1934
G. A. Pinna et al. / Bioorg. Med. Chem. 10 (2002) 1929–1937
(3.43); 1H NMR (CDCl3) d 1.13 (t, 3H, J=7.4 Hz),
1.44–1.65 (m, 1H), 1.65–2.00 (m, 4H), 2.12–2.47 (m,
4H), 2.70–3.20 (m, 5H), 3.85–3.95 (m, 1H), 4.63–4.75
(m, 1H), 6.16 (t, 1H, J=7.0 Hz), 7.00–7.60 (m, 9H).
Anal. calcd for C25H29ClN2O: C, 73.42; H, 7.15; Cl,
8.67; N, 6.85. Found: C, 73.22; H, 7.13; Cl, 8.49; N,
6.82.
J=6.4 Hz), 7.00–7.70 (m, 5H). Anal. calcd for
C20H28N2O: C, 76.88; H, 9.03; N, 8.97. Found: C,
76.65; H, 9.00; N, 8.94.
9-[(2E)-3-(2-Cyclohexyl)-3-phenylprop-2-enyl]-9-propio-
nyl-3,9-diazabicyclo[3.3.1]nonane 2c. Purified by FC
(eluent: petroleum ether/EtOAc 7:3), yield 14%; Rf 0.41
(petroleum ether/EtOAc 7:3); mp 225 ꢀC (as fumarate);
1
3-{3,3-bis[3-(Trifluoromethyl)-phenyl]-prop-2-enyl}-9-pro-
pionyl-3,9-diazabicyclo[3.3.1]nonane 1g. Purified by FC
(eluent: petroleum ether/EtOAc 7:3), yield 38%; Rf 0.43
(petroleum ether/EtOAc 7:3); mp 128–135 ꢀC (as
hydrochloride); IR 1630; UV 205.0 (4.32), 224.0 (3.86);
1H NMR (CDCl3) d 1.15 (t, 3H, J=7.4 Hz), 1.45–1.68
(m, 1H), 1.68–2.00 (m, 4H), 2.14–2.40 (m, 4H), 2.70–
3.10 (m, 5H), 3.87–3.97 (m, 1H), 4.65–4.75 (m, 1H), 6.30
(t, 1H, J=7.0 Hz), 7.23–7.70 (m, 8H). Anal. calcd for
C27H28F6N2O: C, 63.52; H, 5.53; F, 22.33; N, 5.49.
Found: C, 63.39; H, 5.51; F, 22.29; N, 5.47.
IR 1640; UV 220.4 (3.99); H NMR (CDCl3) d 1.15 (t,
3H, J=7.4 Hz), 1.35–2.25 (m, 17H), 2.25–2.40 (m, 2H),
2.85–2.95 (m, 2H), 3.05–3.20 (m, 2H), 3.50–3.60 (m,
2H), 4.20–4.35 (m, 2H), 5.11 (s, 1H), 7.10–7.70 (m, 5H).
Anal. calcd for C25H36N2O: C, 78.90; H, 9.53; N, 7.36.
Found: C, 78.69; H, 9.51; N, 7.33.
9-(3,3-Diphenylprop-2-enyl)-3-propionyl-3,9-diazabicy-
clo-[3.3.1]nonane 2d. Purified by FC (eluent: CH2Cl2/
CH3COCH3 7:3 then CH2Cl2/CH3COCH3 6:4), yield
54%; Rf 0.60 (CH2Cl2/CH3COCH3 6:4); mp 102–105 ꢀC
(dec) (as hydrochloride); IR 1650; UV 213.2 (4.26),
249.8 (4.15); 1H NMR (CDCl3) d 1.13 (t, 3H,
J=7.4 Hz), 1.35–1.70 (m, 2H), 1.70–1.98 (m, 2H), 2.20–
2.35 (m, 2H), 2.70–2.90 (m, 2H), 2.90–3.14 (m, 1H),
3.30–3.52 (m, 5H), 4.29 (d, 2H, J=13.2 Hz), 6.18 (t, 1H,
J=6.6 Hz), 7.10–7.50 (m, 10H). Anal. calcd for
C25H30N2O: C, 80.17; H, 8.07; N, 7.48. Found: C,
79.95; H, 8.03; N, 7.46.
