4676 Journal of Medicinal Chemistry, 2010, Vol. 53, No. 12
Tasso et al.
warm to ambient temperature, refluxed under nitrogen for 24 h,
and then quenched with sequential addition of H2O (1 mL),
NaOH 6N (1.5 mL), and H2O (1 mL). The precipitate was filtered
and thoroughly washed with THF.
-CH2-Cl). Anal. Calcd for C12H22ClNS: C, 58.16; H, 8.95; N,
5.65; S, 12.94. Found: C, 58.46; H, 9.10; N, 5.78; S, 12.92.
Functional Studies. All methods used for the functional
studies have been already described6,10-18 and are provided,
with some additional details, as Supporting Information.
After evaporation to dryness, the residue was taken up in dry
ether and filtered to remove the insoluble part. The organic
solution was evaporated and the oily residue was chromato-
graphed on alumina (1:30) eluting with dry ether. Thus 180 mg
of 13 (yield = 46%) were obtained.
Acknowledgment. Financial support from Italian MIUR
and the Universities of Bologna and Genoa are gratefully
acknowledged. We thank O. Gagliardo for performing the
elemental analyses.
1
Data for free base: oil. H NMR (CDCl3): δ 1.16-2.14 (m,
16H of Lup), 2.31 (s, 6H, 2CH3), 2.79-3.14 (m, 2H, HR near N
of Q þ 2H, CH2-NH þ 1H, NH, collapses with D2O), 6.75-7.05
(m, 3H, aromatic protons).
Supporting Information Available: Further details for func-
tional assays and additional references. This material is avail-
Data for hydrochloride: mp 184-186 °C. Anal. Calcd for
C19H30N2 HCl: C, 70.67; H, 9.68; N, 8.67; S. Found: C, 70.77;
H, 9.42; N, 8.65.
3
N-[2-(1S,9aR)(Octahydro-2H-quinolizin-1-yl)ethyl]-2,4,6-tri-
methylaniline (14). A solution of anilide 16 (0.4 g, 1.27 mmol) in
dry THF (20 mL) was added dropwise to a suspension of
powdered LiAlH4 (0.33 g, 8.7 mmol) in dry THF (15 mL)
cooled to 0 °C by ice-water bath. The reaction mixture was
allowed to warm to ambient temperature, refluxed under
nitrogen for 24 h, and then quenched with sequential addition
of H2O (1 mL), NaOH 6N (1.5 mL), and H2O (1 mL). The
mixture was filtered, and the inorganic residue was thoroughly
washed with THF.
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1
title compound. Oil. H NMR (CDCl3): δ 1.04-2.58 (m with
superimposed two s at 2.15 and 2.18, 18H of Lup þ 6H, 2 o-CH3
þ 3H, p-CH3), 2.64-2.98 (m, 2H, HR near N of Q þ 1H, NH,
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C, 79.94; H, 10.73; N, 9.32. Found: C, 79.95; H, 10.69; N, 9.31.
N-{2-[(1R,9aR)-(Octahydro-2H-quinolizin-1-yl)methylthio]-
ethyl}-2,6-dimethylaniline (15). A mixture of S-(2-chloroethyl)-
thiolupinine (0.18 g, 0.72 mmol) and 2,6-dimethylaniline (0.09
mL, 0.72 mmol) was introduced into an Aldrich pressure tube
flushed with nitrogen. The sealed tube was heated at 110 °C for
72 h. The mixture was treated with 1N HCl, and the acidic phase
was extracted with ether to remove the unreacted 2,6-dimethyla-
niline. The aqueous phase was alkalinized and extracted with
CH2Cl2. After drying (Na2SO4), the solvent was evaporated and
the residue was chromatographed on alumina (1:30) eluting with
dry ether. Thus 0.05 g (yield = 21%) of 15 was obtained. Oil.
1H NMR (CDCl3): δ 1.18-2.32 (m, 14H of Lup), 2.47 (s, 6H,
2CH3), 2.72-3.11 (m, 2H, HR near N of Q þ 2H, CH2-S, þ 2H,
S-CH2-Q þ 1H, NH collapses with D2O), 3.22-3.43 (m, 2H,
N-CH2), 6.92-7.24 (m, 3H, aromatic protons). Anal. Calcd
for C20H32NS: C, 72.23; H, 9.70; N, 8.42; S, 9.64. Found: C,
72.48; H, 9.56; N, 8.25; S, 9.92.
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