L.-Y. Hu et al. / Bioorg. Med. Chem. 8 (2000) 1203±1212
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of 3,3-dimethylbutyraldehyde. Yield: 59%; an oil; H
55%; an oil; H NMR (CDCl3, ppm) d1.56±1.74 (m, 13
H), 2.05 (b, 1H), 2.98 (br, 1H), 3.02 (s, 3H), 3.35 (br,
1H), 3.56 (br, 1H), 3.71 (br, 1H), 4.96 (s, 2H), 5.05 (br,
1H), 6.71 (br, 1H), 6.83 (d, 2H, J=9.0 Hz), 7.25±7.40
(m, 6H), 7.54 (d, 2H, J=.5 Hz), 7.85±7.91 (m, 2H);
MS m/z: 519 (M+1); HRMS (C31H38N2O1S1): calcd
519.2667, found 519.2681, HPLC purity: 95%.
NMR (CDCl3, ppm) d 1.55 (s, 2H) 1.62±1.80 (m, 6H),
1.93 (t, 3H, J=11.2 Hz), 2.32 (t, 2H, J=7.6 Hz), 2.59 (t,
2H, J=7.8 Hz), 2.95 (d, 2H, J=11.7 Hz), 3.30±3.35 (m,
1H), 3.70 (d, 2H, J=5.6 Hz), 4.96 (s, 2H), 5.04 (s, 1H),
6.67 (d, 2H, J=9.0 Hz), 6.83 (d, 2H, J=9.0 Hz), 7.15
(d, 3H, J=6.35 Hz), 7.24±7.27 (m, 6H), 7.29±7.40 (m,
4H); MS m/z: 469 (M+1); anal. (C32H40N2O1) C, H, N.
(4-Benzyloxy-phenyl)-[1-(4-tert-butyl-benzyl)-piperidin-4-
yl]-(3-methyl-but-2-enyl)-amine (13). This compound
was prepared in an analogous manner to that used for
4, except that 4-tert-butyl-benzaldehyde was used
instead of 3,3-dimethylbutyraldehyde. Yield 76%; 1H
NMR (CDCl3, ppm) d 1.28 (s, 9H), 1.55 (br, 1H), 1.62
(s, 6H), 1.71 (br, 2H), 1.98 (br, 2H), 2.92 (br, 2H), 3.31±
3.39 (m, 1H), 3.44 (br, 1H), 3.70 (d, 2H, J=4.9 Hz),
4.95 (s, 2H), 5.03 (br, 1H), 6.67 (d, 2H, J=9.0 Hz), 6.82
(d, 2H, J=9.0 Hz), 7.25±7.39 (m, 5H); MS m/z: 497
(M+1); anal. (C34H44N2O1) C, H, N.
(4-Benzyloxy-phenyl)-(1-benzyl-piperidin-4-yl)-(3-methyl-
but-2-enyl)-amine (8). This compound was prepared in
an analogous manner to that used for 4, except that
benzaldehyde was used instead of 3,3-dimethylbutyr-
aldehyde. The product was made as the HCl salt. Yield:
1
90%, an oil; H NMR (CD3OD, ppm) d 1.63 (s, 3H),
1.63 (s, 3H), 1.63±1.72 (br., 4H), 2.02 (br., 2H), 2.93 (s,
1H), 2.95 (s, 1H), 3.27 (m, 1H), 3.49 (s, 2H), 3.71 (d, 2H,
J=4.9 Hz), 4.96 (s, 2H), 5.04 (m, 1H), 6.73 (d, 2H,
J=9.3 Hz), 6.84 (d, 2H, J=9.0 Hz), 7.26±7.40 (m, 10
H); MS m/z: 441 (M+1 for C30H36N2O1); anal. (C30H36
N2O1.2HCl.0.5H2O) C, H, N.
(4-Benzyloxy-phenyl)-[1-(4-dimethylamino-benzyl)-piper-
idin-4-yl]-(3-methyl-but-2-enyl)-amine (14). This com-
pound was prepared in an analogous manner to that
used for 4, except that 4-dimethylaminobenzaldehyde
was used instead of 3,3-dimethylbutyraldehyde. Yield:
4-{4-[(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-amino]-
piperidin-1-ylmethyl}-phenol (9). This compound was
prepared in an analogous manner to that used for 4,
except that 4-hydroxybenzaldehyde was used instead of
3,3-dimethylbutyraldehyde. Yield: 31%; 1H NMR
(CDCl3, ppm) d 1.59 (s, 3H), 1.60 (s, 3H), 1.72 (m, 4H),
2.01 (m, 2H), 2.98 (d, 2H, J=11.2 Hz), 3.35±3.42 (m,
3H), ), 3.68 (d, 2H, J=4.2 Hz), 4.95 (s, 2H), 5.02 (s,
1H), 6.63 (d, 2H, J=8.3 Hz), 6.67 (d, 2H, J=9.0 Hz),
6.82 (d, 2H, J=9.0 Hz), 7.25±7.40 (m, 5H); MS m/z: 457
(M+1); anal. (C30H36N2O2.0.25 H2O) C, H, N.