3-[3,3-bis(4-Chlorophenyl)-prop-2-enyl]-9-propionyl-3,9-
diazabicyclo[3.3.1]nonane 1h. Purified by FC (eluent:
petroleum ether/EtOAc 7:3), yield 43%; Rf 0.28 (petro-
leum ether/EtOAc 7:3); mp 112–115 ꢀC (as hydrochlor-
1
ide); IR 1640; UV 208.6 (4.00), 253.4 (3.80); H NMR
(CDCl3) d 1.14 (t, 3H, J=7.4 Hz), 1.40–1.65 (m, 1H),
1.65–1.98 (m, 4H), 2.12–2.40 (m, 4H), 2.63–3.10 (m,
5H), 3.85–3.95 (m, 1H), 4.65–4.75 (m, 1H), 6.15 (t, 1H,
J=6.8 Hz), 7.00–7.50 (m, 8H). Anal. calcd for
C25H28Cl2N2O: C, 67.72; H, 6.36; Cl, 15.99; N, 6.32.
Found: C, 67.48; H, 6.33; Cl, 15.96; N, 6.28.
9-[(2E)-3-(2-Chlorophenyl)-3-phenylprop-2-enyl]-3-pro-
pionyl-3,9-diazabicyclo[3.3.1]nonane 2e. Purified by FC
(eluent: CH2Cl2/CH3COCH3 7:3), yield 35%; Rf 0.33
(CH2Cl2/CH3COCH3 7:3); mp 125–127 ꢀC (as hydro-
1
3-[3,3-bis(4-Fluorophenyl)-prop-2-enyl]-9-propionyl-3,9-
diazabicyclo[3.3.1]nonane 1i. Purified by FC (eluent:
petroleum ether/EtOAc 7:3), yield 54%; Rf 0.45 (petro-
leum ether/EtOAc 7:3); mp 123 ꢀC (as hydrochloride);
IR 1640; UV 205.6 (3.94), 249.0 (3.60); 1H NMR
(CDCl3) d 1.14 (t, 3H, J=7.4 Hz), 1.40–1.65 (m, 1H),
1.65–1.98 (m, 4H), 2.10–2.40 (m, 4H), 2.63–3.10 (m,
5H), 3.85–3.95 (m, 1H), 4.65–4.73 (m, 1H), 6.10 (t, 1H,
J=7.0 Hz), 6.85–7.50 (m, 8H). Anal. calcd for
C25H28F2N2O: C, 73.15; H, 6.88; F, 9.26; N, 6.82.
Found: C, 72.94; H, 6.85; F, 9.24; N, 6.80.
chloride); IR 1630; UV 221.0 (4.16), 254.1 (4.07); H
NMR (CDCl3) d 1.13 (t, 3H, J=7.4 Hz), 1.34–1.63 (m,
4H), 1.63–2.00 (m, 2H), 2.20–2.30 (m, 2H), 2.76–2.91 (m,
2H), 2.96–3.10 (m, 1H), 3.20–3.60 (m, 4H), 4.25–4.36 (m,
1H), 6.18 (t, 1H, J=6.6 Hz), 7.00–7.60 (m, 9H). Anal.
