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J. W. Huffman et al. / Bioorg. Med. Chem. 13 (2005) 89–112
122.0, 122.1, 122.9, 124.1, 125.2, 125.7, 126.0, 126.4,
127.4, 128.0, 130.9, 132.3, 136.0, 139.1, 141.1, 145.7,
192.9; MS (EI) m/z 369 (100), 352 (40), 326 (87); HRMS
Calcd for C26H27NO: 369.2093, Found 369.2088.
CDCl3) d 0.87 (t, J = 6.8Hz, 3H), 1.03 (t, J = 7.3Hz,
3H), 1.24–1.35 (m, 4H), 1.47–1.59 (m, 2H), 1.76–1.86
(m, 4H), 3.16 (t, J = 7.8Hz, 2H), 4.06 (t, J = 7.2Hz,
2H), 7.34–7.42 (m, 5H), 7.45–7.53 (m, 2H), 7.56–7.60
(m, 2H), 8.15 (d, J = 8.4Hz, 1H), 8.28 (d, J = 8.3Hz,
1H); 13C NMR (75.5MHz, CDCl3) d 13.8, 14.0, 22.1,
22.9, 28.8, 29.4, 32.9, 33.1, 47.0, 109.9, 117.6, 122.7,
122.9, 123.4, 124.0, 124.5, 125.7, 126.0, 126.1, 126.7,
127.0, 131.2, 132.1, 137.0, 137.4, 137.8, 141.3, 192.3;
MS (EI) m/z 397 (100), 380 (59), 340 (82); HRMS Calcd
for C28H31NO: 397.2406, Found 397.2400.
5.1.13.
2-Methyl-1-pentyl-3-(4-propyl-1-naphthoyl)-
indole, JWH-181. JWH-181 was prepared from 4-pro-
pyl-1-naphthoic acid and 2-methyl-1-pentylindole by
method C. From 0.11g (0.51mmol) of 4-propyl-1-
naphthoic acid and 0.12g (0.62mmol) of 2-methyl-1-
pentylindole there was obtained after chromatography
(petroleum ether/ether, 9:1) 0.11g (54%) of JWH-181
as a gum: 1H NMR (300MHz, CDCl3) d 0.93 (t,
J = 7.4Hz, 3H), 1.05 (t, J = 7.3Hz, 3H), 1.36–1.40 (m,
4H), 1.80–1.87 (m, 4H), 2.48 (s, 3H), 3.13 (t,
J = 7.6Hz, 2H), 4.12 (t, J = 7.6Hz, 2H), 7.00 (d,
J = 7.5Hz, 1H), 7.15–7.22 (m, 2H), 7.30–7.35 (m, 2H),
7.40–7.55 (m, 3H), 8.13 (d, J = 8.5Hz, 1H), 8.17
(d, J = 8.4Hz, 1H); 13C NMR (75.5MHz, CDCl3) d
12.5, 13.9, 14.2, 22.4, 23.8, 29.1, 29.3, 35.4, 43.3, 109.3,
115.1, 121.3, 121.8, 122.1, 124.1, 125.2, 125.6, 126.3,
126.4, 127.1, 130.8, 132.2, 136.0, 138.8, 141.0, 145.3,
193.8; MS (EI) m/z 397 (100), 382 (56), 354 (81); HRMS
Calcd for C28H31NO: 397.2406, Found 397.2394.
5.1.17. 2-Methyl-1-propyl-3-(4-butyl-1-naphthoyl)indole,
JWH-241. JWH-241 was prepared from 4-butyl-1-
naphthoic acid and 2-methyl-1-propylindole by method
C. From 0.18g (0.79mmol) of 4-butyl-1-naphthoic acid
and 0.16g (0.95mmol) of 2-methyl-1-propylindole there
was obtained after chromatography (petroleum ether/
ether, 9:1) 0.18g (62%) of JWH-241 as a gum: 1H
NMR (300MHz, CDCl3) d 0.97–1.03 (m, 6H), 1.44–
1.56 (m, 2H), 1.77–1.90 (m, 4H), 2.49 (s, 3H), 3.16 (t,
J = 7.7Hz, 2H), 4.13 (t, J = 7.9Hz, 2H), 7.02 (d,
J = 7.4Hz, 1H), 7.16–7.25 (m, 2H), 7.30–7.36 (m, 2H),
7.42–7.56 (m, 3H), 8.13 (d, J = 8.5Hz, 1H), 8.25
(d, J = 8.3Hz, 1H); 13C NMR (75.5MHz, CDCl3) d
11.4, 12.5, 14.0, 22.8, 22.9, 32.9, 33.1, 44.8, 109.4,
115.0, 121.3, 121.7, 122.1, 124.0, 125.0, 125.7, 125.9,
126.2, 126.4, 127.1, 130.8, 132.2, 136.1, 138.8, 141.3,
145.4, 193.7; MS (EI) m/z 383 (100), 366 (34), 326
(95); Calcd for C27H29NO: 383.2249, Found 383.2246.
