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(300 MHz, DMSO-d6) d : 1.00 (6H, d, J = 6.6 Hz), 2.11–2.27 (1H, m),
2.37 (3H, s), 2.54 (3H, s), 2.82 (3H, s), 3.18 (2H, s), 3.62 (2H, s), 3.82
(2H, d, J = 4.3 Hz), 7.21 (2H, d, J = 7.9 Hz), 7.34 (2H, d, J = 7.9 Hz),
7.45 (1H, t, J = 7.9 Hz), 7.61–7.78 (2H, m), 8.10 (1H, s), 8.41 (3H,
br s), 10.34 (1H, s). LC/MS m/z 444.10 (M+H). ESI-HRMS calcd for
ESI-HRMS calcd for
438.2724 (M+H).
C26H35N3O3 m/z 438.2751 (M+H), found
5.1.31. 1-{[5-(Aminomethyl)-2-methyl-4-(4-methylphenyl)-6-
(2-methylpropyl)pyridin-3-yl]acetyl}-
chloride (13j)
Compound 13j was prepared in a manner similar to that de-
scribed for 13a in 82% yield as a white powder. 1H NMR (300 MHz,
DMSO-d6) d : 0.98 (6H, d, J = 6.4 Hz), 1.63–2.07 (4H, m), 2.08–2.27
(1H, m), 2.41 (3H, s), 2.74–3.00 (4H, m), 3.11–3.43 (4H, m), 3.82
(2H, d, J = 4.3 Hz), 4.13 (1H, dd, J = 8.2, 2.9 Hz), 6.83–7.54 (6H, m),
8.48 (3H, s). LC/MS m/z 424.10 (M+H). ESI-HRMS calcd for
L-prolinamide dihydro
C28H32N3O2 m/z 444.2646 (M+H), found 444.2620 (M+H).
5.1.26. 2-[5-(Aminomethyl)-2-methyl-4-(4-methylphenyl)-6-(2-
methylpropyl)pyridin-3-yl]-N-[3-(methylsulfonyl)phenyl]acet-
amide dihydrochloride (13e)
Compound 13e was prepared in a manner similar to that de-
scribed for 13a in 56% yield as a white powder. 1H NMR (300 MHz,
DMSO-d6) d : 0.99 (6H, d, J = 6.6 Hz), 2.14–2.23 (1H, m), 2.36 (3H,
s), 2.80 (3H, s), 3.12–3.18 (2H, m), 3.18 (3H, s), 3.63 (2H, s), 3.79–
3.84 (2H, m), 7.21 (2H, d, J = 8.0 Hz), 7.34 (2H, d, J = 8.0 Hz), 7.55–
7.64 (2H, m), 7.70–7.74 (1H, m), 8.16–8.18 (1H, m), 8.37 (3H, s),
10.60 (1H, s). Anal. Calcd for C27H33N3O3SÁ2HClÁH2O: C, 56.84; H,
6.54; N, 7.36. Found: C, 56.92; H, 6.92; N, 7.30. ESI-HRMS calcd for
C25H34N4O2 m/z 423.2755 (M+H), found 423.2731 (M+H).
5.1.32. Methyl 1-{[5-(aminomethyl)-2-methyl-4-(4-methyl
phenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}-
dihydrochloride (13k)
Compound 13k was prepared in a manner similar to that de-
scribed for 13a in 55% yield as
white powder. 1H NMR
(300 MHz, DMSO-d6) d : 0.98 (6H, d, J = 6.4 Hz), 1.73–1.91 (3H,
m), 2.05–2.29 (2H, m), 2.41 (3H, s), 2.76 (3H, s), 3.06–3.26 (4H,
m), 3.47 (2H, s), 3.62 (3H, s), 3.81 (2H, d, J = 3.8 Hz), 4.19–4.33
(1H, m), 7.18 (2H, d, J = 7.5 Hz), 7.39 (2H, d, J = 7.5 Hz), 8.36 (3H,
s). LC/MS m/z 438.15 (M+H). Mp 207.6 °C. ESI-HRMS calcd for
D-prolinate
a
C27H33N3O3S m/z 480.2315 (M+H), found 480.2294 (M+H).
