3060 J ournal of Medicinal Chemistry, 2000, Vol. 43, No. 16
Oguchi et al.
Hz), 7.08 (2 H, d, J ) 8.6 Hz), 7.15 (3 H, t, J ) 7.1 Hz), 7.20-
7.26 (7 H, m), 7.31 (6 H, m), 7.96 (1 H, dd, J ) 1.2 and 7.5
Hz), 8.28 (1 H, dd, J ) 1.2 and 4.5 Hz).
5-[4-(3-E t h yl-3H-im id a zo[4,5-b]p yr id in -2-ylm et h oxy)-
ben zyl]-3-tr ip h en ylm eth ylth ia zolid in e-2,4-d ion e (11d ).
This compound was prepared using the same procedure as for
acetate, to give 0.38 g (0.94 mmol) of 12a : yield 53%; mp 222-
223 °C; IR (KBr) 1694, 1511, 1396, 1237 cm-1; MS m/z 402
1
(M+); H NMR (DMSO-d6) δ 3.07 (1 H, dd, J ) 9.2 and 14.1
Hz), 3.33 (1 H, dd, J ) 4.3 and 14.1 Hz), 3.84 (3 H, s), 4.88 (1
H, dd, J ) 4.3 and 9.2 Hz), 5.44 (2 H, s), 7.07 (2 H, d, J ) 8.6
Hz), 7.20 (2 H, d, J ) 8.6 Hz), 7.36 (1 H, d, J ) 8.3 Hz), 8.15
(1 H, d, J ) 8.3 Hz), 12.02 (1 H, s). Anal. (C18H15ClN4O3S) C,
H, N, Cl, S.
the preparation of 11a : IR (KBr) 1690, 1510, 1299, 706 cm-1
;
MS m/z 624 (M+); H NMR (DMSO-d6) δ 1.37 (3 H, t, J ) 7.2
Hz), 3.12 (1 H, dd, J ) 8.0 and 14.3 Hz), 3.30 (1 H, dd, J ) 4.5
and 14.3 Hz), 4.37 (2 H, q, J ) 7.2 Hz), 5.02 (1 H, dd, J ) 4.5
and 8.0 Hz), 5.43(2 H, d, J ) 1.8 Hz), 7.03 (2 H, d, J ) 8.7
Hz), 7.1-7.2 (5 H, m), 7.2-7.3 (6 H, m), 7.3-7.4 (7 H, m), 8.10
(1 H, dd, J ) 1.2 and 7.5 Hz), 8.40 (1 H, dd, J ) 1.2 and 5.1
Hz).
1
5-[4-(3-Meth yl-3H-im id a zo[4,5-b]p yr id in -2-ylm eth oxy)-
ben zyl]t h ia zolid in e-2,4-d ion e (12b ). A solution of 0.50 g
(0.82 mmol) of 11b in 100 mL of methanol was stirred under
an atmosphere of hydrogen and in the presence of 1.00 g of
10% w/w palladium-on-charcoal, first at room temperature for
2 h then at 50 °C for 3 h. The reaction mixture was filtered to
remove the catalyst and filtrate was concentrated by evapora-
tion under reduced pressure. The concentrate thus obtained
was purified by column chromatogaphy through silica gel,
using a gradient elution method, with a mixture of ethyl
acetate and ethanol, in ratios ranging from 1:0 to 10:1 by
volume, as the eluent, to give 77 mg (0.21 mmol) of 12b: yield
26%; mp 223-225 °C; IR (KBr) 1693 cm-1; MS m/z 368 (M+);
1H NMR (DMSO-d6) δ 3.06 (1 H, dd, J ) 9.1 and 14.2 Hz),
3.32 (1 H, dd, J ) 4.4 and 14.2 Hz), 3.87 (3 H, s), 4.88 (1 H,
dd, J ) 4.4 and 9.1 Hz), 5.44 (2 H, s), 7.08 (2 H, d, J ) 8.7
Hz), 7.20 (2 H, d, J ) 8.7 Hz), 7.30 (1 H, dd, J ) 4.4 and 8.0
Hz), 8.08 (1 H, dd, J ) 1.2 and 8.0 Hz), 8.39 (1 H, dd, J ) 1.2
and 4.4 Hz), 12.02 (1 H, s). Anal. (C18H16N4O3S‚1/5H2O) C, H,
N, S.
5-{4-[3-(4-P h en ylb en zyl)-3H -im id a zo[4,5-b]p yr id in -2-
ylm et h oxy]b en zyl}-3-t r ip h en ylm et h ylt h ia zolid in e-2,4-
d ion e (11e). This compound was prepared using the same
procedure as for the preparation of 11a : 1H NMR (CDCl3) δ
3.04 (1 H, dd, J ) 8.9 and 14.1 Hz), 3.39 (1 H, dd, J ) 3.9 and
14.1 Hz), 4.32 (1 H, dd, J ) 3.9 and 8.9 Hz), 5.24 (2 H, s), 5.70
(2 H, s), 6.91 (2 H, d, J ) 8.6 Hz), 7.1-7.6 (27H, m), 8.10 (1 H,
dd, J ) 1.3 and 8.0 Hz), 8.46 (1 H, dd, J ) 1.4 and 4.8 Hz).
