7486
J. S. Fortin et al. / Bioorg. Med. Chem. 16 (2008) 7477–7488
78%; mp: 157–163 °C; IR (KBr)
m
: 3133 (NH), 1704 (C@O) cmꢁ1; 1H
J = 8.4 Hz, Ar), 7.31 (m, 1H, Ar), 6.21 (t, 1H, J = 7.2 Hz, Ar), 6.21 (s,
1H, NH), 3.16 (m, 2H, CH2), 1.09 (t, 3H, CH3); 13C NMR (DMSO-
d6) d: 155.3, 138.3, 133.9, 128.7, 128.2, 127.4, 126.8, 126.2, 123.5,
119.6, 112.5, 34.0, 15.5.
NMR (CDCl3) d: 10.21 (s, 1H, NH), 9.30 (s, 1H, NH), 7.47 (d, 2H,
J = 8.9 Hz, Ar), 7.34 (t, 2H, J = 7.9 Hz, Ar), 7.11 (t, 1H, J = 7.4 Hz,
Ar), 7.00 (d, 4H, J = 6.9 Hz, Ar), 4.19 (s, 2H, CH2); 13C NMR (CDCl3)
d: 168.0, 157.4, 154.1, 150.1, 131.9, 129.8, 123.3, 122.2, 119.6,
118.7, 42.5. MS (ESI) m/z: 305.1 (M++1).
4.5.2. 1-(2-Chloroacethyl)-3-(4-biphenyl)urea (65)
Compound 65 was synthesized from the nucleophilic addition
of 4-phenylaniline to ethylisocyanate. Yield: 86%; mp: 205–
208 °C; IR (KBr)
(DMSO-d6) d: 8.53 (s, 1H, NH), 7.61 (d, 2H, J = 7.7 Hz, Ar), 7.50
(m, 4H, Ar), 7.42 (t, 2H, J = 7.4 Hz, Ar), 7.32 (t, 1H, J = 7.2 Hz, Ar),
6.14 (s, 1H, NH), 3.13 (m, 2H, CH2), 1.07 (t, 3H, CH3); 13C NMR
(DMSO-d6) d: 155.1, 140.2, 140.0, 133.7, 128.9, 126.9, 126.6,
126.0, 118.0, 34.0, 15.5.
4.4.11. 1-(2-Chloroacethyl)-3-(3-phenoxyphenyl)urea (53)
Compound 53 was prepared from the nucleophilic addition of
3-phenoxybenzenamine to 2-chloroacethylisocyanate. Yield: 77%;
m ;
: 3364 (NH), 1712 (C@O) cmꢁ1 1H NMR
mp: 140–144 °C; IR (KBr)
m ;
: 3269 (NH), 1708 (C@O) cmꢁ1 1H
NMR (CDCl3) d: 10.27 (s, 1H, NH), 9.39 (s, 1H, NH), 7.34 (t, 2H,
J = 7.7 Hz, Ar), 7.27 (d, 2H, J = 8.1 Hz, Ar), 7.16 (m, 2H, Ar), 7.10
(d, 2H, J = 8.1 Hz, Ar), 6.81 (d, 1H, J = 8.2 Hz, Ar), 6.00 (s, 2H,
CH2); 13C NMR (CDCl3) d: 168.1, 158.1, 156.7, 150.2, 138.0, 130.2,
129.8, 123.7, 119.3, 115.0, 110.9, 42.4. MS (ESI) m/z: 305.1 (M++1).
4.5.3. 1-(4-(Cyclopentyloxy)phenyl)-3-ethylurea (66)
Compound 66 was synthesized from the nucleophilic addition
of 4-(cyclopentyloxy)benzenamine to ethylisocyanate. Yield: 91%;
mp: 166–168 °C; IR (KBr)
NMR (CDCl3) d: 7.14 (d, 2H, J = 8.8 Hz, Ar), 6.77 (m, 3H, Ar, NH),
5.08 (s, 1H, NH), 4.68 (s, 1H, CH), 3.22 (m, 2H, CH2), 1.82 (m, 6H,
CH2), 1.63 (m, 2H, CH2), 1.09 (t, 3H, J = 7.2 Hz, CH3); 13C NMR
(CDCl3) d: 156.9, 155.3, 130.9, 124.4, 116.2, 79.6, 35.1, 32.8, 24.0,
15.5.
