E. J. Homan et al. / Bioorg. Med. Chem. 7 (1999) 1111±1121
1119
(base, 50 MHz, CDCl3): d 23.7, 24.8, 31.9, 40.0, 52.6,
54.6, 55.0, 55.6, 106.8, 121.5, 125.1, 126.1, 126.7, 128.2,
128.4, 137.8, 140.8, 157.2; MS (CI with AcOH): m/z 311
(M+1).
6H), 3.51±3.59 (m, 2H), 3.81 (s, 3H), 6.69 (dd, J=
7.3 Hz, 7.3 Hz, 2H), 7.00 (bs, 1H), 7.10 (t, J=7.8 Hz,
1H), 7.38±7.54 (m, 3H), 7.76 (d, J=8.1 Hz, 2H); 13C
NMR (base, 50 MHz, CDCl3): d 23.0, 25.4, 31.5, 36.9,
51.4, 55.0, 59.2, 106.9, 121.4, 124.9, 126.2, 126.8,
131.1, 134.6, 136.9, 157.1, 167.3; MS (CI with AcOH):
m/z 325 (M+1); Anal. calcd for C21H26N2O2 C2H2O4
1/4H2O: C 63.79, H 6.65, N 6.47; obsd C 63.46, H
6.75, N 6.57.
5-Methoxy-2-[N-(2-benzamidoethyl)-N-benzylamino]tetra-
lin hydrochloride (14). This compound was essentially
prepared as described for 4, starting from 13. Yield
.
.
53%; mp 112±114 ꢀC; IR: cm 3261 (b), 2941, 2835,
1
1
2489 (b), 1655, 1588, 1535; H NMR (base, 200 MHz,
CDCl3): d 1.64±1.72 (m, 1H), 2.18±2.23 (m, 1H), 2.50±
2.64 (m, 1H), 2.87±2.96 (m, 4H), 3.05±3.16 (m, 2H),
3.48±3.54 (m, 2H), 3.71±3.87 (m, 5H), 6.73 (dd,
J=13.7 Hz, 7.7 Hz, 2H), 7.04±7.09 (m, 1H), 7.15 (t,
J=7.7 Hz, 1H), 7.23±7.57 (m, 8H), 7.79 (dd, J=8.1 Hz,
1.7 Hz, 2H); 13C NMR (base, 50 MHz, CDCl3): d 23.8,
25.1, 32.1, 38.0, 48.1, 54.6, 55.2, 56.1, 107.1, 121.6,
125.0, 126.4, 127.0, 127.3, 128.5, 128.6, 128.8, 131.3,
134.7, 137.3, 140.0, 157.2, 167.3; MS (CI with NH3): m/
z (rel. intensity) 106 (21), 139 (20), 174 (32), 206 (78),
280 (14), 325 (28), 415 (100, M+1); Anal. calcd for
5-Methoxy-2-[N-(2-benzamidoethyl)-N-ethylamino]tetra-
lin hydrochloride (17). This compound was prepared
essentially as described for 16, using acetaldehyde
instead of formaldehyde. Yield 88%; mp 104±105 ꢀC;
1
IR: cm 3422 (b), 3271 (b), 2938, 2836, 2617 (b), 2472
1
(b), 2357, 1649, 1588, 1534; H NMR (base, 200 MHz,
CDCl3): d 1.12 (t, J=7.3 Hz, 3H), 1.24±1.73 (m, 1H),
2.02±2.17 (m, 1H), 2.47±3.07 (m, 9H), 3.40±3.60 (m,
2H), 3.81 (s, 3H), 6.68 (t, J=7.3 Hz, 2H), 7.10 (t,
J=8.1 Hz, 1H), 7.18 (bs, 1H), 7.39±7.54 (m, 3H), 7.80±
7.85 (m, 2H); 13C NMR (base, 50 MHz, CDCl3): d 14.1,
23.6, 25.7, 32.3, 38.1, 44.1, 480, 55.2, 55.8, 107.0, 121.5,
125.0, 126.3, 126.9, 128.5, 131.2, 134.7, 137.4, 157.2,
167.2; MS (CI with NH3): m/z (rel. intensity) 161 (14),
193 (20), 218 (57), 305 (7), 353 (100, M+1); Anal. calcd
.
.
C27H30N2O2 HCl 3/4H2O: C 69.80, H 7.07, N 6.03;
obsd C 69.95, H 7.09, N 6.11.
5-Methoxy-2-[N-(2-benzamidoethyl)amino]tetralin oxalate
(15). A solution of the free base of 14 (0.56 g, 1.4 mmol)
in absolute EtOH (50 mL) was transferred to a Parr
¯ask, 10% Pd-on-C catalyst (0.30 g) was added and the
solution was hydrogenated overnight under 4 atm H2 at
room temperature. The catalyst was removed by ®ltra-
tion and the solvent was evaporated, yielding 0.36 g
(1.1 mmol, 82%) of the pure base of 15 as a colourless
.
.
for C22H28N2O2 HCl 1/4H2O: C 67.15, H 7.57, N 7.12;
obsd C 67.43, H 7.92, N 7.17.