5-[4-(6-Ch lor o-3-m eth yl-3H-im id a zo[4,5-b]p yr id in -2-yl-
m et h oxy)ben zyl]-3-t r ip h en ylm et h ylt h ia zolid in e-2,4-d i-
on e (11f). This compound was prepared using the same
procedure as for the preparation of 11a : mp 82-84 °C
(softening); IR (KBr) 1689, 1511, 1299, 1232, 706 cm-1; MS
m/z 644 (M+); 1H NMR (DMSO-d6) δ 3.12 (1 H, dd, J ) 8.1
and 14.3 Hz), 3.31 (1 H, dd, J ) 4.6 and 14.3 Hz), 3.86 (3 H,
s), 5.02 (1 H, dd, J ) 4.6 and 8.1 Hz), 5.44 (2 H, d, J ) 0.9
Hz), 7.02 (2 H, d, J ) 8.7 Hz), 7.1-7.2 (5 H, m), 7.2-7.3 (6 H,
m), 7.3-7.4 (6 H, m), 8.27 (1 H, d, J ) 2.2 Hz), 8.43 (1 H, d, J
) 2.2 Hz).
5-[4-(6-Br om o-3-m eth yl-3H-im id a zo[4,5-b]p yr id in -2-yl-
m et h oxy)ben zyl]-3-t r ip h en ylm et h ylt h ia zolid in e-2,4-d i-
on e (11g). This compound was prepared using the same
procedure as for the preparation of 11a : mp 97-100 °C
(softening); IR (KBr) 1690, 1511, 1298 cm-1; MS m/z 688 (M+);
1H NMR (DMSO-d6) δ 3.12 (1 H, dd, J ) 8.1 and 14.3 Hz),
3.31 (1 H, dd, J ) 4.6 and 14.3 Hz), 3.86 (3 H, s), 5.02 (1 H,
dd, J ) 4.6 and 8.1 Hz), 5.44 (2 H, s), 7.02 (2 H, d, J ) 8.7
Hz), 7.13 (2 H, d, J ) 8.7 Hz), 7.1-7.2 (3 H, m), 7.2-7.3 (6 H,
m), 7.3-7.4 (6 H, m), 8.38 (1 H, d, J ) 2.0 Hz), 8.49 (1 H, d, J
) 2.0 Hz).
5-[4-(3,7-Dim eth yl-3H-im idazo[4,5-b]pyr idin -2-ylm eth ox-
y)ben zyl]-3-tr ip h en ylm eth ylth ia zolid in e-2,4-d ion e (11h ).
This compound was prepared using the same procedure as for
the preparation of 11a : mp 92-105 °C (softening); IR (KBr)
1690, 1510, 1450, 1297, 1240 cm-1; MS m/z 624 (M+); 1H NMR
(DMSO-d6) δ 2.58 (3 H, s), 3.12 (1 H, dd, J ) 8.0 and 14.2 Hz),
3.30 (1 H, dd, J ) 4.5 and 14.2 Hz), 3.84 (3 H, s), 5.02 (1 H,
dd, J ) 4.5 and 8.0 Hz), 5.41 (2 H, s), 7.03 (2 H, d, J ) 8.7
Hz), 7.1-7.2 (6 H, m), 7.2-7.3 (6 H, m), 7.3-7.4 (6 H, m), 8.25
(1 H, d, J ) 4.9 Hz).
5-[4-(3,5,7-Tr im eth yl-3H-im idazo[4,5-b]pyr idin -2-ylm eth -
oxy)ben zyl]-3-tr iph en ylm eth ylth iazolidin e-2,4-dion e (11i).
This compound was prepared using the same procedure as for
the preparation of 11a : mp 96-99 °C (softening); IR (KBr)
1692, 1510, 1299 cm-1; MS m/z 639 (M + H)+; 1H NMR
(DMSO-d6) δ 2.52 (3 H, s), 2.54 (3 H, s), 3.12 (1 H, dd, J ) 8.1
and 14.2 Hz), 3.30 (1 H, dd, J ) 4.8 and 14.2 Hz), 3.80 (3 H,
s), 5.02 (1 H, dd, J ) 4.8 and 8.1 Hz), 5.37 (2 H, s), 6.99 (1 H,
s), 7.02 (2 H, d, J ) 8.7 Hz), 7.13 (2 H, d, J ) 8.7 Hz), 7.1-7.2
(3 H, m), 7.2-7.3 (6 H, m), 7.3-7.4 (6 H, m).