4.4.12. 1-(4-(Benzyloxy)phenyl)-3-(2-chloroacetyl)urea (54)
Compound 54 was synthesized from the nucleophilic addition
of 4-(benzyloxy)aniline to 2-chloroacethylisocyanate. Yield: 97%;
m ;
: 3334 (NH), 1638 (C@O) cmꢁ1 1H
mp: 198–202 °C; IR (KBr)
m ;
: 3226 (NH), 1709 (C@O) cmꢁ1 1H
NMR (DMSO-d6) d: 10.86 (s, 1H, NH), 10.02 (s, 1H, NH), 7.40 (m,
7H, Ar), 7.00 (d, 2H, J = 8.8 Hz, Ar), 5.09 (s, 2H, CH2), 4.39 (s, 2H,
CH2); 13C NMR (DMSO-d6) d: 168.6, 154.9, 150.3, 137.2, 130.6,
128.4, 127.8, 127.7, 121.6, 115.1, 69.4, 43.2. MS (ESI) m/z: 319.1
(M++1).
4.5.4. 1-(3-(Cyclopentyloxy)phenyl)-3-ethylurea (67)
Compound 67 was synthesized from the nucleophilic addition of
3-(cyclopentyloxy)benzenamine to ethylisocyanate. Yield: 77%;
mp: 134–139 °C; IR (KBr)
NMR (CDCl3) d: 7.12 (m, 2H, Ar, NH), 6.98 (s, 1H, Ar), 6.74 (d, 1H,
J = 7.9 Hz, Ar), 6.55 (d, 1H, J = 8.1 Hz, Ar), 5.39 (s, 1H, NH), 4.69 (s,
1H, CH), 3.24 (m, 2H, CH2), 1.77 (m, 6H, CH2), 1.72 (m, 2H, CH2),
1.10 (t, 3H, J = 7.3 Hz, CH3); 13C NMR (CDCl3) d: 158.9, 156.2, 140.1,
129.8, 112.4, 110.8, 108.0, 79.3, 35.1, 32.8, 24.0, 15.4.
4.4.13. 1-(3-(Benzyloxy)phenyl)-3-(2-chloroacetyl)urea (55)
Compound 55 was synthesized from the nucleophilic addition
of 3-(benzyloxy)aniline to 2-chloroacethylisocyanate. Yield: 22%;
m ;
: 3311 (NH), 1644 (C@O) cmꢁ1 1H
mp: 156–161 °C; IR (KBr)
m ;
: 3132 (NH), 1704 (C@O) cmꢁ1 1H
NMR (DMSO-d6) d: 10.91 (s, 1H, NH), 10.16 (s, 1H, NH), 7.34 (m,
7H, Ar), 7.10 (d, 1H, J = 8.0 Hz, Ar), 6.79 (d, 1H, J = 8.1 Hz, Ar),
5.11 (m, 2H, CH2), 4.41 (m, 2H, CH2); 13C NMR (DMSO-d6) d:
168.7, 158.8, 150.1, 138.6, 137.0, 129.9, 128.5, 127.9, 127.7,
112.2, 110.2, 106.4, 69.3, 43.3. MS (ESI) m/z: 319.1 (M++1).
4.5.5. 1-(4-(Cyclohexyloxy)phenyl)-3-ethylurea (68)
Compound 68 was synthesized from the nucleophilic addition
of 4-(cyclohexyloxy)benzenamine to ethylisocyanate. Yield: 44%;
mp: 139–145 °C; IR (KBr)
NMR (CDCl3) d: 7.14 (d, 2H, J = 8.8 Hz, Ar), 6.79 (m, 3H, Ar, NH),
5.08 (s, 1H, NH), 4.15 (m, 1H, CH), 3.22 (m, 2H, CH2), 1.94 (m,
2H, CH2), 1.79 (m, 2H, CH2), 1.40 (m, 6H, 3ꢂ CH2), 1.08 (t, 3H,
J = 7.2 Hz, CH3); 13C NMR (CDCl3) d: 156.9, 154.9, 131.1, 124.3,
116.9, 76.0, 35.1, 31.8, 25.6, 23.8, 15.4.
