4034
T. Kuramochi et al. / Bioorg. Med. Chem. 13 (2005) 4022–4036
(400 MHz, DMSO-d6) d 4.38 (2H, d, J = 5.6 Hz), 5.16
(2H, s), 5.85 (2H, br s), 6.51–6.54 (4H, m), 7.06–7.13
(5H, m), 7.15–7.20 (1H, m), 7.24–7.29 (2H, m), 7.41–
7.47 (1H, m), 7.56–7.61 (1H, m), 8.28 (1H, dd, J = 8.4,
2.4 Hz), 8.66 (1H, d, J = 2.4 Hz), 9.14 (1H, t,
J = 5.6 Hz); MS (FAB) m/z 445 (M+H)+. Anal. Calcd
for C25H21N4O3F: C, 64.43; H, 5.06; N, 12.02; F, 4.08.
Found: C, 64.45; H, 4.73; N, 12.09; F, 4.15.
5.1.52. N-[(2-Aminopyridin-4-yl)methyl]-6-{4-[(3-chloro-
benzyl)oxy]phenoxy}nicotinamide (29g). Compound 29g
was prepared from 28g by a procedure similar to that
described for 23a. Compound 29g was obtained as a
beige powder (77%): mp 185–186 °C; 1H NMR
(400 MHz, DMSO-d6) d 4.33 (2H, d, J = 5.6 Hz), 5.15
(2H, s), 5.90 (2H, br s), 6.36 (1H, s), 6.41–6.43 (1H,
m), 7.06–7.13 (5H, m), 7.39–7.47 (3H, m), 7.54 (1H, s),
7.81 (1H, d, J = 5.2 Hz), 8.27 (1H, dd, J = 8.4, 2.4 Hz),
8.65 (1H, d, J = 2.4 Hz), 9.06 (1H, t, J = 5.6 Hz); MS
(FAB) m/z 461 (M+H)+. Anal. Calcd for
C25H21N4O3Cl: C, 65.15; H, 4.59; N, 12.16; Cl, 7.69.
Found: C, 64.86; H, 4.46; N, 12.15; Cl, 7.98.
5.1.48. N-[(2-Aminopyridin-4-yl)methyl]-6-{4-[(4-fluoro-
benzyl)oxy]phenoxy}nicotinamide (29c). Compound 29c
was prepared from 28c by a procedure similar to that de-
scribed for 23a. Compound 29c was obtained as a beige
solid (73%): mp 199–200 °C; 1H NMR (400 MHz,
DMSO-d6) d 4.34 (2H, d, J = 6.0 Hz), 5.10 (2H, s),
5.98 (2H, br s), 6.37 (1H, s), 6.43–6.44 (1H, m), 7.05–
7.12 (5H, m), 7.21–7.26 (2H, m), 7.51–7.54 (2H, m),
7.81 (1H, d, J = 5.6 Hz), 8.27 (1H, dd, J = 8.4, 2.4 Hz),
8.65 (1H, d, J = 2.4 Hz), 9.07 (1H, t, J = 6.0 Hz); MS
(FAB) m/z 445 (M+H)+. Anal. Calcd for C25H21N4O3F:
C, 67.02; H, 4.81; N, 12.50; F, 4.24. Found: C, 66.95; H,
4.66; N, 12.52; F, 4.19.
5.1.53. N-[(2-Aminopyridin-4-yl)methyl]-6-{4-[(3-cyano-
benzyl)oxy]phenoxy}nicotinamide (29h). Compound 29h
was prepared from 28h by a procedure similar to that
described for 23a. Compound 29h was obtained as a
beige powder (64%): mp 153–154 °C; 1H NMR
(400 MHz, DMSO-d6) d 4.33 (2H, d, J = 5.6 Hz), 5.19
(2H, s), 5.84 (2H, br s), 6.34 (1H, s), 6.40–6.42 (1H,
m), 7.06–7.14 (5H, m), 7.64 (1H, t, J = 8.0 Hz), 7.80–
7.84 (3H, m), 7.94 (1H, s), 8.27 (1H, dd, J = 8.4,
2.8 Hz), 8.33–8.34 (1H, m), 8.65 (1H, d, J = 2.4 Hz),
9.05 (1H, t, J = 6.0 Hz); MS (FAB) m/z 452 (M+H)+.
Anal. Calcd for C26H21N5O3: C, 69.17; H, 4.69; N,
15.51. Found: C, 68.88; H, 4.68; N, 15.53.
5.1.49. N-[(2-Aminopyridin-4-yl)methyl]-6-{4-[(2-methyl-
benzyl)oxy]phenoxy}nicotinamide (29d). Compound 29d
was prepared from 28d by a procedure similar to that
described for 23a. Compound 29d was obtained as a
beige solid (73%): mp 119–121 °C; 1H NMR
(400 MHz, DMSO-d6) d 2.35 (3H, s), 4.33 (2H, d,
J = 5.6 Hz), 5.10 (2H, s), 5.84 (2H, br s), 6.34 (1H, s),
6.40–6.42 (1H, m), 7.06–7.13 (5H, m), 7.20–7.28 (3H,
m), 7.43 (1H, d, J = 7.2 Hz), 8.28 (1H, dd, J = 8.4,
2.4 Hz), 8.66 (1H, d, J = 2.4 Hz), 9.08 (1H, t,
J = 6.0 Hz); MS (FAB) m/z 441 (M+H)+; HRMS:
(M+H)+ Calcd for C26H25O3N4, 441.1927. Found:
441.1947.
