Synthesis of Phenalene and Acenaphthene Derivatives
J ournal of Medicinal Chemistry, 2000, Vol. 43, No. 22 4059
butanoyl chloride. A white solid was obtained: yield 44%; mp
100 °C; 1H NMR (CDCl3) δ 0.94 (t, 3H, J ) 7.3 Hz), 1.56-1.75
(m, 2H), 1.97-2.10 (m, 2H), 2.14 (t, 2H, J ) 7.3 Hz), 2.86-
3.02 (ddd, 1H, J ) 5.4 Hz, J ) 17.4 Hz, J ) 10.7 Hz), 3.08-
3.38 (m, 3H), 3.53-3.67 (m, 1H), 3.91 (s, 3H), 6.01 (brs, 1H),
7.20-7.29 (m, 3H, HAr), 7.62-7.71 (m, 2H, HAr); 13C NMR
(CDCl3) δ 14.00, 19.41, 19.84, 24.53, 38.85, 39.04, 43.27, 56.30,
112.87, 120.11, 123.14, 124.64, 126.84, 127.08, 129.15, 130.38,
135.60, 153.18, 173.47. Anal. (C19H23NO2) C, H, N.
clop r op ylca r boxa m id e (17d ). The compound was obtained
from the amine 12a and cyclopropanecarbonyl chloride: yield
38%; mp 118 °C; 1H NMR (CDCl3) δ 0.67-0.72 (m, 2H), 0.92-
0.96 (m, 2H), 1.22-1.28 (m, 1H), 1.74-1.89 (m, 2H), 1.99-
2.09 (m, 2H), 2.88-3.18 (m, 3H), 3.25-3.56 (m, 2H), 3.95 (s,
3H), 5.57 (s, 1H, NH), 7.20-7.27 (m, 3H, Har), 7.63 (dd, 1H, J
) 7.9 Hz, J ) 1.5 Hz, Har), 7.71 (d, 1H, J ) 9.0 Hz, Har); 13C
NMR (CDCl3) δ 7.00, 14.67, 19.68, 26.42, 34.72, 36.80, 37.83,
56.22, 112.61, 120.15, 123.06, 124.19, 126.28, 126.91, 129.06,
130.00, 137.32, 152.96, 173.62. Anal. (C20H23NO2) C, H, N.
N-[2-(4,9-Dim eth oxy-2,3-d ih yd r op h en a len -1-yl)eth yl]-
cyclop r op ylca r boxa m id e (19d ). The compound was ob-
tained from the amine 12c and cyclopropanecarbonyl chlo-
ride: yield 31%; mp 120 °C; 1H NMR (CDCl3) δ 0.67-0.74 (m,
2H), 0.92-0.99 (m, 2H), 1.26-1.34 (m, 1H), 1.51-2.15 (m, 4H),
2.78 (ddd, 1H, J ) 5.0 Hz, J ) 17.8 Hz, J ) 13.5 Hz), 3.03-
3.59 (m, 4H), 3.92-3.94 (2s, 6H), 6.18 (brs, 1H), 7.08-7.13 (2d,
2H, J ) 9.0 Hz, Har), 7.62-7.66 (2d, 2H, Har); 13C NMR (CDCl3)
δ 6.90; 14.88, 18.47, 25.40, 28.63, 33.66, 37.90, 56.17, 56.34,
110.81, 118.97, 122.74, 124.72, 126.83, 127.36, 130.90, 152.72,
153.42, 173.34. Anal. (C21H25NO3) C, H, N.
