F. Berardi et al. / Bioorg. Med. Chem. 9 (2001) 1325±1335
1333
1-(6-Chlorohexyl)-6-methoxy-1,2,3,4-tetrahydronaphthalene
(22b). 1H NMR (90 MHz) 1.22±1.98 (m, 14H,
(CH2)2CH(CH2)5), 2.57±2.88 (m, 3H, benzylic), 3.52 (t,
2H, J=7 Hz, CH2Cl), 3.80 (s, 3H, CH3), 6.60±7.20 (m,
3H, aromatic); GC/MS m/z 282 (M++2, 1), 281
(M++1, 1), 280 (M+, 4), 161 (100).
140.19, 145.77, 158.81; GC/MS m/z 330 (M++1, 2),
329 (M+, 7), 147 (16), 126 (100).
1-[6-(2,3-Dihydro-5-methoxy-1H-inden-1-yl)hexyl]-3,3-di-
methylpiperidine (33). 1H NMR 0.97 (s, 6H, 2 CH3),
1.25±1.79 (m, 15H, CH(CH2)5, piperidine CH2CH2 and
endo CHH), 1.85±2.30 (m, 7H, NCH2C(CH3)2,
CH2NCH2 and endo CHH), 2.71±3.35 (m, 3H, benzylic),
3.76 (s, 3H, OCH3), 6.67±7.24(m, 3H, aromatic); GC/
MS m/z 344 (M++1, 5), 343 (M+, 21), 126 (100).
1-[2-(2,3-Dihydro-1H-inden-1-yl)ethyl]-3,3-dimethylpiper-
1
idine (24). H NMR 0.94(s, 6H, 2CH ), 1.15±1.35 (m,
3
2H, CH2C(CH3)2), 1.50±1.78 (m, 4H, piperidine CH2
and endo CH2), 1.95±2.19 (m, 3H, CHCH2 and
NCHHC(CH3)2), 2.20±2.45 (m, 5H, CH2NCH2 and
NCHHC(CH3)2), 2.75±3.02 (m, 2H, benzylic CH2),
3.07±3.20 (m, 1H, benzylic CH), 7.05±7.32 (m, 4H, aro-
matic); GC/MS m/z 258 (M++1, 10), 257 (M+, 43),
127 (25), 126 (100), 115 (20).
3,3-Dimethyl-1-[6-(1,2,3,4-tetrahydronaphthalen-1-yl)-
hexyl]piperidine (38). 1H NMR 0.95 (s, 6H, 2 CH3),
1.17±1.89 (m, 18H, (CH2)2CH(CH2)5 and piperidine
CH2CH2), 1.90±2.49 (m, 6H, CH2NCH2 e NCH2C-
(CH3)2), 2.71±2.74(m, 3H, benzylic), 7.01±7.15 (m, 4H,
aromatic); GC/MS m/z 328 (M++1, 3), 327 (M+, 11),
126 (100).
1-[4-(2,3-Dihydro-1H-inden-1-yl)butyl]-3,3-dimethylpiper-
1
idine (26). H NMR 0.95 (s, 6H, 2 CH3), 1.22 (t, 2H,
J=6 Hz, CH2C(CH3)2), 1.35±1.90 (m, 9H, CH(CH2)3,
piperidine CH2 and endo CHH), 2.03 (br s, 2H,
NCH2C(CH3)2), 2.21±2.32 (m, 5H, CH2NCH2, endo
CHH), 2.76±3.13 (m, 3H, benzylic), 7.10±7.22 (m, 4H,
aromatic); 13C NMR 22.95, 25.88, 27.46, 27.83, 30.99,
31.70, 32.42, 35.23, 37.96, 45.10, 55.41, 59.36, 66.38,
123.82, 124.65, 122.23, 126.42, 144.28, 148.00; GC/MS
m/z 286 (M++1, 1), 285 (M+, 6), 126 (100), 117 (20).
3,3-Dimethyl-1-[2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-
1-yl)ethyl]piperidine (41). 1H NMR 0.94(2 s, 6H, 2 CH 3),
1.15±1.25 (m 2H, CH2C(CH3)2), 1.45±1.74 (m, 6H, endo
CH2CH2 and piperidine CH2), 1.75±1.88 (m, 2H,
CHCH2), 1.89±2.15 (m, 2H, NCH2C(CH3)2), 2.20±2.45
(m, 4H, CH2NCH2), 2.65±2.85 (m, 3H, benzylic), 3.75
(s, 3H, OCH3), 6.65±7.12 (m, 3H, aromatic); GC/MS m/
z 302 (M++1, 8), 301 (M+, 33), 160 (20), 126 (100).
1-[5-(2,3-Dihydro-1H-inden-1-yl)pentyl]-3,3-dimethylpiper-
1
3,3-Dimethyl-1-[4-(6-methoxy-1,2,3,4-tetrahydronaphthalen-
1-yl)butyl]piperidine (43). This compound has been
idine (27). H NMR 0.95 (s, 6H, 2 CH3), 1.22 (t, 2H,
1
J=6 Hz, CH2C(CH3)2), 1.29±1.88 (m, 11H, CH(CH2)4,
piperidine CH2 and endo CHH), 2.04(br s, 2H,
NCH2C(CH3)2), 2.20±2.31 (m, 5H, CH2NCH2 and endo
CHH), 2.21±3.12 (m, 3H, benzylic), 7.10±7.22 (m, 4H,
aromatic); GC/MS m/z 300 (M++1, 1), 299 (M+, 6),
126 (100), 117 (18).
already characterized20 by H NMR and GC/MS; 13C
NMR 20.07, 22.78, 25.44, 27.23, 27.83, 30.36, 30.95,
37.04, 37.12, 37.83, 55.29, 55.39, 59.29, 66.19, 112.05,
113.64, 129.69, 133.99, 138.43, 157.43.