calcd for C25H29ClN2O: C, 73.42; H, 7.15; Cl, 8.67; N,
6.85. Found: C, 73.22; H, 7.11; Cl, 8.63; N, 6.82.
9-[(2E)-3-(3-Chlorophenyl)-3-phenylprop-2-enyl]-3-pro-
pionyl-3,9-diazabicyclo[3.3.1]nonane 2f. Purified by FC
(eluent: CH2Cl2/CH3COCH3 7:3), yield 86%; Rf 0.63
(CH2Cl2/CH3COCH3 7:3); mp 122–126 ꢀC (as hydro-
1
3-(3,3-Diphenylpropyl)-9-propionyl-3,9-diazabicyclo[3.3.1]-
nonane 1j. Purified by FC (eluent: petroleum ether/
EtOAc 7:3), yield 27%; Rf 0.23 (petroleum ether/EtOAc
7:3); mp 141–145 ꢀC (as hydrochloride); IR 1660; UV
chloride); IR 1630; UV 214.0 (3.97), 235.0 (3.70); H
NMR (CDCl3) d 1.13 (t, 3H, J=7.2 Hz), 1.37–1.70 (m,
5H), 1.70–2.10 (m, 2H), 2.20–2.50 (m, 2H), 2.80–3.10
(m, 3H), 3.20–3.60 (m, 3H), 4.20–4.42 (m, 1H), 6.35 (t,
1H, J=6.4 Hz), 7.10–7.70 (m, 9H). Anal. calcd for
C25H29ClN2O: C, 73.42; H, 7.15; Cl, 8.67; N, 6.85.
Found: C, 73.31; H, 7.12; Cl, 8.52; N, 6.83.
1
197.1 (3.98), 245.0 (2.58); H NMR (CDCl3) d 1.07 (t,
3H, J=7.6 Hz), 1.40–1.60 (m, 1H), 1.60–1.85 (m, 4H),
2.00–2.30 (m, 4H), 2.64–2.94 (m, 6H), 3.74–3.84 (m,
2H), 4.02 (t, 1H, J=7.2 Hz), 4.55–4.65 (m, 1H), 7.04–
7.30 (m, 10H). Anal. calcd for C25H32N2O: C, 79.75; H,
8.57; N, 7.44. Found: C, 79.49; H, 8.54; N, 7.43.
9-{3,3-bis[3-(Trifluoromethyl)-phenyl]-prop-2-enyl}-3-pro-
pionyl-3,9-diazabicyclo[3.3.1]nonane 2g. Purified by FC
(eluent: CH2Cl2/CH3COCH3 7:3), yield 71%; Rf 0.65
9-[(2E)-3-Phenylbut-2-enyl]-3-propionyl-3,9-diazabicy-
clo[3.3.1]nonane 2b. Purified by FC (eluent: petroleum
ether/EtOAc 6:4), yield 50%; Rf 0.10 (petroleum ether/
EtOAc 7:3); mp 195–200 ꢀC (as fumarate); IR 1650; UV
(CH2Cl2/CH3COCH3
7:3);
mp
91–92 ꢀC
(as
hydrochloride); IR 1620; UV 205.0 (3.72), 244.0 (3.25);
1H NMR (CDCl3) d 1.14 (t, 3H, J=7.4 Hz), 1.34–1.72
(m, 4H), 1.72–2.00 (m, 2H), 2.10–2.50 (m, 2H), 2.80–
3.65 (m, 7H), 4.34 (d, 1H, J=13.6 Hz), 6.29 (t, 1H,
J=6.8 Hz), 7.20–7.80 (m, 8H). Anal. calcd for
C27H28F6N2O: C, 63.52; H, 5.53; F, 22.33; N, 5.49.
Found: C, 63.41; H, 5.49; F, 22.30; N, 5.46.
1
203.4 (3.91), 209.0 (3.83); H NMR (CDCl3) d 1.17 (t,
3H, J=7.4 Hz), 1.45–1.85 (m, 4H), 1.85–2.22 (m, 2H),
2.11 (s, 3H), 2.22–2.50 (m, 2H), 2.90–3.20 (m, 2H),
3.40–3.80 (m, 4H), 4.30–4.50 (m, 2H), 5.84 (t, 1H,