T. Nguyen et al.
Bioorganic & Medicinal Chemistry 41 (2021) 116215
1H NMR (300 MHz, CDCl3) δ 7.19 (m, 4H), 7.05 (d, J = 8.5 Hz, 2H), 6.87
(d, J = 8.7 Hz, 2H), 6.34 (s, 1H), 4.72 (t, J = 5.6 Hz, 1H), 3.45 (q, J = 6.4
Hz, 2H), 3.11 (m, 4H), 2.73 (t, J = 6.7 Hz, 2H), 1.71 (quin, J = 5.6 Hz,
4H), 1.57 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 155.3 (1C), 151.0 (1C),
137.2 (1C), 129.4 (2C), 129.2 (1C), 129.1 (2C), 128.6 (1C), 121.8 (2C),
116.8 (2C), 50.8 (1C), 41.6 (1C), 35.1 (1C), 25.8 (1C), 24.2 (1C). HRMS
(ESI) m/z [M + H]+ calcd: 358.1681; found: 358.1674.
was prepared from 2-methyl-1-phenylpropan-2-amine (35) (0.06 g,
0.38 mmol) following the general procedure A as white solid (0.07 g,
57%). 1H NMR (300 MHz, CDCl3) δ 7.20–7.27 (m, 5H), 7.12–7.19 (m,
4H), 6.21 (s, 1H), 4.41 (s, 1H), 3.03 (s, 2H), 1.33 (s, 6H). 13C NMR (75
MHz, CDCl3) δ 154.4 (1C), 138.1 (1C), 137.4 (1C), 130.6 (2C), 129.2
(2C), 128.7 (1C), 128.1 (2C), 126.4 (1C), 122.0 (2C), 53.7 (1C), 45.5
(1C), 27.9 (2C). HRMS (ESI) m/z [M + H]+ calcd: 303.1259; found:
303.1255.
1-(4-Chlorophenyl)-3-{2-[4-(pyrrolidin-1-yl)phenyl]ethyl}-
urea (10) was prepared from 2-[4-(pyrrolidin-1-yl)phenyl]ethanamine
hydrochloride (0.07 g, 0.44 mmol) which was prepared as described
previously29 following the general procedure A as white solid (0.12 g,
79%). 1H NMR (300 MHz, CDCl3) δ 7.13–7.24 (m, 4H), 7.04 (d, J = 8.5
Hz, 2H), 6.51 (d, J = 8.5 Hz, 2H), 6.11 (s, 1H), 4.61 (br. s., 1H), 3.46 (q,
J = 6.5 Hz, 2H), 3.23–3.29 (m, 4H), 2.73 (t, J = 6.6 Hz, 2H), 2.00 (td, J
= 3.30, 6.59 Hz, 4H). 13C NMR (75 MHz, CDCl3) δ 155.2 (1C), 146.9
(1C), 137.2 (1C), 129.5 (2C), 129.1 (2C), 128.6 (1C), 125.1 (1C), 121.9
(2C), 111.9 (2C), 47.7 (1C), 41.9 (1C), 35.0 (1C), 25.4 (1C). HRMS (ESI)
m/z [M + H]+ calcd: 344.1524; found: 344.1523.
1-(4-Chlorophenyl)-3-(2,2-difluoro-2-phenylethyl)urea (17) was
prepared from 2,2-difluoro-2-phenylethanamine (36) (0.06 g, 0.29
mmol) following the general procedure A as white solid (0.05 g, 52%).
1H NMR (300 MHz, DMSO‑d6) δ 8.72 (s, 1H), 7.49–7.62 (m, 5H),
7.36–7.43 (m, 2H), 7.24–7.30 (m, 2H), 6.57 (t, J = 6.2 Hz, 1H), 3.88 (dt,
J = 6.2, 14.98 Hz, 2H). 13C NMR (75 MHz, CD3OD) δ 157.5 (1C), 139.6
(1C), 136.6 (t, J = 25 Hz, 1C), 131.4 (1C), 129.7 (d, J = 5 Hz, 2C), 128.4
(1C) 126.4 (t, J = 6 Hz, 2C), 125.3 (1C), 122.1 (1C), 121.5 (2C), 118.9
(1C), 46.8 (t, J = 30.7 Hz, 1C). HRMS (ESI) m/z [M + H]+ calcd:
311.0757; found: 311.0768.
1-(4-Chlorophenyl)-3-{2-[4-(diethylamino)phenyl]ethyl}-urea
(11) was prepared from 4-(2-aminoethyl)-N,N-diethylaniline hydro-
chloride (0.04 g, 0.28 mmol) which was prepared as described previ-
ously29 following the general procedure A as white solid (0.80 g, 82%).
