2612
S. Srivastava et al. / Bioorg. Med. Chem. 7 (1999) 2607±2613
73.21, H, 7.71, N, 5.56. C15H19NO2 requires C, 73.44,
H, 7.80, N, 5.70%).
(dd, 1H, J=14, 6 Hz, Ar±CH2), 3.71 (s, 3H, Ar±OCH3),
5.02 (dd, 1H, J=14, 6 Hz, CH±NO2), 5.88 (t, 1H, J=8
Hz, CHC), 6.74 (d, 2H, J=9 Hz, Ar±H), 7.02 (d, 2H,
J=9 Hz, Ar±H) (Found: C, 70.24, H, 7.86, N, 4.53.
C17H23NO3 requires C, 70.56, H, 8.01, N, 4.53%).
11b. M.P. oil; EIMS m/z 259 (M+); 1H NMR d 1.60 (m,
6H, 3ÂCH2), 2.24 (m, 4H, 2ÂCH2), 2.32 (s, 3H, Ar±
CH3), 3.04 (dd, 1H, J=14, 6 Hz, CH2±Ar), 3.42 (dd,
1H, J=14, 6 Hz, CH2±Ar), 5.04 (dd, 1H, J=14, 6Hz,
CH±NO2), 6.04 (t, 1H, J=6 Hz, CHC), 7.04 (d, 2H,
J=9 Hz, Ar±H), 7.10 (d, 2H, J=9 Hz, Ar±H), (Found:
C, 74.33, H, 8.47, N, 5.36. C16H21NO2 requires C,
74.13, H, 8.10, N, 5.40%).
12e. M.P. oil; EIMS m/z 319 (M+); 1H NMR d 1.54 (m,
8H, 4ÂCH2), 2.26 (m, 4H, 2ÂCH2), 2.98 (dd, 1H,
J=14, 6 Hz, Ar±CH2), 3.39 (dd, 1H, J=14, 6 Hz, Ar±
CH2), 3.78 (s, 6H, 2ÂAr±OCH3), 5.18 (t, 1H, J=8 Hz,
CHC), 6.76 (m, 3H, Ar±H) (Found: C, 67.48, H, 7.76,
N, 4.32. C18H25NO4 requires C, 67.68, H, 7.89, N, 4.38%).
11c. M.P. oil; EIMS m/z 279 (M+); 1H NMR d 1.86 (m,
6H, 3ÂCH2), 2.24 (m, 4H, 2ÂCH2), 3.24 (dd, 1H,
J=14, 6 Hz, CH2±Ar), 3.48 (dd, 1H, J=14, 6 Hz, CH2±
Ar), 5.18 (dd, 1H, J=14, 6 Hz, CH±NO2), 5.90 (t, 1H,
J=6.6 Hz, CHC), 7.14 (m, 4H, Ar±H), (Found: C,
64.03, H, 6.51, N, 5.23. C15H18ClNO2 requires C, 64.39,
H, 6.48, N, 5.00%).
General procedure for 1-amino-1-(cycloalken-1-yl)-2-
substituted phenyl ethanes (13±15,a±e)
A mixture of appropriate compound from 10±12(a±e) (7
mmol) and Raney±Ni (300 mg, wet) in methanol (30
mL) was subjected to hydrogenation at 4.5 kg/cm3 for
3±4 h. Thereafter, the catalyst was ®ltered over Celite
and the ®ltrate was concentrated to furnish compounds
13±15(a±e), which were subjected to the next step with-
out further puri®cation.
11d. M.P. oil; EIMS m/z 275 (M+); 1H NMR d 1.85 (m,
6H, 3ÂCH2), 3.04 (dd, 1H, J=14, 6 Hz, CH2±Ar), 3.42
(dd, 1H, J=14, 6 Hz, CH2±Ar), 3.70 (s, 3H, Ar±OCH3),
5.00 (dd, 1H, J=14, 6 Hz, CH±NO2), 5.95 (t, 1H,
J=6.6 Hz, CHC), 6.76 (d, 2H, J=9 Hz, Ar±H), 7.02
(d, 2H, J=9 Hz, Ar±H), (Found: C, 69.78, H, 7.82, N,
4.64. C16H21NO3 requires C, 69.81, H, 7.63, N, 5.09%).
General procedure for 1-amino-1-cycloalkyl-2-substituted
phenyl ethanes (16±18,a±e)
A mixture of appropriate compound from 13±15(a±e)
(crude from the above step) and 10% Pd-C (150 mg) in
methanol (30 mL) was subjected to hydrogenation at
4.5 kg/cm3 for 24 h. The reaction mixture was then ®l-
tered over a bed of Celite and the excess solvent was
removed under vacuo to obtain amines 16±18(a±e) as
oils or solids in 85±90% yields. The pure amines were
obtained as their corresponding oxalate salts.
