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Gerard Aime Pinna et al. / Bioorg. Med. Chem. 11 (2003) 4015–4026
4021
(5b–l) (1.42 mmol) and K2CO3 (3.55 mmol) in acetone
(9 mL) was refluxed for 24 h under magnetic stirring.
The inorganic salt was filtered off, the filtrate evapo-
rated and the oily residue purified by flash chromato-
graphy to give the desired 1b–l and 2b–l as oils. All final
compounds were converted into the HCl salts.
3.18 (m, 1H), 3.85–3.92 (m, 1H), 4.47–4.55 (m, 1H), 5.49
(t, 1H, J=6.5 Hz), 7.08–7.42 (m, 4H). Anal. calcd for
C21H27ClN2O: C, 70.27; H, 7.58; Cl, 9.88; N, 7.81.
Found: C, 70.05; H, 7.56; Cl, 9.85; N, 7.79.
9-Propionyl-10-[30 -methyl-30 -(m-chlorophenyl)-prop-20-
en-10-yl]-9,10-diazatricyclo[4.2.1.12,5] decane (1g). Puri-
fied by FC (eluent: petroleum ether/EtOAc 1:1), yield
97%; Rf 0.40 (petroleum ether/EtOAc 1:1); mp 110–
112 ꢁC (as hydrochloride); IR: 1630; UV: 250.2 (4.10);
1H NMR (CDCl3) d: 1.15 (t, 3H, J=7.2 Hz), 1.40–2.15
(m, 12H), 2.26 (q, 2H, J=7.2 Hz), 2.95–3.10 (m, 3H),
3.80–3.95 (m, 1H), 4.40–4.60 (m, 1H), 5.83 (t, 1H,
J=6.8 Hz), 7.22–7.40 (m, 4H). Anal. calcd for
C21H27ClN2O: C, 70.27; H, 7.58; Cl, 9.88; N, 7.81.
Found: C, 70.09; H, 7.55; Cl, 9.87; N, 7.78.
9-Propionyl-10-(30-phenyl-30-methylprop-20-en-10-yl)-9,10-
diazatricyclo[4.2.1.12,5]decane (1b). Purified by FC (elu-
ent: petroleum ether/EtOAc 1:1), yield 52%; Rf 0.40
(petroleum ether/EtOAc 1:1); mp 158–160 ꢁC (as
1
hydrochloride); IR: 1630; UV: 244.2 (3.89); H NMR
(CDCl3) d: 1.16 (t, 3H, J=7.8 Hz), 1.40–2.20 (m, 11H),
2.29 (q, 2H, J=7.6 Hz), 3.00–3.10 (m, 2H), 3.80–3.90
(m, 2H), 4.43–4.53 (m, 2H), 5.85 (t, 1H, J=6.6 Hz),
7.20–7.43 (m, 5H). Anal. calcd for C21H28N2O: C,
77.73; H, 8.70; N, 8.64. Found: C, 78.00; H, 8.73; N,
8.67.
9-Propionyl-10-[30-methyl-30-(p-chlorophenyl)-prop-20-en-
10-yl]-9,10-diazatricyclo[4.2.1.12,5] decane (1h). Purified
by FC (eluent: petroleum ether/EtOAc 1:1), yield 87%;
Rf 0.40 (petroleum ether/EtOAc 1:1); mp 145–147 ꢁC (as
9-Propionyl-10-(30 -trifluoromethyl-30 -phenylprop-20 -en-
10-yl)-9,10-diazatricyclo[4.2.1.12,5] decane (1c). Purified
by FC (eluent: petroleum ether/EtOAc 1:1), yield 93%;
Rf 0.37 (petroleum ether/EtOAc 1:1); mp 128–130 ꢁC (as
1
hydrochloride); IR: 1630; UV: 250.2 (3.92); H NMR
(CDCl3) d: 1.15 (t, 3H, J=7.4 Hz), 1.45–2.20 (m, 12H),
2.28 (q, 2H, J=7.4 Hz), 2.95–3.10 (m, 3H), 3.80–3.95
(m, 1H), 4.45–4.60 (m, 1H), 5.85 (t, 1H, J=7.0 Hz),
7.15–7.45 (m, 4H). Anal. calcd for C21H27ClN2O: C,
70.27; H, 7.58; Cl, 9.88; N, 7.81. Found: C, 70.12; H,
7.56; Cl, 9.87; N, 7.80.
1
hydrochloride); IR: 1635; UV: 236.2 (4.17); H NMR
(CDCl3) d: 1.13 (t, 3H, J=7.8 Hz), 1.20–2.10 (m, 8H),
2.26 (q, 2H, J=7.8 Hz), 2.65–3.00 (m, 2H), 3.80–4.00
(m, 2H), 4.45–4.58 (m, 2H), 6.48–6.60 (m, 1H), 7.20–
7.51 (m, 5H). Anal. calcd for C21H25F3N2O: C, 66.65;
H, 6.66; F, 15.06; N, 7.40. Found: C, 66.38; H, 6.64; F,
15.03; N, 7.38.
9-Propionyl-10-[30-methyl-30-(m,p-dichlorophenyl)-prop-
20-en-10-yl]-9,10-diazatricyclo [4.2.1.12,5]decane (1i).