1H NMR (300 MHz, CDCl3) δ 7.09–7.19 (m, 4H), 7.01 (br. s., 1H), 6.98
(d, J = 8.5 Hz, 2H), 6.58 (d, J = 8.5 Hz, 2H), 5.28 (d, J = 5.3 Hz, 1H),
3.38 (q, J = 6.7 Hz, 2H), 3.29 (q, J = 7.0 Hz, 4H), 2.65 (t, J = 6.9 Hz,
2H), 1.12 (t, J = 7.0 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ 156.0 (1C),
146.6 (1C), 137.5 (1C), 129.6 (2C), 129.0 (2C), 128.2 (1C), 125.3 (1C),
121.6 (2C), 112.2 (2C), 44.3 (1C), 41.8 (1C), 35.1 (1C), 12.6 (1C). HRMS
(ESI) m/z [M + H]+ calcd: 346.1681; found: 346.1675.
1-(4-Chlorophenyl)-3-[(1-phenylcyclopropyl)methyl]urea (18)
was prepared from 1-phenylcyclopropanemethylamine (0.03 g, 0.20
mmol) following the general procedure A as white solid (0.04 g, 68%).
1H NMR (300 MHz, CDCl3) δ 7.28–7.39 (m, 4H), 7.10–7.24 (m, 5H),
6.22 (br. s., 1H), 4.70 (br. s., 1H), 3.43 (d, J = 5.5 Hz, 2H), 0.89 (s, 4H).
13C NMR (75 MHz, CDCl3) δ 155.2 (1C), 142.8 (1C), 137.1 (1C), 129.1
(2C), 128.6 (2C), 128.5 (2C), 126.7 (1C), 121.8 (2C), 49.2 (1C), 29.7
(1C), 25.8 (1C), 12.3 (1C). HRMS (ESI) m/z [M + H]+ calcd: 301.1102;
found: 301.1096.
1-(1-Benzylcyclopropyl)-3-(4-chlorophenyl)urea (19) was pre-
pared from (1-benzylcyclopropyl)amine (0.04 g, 0.20 mmol) following
the general procedure A as white solid (0.03 g, 48%). 1H NMR (300
MHz, CDCl3) δ 7.29–7.34 (m, 2H), 7.27–7.28 (m, 1H), 7.20–7.24 (m,
2H), 7.17–7.20 (m, 2H), 7.10–7.15 (m, 2H), 6.34 (s, 1H), 4.86 (s, 1H),
2.86 (s, 2H), 0.91–0.98 (m, 4H). 13C NMR (75 MHz, CDCl3) δ 153.5 (1C),
136.9 (1C), 135.5 (1C), 127.9 (2C), 127.3 (2C), 127.2 (2C), 126.8 (1C),
125.5 (1C), 119.6 (2C), 41.5 (1C), 33.3 (1C), 29.3 (1C), 13.0 (1C). HRMS
(ESI) m/z [M + H]+ calcd: 301.1102; found: 301.1100.
3-(4-Chlorophenyl)-1-{2-[4-(dimethylamino)phenyl]ethyl}-
urea (12) was prepared from 4-dimethylaminophenethylamine (0.03 g,
0.18 mmol) following the general procedure A as white solid (0.01 g,
17%). 1H NMR (300 MHz, DMSO‑d6) δ 8.63–8.71 (m, 1H), 7.41 (d, J =
9.0 Hz, 2H), 7.24 (d, J = 8.9 Hz, 2H), 7.04 (d, J = 8.7 Hz, 2H), 6.68 (d, J
= 8.7 Hz, 2H), 6.08–6.16 (m, 1H), 3.26 (d, J = 6.2 Hz, 2H), 2.85 (s, 6H),
2.61 (t, J = 7.2 Hz, 2H). 13C NMR (75 MHz, DMSO‑d6) δ 154.9 (1C),
149.1 (1C), 139.5 (1C), 129.0 (2C), 128.4 (2C), 126.9 (1C), 124.3 (1C),
119.0 (2C), 112.7 (2C), 40.9 (1C), 40.3 (1C), 34.8 (1C). HRMS (ESI) m/z
[M + H]+ calcd: 318.1367; found: 318.1370.
trans-1-(4-Chlorophenyl)-3-[(2-phenylcyclopropyl)methyl-]
urea (20) was prepared from trans-1-(2-phenylcyclo-propyl)meth-
anamine (38) (0.08 g, 0.45 mmol) following the general procedure A as
white solid (0.07 g, 51%). 1H NMR (300 MHz, DMSO‑d6) δ 8.62 (s, 1H),
7.38–7.46 (m, 2H), 7.20–7.29 (m, 4H), 7.11–7.15 (m, 1H), 7.04–7.10
(m, 2H), 6.32 (t, J = 5.6 Hz, 1H), 3.16–3.28 (m, 1H), 2.99–3.11 (m, 1H),
1.79–1.88 (m, 1H), 1.21–1.35 (m, 1H), 0.83–0.96 (m, 2H). 13C NMR (75
MHz, DMSO‑d6) δ 155.0 (1C), 142.8 (1C), 139.5 (1C), 128.4 (2C), 128.1
(2C), 125.5 (2C), 125.2 (1C), 124.4 (1C), 119.1 (2C), 42.9 (1C), 23.4
(1C), 21.3 (1C), 14.3 (1C). HRMS (ESI) m/z [M + H]+ calcd: 301.1102;
found: 301.1099.
