Med Chem Res
104.4, 104.2, 101.8, 46.1 (2C); IR (KBr) mmax/cm-1 3435
(N–H str), 3148 (C–H), 1648 (C=N), 1637 (C=O urea),
1300 (C–F), 1240 (C–O), 1173 (C–H), 825 (C–N); MS
(APCI); m/z 427.2 [M?H]?; HPLC; 98 %.
1-(3-Chloro-2-fluorophenyl)-3-(2-((6,8-difluoroquinolin-4-
yl)amino)ethyl)urea (9) Yield 79 %, m.p. 218–220 °C;
1H NMR (DMSO-d6, 300 MHz, dppm): 8.62 (d, 1H,
J = 4.5 Hz), 8.57 (s, 1H), 8.10 (m, 1H), 7.77 (d, 1H,
J = 4.5 Hz), 7.23 (brs, 1H), 7.11 (d, 1H, J = 5.7 Hz),
6.89–6.86 (m, 2H), 6.74 (dd, 1H, J = 12 Hz, J = 2.1 Hz),
3.42–3.34 (m, 4H); IR (KBr) mmax/cm-1 3430 (N–H str),
3135 (C–H), 1678 (C=N), 1647 (C=O urea), 1367 (C–F),
1163 (C–H), 825 (C–N), 615 (C–Cl): MS (APCI); MS
(APCI); m/z 395.2 [M?H]?; HPLC; 98 %.
1-(2-((6,8-Difluoroquinolin-4-yl)amino)ethyl)-3-(4-(trifluoro-
methoxy)phenyl)urea (5) Yield 78 %, m.p. 232–234 °C;
1H NMR (DMSO-d6, 300 MHz, dppm): 8.82 (s, 1H), 8.61
(d, 1H, J = 3.3 Hz), 7.77 (d, 1H, J = 3.3 Hz), 7.50 (d, 2H,
J = 7.8 Hz), 7.24–7.21 (m, 3H), 6.87 (d, 1H, J = 9.6 Hz),
6.74 (d, 1H, J = 11.4 Hz), 6.44 (brs, 1H), 3.4–3.34 (m,
4H); IR (KBr) mmax/cm-1 3450 (N–H str), 3149 (C–H),
1660 (C=N), 1637 (C=O urea), 1366 (C–F), 1230 (C–O),
1173 (C–H), 825 (C–N); MS (APCI); m/z 427.3 [M?H]?;
HPLC; 96 %.
1-(2-((6,8-Difluoroquinolin-4-yl)amino)ethyl)-3-(5-fluoro-
2-methylphenyl)urea (10) Yield 77 %, m.p. 225–227 °C;
1H NMR (DMSO-d6, 300 MHz, dppm): 8.62 (d, 1H,
J = 4.8 Hz), 8.57 (s, 1H), 7.83 (d, 1H, J = 3.3 Hz),
7.8–7.78 (m, 2H), 7.23 (brs, 1H), 7.12 (s, 1H), 6.95 (brs,
1H), 6.88 (dd, 1H, J = 10.2 Hz, J = 2.4 Hz), 6.75–6.66 (m,
2H), 3.42–3.34 (m, 4H), 2.12 (s, 3H); 13C NMR (DMSO-d6,
300 MHz, d ppm): 161.3, 161.1, 148.8, 148.6, 146.7, 142.5,
137.6, 129.9, 128.4, 123.9, 122.3, 119.5, 112.8, 104.2, 102.7,
102.0, 46.1 (2C), 18.6; IR (KBr) mmax/cm-1 3400 (N–H str),
3153 (C–H), 1645 (C=N), 1561 (C=O urea), 1300 (C–F),
1173 (C–H), 751 (C–N); MS (APCI); m/z 375 [M?H]?;
HPLC; 98 %.
1-(2-((6,8-Difluoroquinolin-4-yl)amino)ethyl)-3-(2-(trifluo-
romethyl)phenyl)urea (6) Yield 79 %, m.p. 199–201 °C;
1H NMR (DMSO-d6, 300 MHz, dppm): 8.63 (d, 1H,
J = 4.8 Hz), 7.95 (d, 1H, J = 8.1 Hz), 7.85 (s, 1H), 7.78
(d, 1H, J = 4.8 Hz), 7.63–7.59 (m, 2H), 7.23–7.18 (m,
3H), 6.88 (dd, 1H, J = 10.2 Hz, J = 4.4 Hz), 6.74 (dd,
1H, J = 12 Hz, J = 2.4 Hz), 3.42–3.34 (m, 4H); 13C NMR
(DMSO-d6, 300 MHz, d ppm): 161.5, 161.1, 148.8, 148.7,
146.7, 141.5, 137.1, 128.6, 128.1, 123.9 (2C), 122.3, 119.5,
112.8, 104.2, 102.7, 101.8, 46.3 (2C); IR (KBr) mmax/cm-1
3450 (N–H str), 3150 (C–H), 1675 (C=N), 1603 (C=O
urea), 1448 (C–F), 1198 (C–H), 757 (C–N); MS (APCI); m/z
411.1 [M?H]?; HPLC; 97 %.
