1448
O. Krull, B. Wunsch / Bioorg. Med. Chem. 12(2004) 1439–1451
¨
ified by fc (1 cm, CH2Cl2/CH3OH 80:10, fractions 3 mL,
Rf=0.16). Pale yellow oil, yield 40.9 mg (30%).
C14H15NO (213.3). MS (EI/CI, 70 eV): m/z=213 (M+),
198 (M+–NH), 170 (M+–(CH2)2NH). IR (film): ꢀ~
[cmꢀ1]=3326, 1472. 1H NMR (CDCl3): d=1.99 (br,
1H, R2N–H), 2.81 (dt, J=10.0/2.9 Hz, 1H, Ar–CH2–
CH2–NHR), 2.85 (dt, J=10.0/2.0 Hz, 1H, Ar–CH2–
CH2–NHR), 3.00 (dt, J=9.5/2.6 Hz, 1H, Ar–CH2–
CH2–NHR), 3.09 (dt, J=9.2/2.3 Hz, 1H, Ar–CH2–
CH2–NHR), 3.21 (dd, J=14.0/2.1 Hz, 1H, Ar–
CH(Fur.)–CH2–NHR), 3.63 (dd, J=13.9/6.0 Hz, 1H,
Ar-CH(Fur.)–CH2–NHR), 4.22 (dd, J=5.8/1.8 Hz, 1H,
Ar-CH(Fur.)–CH2–NHR), 5.86 (dd, J=3.1/0.9 Hz, 1H,
3-Hfur.), 6.33 (dd, J=3.1/1.8 Hz, 1H, 4-Hfur.), 7.00 (dd,
J=6.4/2.1 Hz, 1H, 9-Harom.), 7.11–7.21 (m, 3H, 6-
Harom. to 8-Harom.), 7.42 (dd, J=1.8/0.8 Hz, 1H, 5-
Hfur.).
NHR), 3.21 (br, 1H, R2N–H), 3.29 (dd, J=13.9/2.0 Hz,
1H, Ar–CH(Pyr.)–CH2–NHR), 4.00 (dd, J=13.9/5.6
Hz, 1H, Ar–CH(Pyr.)–CH2–NHR), 4.30 (dd, J=5.8/1.5
Hz, 1H, Ar–CH(Pyr.)–CH2–NHR), 6.91 (d, J=7.9 Hz,
1H, 9-Harom.), 7.04 (dd, J=5.8/2.7 Hz, 1H, 3-Hpyr.),
7.10–7.19 (m, 4H, 6-Harom. to 8-Harom. and 5-Hpyr.),
7.56 (td, J=7.8/1.8 Hz, 1H, 4-Hpyr.), 8.63 (dd, J=4.9/
0.8 Hz, 1H, 6-Hpyr.).
5.26. (ꢂ)-1-(Indol-3-yl)-2,3-dihydro-1H-3-benzazepine
(12) and (ꢂ)-1-(Indol-3-yl)-2,3,4,5-tetrahydro-1H-3-benz-
azepine (4h)
Amixture of 10h (320 mg, 903 mmol), Zn dust (1.18 g,
18.0 mmol), 1 N HCl (18 mL 18 mmol) and THF (25
mL) was heated to reflux for 14 h. After addition of 2 N
NaOH (pH 9–11) the mixture was extracted with Et2O
(4ꢃ20 mL), the Et2O layer was dried (MgSO4), con-
centrated in vacuo and the residue (298.0 mg) was pur-
ified by fc (2 cm, CH2Cl2/CH3OH 80:10, fractions 5
mL).