5.1.14. 4-Butyl-1-naphthoic acid (17). Acid 17 was pre-
pared in a manner analogous to that employed for
4-ethyl-1-naphthoic acid: mp 136–137ꢁC (lit. mp 148–
1
148.5 ꢁC, Ref. 26); H NMR (300MHz, CDCl3) d 0.99
(t, J = 7.3Hz, 3H), 1.42–1.54 (m, 2H), 1.73–1.81 (m,
2H), 3.14 (t, J = 7.7Hz, 2H), 7.41 (d, J = 7.3Hz, 1H),
7.56–7.67 (m, 2H), 8.14 (d, J = 8.2Hz, 1H), 8.33 (d,
J = 7.5Hz, 1H), 9.15 (d, J = 8.2Hz, 1H); 13C NMR
(75.5MHz, CDCl3) d 14.0, 22.9, 32.8, 33.4, 123.9,
124.3, 124.9, 126.0, 126.6, 127.5, 131.6, 132.1, 132.3,
146.3, 172.9; MS (EI) m/z 228 (53), 185 (100), 157 (36).
5.1.18. 2-Methyl-1-pentyl-3-(4-butyl-1-naphthoyl)indole,
JWH-242. JWH-242 was prepared from 4-butyl-1-
naphthoic acid and 2-methyl-1-pentylindole by method
C. From 0.17g (0.75mmol) of 4-butyl-1-naphthoic acid
and 0.18g (0.89mmol) of 2-methyl-1-pentylindole there
was obtained after chromatography (petroleum ether/
ether, 9:1) 0.17g (56%) of JWH-242 as a gum: 1H
NMR (300MHz, CDCl3) d 0.92 (t, J = 6.9Hz, 3H),
1.00 (t, J = 7.3Hz, 3H), 1.39–1.45 (m, 4H), 1.47–1.55
(m, 2H), 1.74–1.84 (m, 4H), 2.48 (s, 3H), 3.16 (t,
J = 7.7Hz, 2H), 4.12 (t, J = 7.6Hz, 2H), 7.02 (t,
J = 7.4Hz, 1H), 7.16–7.26 (m, 2H), 7.32–7.36 (m, 2H),
7.40–7.56 (m, 3H), 8.14 (d, J = 8.5Hz, 1H), 8.18
(d, J = 8.5Hz, 1H); 13C NMR (75.5MHz, CDCl3) d
12.5, 13.9, 14.0, 22.4, 22.8, 29.1, 29.3, 32.9, 33.1, 43.3,
109.3, 121.3, 121.8, 122.1, 124.0, 125.1, 125.7, 125.9,
126.2, 126.4; MS (EI) m/z 411 (89), 396 (60), 354
(100); Calcd for C29H33NO: 411.2562, Found 411.2563.
5.1.15. 1-Propyl-3-(4-butyl-1-naphthoyl)indole, JWH-
239. JWH-239 was prepared from 4-butyl-1-naphthoic
acid and 1-propylindole by method C. From 0.18g
(0.79mmol) of 4-butyl-1-naphthoic acid and 0.15g
(0.95mmol) of 1-propylindole there was obtained after
chromatography (petroleum ether/ether, 9:1) 0.19g
(62%) of JWH-239 as a gum: 1H NMR (300MHz,
CDCl3) d 0.90 (t, J = 7.4Hz, 3H), 1.02 (t, J = 7.3Hz,
3H), 1.46–1.58 (m, 2H), 1.71–1.88 (m, 4H), 3.15 (t,
J = 7.8Hz, 2H), 4.04 (t, J = 7.1Hz, 2H), 7.35–7.43 (m,
5H), 7.46–7.50 (m, 2H), 7.52–7.60 (m, 2H), 8.14 (d,
J = 8.3Hz, 1H), 8.27 (d, J = 8.2Hz, 1H); 13C NMR
(75.5MHz, CDCl3) d 11.3, 14.0, 22.9, 23.1, 32.9, 33.1,
48.7, 109.9, 117.6, 122.7, 122.9, 123.5, 124.0, 124.5,
125.7, 126.0, 126.2, 126.7, 127.0, 131.2, 132.1, 137.0,
137.4, 137.9, 141.3, 192.3; MS (EI) m/z 369 (100), 352
(70), 340 (53); HRMS Calcd for C26H27NO: 369.2093,
Found 369.2094.
5.1.19. 1-Propyl-3-(7-methyl-1-naphthoyl)indole, JWH-
076 (method A). JWH-076 was prepared from 1-propyl-
indole and 7-methyl-1-naphthoyl chloride by method
B. From 0.186g (0.65mmol) of 3-(7-methyl-1-napht-
hoyl)indole and 0.5mL (5. 5mmol) of 1-bromopropane
there was obtained after chromatography (petroleum
ether/ethyl acetate, 1:3) 0.207g (97%) of JWH-076 as a
tan gum: 1H NMR (300MHz, CDCl3) d 0.90 (t,
J = 7.3Hz, 3H), 1.85 (q, J = 7.3Hz, 2H), 2.44 (s, 3H),
4.05 (t, J = 7.2Hz, 2H), 7.35–7.47 (m, 6H), 7.62 (d,
J = 6.8Hz, 1H), 7.81 (d, J = 8.3Hz, 1H), 7.92 (d,
J = 8.1Hz, 1H), 7.98 (s, 1H), 8.52 (t, J = 5.4Hz, 1H);
13C NMR (75.5MHz, CDCl3) d 11.3, 21.9, 23.1, 48.7,
5.1.16. 1-Pentyl-3-(4-butyl-1-naphthoyl)indole, JWH-
240. JWH-240 was prepared from 4-butyl-1-naphthoic
acid and 1-pentylindole by method C. From 0.17g
(0.75mmol) of 4-butyl-1-naphthoic acid and 0.17g
(0.89mmol) of 1-pentylindole there was obtained after
chromatography (petroleum ether/ether, 9:1) 0.17g
(58%) of JWH-240 as a gum: 1H NMR (300MHz,