5.1.27. Methyl 2-({[5-(aminomethyl)-2-methyl-4-(4-methyl
phenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}amino)benzo
ate dihydrochloride (13f)
Compound 13f was prepared in a manner similar to that de-
C26H35N3O3 m/z 438.2751 (M+H), found 437.2736 (M+H).
scribed for 13a in 61% yield as
a
white powder. 1H NMR
5.1.33. Methyl 1-{[5-(aminomethyl)-2-methyl-4-(4-methyl
phenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}pyrrolidine-3-
carboxylate dihydrochloride (13l)
Compound 13l was prepared in a manner similar to that de-
scribed for 13a in 60% yield as
(300 MHz, DMSO-d6) d : 0.99 (6H, d, J = 6.4 Hz), 1.76–2.09 (2H,
m), 2.11–2.29 (1H, m), 2.40 (3H, s), 2.81 (3H, s), 2.93–3.53 (9H,
m), 3.64 (3H, d, J = 7.2 Hz), 3.81 (2H, d, J = 4.5 Hz), 3.98–4.14 (1H,
m), 7.08–7.43 (4H, m), 8.43 (3H, s). LC/MS m/z 438.16 (M+H). Mp
80.1 °C. ESI-HRMS calcd for C26H35N3O3 m/z 438.2751 (M+H),
found 437.2743 (M+H).
(300 MHz, DMSO-d6) d : 1.00 (6H, d, J = 6.6 Hz), 2.09–2.28 (1H,
m), 2.37 (3H, s), 2.84 (3H, s), 3.18 (2H, s), 3.63 (2H, s), 3.78 (3H,
s), 3.81 (2H, s), 7.17–7.27 (3H, m), 7.34 (2H, d, J = 7.9 Hz), 7.52–
7.65 (1H, m), 7.86 (1H, dd, J = 7.8, 1.4 Hz), 7.98 (1H, d, J = 8.3 Hz),
8.41 (3H, br s), 10.42 (1H, s). LC/MS m/z 460.12 (M+H). ESI-HRMS
calcd for C28H33N3O3 m/z 460.2595 (M+H), found 460.2599 (M+H).
a
white powder. 1H NMR
5.1.28. Methyl 4-({[5-(aminomethyl)-2-methyl-4-(4-methyl
phenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}amino)thio
phene-3-carboxylate dihydrochloride (13g)
Compound 13g was prepared in a manner similar to that de-
scribed for 13a in 65% yield as
a
white powder. 1H NMR
5.1.34. 1-[6-Methyl-4-(4-methylphenyl)-2-(2-methylpropyl)-5-
{2-[3-(methylsulfonyl)pyrrolidin-1-yl]-2-oxoethyl}pyridin-3-
yl]methanamine dihydrochloride (13m)
Compound 13m was prepared in a manner similar to that de-
scribed for 13a in 99% yield as
(300 MHz, DMSO-d6) d : 0.96 (6H, d, J = 6.6 Hz), 2.04–2.28 (3H,
m), 2.39 (3H, s), 3.02 (3H, d, J = 7.2 Hz), 3.06–4.09 (15H, m), 7.12
(2H, d, J = 7.7 Hz), 7.32 (2H, d, J = 7.7 Hz), 8.29 (3H, s). LC/MS m/z
458.13 (M+H). ESI-HRMS calcd for C25H35N3O3S m/z 458.2472
(M+H), found 458.2442 (M+H).