11e. M.P. oil; EIMS m/z 305 (M+); 1H NMR d 1.85 (m,
6H, 3ÂCH2), 2.22 (m, 4H, 2ÂCH2), 3.08 (dd, 1H,
J=14, 6 Hz, CH2±Ar), 3.56 (dd, 1H, J=14, 6 Hz, CH2±
Ar), 3.78 (brs, 6H, 2ÂAr±OCH3), 5.12 (dd, 1H, J=14, 6
Hz, CH±NO2), 6.02 (t, 1H, J=6 Hz, CHC), 6.78 (m,
3H, Ar±H) (Found: C, 66.49, H, 7.61, N, 4.56.
C17H23NO4 requires C, 66.86, H, 7.59, N, 4.58%).
12a. M.P. oil; EIMS m/z 259 (M+); 1H NMR d 1.54 (m,
8H, 4ÂCH2), 2.24 (m, 4H, 2ÂCH2), 3.10 (dd, 1H,
J=14, 6 Hz, Ar±CH2), 3.50 (dd, 1H, J=14, 6 Hz, Ar±
CH2), 5.08 (dd, 1H, J=14, 6 Hz, CH±NO2), 6.02 (t, 1H,
J=8 Hz, CHC), 7.30 (m, 5H, Ar±H) (Found: C,
74.28, H, 8.22, N, 5.59. C16H21NO2 requires C, 74.13,
H, 8.10, N, 5.40%).
General procedure for oxalate salts of amines
16±18(a±e)
To a solution of appropriate amine derivative from 16±
18(a±e) (2 mmol) in dry methanol (8 mL) was added a
solution of oxalic acid dihydrate (2 mmol) in dry
methanol (8 mL) slowly. The mixture was stirred at
room temperature for 20 min. Thereafter, dry ether
(60 mL) was added to the reaction mixture and it was
left in refrigerator for 8±10 h. The separated solid was
®ltered, washed with dry ether and dried over P2O5 in a
dessicator.
12b. M.P. oil; EIMS m/z 273 (M+); 1H NMR d 1.50 (m,
8H, 4ÂCH2), 2.28 (m, 4H, 2ÂCH2), 2.34 (s, 3H, Ar±
CH2), 3.08 (dd, 1H, J=14, 6 Hz, Ar±CH2), 3.49 (dd,
1H, J=14, 6 Hz, Ar±CH2), 5.16 (dd, 1H, J=14, 6 Hz,
CH±NO2), 5.98 (t, 1H, J=6 Hz, CHC), 7.08 (d, 2H,
J=9 Hz, Ar±H), 7.14 (d, 2H, J=9 H, Ar±H), (Found:
C, 74.33, H, 8.23, N, 4.85. C17H23NO2 requires C,
74.72, H, 8.42, N, 5.12%).
16a. M.P. oil; IR (cm 1) 3400 (N±H); EIMS m/z 203
1
(M+); H NMR d 1.91 (m, 5H, 2ÂCH2 and CH), 1.71
(m, 6H, 3ÂCH2), 2.96 (m, 1H, CH2±Ar), 3.34 (m, 1H,
CH2±Ar), 3.46 (m, 1H, CH±NH2), 7.28 (m, 5H, Ar±H),
8.34 (brs, 2H, NH2) (Found: C, 82.41, H, 10.04, N, 7.05.
C14H21N requires C, 82.71, H, 10.04, N, 6.89%).
12c. M.P. oil; EIMS m/z 293 (M+); 1H NMR d 1.56 (m,
8H, 4ÂCH2), 2.30 (m, 4H, 2ÂCH2), 3.04 (dd, 1H,
J=14, 6 Hz, Ar±CH2), 3.46 (dd, 1H, J=14, 6 Hz, Ar±
CH2), 5.14 (dd, 1H, J=14, 6 Hz, CH±NO2), 6.02 (t, 1H,
J=8 Hz, CHC), 7.20 (m, 4 H, Ar±H) (Found: C,
65.52, H, 6.71, N, 4.58. C16H20ClNO2 requires C, 65.41,
H, 6.86, N, 4.76%).
16b. M.P. oil IR (cm 1) 3386 (N±H); EIMS m/z 217
(M+); 1H NMR (DMSO-d6) d 0.98 (m, 5H, 2ÂCH2 and
CH), 1.52 (m, 6H, 3ÂCH2), 2.09 (s, 3H, Ar±CH3), 2.54
(m, 1H, CH2±Ar), 2.84 (m, 1H, CH2±Ar), 3.14 (m, 1H,
CH±NH2), 6.44 (d, 2H, J=9 Hz, Ar±H), 7.04 (d, 2H,
J=9 Hz, Ar±H) (Found: C, 82.98, H, 10.51, N, 6.58.
C15H23N requires C, 82.90, H, 10.66, N, 6.45%).
12d. M.P. oil; EIMS m/z 289 (M+); 1H NMR d 1.90 (m,
12H, 6ÂCH2), 2.98 (dd, 1H, J=14, 6 Hz, Ar±CH2), 3.42