5.24. (ꢂ)-1-(Thiophen-2-yl)-2,3,4,5-tetrahydro-1H-3-
benzazepine (4f)
Amixture of 10f (117 mg, 364 mmol), Zn dust (235 mg,
3.6 mmol), 1 N HCl (3.6 mL 3.6 mmol) and THF (10
mL) was heated to reflux for 12 h. After addition of 2 N
NaOH (pH 9–11) the mixture was extracted with Et2O
(4ꢃ20 mL), the Et2O layer was dried (MgSO4), con-
centrated in vacuo and the residue (66.8 mg) was pur-
ified by fc (1 cm, CH2Cl2/CH3OH 80:10, fractions 3 mL,
Rf=0.21). Pale yellow oil, yield 46.9 mg (56%).
C14H15NS (229.4) calcd C 73.3H 6.59 N 6.11 S 13.38
found C 73.1H 6.82 N 6.13 S 13.28. MS (EI, 70 eV):
m/z=229 (M+), 200 (M+–CH2NH), 186 (M+
–(CH2)2NH). IR (film): ꢀ~ [cmꢀ1]=3401, 1453. 1H NMR
(CDCl3): d=2.19 (br, 1H, R2N–H), 2.72–2.91 (m, 2H,
Ar–CH2–CH2–NHR), 2.94 (dt, J=13.4/3.1 Hz, 1H, Ar–
CH2–CH2–NHR), 3.14 (dt, J=13.7/3.0 Hz, 1H, Ar–
CH2–CH2–NHR), 3.34 (dd, J=14.0/2.1 Hz, 1H, Ar-
CH(Thioph.)–CH2–NHR), 3.61 (dd, J=14.2/5.6 Hz,
1H, Ar–CH(Thioph.)–CH2–NHR), 4.38 (dd, J=5.2/1.5
Hz, 1H, Ar–CH(Thioph.)–CH2–NHR), 6.62 (dd,
J=3.7/1.2 Hz, 1H, 3-Hthioph.), 6.96 (dd, J=5.0/3.5 Hz,
1H, 4-Hthioph.), 7.10 (dd, J=6.7/2.4 Hz, 1H, 9-Harom.),
7.13–7.23 (m, 3H, 6-Harom. to 8-Harom.), 7.22 (dd,
J=5.2/1.2 Hz, 1H, 5-Hthioph.).
12 (Rf=0.28): Pale yellow solid, yield 96.3 mg (41%).
C18H16N2 (260.3) calcd C 83.0H 6.19 N 10.76 found C
81.5H 6.24 N 10.42. MS (EI, 70 eV): m/z=260 (M+),
230 (M+–HCH2NH), 219 (M+–(CH)2NH). HR–MS:
calcd 260.1313 found 260.1313. IR (film): ꢀ~
1
[cmꢀ1]=3453, 1586, 1556. H NMR (CDCl3): d=2.87
(d, J=7.6 Hz, 2H, Ar–CH(Ind)–CH2-NHR), 3.45 (s,
1H, R2N-H), 4.35 (t, J=7.7 Hz, 1H, Ar–CH(Ind)–CH2–
NHR), 6.65 (d, J=11.6 Hz, 1H, Ar–CH¼CH–NHR),
6.83 (d, J=11.6 Hz, 1H, Ar–CH¼CH-NHR), 7.11 (dd,
J=7.0/1.5 Hz, 1H, 9-Harom.), 7.14 (d, J=2.6 Hz, 1H, 2-
HInd.), 7.17 (dd, J=7.0/1.5 Hz, 1H, 6-Harom.), 7.20-7.27
(m, 2H, 7-Harom. and 8-Harom.), 7.31–7.34 (m, 3H, 5-
HInd. to 7-HInd.), 7.73 (dd, J=6.4/2.1 Hz, 1H, 4-HInd.),
8.49 (br, 1H, N-HInd.). 13C NMR (CDCl3): d=35.0 (1
C, Ar–CH(Ind.)–CH2–NR2), 65.2 (1 C, Ar-CH(Ind.)–
CH2–NR2), 111.4 (1 C, Ar–CH¼CH–NR2), 122.7 (1 C,
CHarom.), 126.5 (1 C, CHarom.), 127.0 (1 C, CHarom.),
127.3 (1 C, CHarom.), 127.6 (1 C, CHarom.), 128.1 (1 C,
CHarom.), 128.2 (1 C, Ar–CH¼CH–NR2), 128.5 (1 C,
CHarom.), 128.9 (1 C, CHarom.), 129.8 (1 C, CHarom.),
136.5 (1 C, Carom.), 140.4 (1 C, Carom.), 140.9 (1 C,
Carom.), 141.3 (1 C, Carom.), 143.4 (1 C, Carom.).