5-{4-[3-(3-Met h yl-3H -im id a zo[4,5-b]p yr id in -2-yl)p r o-
p oxy]ben zyl}th ia zolid in e-2,4-d ion e (12c). This compound
was prepared using the same procedure as for the preparation
of 12a : mp 185-186 °C; IR (KBr) 1697, 1512, 1248 cm-1; MS
m/z 396 (M+); 1H NMR (DMSO-d6) δ 2.27 (2 H, m), 3.0-3.1 (3
H, m), 3.30 (1 H, dd, J ) 4.4 and 14.3 Hz), 3.76 (3 H, s), 4.11
(2 H, m), 4.86 (1 H, dd, J ) 4.4 and 8.8 Hz), 6.88 (2 H, d, J )
8.7 Hz), 7.15 (2 H, d, J ) 8.7 Hz), 7.21 (1 H, dd, J ) 5.1 and
8.0 Hz), 7.95 (1 H, dd, J ) 1.4 and 8.0 Hz), 8.27 (1 H, dd, J )
1.4 and 5.1 Hz), 11.99 (1 H, s). Anal. (C20H20N4O3S) C, H, N,
S.
5-[4-(3-E t h yl-3H-im id a zo[4,5-b]p yr id in -2-ylm et h oxy)-
ben zyl]t h ia zolid in e-2,4-d ion e (12d ). This compound was
prepared using the same procedure as for the preparation of
12a : mp 210-212 °C; IR (KBr) 1695, 1513, 1405, 1250, 1228
1
cm-1; MS m/z 382 (M+); H NMR (DMSO-d6) δ 1.40 (3 H, t, J
) 7.1 Hz), 3.07 (1 H, dd, J ) 9.1 and 14.1 Hz), 3.32 (1 H, dd,
J ) 4.4 and 14.1 Hz), 4.38 (2 H, q, J ) 7.1 Hz), 4.88 (1 H, dd,
J ) 4.4 and 9.1 Hz), 5.44 (2 H, s), 7.08 (2 H, d, J ) 8.7 Hz),
7.21 (2 H, d, J ) 8.7 Hz), 7.30 (1 H, dd, J ) 5.1 and 8.0 Hz),
8.09 (1 H, dd, J ) 1.4 and 8.0 Hz), 8.39 (1 H, dd, J ) 1.4 and
5.1 Hz), 12.02 (1 H, s). Anal. (C19H18N4O3S‚3/20H2O) C, H, N,
S.
5-{4-[3-(4-P h en ylb en zyl)-3H -im id a zo[4,5-b]p yr id in -2-
ylm eth oxy]ben zyl}th ia zolid in e-2,4-d ion e (12e). This com-
pound was prepared using the same procedure as for the
preparation of 12a : mp 189-191 °C; IR (KBr) 1699, 1511, 1239
1
cm-1; MS m/z 520 (M+); H NMR (DMSO-d6) δ 3.04 (1 H, dd,
J ) 9.1 and 14.2 Hz), 3.30 (1 H, dd, J ) 4.3 and 14.2 Hz), 4.85
(1 H, dd, J ) 4.3 and 9.1 Hz), 5.40(2 H, s), 5.66(2 H, s), 6.92
(2 H, d, J ) 8.7 Hz), 7.15 (2 H, d, J ) 8.7 Hz), 7.28 (2 H, d, J
) 8.2 Hz), 7.3-7.4 (2 H, m), 7.44 (2 H, t, J ) 7.4 Hz), 7.57 (2
H, d, J ) 8.2 Hz), 7.61 (2 H, d, J ) 7.4 Hz), 8.16 (1 H, dd, J )
1.4 and 8.1 Hz), 8.42 (1 H, dd, J ) 1.4 and 5.6 Hz), 12.01 (1 H,
s). Anal. (C30H24N4O3S‚1/4H2O) C, H, N, S.
5-[4-(6-Ch lor o-3-m eth yl-3H-im id a zo[4,5-b]p yr id in -2-yl-
m eth oxy)ben zyl]th ia zolid in e-2,4-d ion e (12f). This com-
pound was prepared using the same procedure as for the
preparation of 12a : mp 203-205 °C; IR (KBr) 1695, 1512,
1482, 1233 cm-1; MS m/z 402 (M+); 1H NMR (DMSO-d6) δ 3.07
(1 H, dd, J ) 9.3 and 14.2 Hz), 3.32 (1 H, dd, J ) 4.3 and 14.2
Hz), 3.87 (3 H, s), 4.88 (1 H, dd, J ) 4.3 and 9.3 Hz), 5.45 (2
H, s), 7.07 (2 H, d, J ) 8.6 Hz), 7.20 (2 H, d, J ) 8.6 Hz), 8.28
(1 H, d, J ) 2.2 Hz), 8.43 (1 H, d, J ) 2.2 Hz), 12.02 (1 H, br
s). Anal. (C18H15ClN4O3S) C, H, N, Cl, S.
5-[4-(5-Ch lor o-3-m eth yl-3H-im id a zo[4,5-b]p yr id in -2-yl-
m eth oxy)ben zyl]th ia zolid in e-2,4-d ion e (12a ). In a mixture
of 16 mL of acetic acid and water (3:1, v/v), 1.16 g (1.80 mmol)
of 11a was dissolved. The resulting mixture was stirred at 70
°C for 2 h. The reaction mixture was neutralized by the
addition of sodium hydrogen carbonate, after which it was
extracted with ethyl acetate. The extract was washed with
brine and dried over anhydrous sodium sulfate, after which
the solvent was removed by distillation under reduced pres-
sure. The residue thus obtained was crystallized with ethyl