1
18%; H NMR (CDCl3, ppm) d 1.62 (s, 6H), 1.70 (br,
2H), 1.94±1.98 (m, 2H), 2.90 (s, 6H), 2.91±2.94 (m, 1H),
3.30±3.40 (m, 3H), 3.70 (d, 2H, J=3.9 Hz), 4.95 (s, 2H),
5.02 (s, 1H), 6.66 (d, 4H, J=8.5 Hz), 6.82 (d, 2H, J=9.0
Hz), 7.13 (d, 2H, J=8.1 Hz), 7.25±7.40 (m, 5H); MS m/
z: 484 (M+1); anal. (C32H41N3O1.0.25H2O) C, H, N.
(4-Benzyloxy-phenyl)-(3-methyl-but-2-enyl)-[1-(1H-pyrrol-
2-ylmethyl)-piperidin-4-yl]-amine (15). This compound
was prepared in an analogous manner to that used for
4, except that pyrrole-2-carboxaldehyde was used
instead of 3,3-dimethylbutyraldehyde. The product was
converted into the HCl salt. Yield: 40%; 1H NMR
(CD3OD, ppm) d 1.62 (s, 6H), 1.64±1.68 (m, 1H), 1.76
(d, 2H, J=12.5 Hz), 2.03 (t, 2H, J=11.0 Hz), 2.92 (d,
2H, J=12.0 Hz), 3.31±3.38 (m, 1H), 3.49 (s, 2H), 3.69
(d, 2H, J=5.4 Hz), 4.96 (s, 2H), 5.04 (m, 1H), 5.99 (s,
1H), 6.08 (dd, 1H, J=5.9, 2.7 Hz), 6.68±6.72 (m, 3H),
6.83 (d, 2H, J=9.3 Hz), 7.25±7.40 (m, 5H), 8.60 (br,
1H); MS m/z: 430 (M+1 for C28H35N3O1); anal.
(C28H35N3O1.3HCl) C, H, N.
(4-Benzyloxy-phenyl)-[1-(4-¯uoro-benzyl)-piperidin-4-yl]-
(3-methyl-but-2-enyl)-amine (10). This compound was
prepared in an analogous manner to that used for 4,
except that 4-¯uorobenzaldehyde was used instead of
3,3-dimethylbutyraldehyde. Yield: 80%; an oil; 1H
NMR (CDCl3, ppm) d 1.56±1.71 (m, 9H), 2.00 (br.,
2H), 2.89 (m, 2H), 3.32±3.46 (m, 5H), 3.69 (br s, 2H),
4.96 (s, 2H), 5.03 (s, 1H), 6.67 (d, 2H, J=8.5 Hz), 6.83
(d, 2H, J=9.0 Hz), 6.94±7.03 (m, 3H), 7.25±7.40 (m,
6H); MS m/z: 459 (M+1); anal. (C30H35N2O1F1) C,
H, N.
(4-Benzyloxy-phenyl)-[1-(4-bromo-benzyl)-piperidin-4-yl]-
(3-methyl-but-2-enyl)-amine (11). This compound was
prepared in an analogous manner to that used for 4,
except that 4-bromobenzaldehyde was used instead of
3,3-dimethylbutyraldehyde. Yield: 40%; an oil; 1H
NMR (CDCl3, ppm) d 1.63 (s, 6H), 1.60±1.80 (m, 4H),
2.01 (m, 2H), 2.89 (d, 2H, J=11.5 Hz), 3.27 (m,1 H),
3.41 (s, 2H), 3.70 (d, 2H, J=4.6 Hz), 4.96 (s, 2H), 5.03
(m, 1H), 6.68 (d, 2H, J=9.0 Hz), 6.83 (d, 2H, J=9.0
Hz), 7.14±7.46 (m, 9H); MS m/z: 521 (M+1); anal.
(4-Benzyloxy-phenyl)-(1-furan-2-ylmethyl-piperidin-4-yl)-
(3-methyl-but-2-enyl)-amine (16). This compound was
prepared in an analogous manner to that used for 4,
except that furan-2-carboxaldehyde was used instead of
3,3-dimethylbutyraldehyde. Yield: 60%; an oil; 1H
NMR (CDCl3, ppm) d 1.61 (s, 6H), 1.72 (m, 4H), 2.01
(m, 2H), 2.97 (d, 2H, J=11.2 Hz), 3.32 (m, 1H), 3.51 (s,
2H), 3.70 (d, 2H, J=4.9 Hz), 4.96 (s, 2H), 5.02 (s, 1H),
6.16 (br., 1H), 6.28 (br., 1H), 6.68 (d, 2H, J=9.0 Hz),
6.82 (d, 2H, J=9.0 Hz), 7.25±7.80 (m, 6H); MS m/z: 431
(M+1); anal. (C28H34N2O2) C, H, N.
.
(C30H35N2O1Br1 H2O): C, H, N.
(4-Benzyloxy-phenyl)-[1-(4-methanesulfonyl-benzyl)-piper-
idin-4-yl]-(3-methyl-but-2-enyl)-amine (12). This com-
pound was prepared in an analogous manner to that
used for 4, except that 4-methylsulfonylbenzaldehyde
was used instead of 3,3-dimethylbutyraldehyde. Yield:
(4-Benzyloxy-phenyl)-[1-(1H-imidazol-4-ylmethyl)-piper-
idin-4-yl]-(3-methyl-but-2-enyl)-amine (17). This com-
pound was prepared in an analogous manner to that
used for 4, except that 4-formylimidazole was used