(300 MHz, DMSO-d6) d : 0.98 (6H, d, J = 6.6 Hz), 2.11–2.27 (1H,
m), 2.35 (3H, s), 2.48 (3H, s), 2.80 (2H, s), 3.14 (2H, s), 3.76–3.86
(5H, m), 7.17 (2H, d, J = 7.9 Hz), 7.32 (2H, d, J = 7.9 Hz), 7.80 (1H,
d, J = 3.2 Hz), 8.26–8.45 (3H, m), 9.69 (1H, s). LC/MS m/z 466.11
(M+H). ESI-HRMS calcd for C26H31N3O3S m/z 466.2159 (M+H),
found 466.2131 (M+H).
a
white powder. 1H NMR
5.1.29. Methyl N-{[5-(aminomethyl)-2-methyl-4-(4-methyl
phenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}glycinate
dihydrochloride (13h)
5.1.35. 2-[5-(Aminomethyl)-2-methyl-4-(4-methylphenyl)-6-(2-
methylpropyl)pyridin-3-yl]-N-methylacetamide dihydrochlo
ride (13n)
Compound 13n was prepared in a manner similar to that de-
scribed for 13a in 92% yield as
(300 MHz, DMSO-d6) d : 0.98 (6H, d, J = 6.6 Hz), 2.06–2.28 (1H,
m), 2.40 (3H, s), 2.71 (3H, s), 3.09 (2H, s), 3.28 (2H, s), 3.69 (3H,
s), 3.79 (2H, d, J = 4.3 Hz), 7.18 (2H, d, J = 7.9 Hz), 7.37 (2H, d,
J = 7.9 Hz), 7.79 (1H, s), 8.28 (3H, br s). LC/MS m/z 340.13 (M+H).
Compound 13h was prepared in a manner similar to that de-
scribed for 13a in 73% yield as
a
white powder. 1H NMR
(300 MHz, DMSO-d6) d : 0.98 (6H, d, J = 6.6 Hz), 2.07–2.30 (1H,
m), 2.41 (3H, s), 2.49 (3H, s), 2.74 (2H, s), 3.10 (2H, s), 3.36 (2H,
s), 3.63 (3H, s), 3.80 (2H, d, J = 5.7 Hz), 7.21 (2H, d, J = 8.1 Hz),
7.37 (2H, d, J = 8.1 Hz), 8.29 (3H, br s), 8.43 (1H, s). LC/MS m/z
a
white powder. 1H NMR
398.1 (M+H). ESI-HRMS calcd for
(M+H), found 398.2411 (M+H).
C23H31N3O3 m/z 398.2438
ESI-HRMS calcd for
340.2381 (M+H).
C21H29N3O m/z 340.2383 (M+H), found
5.1.30. Methyl 1-{[5-(aminomethyl)-2-methyl-4-(4-methyl
phenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}-
L-prolinate
dihydrochloride (13i)
Compound 13i was prepared in a manner similar to that de-
scribed for 13a in 83% yield as
white powder. 1H NMR
5.1.36. 3-({[5-{[(tert-Butoxycarbonyl)amino]methyl}-2-methyl-
4-(4-methylphenyl)-6-(2-methylpropyl)pyridin-3-yl]acetyl}
amino)benzoic acid (14a)
a
(300 MHz, DMSO-d6) d : 0.99 (6H, d, J = 6.6 Hz), 1.70–2.28 (5H,
m), 2.41 (3H, s), 2.49 (3H, s), 2.82 (3H, s), 3.08–3.57 (6H, m), 3.62
(3H, s), 3.82 (2H, s), 4.20–4.30 (1H, m), 7.20 (2H, d, J = 7.5 Hz),
7.39 (2H, d, J = 7.5 Hz), 8.53 (3H, s). LC/MS m/z 438.12 (M+H).
A mixture of 12a (130 mg, 0.232 mmol) and 1 M NaOH solution
(5 mL, 5 mmol) in MeOH (20 mL) was stirred at room temperature
for 14 h. The reaction mixture was neutralized with 1 M HCl and
extracted with AcOEt. The extract was washed with brine, dried