3-(4-Chlorophenyl)-1-(3-phenylmethyl)urea (13) was prepared
from benzylamine (0.05 ml, 0.32 mmol) following the general proced-
ure A as white solid (0.06 g, 71%). 1H NMR (300 MHz, DMSO‑d6) δ 8.71
(s, 1H), 7.44 (d, J = 8.9 Hz, 2H), 7.20–7.37 (m, 7H), 6.66 (t, J = 5.8 Hz,
1H), 4.30 (d, J = 6.0 Hz, 2H). 13C NMR (75 MHz, DMSO‑d6) δ 155.0
(1C), 140.2 (1C), 139.4 (1C), 128.4 (2C), 128.3 (2C), 127.1 (2C), 126.7
(1C), 124.5 (1C), 119.2 (2C), 42.7 (1C). HRMS (ESI) m/z [M + H]+
calcd: 261.0789; found: 261.0797.
3-(4-Chlorophenyl)-1-(3-phenylpropyl)urea (14) was prepared
from 3-phenylpropylamine (0.05 ml, 0.32 mmol) following the general
procedure A as white solid (0.08 g, 82%). 1H NMR (300 MHz, CDCl3) δ
7.17–7.31 (m, 7H), 7.09 (d, J = 6.8 Hz, 2H), 5.42 (t, J = 5.4 Hz, 1H),
3-(4-Chlorophenyl)-1-[2-(pyridin-2-yl)ethyl]urea (21) was pre-
pared from 2-(2-aminoethyl)pyridine (0.04 g, 0.32 mmol) following the
general procedure A as white solid (0.08 g, 84%). 1H NMR (300 MHz,
CDCl3) δ 8.38 (d, J = 4.1 Hz, 1H), 7.87 (br. s., 1H), 7.55–7.62 (m, 1H),
7.10–7.24 (m, 6H), 6.15–6.24 (m, 1H), 3.62 (q, J = 5.8 Hz, 2H),
2.94–3.01 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 159.6 (1C), 156.0 (1C),
148.8 (1C), 137.8 (1C), 136.9 (1C), 129.0 (2C), 128.0 (1C), 123.6 (1C),
121.7 (1C), 121.3 (2C), 39.6 (1C), 37.6 (1C). HRMS (ESI) m/z [M + H]+
calcd: 276.0898; found: 276.0895.
3.18 (q, J = 6.8 Hz, 2H), 2.57 (t, J = 7.6 Hz, 2H), 1.70–1.78 (m, 2H). 13
C
NMR (75 MHz, CDCl3) δ 156.1 (1C), 141.3 (1C), 137.4 (1C), 129.1 (2C),
128.5 (2C), 128.4 (1C), 128.3 (2C), 126.0 (1C), 121.5 (2C), 39.9 (1C),
33.1 (1C), 31.6 (1C). HRMS (ESI) m/z [M + H]+ calcd: 289.1102; found:
289.1100.
1-(4-Chlorophenyl)-3-(2-methyl-2-phenylpropyl)urea (15) was
prepared from 3-phenylpropylamine (32) (0.10 g, 0.56 mmol) following
the general procedure A as white solid (0.14 g, 81%). 1H NMR (300
MHz, CDCl3) δ 7.34 (d, J = 4.1 Hz, 4H), 7.20–7.25 (m, 1H), 7.16–7.20
(m, 2H), 7.05–7.11 (m, 2H), 6.14 (br. s., 1H), 4.37 (br. s., 1H), 3.45 (d, J
= 6.0 Hz, 2H), 1.35 (s, 6H). 13C NMR (75 MHz, CDCl3) δ 155.4 (1C),
146.6 (1C), 137.2 (1C), 129.0 (2C), 128.6 (2C), 128.5 (1C), 126.3 (1C),
126.0 (2C), 121.6 (2C), 51.7 (1C), 38.9 (1C), 30.9 (1C), 26.6 (1C). HRMS
(ESI) m/z [M + H]+ calcd: 303.1259; found: 303.1259.
3-(4-Chlorophenyl)-1-[2-(pyridin-3-yl)ethyl]urea (22) was pre-
pared from 3-(2-aminoethyl)pyridine (0.04 g, 0.32 mmol) following the
general procedure A as white solid (0.08 g, 91%). 1H NMR (300 MHz,
CDCl3) δ 8.30–8.38 (m, 2H), 7.53–7.63 (m, 2H), 7.18–7.26 (m, 5H), 5.49
(t, J = 5.5 Hz, 1H), 3.52 (q, J = 5.7 Hz, 2H), 2.78–2.87 (m, 2H). 13C NMR
(75 MHz, CDCl3) δ 155.6 (1C), 149.8 (1C), 147.6 (1C), 137.5 (1C), 136.8
(1C), 135.0 (1C), 129.1 (2C), 128.2 (1C), 123.9 (1C), 121.0 (2C), 40.7
(1C), 33.3 (1C). HRMS (ESI) m/z [M + H]+ calcd: 276.0898; found:
276.0894.
1-(4-Chlorophenyl)-3-(2-methyl-1-phenylpropan-2-yl)urea (16)
3-(4-Chlorophenyl)-1-[2-(pyridin-4-yl)ethyl]urea (23) was
9