5.1.54. N-[(2-Aminopyridin-4-yl)methyl]-6-{4-[(3-nitro-
benzyl)oxy]phenoxy}nicotinamide (29i). Compound 29i
was prepared from 28i by a procedure similar to that de-
scribed for 23a. Compound 29i was obtained as a light
yellow powder (84%): mp 120–123 °C; 1H NMR
(400 MHz, DMSO-d6) d 4.33 (2H, d, J = 5.6 Hz), 5.29
(2H, s), 5.84 (2H, br s), 6.34 (1H, s), 6.40–6.42 (1H,
m), 7.06–7.15 (5H, m), 7.73 (1H, t, J = 8.0 Hz), 7.81
(1H, d, J = 5.2 Hz), 7.95 (1H, d, J = 7.6 Hz), 8.21 (1H,
dd, J = 8.0, 2.0 Hz), 8.27 (1H, dd, J = 8.8, 2.8 Hz),
8.33–8.34 (1H, m), 8.64 (1H, d, J = 2.4 Hz), 9.05 (1H,
t, J = 6.0 Hz); MS (FAB) m/z 472 (M+H)+. Anal. Calcd
for C25H21N5O5Æ0.1H2O: C, 63.45; H, 4.51; N, 14.80.
Found: C, 63.27; H, 4.38; N, 14.79.
5.1.50. N-[(2-Aminopyridin-4-yl)methyl]-6-{4-[(3-methyl-
benzyl)oxy]phenoxy}nicotinamide (29e). Compound 29e
was prepared from 28e by a procedure similar to that de-
scribed for 23a. Compound 29e was obtained as a
slightly yellow powder (72%): mp 177–178 °C; 1H
NMR (400 MHz, DMSO-d6) d 2.33 (3H, s), 4.33 (2H,
d, J = 6.0 Hz), 5.08 (2H, s), 5.87 (2H, br s), 6.34 (1H,
s), 6.41–6.42 (1H, m), 7.05–7.16 (6H, m), 7.24–7.31
(3H, m), 7.81 (1H, d, J = 5.2 Hz), 8.27 (1H, dd,
J = 8.4, 2.4 Hz), 8.65 (1H, d, J = 2.4 Hz), 9.06 (1H, t,
J = 5.6 Hz); MS (FAB) m/z 441 (M+H)+. Anal. Calcd
for C26H24N4O3: C, 70.89; H, 5.49; N, 12.72. Found:
C, 70.76; H, 5.43; N, 12.82.
5.1.55. N-[(2-Aminopyridin-4-yl)methyl]-6-(4-{[3-(trifluoro-
methyl)benzyl]oxy}phenoxy)nicotinamide (29j). Com-
pound 29j was prepared from 28j by a procedure
similar to that described for 23a. Compound 29j was ob-
tained as a beige powder (65%): mp 140–141 °C; 1H
NMR (400 MHz, DMSO-d6)
d
4.33 (2H, d,
J = 5.6 Hz), 5.24 (2H, s), 5.85 (2H, br s), 6.34 (1H, s),
6.40–6.42 (1H, m), 7.06–7.14 (5H, m), 7.64–7.73 (2H,
m), 7.79–7.84 (3H, m), 7.94 (1H, s), 8.27 (1H, dd,
J = 8.4, 2.8 Hz), 8.65 (1H, d, J = 2.4 Hz), 9.06 (1H, t,
J = 6.0 Hz); MS (FAB) m/z 495 (M+H)+. Anal. Calcd
for C26H21N4O3F: C, 63.15; H, 4.28; N, 11.33; F,
11.53. Found: C, 63.30; H, 4.15; N, 11.32; F, 11.83.
5.1.51. N-[(2-Aminopyridin-4-yl)methyl]-6-{4-[(3-methyl-
benzyl)oxy]phenoxy}nicotinamide (29f). Compound 29f
was prepared from 28f by a procedure similar to that de-
scribed for 23a. Compound 29f was obtained as a beige
powder (83%): mp 212–213 °C; 1H NMR (400 MHz,
DMSO-d6) d 2.31 (3H, s), 4.33 (2H, d, J = 5.6 Hz),
5.07 (2H, s), 5.84 (2H, br s), 6.34 (1H, s), 6.40–6.42
(1H, m), 7.03–7.11 (5H, m), 7.21 (2H, d, J = 8.0 Hz),
7.35 (2H, d, J = 7.6 Hz), 7.81 (1H, d, J = 5.2 Hz), 8.27
(1H, dd, J = 8.8, 2.4 Hz), 8.64 (1H, d, J = 2.0 Hz), 9.04
(1H, t, J = 6.0 Hz); MS (FAB) m/z 441 (M+H)+. Anal.
Calcd for C26H24N4O3: C, 70.89; H, 5.49; N, 12.72.
Found: C, 70.82; H, 5.50; N, 12.72.
5.1.56. N-[(2-Aminopyridin-4-yl)methyl]-6-[4-(3-thienylmeth-
oxy)phenoxy]nicotinamide (29k). Compound 29k was
prepared from 28k by a procedure similar to that de-
scribed for 23a. Compound 29k was obtained as a white
powder (84%): mp 208–209 °C; 1H NMR (400 MHz,
DMSO-d6) d 4.33 (2H, d, J = 5.6 Hz), 5.11 (2H, s),