5.25. (ꢂ)-1-(Pyridin-2-yl)-2,3,4,5-tetrahydro-1H-3-benz-
4h (Rf=0.25): Pale yellow oil, yield 66.4 mg (28%).
C18H18N2 (262.4). MS (EI, 70 eV): m/z=262 (M+), 247
azepine (4g)
Amixture of 10g (140 mg, 443 mmol), Zn dust (289 mg,
4.4 mmol), 1 N HCl (4.4 mL 4.4 mmol) and THF (10
mL) was heated to reflux for 12 h. After addition of 2 N
NaOH (pH 9–11) the mixture was extracted with Et2O
(4ꢃ20 mL), the Et2O layer was dried (MgSO4), con-
centrated in vacuo and the residue (121.9 mg) was pur-
ified by fc (1 cm, CH2Cl2/CH3OH 80:10, fractions 5 mL,
Rf=0.16). Pale yellow oil, yield 34,6 mg (25%).
C15H16N2 (224.3). MS (EI/CI, 70 eV): m/z=224 (M+),
209 (M+–NH), 181 (M+–(CH2)2NH). HR–MS: calcd
223.1236 found 223.1235. IR (film): ꢀ~ [cmꢀ1]=3346,
(M+–NH),
H(CH2)2NH). HR–MS: calcd 262.1467 found 262.1470.
232
(M+–HCH2NH),
218
(M+–
IR (film): ꢀ [cmꢀ1]=3278, 1605. 1H NMR (CDCl3):
~
d=2.79 (br, 1H, R2N-H), 2.83–2.86 (m, 2H, Ar–CH2–
CH2-NHR), 2.98–3.02 (m, 2H, Ar–CH2–CH2–NHR),
3.37 (dd, J=13.7/2.1 Hz, 1H, Ar–CH(Ind.)–CH2–
NHR), 3.68 (dd, J=13.7/7.0 Hz, 1H, Ar–CH(Ind.)–
CH2–NHR), 4.54 (dd, J=7.3/1.8 Hz, 1H, Ar–CH(Ind.)-
CH2–NHR), 7.02 (dd, J=7.0/0.9 Hz, 1H, 9-Harom.),
7.06 (dd, J=7.0/0.9 Hz, 1H, 6-Harom.), 7.09 (d, J=2.7
Hz, 1H, 2-HInd.), 7.15-7.29 (m, 4H, 7-Harom., 8-Harom.
,
1
1469. H NMR (CDCl3): d=2.76 (dt, J=8.5/4.5 Hz,
5-HInd. and 6-HInd.), 7.34 (d, J=8.2 Hz, 1H, 7-HInd.),
7.45 (d, J=7.6 Hz, 1H, 4-HInd.), 8.86 (br, 1H, N-HInd.).
13C NMR (CDCl3): d=35.1 (1 C, Ar–CH(Ind.)–CH2–
NR2), 41.6 (1 C, Ar–CH2–CH2–NR2), 54.3 (1 C, Ar–
1H, Ar–CH2–CH2–NHR), 2.93 (dt, J=8.8/3.9 Hz, 1H,
Ar–CH2–CH2–NHR), 3.12 (t, J=4.1 Hz, 1H, Ar–CH2–
CH2–NHR), 3.17 (t, J=4.3 Hz, 1H, Ar–CH2–CH2-