S. Nagashima et al. / Bioorg. Med. Chem. 16 (2008) 6509–6521
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5.1.36. 4-[(2-Fluorobenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25j)
(4H, m), 4.74 (2H, d, J = 5.8 Hz), 6.76 (2H, d, J = 8.8 Hz), 7.15 (1H,
br), 7.43 (2H, br d, J = 8.8 Hz), 7.54–7.62 (3H, m), 7.69 (1H, s),
7.73 (1H, br), 8.52 (1H, s), 9.28 (1H, br), 9.58 (1H, s); FAB MS m/e
[M+H]+ 473. Anal. Calcd for C23H23N6O2F3: C, 58.47; H, 4.91; N,
17.79; F, 12.06. Found: C, 58.70; H, 5.04; N, 17.69; F, 12.00.
Compound 25j was prepared from compound 32 and 2-fluorob-
enzylamine in 35% yield as a colorless needle, using a similar ap-
proach to that described for 25f: mp >260 °C (dec) (MeOH–THF);
1H NMR (DMSO-d6) d 3.01–3.03 (4H, m), 3.72–3.74 (4H, m), 4.71
(2H, d, J = 5.9 Hz), 6.80 (2H, d, J = 8.8 Hz), 7.13–7.34 (5H, m), 7.45
(2H, d, J = 8.8 Hz), 7.79 (1H, br), 8.52 (1H, s), 9.34 (1H, s), 9.54 (1H,
s); FAB MS m/e [M+H]+ 423. Anal. Calcd for C22H23N6O2F: C, 62.55;
H, 5.49; N, 19.89; F, 4.50. Found: C, 62.20; H, 5.45; N, 19.82; F, 4.51.
5.1.42. 4-[(3-Methoxybenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25p)
Compound 25p was prepared from compound 32 and 3-
methoxybenzylamine in 29% yield as a colorless solid, using a sim-
ilar approach to that described for 25f: mp 220–222 °C (MeOH–
THF); 1H NMR (DMSO-d6) d 3.00–3.02 (4H, m), 3.70 (3H, s), 3.71–
3.74 (4H, m), 4.63 (2H, d, J = 5.4 Hz), 6.71–6.80 (3H, m), 6.82–
6.89 (2H, m), 7.11 (1H, br), 7.23–7.27 (1H, m), 7.51 (2H, d,
J = 8.8 Hz), 7.75 (1H, br), 8.51 (1H, s), 9.28 (1H, br), 9.49 (1H, s);
FAB MS m/e [M+H]+ 435. Anal. Calcd for C23H26N6O3ꢁ0.2H2O: C,
63.06; H, 6.07; N, 19.18. Found: C, 62.93; H, 5.92; N, 19.16.
5.1.37. 2-[(4-Morpholin-4-ylphenyl)amino]-4-[(2-trifluoro-
methylbenzyl)amino]pyrimidine-5-carboxamide (25k)
Compound 25k was prepared from compound 32 and 2-trifluo-
romethylbenzylamine in 15% yield as a yellow solid, using a similar
approach to that described for 25f: mp 263–267 °C (MeOH–THF);
1H NMR (DMSO-d6) d 2.96–2.98 (4H, m), 3.71–3.73 (4H, m), 4.87
(2H, d, J = 5.4 Hz), 6.70 (2H, br d, J = 7.3 Hz), 7.15 (1H, br), 7.37
(2H, br d, J = 7.3 Hz), 7.48–7.50 (2H, m), 7.63 (1H, t, J = 7.4 Hz),
7.77–7.91 (2H, m), 8.55 (1H, s), 9.28 (1H, br), 9.56 (1H, s); FAB
MS m/e [M+H]+ 473. Anal. Calcd for C23H23N6O2F3: C, 58.47; H,
4.91; N, 17.79; F, 12.06. Found: C, 58.25; H, 4.98; N, 17.77; F, 12.06.