Purified by FC (eluent: petroleum ether/EtOAc 1:1),
yield 95%; Rf 0.40 (petroleum ether/EtOAc 1:1); mp
162–164 ꢁC (as hydrochloride); IR: 1630; UV: 236.2
9-Propionyl-10-(30-cyclohexyl-30-phenylprop-20-en-10-yl)-
9,10-diazatricyclo[4.2.1.12,5]decane (1d). Purified by FC
(eluent: petroleum ether/EtOAc 1:1), yield 98%; Rf 0.37
(petroleum ether/EtOAc 1:1); mp 135–136 ꢁC (as
1
(4.08); H NMR (CDCl3) d: 1.15 (t, 3H, J=7.6 Hz),
1
hydrochloride); IR: 1680; UV: 240.1 (4.00); H NMR
1.44–2.12 (m, 12H), 2.29 (q, 2H, J=7.6 Hz), 2.98 (d,
2H, J=6.4 Hz), 3.05–3.12 (m, 1H), 3.82–3.98 (m, 1H),
4.48–4.55 (m, 1H), 5.48 (t, 1H, J=6.4 Hz), 7.08–7.40
(m, 3H). Anal. calcd for C21H26Cl2N2O: C, 64.12; H,
6.66; Cl, 18.03; N, 7.12. Found: C, 64.01; H, 6.64; Cl,
17.99; N, 7.09.
(CDCl3) d: 1.12 (t, 3H, J=7.6 Hz), 1.21–2.10 (m, 21H),
2.24 (q, 2H, J=7.4 Hz), 2.57–2.65 (m, 1H), 2.85–2.95
(m, 1H), 3.75–3.85 (m, 1H), 4.40–4.50 (m, 1H), 5.46 (t,
1H, J=6.8 Hz), 7.00 (d, 1H, J=7.4 Hz), 7.14–7.32 (m,
3H), 7.52 (d, 1H, J=7.0 Hz). Anal. calcd for
C26H36N2O: C, 79.54; H, 9.24; N, 7.14. Found: C,
79.22; H, 9.20; N, 7.17.
9-Propionyl-10-[30 -methyl-30 -(o,p-dichlorophenyl)-prop-
20-en-10-yl]-9,10-diazatricyclo [4.2.1.12,5]decane (1j).
Purified by FC (eluent: petroleum ether/EtOAc 1:1),
yield 98%; Rf 0.37 (petroleum ether/EtOAc 1:1); mp
128–130 ꢁC (as hydrochloride); IR: 1630; UV: 236.2
9-Propionyl-10-(30,30-diphenylprop-20-en-10-yl)-9,10-dia-
zatricyclo[4.2.1.12,5]decane (1e). Purified by FC (eluent:
petroleum ether/EtOAc 1:1), yield 93%; Rf 0.37 (petro-
leum ether/EtOAc 1:1); mp 112–113 ꢁC (as hydrochlor-
1
(4.17); H NMR (CDCl3) d: 1.16 (t, 3H, J=7.4 Hz),
1
ide); IR: 1630; UV: 245.1 (4.19); H NMR (CDCl3) d:
1.45–2.17 (m, 12H), 2.29 (q, 2H, J=7.4 Hz), 2.92–3.10
(m, 3H), 3.80–3.98 (m, 1H), 4.45–4.54 (m, 1H), 5.83–
5.90 (m, 1H), 7.23–7.50 (m, 3H). Anal. calcd for
C21H26Cl2N2O: C, 64.12; H, 6.66; Cl, 18.03; N, 7.12.
Found: C, 64.05; H, 6.63; Cl, 17.98; N, 7.10.
1.13 (t, 3H, J=7.6 Hz), 1.35–2.18 (m, 8H), 2.26 (q, 2H,
J=7.4 Hz), 2.86 (d, 2H, J=6.8 Hz), 2.92–3.08 (m, 2H),
3.80–3.89 (m, 1H), 4.44–4.50 (m, 1H), 6.17 (t, 1H,
J=6.8 Hz), 7.11–7.32 (m, 10H). Anal. calcd for
C26H30N2O: C, 80.79; H, 7.83; N, 7.25. Found: C,
80.62; H, 7.83; N, 7.23.
9-Propionyl-10-[(30,30-di-p-fluorophenyl)-prop-20-en-10-yl]-
9,10-diazatricyclo[4.2.1.12,5] decane (1k). Purified by FC
(eluent: petroleum ether/EtOAc 1:1), yield 94%; Rf 0.40
(petroleum ether/EtOAc 1:1); mp 126–128 ꢁC (as
9-Propionyl-10-[30-methyl-30-(o-chlorophenyl)-prop-20-en-
10-yl]-9,10-diazatricyclo[4.2.1.12,5] decane (1f). Purified
by FC (eluent: petroleum ether/EtOAc 1:1), yield 88%;
Rf 0.37 (petroleum ether/EtOAc 1:1); mp 141–143 ꢁC (as
1
hydrochloride); IR: 1680; UV: 249.4 (4.26); H NMR
(CDCl3) d: 1.14 (t, 3H, J=7.4 Hz), 1.40–2.32 (m, 10H),
2.85 (d, 2H, J=6.8 Hz), 2.95–3.05 (m, 2H), 3.80–3.92
(m, 1H), 4.40–4.51 (m, 1H), 6.11 (t, 1H, J=6.8 Hz),
6.90–7.28 (m, 8H). Anal. calcd for C26H28F2N2O: C,
1
hydrochloride); IR: 1630; UV: 230.0 (3.81); H NMR
(CDCl3) d: 1.15 (t, 3H, J=7.6 Hz), 1.50–2.15 (m, 12H),
2.30 (q, 2H, J=7.6 Hz), 2.99 (d, 2H, J=6.6 Hz), 3.04–