5-Methoxy-2-[N-(2-benzamidoethyl)-N-allylamino]tetra-
lin hydrochloride (18). Allyl bromide (0.10 g, 0.8 mmol)
was added to a stirred suspension of 15 (0.10 g,
0.2 mmol), Cs2CO3 (0.23 g, 0.7 mmol) and a catalytic
amount of KI in MeCN (50 mL). The reaction mixture
was re¯uxed overnight, cooled to room temperature and
then the solids were removed by ®ltration.The ®ltrate
was concentrated in vacuo, which gave the crude ter-
tiary amine as a yellow oil. Puri®cation by silica column
chromatography [eluent: MeOH/CH2Cl2, 1/20 (v/v)]
gave the pure base of 18 as a colourless oil. Yield 32 mg
oil: mp 208±210 ꢀC dec (MeOH); IR: cm 3281 (b),
1
3045, 2936, 2836, 2505, 1735, 1632, 1562; 1H NMR
(base, 200 MHz, CDCl3): d 1.55±1.70 (m, 2H), 2.00±2.09
(m, 1H), 2.51±2.67 (m, 2H), 2.81±3.06 (m, 5H), 3.50±
3.58 (m, 2H), 3.81 (s, 3H), 6.68 (dd, J=7.8 Hz, 4.2 Hz,
2H), 6.96 (bs, 1H), 7.10 (t, J=7.9 Hz, 1H), 7.36±7.53
(m, 3H), 7.53±7.79 (m, 2H); 13C NMR (base, 50 MHz,
CDCl3): d 21.4, 28.8, 36.4, 39.8, 45.4, 52.4, 55.0, 106.9,
121.4, 124.8, 126.1, 126.8, 128.4, 131.2, 134.5, 136.2,
157.0, 167.4; MS (CI with AcOH): m/z 325 (M+1);
(0.1 mmol, 36%); mp 100±102 ꢀC; IR: cm 3331 (b),
1
3065, 2930, 2836, 1633, 1601, 1584; 1H NMR (base,
300 MHz, CDCl3): d 1.56±1.70 (m, 1H), 2.03±2.08 (m,
1H), 2.48±2.60 (m, 1H), 2.75±2.90 (m, 4H), 2.96±3.09
(m, 2H), 3.28 (d, J=6.2 Hz, 2H), 3.44±3.57 (m, 2H),
3.80 (s, 3H), 5.12 (d, J=9.9 Hz, 1H), 5.23 (d,
J=17.0 Hz, 1H), 5.80±5.93 (m, 1H), 6.67 (t, J=8.4 Hz,
2H), 6.90 (bs, 1H), 7.09 (t, J=7.9 Hz, 1H), 7.42±7.53
(m, 3H), 7.77 (d, J=8.1 Hz, 2H); 13C NMR (base,
75 MHz, CDCl3): d 23.8, 25.8, 32.5, 37.9, 48.1, 53.6,
55.4, 56.2, 107.2, 117.4, 121.7, 125.1, 126.5, 127.0, 128.8,
131.5, 135.0, 136.9, 137.5, 157.4, 167.4; MS (CI with
NH3): m/z (rel. intensity) 77 (33), 105 (53), 161 (79), 203
(32), 230 (100), 324 (2), 365 (3, M+1); Anal. calcd for
.
Anal. calcd for C20H24N2O2 C2H2O4: C 63.74, H 6.34,
N 6.76; obsd C 63.59, H 6.36, N 6.76.
5-Methoxy-2-[N-(2-benzamidoethyl)-N-methylamino]tetra-
lin oxalate (16). A solution of 15 (0.10 g, 0.3 mmol) in
MeOH (50 mL) was transferred to a Parr ¯ask, 37%
aqueous formaldehyde solution (5 mL) and 10% Pd-on-
C catalyst (0.10 g) were added, and the reaction mixture
was hydrogenated overnight under 4 atm H2 at 55 ꢀC.
The catalyst was removed by ®ltration and the ®ltrate
was concentrated. The residue was dissolved in CH2Cl2
and subsequently washed with 10% aqueous NaHCO3
solution, H2O and brine. After drying (Na2SO4) and
®ltering, the solvent was evaporated, which gave the
crude product as a yellow oil. Puri®cation by silica col-
umn chromatography [eluent: MeOH/CH2Cl2, 1/20 (v/
v)] yielded 80 mg (0.24 mmol, 77%) of the pure base of
.
.
C23H28N2O2 HCl 1/2H2O: C 67.37, H 7.39, N 6.83;
obsd C 67.16, H 7.77, N 6.75.
5-Methoxy-2-[N-(3-phthalimidopropyl)-N-n-propylamino]-
tetralin oxalate (20). A stirred suspension of N-(3-bro-
mopropyl)phthalimide (3.14 g, 11.7 mmol), K2CO3
16 as a colourless oil: mp 141±143 ꢀC; IR: cm 3395
(1.62 g, 11.7 mmol), KI (0.13 g, 0.78 mmol) and
10
1
1
.
19 HCl (1.00 g, 3.9 mmol) in MeCN (150 mL) was
(b), 3065, 2949, 2837, 1719, 1654, 1588, 1542; H NMR
(base, 200 MHz, CDCl3): d 1.62±1.73 (m, 1H), 2.03±2.09
(m, 1H), 2.37 (s, 3H), 2.47±2.64 (m, 1H), 2.74±3.05 (m,
re¯uxed for 24 h. After cooling, the reaction mixture
was ®ltered and the MeCN was evaporated from the