5.1.43. 4-[(3-Hydroxybenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25q)
Compound 25q was prepared from compound 32 and 3-
hydroxybenzylamine in 31% yield as a colorless solid, using a sim-
ilar approach to that described for 25f: mp 241–244 °C (dec)
(MeOH–THF); 1H NMR (DMSO-d6) d 3.00–3.02 (4H, m), 3.71–3.74
(4H, m), 4.58 (2H, d, J = 5.9 Hz), 6.62–6.41 (1H, m), 6.72–6.75
(2H, m), 6.81 (2H, d, J = 8.8 Hz), 7.11–7.14 (2H, m), 7.50 (2H, d,
J = 8.8 Hz), 7.75 (1H, br), 8.51 (1H, s), 9.26 (1H, br), 9.35 (1H, br),
9.47 (1H, s); FAB MS m/e [M+H]+ 421. Anal. Calcd for
5.1.38. 4-{[2-(Methylsulfanyl)benzyl]amino}-2-[(4-morpholin-
4-ylphenyl)amino]pyrimidine-5-carboxamide hydrochloride
(25l)
Compound 25l was prepared from compound 32 and 2-meth-
ylsulfanylbenzylamine in 11% yield and isolated as a yellow solid,
using a similar approach to that described for 25f: mp 212–
213 °C (dec) (MeOH–THF); 1H NMR (DMSO-d6) d 3.10 (4H, m),
3.74–3.77 (4H, m), 4.66 (2H, d, J = 5.3 Hz), 6.92 (2H, br), 7.13–
7.15 (2H, m), 7.30–7.37 (4H, m), 7.60 (1H, br), 8.18 (1H, br), 8.52
(1H, br), 10.19 (1H, br), 10.27 (1H, br); FAB MS m/e [M+H]+ 451.
Anal. Calcd for C23H26N6O2SꢁHCl: C, 56.72; H, 5.59; N, 17.26; Cl,
7.28; S, 6.58. Found: C, 56.44; H, 5.49; N, 17.19; Cl, 7.20; S, 6.52.
C
23H26N6O2ꢁ0.2H2O: C, 62.32; H, 5.80; N, 19.82. Found: C, 62.26;
H, 5.94; N, 19.79.
5.1.44. 4-[(4-Fluorobenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25r)
Compound 25r was prepared from compound 32 and 4-fluorob-
enzylamine in 25% yield as a colorless solid, using a similar ap-
proach to that described for 25f: mp 253–257 °C (MeOH–THF);
1H NMR (DMSO-d6) d 3.01–3.03 (4H, m), 3.72–3.74 (4H, m), 4.64
(2H, d, J = 6.1 Hz), 6.82 (2H, d, J = 9.1 Hz), 7.10 (1H, br), 7.14–7.17
(2H, m), 7.35–7.38 (2H, m), 7.50 (2H, d, J = 9.2 Hz), 7.75 (1H, br),
8.50 (1H, s), 9.25 (1H, s), 9.48 (1H, s); FAB MS m/e [M+H]+ 423.
Anal. Calcd for C22H23N6O2Fꢁ0.2H2O: C, 62.02; H, 5.54; N, 19.73;
F, 4.46. Found: C, 61.81; H, 5.48; N, 19.69; F, 4.73.
5.1.39. 4-[(3-Fluorobenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25m)
Compound 25m was prepared from compound 32 and 3-fluo-
robenzylamine in 30% yield as a pale yellow solid, using a similar
approach to that described for 25f: mp 246–249 °C (MeOH–THF);
1H NMR (DMSO-d6) d 2.97–3.04 (4H, m), 3.71–3.74 (4H, m), 4.67
(2H, d, J = 5.8 Hz), 6.80 (2H, d, J = 8.8 Hz), 7.04–7.18 (4H, m),
7.35–7.41 (1H, m), 7.46 (2H, d, J = 8.8 Hz), 7.75 (1H, br), 8.52 (1H,
s), 9.27 (1H, s), 9.53 (1H, s); FAB MS m/e [M+H]+ 423. Anal. Calcd
for C22H23N6O2Fꢁ0.2H2O: C, 62.02; H, 5.54; N, 19.73; F, 4.46. Found:
C, 61.82; H, 5.43; N, 19.75; F, 4.76.