1-(2-Chloro-5-(trifluoromethyl)phenyl)-3-(2-((6,8-difluoro-
quinolin-4-yl)amino)ethyl)urea (11) Yield 74 %, m.p.
1
182–184 °C; H NMR (DMSO-d6, 300 MHz, dppm): 8.60
(d, 2H, J = 4.8 Hz), 8.40 (s, 1H), 7.77 (d, 1H, J = 4.5 Hz),
7.65 (d, 1H, J = 8.1 Hz), 7.40 (brs, 1H), 7.30 (d, 1H,
J = 8.1 Hz), 7.23 (brs, 1H), 6.88 (d, 1H, J = 8.1 Hz), 6.73
(d, 1H, J = 12 Hz), 3.44–3.34 (m, 4H); IR (KBr) mmax/cm-1
3460 (N–H str), 3246 (C–H), 1645 (C=N), 1637 (C=O urea),
1366 (C–F), 1173 (C–H), 845 (C–N), 645 (C–Cl): MS
(APCI); m/z 445.8 [M?H]?; HPLC; 97 %.
1-(2-((6,8-Difluoroquinolin-4-yl)amino)ethyl)-3-(4-(trifluo-
romethyl)phenyl)urea (7) Yield 80 %, m.p. 219–221 °C;
1H NMR (DMSO-d6, 300 MHz, dppm): 9.22 (s, 1H), 9.04
(s, 1H), 8.61 (d, J = 4.9 Hz, 1H), 7.76 (d, J = 4.5 Hz,
1H), 7.62–7.70 (m, 2H), 7.47–7.61 (m, 3H), 6.85 (s, 2H),
3.41–3.33 (brs, 4H); IR (KBr) mmax/cm-1 3400 (N–H str),
3149 (C–H), 1655 (C=N), 1533 (C=O urea), 1193 (C–F),
1064 (C–H), 899 (C–N); MS (APCI); m/z 411.3 [M?H]?;
HPLC; 96 %.
1-(2-((6,8-Difluoroquinolin-4-yl)amino)ethyl)-3-(4-isopro-
1
pylphenyl)urea (12) Yield 77 %, m.p. 223–225 °C; H
NMR (DMSO-d6, 300 MHz, dppm): 8.80 (s, 1H), 8.32 (d,
2H, J = 8.1 Hz), 8.03 (s, 1H), 7.76 (d, 1H, J = 7.2 Hz),
7.55 (d, 2H, J = 7.5 Hz), 3.41–3.33 (m, 4H), 2.85–2.75
(m, 1H), 1.33 (brs, 6H); IR (KBr) mmax/cm-1 3435 (N–H
str), 3148 (C–H), 1678 (C=N), 1637 (C=O urea), 1300 (C–
F), 1173 (C–H), 855 (C–N); MS (APCI); m/z 385.2
[M?H]?; HPLC; 96 %.
1-(2-((6,8-Difluoroquinolin-4-yl)amino)ethyl)-3-(2-fluoro-
1
phenyl)urea (8) Yield 78 %, m.p. 228–230 °C; H NMR
(DMSO-d6, 300 MHz, dppm): 8.61 (d, J = 4.9 Hz, 1H),
8.37 (d, J = 1.9 Hz, 1H), 8.12 (td, J = 8.3, 1.5 Hz, 1H),
7.76 (d, J = 4.9 Hz, 1H), 7.02–7.26 (m, 3H), 6.79–6.98
(m, 3H), 6.46–6.79 (m, 1H), 3.41 (brs, 4H); 13C NMR
(DMSO-d6, 300 MHz, d ppm): 161.5, 161.1, 148.8, 148.7,
146.7, 142.5, 138.1, 128.4, 128.1, 123.6, 123.2, 119.1,
113.3, 104.4, 102.8, 101.8, 46.3 (2C); IR (KBr) mmax/cm-1
3395 (N–H str), 3154 (C–H), 1675 (C=N), 1650 (C=O
urea), 1355 (C–F), 1023 (C–H), 762 (C–N); MS (APCI); m/z
360.1 [M?H]?; HPLC; 99 %.
1-(2-((6,8-Difluoroquinolin-4-yl)amino)ethyl)-3-(3,4-
dimethylphenyl)urea (13) Yield 78 %, m.p. 210–212 °C;
1H NMR (DMSO-d6, 300 MHz, dppm): 8.60 (s, 1H), 8.37
(s, 1H), 7.76 (s, 1H), 7.23 (s, 1H), 7.15 (s, 1H), 7.10 (s,
1H), 6.97 (s, 1H), 6.87 (d, 1H, J = 8.7 Hz), 6.30 (s, 1H),
3.44–3.34 (m, 4H), 2.15 (s, 3H), 2.13 (s, 3H); IR (KBr)
m
max/cm-1 3400 (N–H str), 3139 (C–H), 1640 (C=N), 1560
123