4.4.14. 1-Adamantan-2-yl-3-(2-chloroacetyl)-urea (60)
Compound 60 was synthesized from the nucleophilic addition
of 2-adamantanamine to 2-chloroacethylisocyanate. Yield: 75%;
m ;
: 3306 (NH), 1636 (C@O) cmꢁ1 1H
mp: 187–192 °C; IR (KBr)
m ;
: 3241 (NH), 1694 (C@O) cmꢁ1 1H
NMR (DMSO-d6) d: 10.66 (s, 1H, NH), 8.59 (s, 1H, NH), 4.30 (s,
2H, CH2), 3.86 (d, 1H, J = 7.2 Hz, CH), 1.80 (m, 12H, CH), 1.64 (m,
2H, CH); 13C NMR (DMSO-d6) d: 168.7, 151.7, 53.1, 43.1, 37.0,
36.5, 31.6, 31.4, 26.5. MS (ESI) m/z: 271.1 (M++1).
4.5.6. 1-(3-(Cyclohexyloxy)phenyl)-3-ethylurea (69)
4.5. General procedure for the preparation of the substituted N-
phenyl-N0-(2-ethyl)ureas 61–80
Compound 69 was synthesized from the nucleophilic addition
of 3-(cyclohexyloxy)benzenamine to ethylisocyanate. Yield: 38%;
mp: 128–131 °C; IR (KBr)
NMR (CDCl3) d: 7.10 (m, 2H, Ar, NH), 7.00 (s, 1H, Ar), 6.75 (d, 1H,
J = 7.7 Hz, Ar), 6.57 (d, 1H, J = 8.2 Hz, Ar), 5.40 (s, 1H, NH), 4.20 (s,
1H, CH), 3.20 (m, 2H, CH2), 1.91 (m, 2H, CH2), 1.74 (m, 2H), 1.49
(m, 3H), 1.49 (m, 3H), 1.11 (t, 3H, J = 7.2 Hz, CH3); 13C NMR (CDCl3)
d: 158.6, 156.2, 140.1, 129.8, 112.7, 111.3, 108.5, 75.4, 35.1, 31.8,
25.6, 23.7, 15.4.
m ;
: 3337 (NH), 1645 (C@O) cmꢁ1 1H
Compounds 61 (1-ethyl-3-(2,3-dihydro-1H-inden-6-yl)urea),10
63 (1-ethyl-3-(9H-fluoren-9-yl)urea),10 64 (1-(4-cyclohexylphe-
nyl)-3-ethylurea),25 76 (1-(4-tert-butylphenyl)-3-ethylurea),10 77
(1-ethyl-3-(4-iodophenyl)urea),10 78 (1-ethyl-3-p-tolylurea)10
,
and 79 (1-ethyl-3-(3,4-dimethylphenyl)urea)10 were prepared as
published previously. Ethylisocyanate (3.6 mmol) was added drop-
wise to a stirred solution of the relevant aniline (3 mmol) in dichlo-
romethane (15 mL). The reaction mixture was stirred overnight at
ambient temperature. The resulting crude precipitate was filtered,
washed with cold ether, and purified by recrystallization from eth-
anol and water.
4.5.7. 1-(4-(Cycloheptyloxy)phenyl)-3-ethylurea (70)
Compound 70 was synthesized from the nucleophilic addition
of 4-(cycloheptyloxy)benzenamine to ethylisocyanate. Yield: 80%;
mp: 143–146 °C; IR (KBr)
m ;
: 3338 (NH), 1640 (C@O) cmꢁ1 1H
NMR (CDCl3) d: 7.15 (d, 2H, J = 8.8 Hz, Ar), 6.81 (d, 2H, J = 8.8 Hz,
Ar), 6.45 (s, 1H, NH), 4.84 (s, 1H, NH), 4.34 (m, 1H, CH), 3.25 (m,
2H, 2 CH2), 1.95 (m, 2H, CH2), 1.69 (m, 4H, 2ꢂ CH2), 1.61 (m, 4H,
2ꢂ CH2), 1.50 (m, 2H, CH2), 1.11 (t, 3H, J = 7.3 Hz, CH3); 13C NMR
(CDCl3) d: 156.8, 155.3, 130.7, 125.0, 116.8, 78.4, 35.2, 33.7, 28.4,
23.0, 15.5.
4.5.1. 1-Ethyl-3-(naphthalen-7-yl)urea (62)
Compound 62 was synthesized from the nucleophilic addition
of naphthalen-2-amine to ethylisocyanate. Yield: 50%; mp: 183–
187 °C; IR (KBr)
(DMSO-d6) d: 8.65 (s, 1H, NH), 8.05 (s, 1H, Ar), 7.75 (t, 3H,
m ;
: 3326 (NH), 1714 (C@O) cmꢁ1 1H NMR