N-[(8-Met h oxya cen a p h t h en -1-yl)m et h yl]b u t a n a m id e
(20c). The compound was obtained from the amine 11e and
butyryl chloride: yield 48%; mp 146 °C; 1H NMR (CDCl3) δ
0.86 (t, 3H, J ) 7.3 Hz), 1.54 (m, 2H), 2.07 (t, 2H, J ) 7.3 Hz),
3.01-3.11 (dd, 1H, J ) 3.0 Hz, J ) 17.3 Hz), 3.37-3.60 (m,
2H), 3.74-3.93 (m, 2H), 3.96 (s, 3H), 6.40 (brs, 1H), 7.15-
7.32 (m, 3H, HAr), 7.52 (d, 1H, J ) 8.1 Hz, HAr), 7.65 (d, 1H, J
) 9.0 Hz, HAr); 13C NMR (CDCl3) δ 13.73, 19.13, 36.00, 38.93,
42.30, 43.96, 56.36, 115.09, 119.68, 122.26, 125.76, 125.98,
N-[(4-Met h oxy-2,3-d ih yd r op h en a len -1-yl)m et h yl]cy-
clop r op ylca r boxa m id e (13d ). It was obtained from the
amine 11a and cyclopropanecarbonyl chloride: yield 43%; mp
1
119 °C; H NMR (CDCl3) δ 0.65-0.83 (m, 2H), 0.92-1.40 (m,
2H), 1.26 (m, 1H), 1.97-2.14 (m, 2H), 2.87-3.04 (ddd, 1H, J
) 5.4 Hz, J ) 17.5 Hz, J ) 10.6 Hz), 3.16 (td, 1H, J ) 4.9 Hz,
J ) 17.5 Hz), 3.26-3.49 (m, 2H), 3.60-3.76 (m, 1H), 3.96 (s,
3H), 5.77 (brs, 1H), 7.25-7.31 (m, 3H, HAr), 7.66-7.76 (m, 2H,
H
Ar); 13C NMR (CDCl3) δ 7.72, 8.71, 15.52, 20.45, 25.22, 39.59,
43.95, 56.89, 113.43, 120.66, 123.67, 125.11, 127.39, 127.60,
129.68, 136.03, 153.72, 174.30. Anal. (C19H21NO2) C, H, N.
N-[(9-Met h oxy-2,3-d ih yd r op h en a len -1-yl)m et h yl]b u -
ta n a m id e (14c). The compound was obtained from the amine
11b and butyryl chloride: yield 81%; mp 114 °C; 1H NMR
(CDCl3) δ 0.93 (t, 3H, J ) 7.4 Hz), 1.45-1.75 (m, 2H), 1.80-
2.20 (m, 2H, CH2), 2.15 (t, 2H, J ) 7.4 Hz), 2.87-3.75 (m, 5H),
3.92 (s, 3H), 6.53 (brs, 1H), 7.20-7.29 (m, 3H, HAr), 7.61 (dd,
1H, J ) 7.8 Hz, HAr), 7.72 (d, 1H, J ) 9.0 Hz, HAr); 13C NMR
(CDCl3) δ 13.85, 19.16, 24.62, 25.64, 32.34, 38.84, 43.20, 56.42,
112.78, 121.56, 123.51, 125.00, 125.92, 128.10, 129.26, 130.18,
134.28, 152.81, 173.08. Anal. (C19H23NO2) C, H, N.
127.08, 129.18, 140.27, 142.81, 151.89, 173.10. Anal. (C18H21
NO2) C, H, N.
-
N-[(4,9-Dim eth oxy-2,3-d ih yd r op h en a len -1-yl)m eth yl]-
p r op a n a m id e (15b). The compound was obtained from the
amine 11c and propionyl chloride: yield 35%; mp 158 °C; H
1
N-[(8-Meth oxya cen a p h th en -1-yl)m eth yl]cyclop r op yl-
ca r boxa m id e (20d ). The compound was obtained from the
amine 11e and cyclopropanecarbonyl chloride: yield 71%; mp
NMR (CDCl3) δ 1.10 (t, 3H, J ) 7.6 Hz), 1.75-2.21 (m, 2H),
2.15 (q, 2H, J ) 7.6 Hz), 2.73-2.91 (ddd, 1H, J ) 4.9 Hz, J )
17.9 Hz, J ) 13.5 Hz), 3.14-3.69 (m, 3H), 3.60-3.75 (m, 1H),
3.93-3.97 (2s, 6H), 6.19 (brs, 1H), 7.13 (d, 2H, J ) 8.9 Hz,
1
185 °C; H NMR (CDCl3) δ 0.64-0.69 (m, 2H), 0.91-0.94 (m,
2H), 1.19-1.31 (m, 1H), 3.01-3.12 (dd, 1H, J ) 3.0 Hz, J )
17.4 Hz), 3.40-3.61 (m, 2H), 3.74-3.93 (m, 2H), 3.97 (s, 3H),
6.61 (s, 1H), 7.16-7.33 (m, 3H, HAr), 7.53 (d, 1H, J ) 8.1 Hz,
H
Ar), 7.63-7.71 (2d, 2H, HAr); 13C NMR (CDCl3) δ 9.85, 18.64,
24.13, 29.79, 31.38, 43.62, 56.18, 56.38, 110.70, 111.04, 118.94,
120.31, 124.77, 126.87, 127.99, 131.02, 153.02, 153.59, 173.81.