5.1.45. 4-[(2,3-Difluorobenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25s)
Compound 25s was prepared from compound 32 and 4-fluorob-
enzylamine in 32% yield as a yellow solid, using a similar approach
to that described for 25f: mp 242–245 °C (MeOH–THF); 1H NMR
(DMSO-d6) d 2.97–3.03 (4H, m), 3.72–3.74 (4H, m), 4.74 (2H, d,
J = 5.9 Hz), 6.77 (2H, d, J = 8.8 Hz), 7.10–7.17 (3H, m), 7.28–7.35
(1H, m), 7.41 (2H, d, J = 8.8 Hz), 7.78 (1H, br), 8.53 (1H, s), 9.29
(1H, s), 9.53 (1H, s); FAB MS m/e [M+H]+ 441. Anal. Calcd for
5.1.40. 4-[(3-Chlorobenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25n)
Compound 25n was prepared from compound 32 and 3-chloro-
benzylamine in 25% yield as a colorless solid, using a similar ap-
proach to that described for 25f: mp 251–254 °C (MeOH–THF);
1H NMR (DMSO-d6) d 3.00–3.03 (4H, m), 3.72–3.74 (4H, m), 4.65
(2H, d, J = 5.8 Hz), 6.79 (2H, d, J = 8.8 Hz), 7.18 (1H, br), 7.27–7.30
(2H, m), 7.34–7.38 (2H, m), 7.44–7.42 (2H, m), 7.75 (1H, br), 8.52
(1H, s), 9.27 (1H, br), 9.54 (1H, s); FAB MS m/e [M+H]+ 439. Anal.
Calcd for C22H23N6O2Clꢁ0.2H2O: C, 59.71; H, 5.33; N, 18.99; Cl,
8.01. Found: C, 59.82; H, 5.11; N, 18.98; Cl, 7.71.
C
22H22N6O2F2ꢁ0.2H2O: C, 59.51; H, 5.08; N, 18.93; F, 8.56. Found:
C, 59.39; H, 4.94; N, 18.86; F, 8.46.
5.1.46. 4-[(2,4-Difluorobenzyl)amino]-2-[(4-morpholin-4-
ylphenyl)amino]pyrimidine-5-carboxamide (25t)
Compound 25t was prepared from compound 32 and 2,4-diflu-
orobenzylamine in 27% yield as a colorless solid, using a similar ap-
proach to that described for 25f: mp 232–234 °C (MeOH–THF); 1H
NMR (DMSO-d6) d 3.00–3.03 (4H, m), 3.72–3.74 (4H, m), 4.67 (2H,
d, J = 5.9 Hz), 6.80 (2H, d, J = 8.8 Hz), 7.00–7.05 (1H, m), 7.12 (1H,
br), 7.26–7.34 (2H, m), 7.46 (2H, d, J = 8.8 Hz), 7.76 (1H, br), 8.52
(1H, s), 9.28 (1H, s), 9.47 (1H, s); FAB MS m/e [M+H]+ 441. Anal.
Calcd for C22H22N6O2F2ꢁ0.4H2O: C, 59.03; H, 5.13; N, 18.77; F,
8.49. Found: C, 59.08; H, 5.00; N, 18.77; F, 8.69.
5.1.41. 2-[(4-Morpholin-4-ylphenyl)amino]-4-[(3-trifluo-
romethylbenzyl)amino]pyrimidine-5-carboxamide (25o)
Compound 25o was prepared from compound 32 and 3-trifluo-
romethylbenzylamine in 17% yield as a pale yellow solid, using a
similar approach to that described for 25f: mp 232–234 °C
(MeOH–THF); 1H NMR (DMSO-d6) d 2.98–3.00 (4H, m), 3.71–3.74