Y. Oguro et al. / Bioorg. Med. Chem. 18 (2010) 7150–7163
7159
6.19. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-pyridin-3-ylurea (11b)
(3H, m), 7.79 (1H, d, J = 3.0 Hz), 7.94 (1H, J = 2.1 Hz), 8.16 (1H, d,
J = 9.1 Hz), 8.29 (1H, s), 8.42 (1H, s), 9.67 (1H, s). Anal. Calcd for
C
25H22ClF3N6O2: C, 54.90; H, 4.05; N, 15.37. Found: C, 54.67; H,
Yield 23%, white solid: mp 233–237 °C (AcOEt); 1H NMR
(DMSO-d6) d 4.11 (3H, s), 6.61 (1H, d, J = 3.0 Hz), 7.32 (1H, dd,
J = 9.0, 2.7 Hz), 7.32–7.37 (1H, m), 7.57 (1H, d, J = 2.7 Hz), 7.80
(1H, d, J = 3.0 Hz), 7.98 (1H, ddd, J = 8.2, 2.5, 1.5 Hz), 8.17 (1H, d,
J = 9.0 Hz), 8.22 (1H, dd, J = 4.5, 1.5 Hz), 8.31 (1H, s), 8.49 (1H, br
s), 8.63 (1H, d, J = 2.5 Hz), 9.56 (1H, br s). Anal. Calcd for
4.14; N, 15.17.
6.25. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-[4-(morpholin-4-ylmethyl)-3-
(trifluoromethyl)phenyl]urea (11k)
C
19H15ClN6O2: C, 57.80; H, 3.83; N, 21.29. Found: C, 57.81; H,
Yield 29%, white solid: mp 149–151 °C (AcOEt–hexane); 1H
NMR (DMSO-d6) d 2.30–2.40 (4H, m), 3.55–3.60 (6H, m), 4.10
(3H, s), 6.60 (1H, d, J = 2.9 Hz), 7.31 (1H, dd, J = 8.9, 2.6 Hz), 7.56–
7.59 (2H, m), 7.68 (1H, d, J = 8.7 Hz), 7.79 (1H, d, J = 2.9 Hz), 8.00
(1H, d, J = 2.1 Hz), 8.18 (1H, d, J = 8.9 Hz), 8.30 (1H, s), 8.42 (1H,
s), 9.70 (1H, s). Anal. Calcd for C26H24ClF3N6O2ꢀH2O: C, 53.94; H,
4.53; N, 14.52. Found: C, 53.86; H, 4.50; N, 14.27.
3.88; N, 21.11.
6.20. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-pyridin-4-ylurea (11c)
Yield 22%, white solid: mp 233–237 °C (AcOEt); 1H NMR
(DMSO-d6) d 4.11 (3H, s), 6.61 (1H, d, J = 3.2 Hz), 7.33 (1H, dd,
J = 9.0, 2.6 Hz), 7.46 (2H, d, J = 6.3 Hz), 7.58 (1H, d, J = 2.6 Hz),
7.80 (1H, d, J = 3.2 Hz), 8.15 (1H, d, J = 9.0 Hz), 8.31 (1H, s), 8.39
(2H, d, J = 6.3 Hz), 8.56 (1H, br s), 9.78 (1H, br s). Anal. Calcd for
6.26. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-{4-[(4-methylpiperazin-1-yl)methyl]-3-
(trifluoromethyl)phenyl}urea (11l)
C
19H15ClN6O2ꢀH2O: C, 55.28; H, 4.15; N, 20.36. Found: C, 55.39;
H, 4.17; N, 20.08.
Yield 23%, white solid: mp 138–139 °C (AcOEt–hexane); 1H
NMR (DMSO-d6) d 2.16 (3H, s), 2.20–2.45 (8H, m), 3.54 (2H, s),
4.10 (3H, s), 6.61 (1H, d, J = 2.9 Hz), 7.31 (1H, dd, J = 8.8, 2.6 Hz),
7.56–7.67 (3H, m), 7.80 (1H, d, J = 2.9 Hz), 8.00 (1H, s), 8.18 (1H,
d, J = 8.8 Hz), 8.30 (1H, s), 8.43 (1H, s), 9.70 (1H, s). Anal. Calcd
for C27H27ClF3N7O2ꢀ1.2H2O: C, 54.45; H, 4.98; N, 16.46. Found: C,
54.73; H, 4.98; N, 16.16.
6.21. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-[4-(trifluoromethyl)pyridin-2-yl]urea (11d)
Yield 21%, white solid: mp 259–260 °C (AcOEt); 1H NMR
(DMSO-d6) d 4.09 (3H, s), 6.58–6.59 (1H, m), 7.31–7.38 (2H, m),
7.59 (1H, d, J = 2.1 Hz), 7.77–7.80 (2H, m), 8.28–8.31 (2H, m),
8.57 (1H, d, J = 5.7 Hz), 10.36 (1H, s), 10.61 (1H, br s). Anal. Calcd
for C20H14ClF3N6O2ꢀ0.2H2O: C, 51.50; H, 3.11; N, 18.02. Found: C,
51.48; H, 2.98; N, 18.16.