Anal. (C19H23NO3) C, H, N.
H
Ar), 7.66 (d, 1H, J ) 9.0 Hz, HAr); 13C NMR (CDCl3) δ 6.97,
7.02, 14.98, 36.03, 42.42, 44.31, 56.46, 115.26, 119.74, 122.32,
125.79, 126.03, 127.16, 129.32, 140.34, 142.91, 152.02, 173.69.
Anal. (C18H19NO2) C, H, N.
N-[(4,9-Dim eth oxy-2,3-d ih yd r op h en a len -1-yl)m eth yl]-
bu ta n a m id e (15c). The compound was obtained from the
amine 11c and butyryl chloride: yield 48%; mp 140 °C; 1H
NMR (CDCl3) δ 0.9 (t, 3H, J ) 7.6 Hz), 1.55-1.75 (m, 2H),
1.75-2.22 (m, 2H), 2.12 (t, 2H, J ) 7.6 Hz), 2.69-2.93 (ddd,
1H), 3.13-3.60 (m, 3H), 3.61-3.74 (m, 1H), 3.93-3.97 (2s, 6H),
6.18 (s, 1H), 7.13 (d, 2H, J ) 8.9 Hz, Har), 7.63-7.71 (2d, 2H,
N-[(Acen a p h th en -1-yl)m eth yl]bu ta n a m id e (21c). The
compound was obtained from the amine 11f and butyryl
chloride: yield 76%; mp 111 °C; 1H NMR (CDCl3) δ 0.86 (t,
3H, J ) 7.4 Hz), 1.57 (m, 2H, J ) 7.4 Hz), 2.07 (t, 2H), 3.08-
3.18 (dd, J ) 3.0 Hz, J ) 17.6 Hz), 3.42-3.85 (m, 3H), 3.89-
3.99 (m, 1H), 5.43 (s, 1H), 7.26-7.32 (m, 2H, HAr), 7.42-7.51
(m, 2H, HAr), 7.60-7.68 (m, 2H, HAr); 13C NMR (CDCl3) δ 13.65,
19.11, 35.29, 38.74, 43.16, 43.78, 119.09, 119.60, 122.47,
123.46, 127.78, 128.13, 131.54, 138.91, 143.98, 145.96, 173.38.
Anal. (C17H19NO) C, H, N.
H
ar); 13C NMR (CDCl3) δ 13.78, 18.62, 19.06, 31.32, 38.88,
43.79, 56.20, 56.41, 110.69, 111.08, 118.95, 120.32, 124.77,
126.82, 127.97, 130.98, 152.94, 153.59, 172.92. Anal. (C20H25
NO3) C, H, N.