3,3-Dimethyl-1-[6-(6-methoxy-1,2,3,4-tetrahydronaphthalen-
1-yl)hexyl]piperidine (45). 1H NMR 0.97 (s, 6H, 2 CH3),
1.23±1.84(m, 18H, (C H2)2CH(CH2)5 and piperidine
1-[6-(2,3-Dihydro-1H-inden-1-yl)hexyl]-3,3-dimethylpiperi-
1
dine (28). H NMR 0.94(s, 6H, 2 CH ), 1.21±1.84(m,
3
CH2CH2), 1.85±2.64(m, 6H, CH 2NCH2
NCH2C(CH3)2), 2.65±2.71 (m, 3H, benzylic), 3.74(s,
e
15H, CH(CH2)5, piperidine CH2CH2 and endo CHH),
2.01 (br s, 2H, NCH2C(CH3)2), 2.15±2.30 (m, 5H,
CH2NCH2 and endo CHH), 2.74±3.08 (m, 3H,
benzylic), 7.09±7.24(m, 4H, aromatic); GC/MS m/z 314
(M++1, 2), 313 (M+, 7), 126 (100), 117 (18).
3H, OCH3), 6.56±7.24(m, 3H, aromatic); GC/MS m/z
358 (M++1, 4), 357 (M+, 14), 126 (100).
3,3-Dimethyl-1-[4-(6-¯uoro-1,2,3,4-tetrahydronaphthalen-
1
1-yl)butyl]piperidine (48). H NMR 0.92 (s, 6H, 2 CH3),
1-[4-(2,3-Dihydro-5-methoxy-1H-inden-1-yl)butyl]-3,3-di-
methylpiperidine (31). 1H NMR 0.92 (s, 6H, 2 CH3),
1.19 (t, 2H, J=6 Hz, CH2C(CH3)2), 1.34±1.82 (m, 9H,
CH(CH2)3, piperidine CH2 and endo CHH), 2.00 (br s,
2H, NCH2C(CH3)2), 2.20±2.31 (m, 5H, CH2NCH2 and
endo CHH), 2.74±3.03 (m, 3H, benzylic), 3.76 (s, 3H,
OCH3), 6.67±7.07 (m, 3H, aromatic); GC/MS m/z 316
(M++1, 4), 315 (M+, 18), 126 (100).
1.19 (br t, 2H, CH2C(CH3)2), 1.28±1.84(m, 12H,
(CH2)2CH(CH2)3 and piperidine CH2), 1.99 (s, 2H,
NCH2C(CH3)2), 2.22±2.26 (m, 4H, CH2NCH2), 2.70±
2.72 (m, 3H, benzylic), 6.70±7.24(m, 3H, aromatic);
GC/MS m/z 318 (M++1, 1), 317 (M+, 5), 149 (15), 126
(100), 109 (15).
3,3-Dimethyl-1-[5-(6-¯uoro-1,2,3,4-tetrahydronaphthalen-
1-yl)pentyl]piperidine (49). 1H NMR 0.92 (s, 6H, 2 CH3),
1.19 (t, 2H, J=6 Hz, CH2C(CH3)2), 1.25±1.88 (m, 14H,
(CH2)2CH(CH2)4 and piperidine CH2), 2.00 (s, 2H,
NCH2C(CH3)2), 2.15±2.24(m, 4H, CH 2NCH2), 2.68±
2.75 (m, 3H, benzylic), 6.70±7.24(m, 3H, aromatic); 13C
NMR 19.68, 22.89, 27.17, 27.46, 27.56, 27.77, 28.01,
30.08, 30.92, 37.16, 37.22, 37.91, 55.35, 59.40, 66.36,
112.51, 112.78, 115.03, 115.29, 130.05, 130.16, 137.36,
139.18, 139.28, 162.49; GC/MS m/z 332 (M++1, 2),
331 (M+, 9), 149 (15), 126 (100).
1-[5-(2,3-Dihydro-5-methoxy-1H-inden-1-yl)pentyl]-3,3-
1
dimethylpiperidine (32). H NMR 0.92 (s, 6H, 2 CH3),
1.19 (t, 2H, J=6 Hz, CH2C(CH3)2), 1.24±1.81 (m, 11H,
CH(CH2)4, piperidine CH2 and endo CHH), 1.99 (br s,
2H, NCH2C(CH3)2), 2.20±2.31 (m, 5H, CH2NCH2 and
endo CHH), 2.71±3.04(m, 3H, benzylic), 3.76 (s, 3H,
OCH3), 6.67±7.08 (m, 3H, aromatic); 13C NMR 22.88,
27.18, 27.86, 28.08, 30.92, 31.87, 32.84, 35.59, 37.89,
44.23, 55.39, 55.61, 59.46, 66.31, 110.07, 112.01, 124.25,