6.27. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-{4-[(1-methylpiperidin-4-yl)oxy]-3-(trifluo
romethyl)phenyl}urea (11m)
Yield 11%, white solid: mp 137–139 °C (AcOEt–hexane); 1H
NMR (DMSO-d6) d 1.65–1.75 (2H, m), 1.85–1.95 (2H, m), 2.19–
2.35 (5H, m), 2.50–2.60 (2H, m), 4.10 (3H, s), 4.45–4.51 (1H, m),
6.60 (1H, d, J = 3.0 Hz), 7.26–7.31 (2H, m), 7.52–7.55 (2H, m),
7.79 (1H, d, J = 3.0 Hz), 7.85 (1H, d, J = 2.4 Hz), 8.17 (1H, d,
J = 9.6 Hz), 8.30 (1H, s), 8.33 (1H, s), 9.47 (1H, s). Anal. Calcd for
6.22. 1-(3-tert-Butyl-1-methyl-1H-pyrazol-5-yl)-3-{2-chloro-4-
[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)oxy]phenyl}urea
(11h)
Yield 6%, white solid: mp 194–196 °C (AcOEt); 1H NMR (DMSO-
d6) d 1.22 (9H, s), 3.65 (3H, s), 4.10 (3H, s), 6.11 (1H, s), 6.60 (1H, d,
J = 3.0 Hz), 7.30 (1H, dd, J = 9.3, 2.7 Hz), 7.56 (1H, d, J = 2.7 Hz), 7.79
(1H, d, J = 3.0 Hz), 8.16 (1H, d, J = 9.3 Hz), 8.30 (1H, s), 8.61 (1H, s),
9.22 (1H, s). Anal. Calcd for C22H24ClN7O2: C, 58.21; H, 5.33; N,
21.60. Found: C, 57.89; H, 5.31; N, 21.35.
C
27H26ClF3N6O3ꢀ2H2O: C, 53.07; H, 4.95; N, 13.75. Found: C,
53.43; H, 4.80; N, 13.48.
6.28. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-[3-methoxy-5-(trifluoromethyl)phenyl]urea
(11n)
6.23. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-[4-methoxy-3-(trifluoromethyl)phenyl]urea
(11i)
Yield 21%, white solid: mp 205–208 °C (AcOEt–hexane); 1H
NMR (DMSO-d6)
d 3.83 (3H, s), 4.11 (3H, s), 6.61 (1H, d,
J = 3.0 Hz), 6.88 (1H, br s), 7.26 (1H, br s), 7.32 (1H, dd, J = 9.0,
2.7 Hz), 7.51 (1H, br s), 7.57 (1H, d, J = 2.7 Hz), 7.80 (1H, d,
J = 3.0 Hz), 8.15 (1H, d, J = 9.0 Hz), 8.30 (1H, s), 8.47 (1H, br s),
9.76 (1H, br s). Anal. Calcd for C22H17ClF3N5O2ꢀH2O: C, 51.82; H,
3.76; N, 13.74. Found: C, 51.98; H, 3.75; N, 13.80.
Yield 33%, white solid: mp 233–237 °C (AcOEt–hexane); 1H
NMR (DMSO-d6)
d 3.86 (3H, s), 4.10 (3H, s), 6.61 (1H, d,
J = 3.0 Hz), 7.24 (1H, d, J = 9.2 Hz), 7.30 (1H, dd, J = 9.0, 2.7 Hz),
7.56 (1H, d, J = 2.7 Hz), 7.59 (1H, dd, J = 9.2, 2.7 Hz), 7.80 (1H, d,
J = 3.0 Hz), 7.88 (1H, d, J = 2.7 Hz), 8.17 (1H, d, J = 9.0 Hz), 8.30
(1H, s), 8.37 (1H, br s), 9.51 (1H, br s). Anal. Calcd for
22H17ClF3N5O3: C, 53.72; H, 3.48; N, 14.24. Found: C, 53.63; H,
3.47; N, 14.22.
6.29. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-[3-(morpholin-4-ylmethyl)-5-(trifluo
romethyl)phenyl]urea (11o)
C
Yield 23%, white solid: mp 134–136 °C (AcOEt–hexane); 1H
NMR (DMSO-d6) d 2.30–2.45 (4H, m), 3.30–3.61 (6H, m), 4.10
(3H, s), 6.60 (1H, d, J = 3.3 Hz), 7.26 (1H, s), 7.28 (1H, dd, J = 8.8,
2.6 Hz), 7.54 (1H, s), 7.56 (1H, d, J = 2.6 Hz), 7.78 (1H, d,
J = 3.3 Hz), 7.94 (1H, s), 8.16 (1H, d, J = 8.8 Hz), 8.30 (1H, s), 8.40
(1H, s), 9.74 (1H, s). Anal. Calcd for C26H24ClF3N6O3ꢀH2O: C,
53.94; H, 4.53; N, 14.52. Found: C, 53.77; H, 4.39; N, 14.32.
6.24. 1-{2-Chloro-4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-
yl)oxy]phenyl}-3-[4-morpholin-4-yl-3-(trifluoromethyl)
phenyl]urea (11j)
Yield 34%, white solid: mp 147–150 °C (AcOEt–hexane); 1H
NMR (DMSO-d6) d 2.80–2.83 (4H, s), 3.68–3.71 (4H, s), 4.10 (3H,
s), 6.60 (1H, d, J = 3.0 Hz), 7.30 (1H, dd, J = 9.1, 2.7 Hz), 7.54–7.63