-
N-[(4,9-Dim eth oxy-2,3-d ih yd r op h en a len -1-yl)m eth yl]-
cyclop r op ylca r boxa m id e (15d ). The compound was ob-
tained from the amine 11c and cyclopropanecarbonyl chlo-
ride: yield 60%; mp 192 °C; 1H NMR (CDCl3) δ 0.64-0.70 (m,
2H), 0.91-0.96 (m, 2H), 1.21-1.32 (m, 1H), 1.73-2.22 (m, 2H),
2.70-2.91 (ddd, 1H), 3.13-3.61 (m, 3H), 3.62-3.75 (m, 1H),
3.95-3.98 (2s, 6H), 6.27 (s, 1H), 7.13 (2d, 2H, J ) 8.9 Hz, J )
9.1 Hz, Har), 7.63-7.71 (2d, 2H, Har); 13C NMR (CDCl3) δ 6.81,
14.86, 18.58, 24.11, 31.47, 43.84, 56.19, 56.36, 110.69, 111.03,
118.97, 120.3, 124.73, 126.79, 127.91, 131.00, 153.01, 173.36.
Anal. (C20H23NO3) C, H, N.
N-[(Acen a p h t h en -1-yl)m et h yl]cyclop r op ylca r b oxa m -
id e (21d ). The compound was obtained from the amine 11f
and cyclopropanecarbonyl chloride: yield 79%; mp 146 °C; 1H
NMR (CDCl3) δ 0.55-0.64 (m, 2H), 0.83-0.90 (m, 2H), 1.09-
1.22 (m, 1H), 3.0-3.10 (dd, J ) 3.4 Hz, J ) 17.5 Hz), 3.40-
3.74 (m, 3H), 3.79-3.96 (m, 1H), 5.69 (s, 1H), 7.17-7.25 (m,
2H, HAr), 7.34-7.43 (m, 2H, HAr), 7.51-7.59 (m, 2H, HAr); 13
C
NMR (CDCl3) δ 7.14, 7.22, 14.78, 35.33, 43.25, 44.11, 119.20,
119.64, 122.49, 123.45, 127.83, 128.14, 131.59, 138.94, 144.07,
146.06, 173.99. Anal. (C17H17NO) C, H, N.
N-[2-(4-Met h oxy-2,3-d ih yd r op h en a len -1-yl)et h yl]b u -
ta n a m id e (17c). The compound was obtained from the amine
12a and butyryl chloride as a colorless oil: yield 24%; 1H NMR
(CDCl3) δ 0.87 (t, 3H, J ) 7.3 Hz), 1.50-1.65 (m, 2H), 1.66-
1.80 (m, 2H), 1.99-2.06 (t, m, 4H, J ) 7.3 Hz), 2.79-3.55 (m,
5H), 3.90 (s, 3H), 5.63 (s, 1H), 7.12-7.24 (m, 3H, Har), 7.60
(dd, 1H, J ) 7.6 Hz, J ) 1.8 Hz, Har), 7.66 (d, 1H, J ) 9.0 Hz,
N-[2-(8-Meth oxya cen a p h th en -1-yl)eth yl]cyclop r op yl-
ca r boxa m id e (22d ). The compound was obtained from the
amine 12e and cyclopropanecarbonyl chloride: yield 73%; mp
1
159 °C; H NMR (CDCl3) δ 0.63-0.72 (m, 2H), 0.88-0.95 (m,
2H), 1.15-1.30 (m, 1H), 1.75-2.31 (m, 2H), 3.02-3.61 (m, 4H),
3.73-3.88 (m, 1H), 3.92 (s, 3H), 5.71 (s, 1H), 7.15-7.31 (m,
3H, HAr), 7.63 (d, 1H, J ) 8.1 Hz, HAr), 7.71 (d, 1H, J ) 8.9
Hz, HAr); 13C NMR (CDCl3) δ 7.0, 14.79, 34.65, 37.63, 38.00,
39.73, 56.21, 115.24, 119.54, 122.19, 125.12, 125.80, 126.95,
131.10, 140.00, 143.35, 152.11, 173.44. Anal. (C19H21NO2) C,
H, N.
H
ar); 13C NMR (CDCl3) δ 13.79, 19.23, 19.63, 26.38, 34.67,
36.85, 37.56, 38.72, 56.21, 112.60, 120.07, 123.05, 124.19,
126.33, 126.92, 129.04, 129.97, 137.89, 152.96, 173.09.
N-[2-(4-Met h oxy-2,3-d ih yd r op h en a len -1-yl)et h yl]cy-