H), 7.42 (1H, d,
J = 8.8 Hz, indole–H), 7.71–7.84 (2H, m, Ar–H), 7.86
(1H, d, J = 8.8 Hz, Ar–H), 7.90 (1H, br s, Ar–H). 13C
NMR d 45.5 (CH2), 45.7 (CH2), 50.9 (CH), 56.0 (· 3)
(CH3), 60.9 (CH3), 101.5 (CH), 108.6 (· 2) (CH), 110.9
4.1.22. 2-(3,4,5-Trimethoxyphenyl)-3-(naphth-2-yl)pyr-
ido[2,3-b]pyrazine (24) and 3-(3,4,5-trimethoxyphenyl)-2-
(naphth-2-yl)pyrido[2,3-b]pyrazine (25). Diketone 11
(245 mg, 0.70 mmol) was dissolved in glacial AcOH
(15 mL) and 2,3-diaminopyridine (164 mg, 1.50 mmol)
was added to the solution. The reaction mixture was re-
fluxed for 4 days. Next, AcOH was evaporated. HCl