b i o c h e m i c a l p h a r m a c o l o g y 7 5 ( 2 0 0 8 ) 1 7 1 7 – 1 7 2 8
1721
6
h, cooled to 100 8C, and poured into a solution of FeCl
81 mg, 0.300 mmol) in water and HCl. After heated to 60 8C for
0 min, the mixture was allowed to cool to room temperature
and then extracted with 5% MeOH in CH Cl
(2Â 50 mL). The
combined organic layers were washed twice with water, dried
over Na SO , concentrated in vacuum, and then purified by
column chromatography (eluted with EtOAc:CH OH = 15:1).
The yielded compound in title was a white solid (12 mg, yield:
0%).
mp 234–235 8C; H NMR (300 MHz, CD
J = 7.0, 3H, CH ), 1.77–1.84 (m, 2H, CH ), 2.18 (s, 3H, NCH
br s, 4H), 2.79 (t, J = 7.0, 2H, CH ), 3.11 (br s, 4H), 4.16 (s, 3H,
), 8.39 (s, 1H); C NMR (75 MHz, CD SOCD ): d 13.59, 21.34,
3
Á6H
2
O
2.1.10. 5-(5-(Sulfamoyl)-3-thienyl)-1-methyl-3-propyl-1,6-
(
dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (13) [27]
2
To a solution of compound 6 (200 mg, 0.46 mmol) in methanol
(20 mL), zinc dust (90 mg, 1.38 mmol) and formic acid (0.2 mL)
were added. The mixture was stirred overnight. Excess zinc
dust was removed by filtration. The filtrate was concentrated
in vacuum and then purified by column chromatography
2
2
2
4
3
3 3
(eluted with CHCl :CH OH = 20:1). The yielded compound in
2
title was a white solid (133 mg, yield: 82%).
1
1
3
SOCD
3
): d 0.92 (t,
), 2.43
mp 307–308 8C; H NMR (300 MHz, CD
J = 6.9, 3H, CH ), 1.73–1.80 (m, 2H), 2.79 (t, J = 7.2, 2H), 4.14 (s, 3H,
NCH ), 7.83 (br s, 2H), 8.15 (s, 1H), 8.63 (s, 1H), 12.51 (br s, 1H);
NMR (75 MHz, CD SOCD ): d 13.78, 21.54, 27.05, 37.77, 124.1,
129.0, 130.4, 134.5, 137.2, 144.6, 145.0, 146.2, 154.1; IR (KBr):
3 3
SOCD ): d 0.95 (t,
3
2
3
3
13
(
2
3
C
1
3
NCH
3
3
3
3
3
2
1
1
7.12, 37.78, 44.98, 45.59, 53.20, 112.0, 112.1, 113.6, 130.9, 136.9,
À1
À
41.3, 142.3, 143.0, 145.5, 153.9; IR (KBr): 3430, 2927, 2217, 1680,
3294, 2958, 1680, 1579 cm ; ESI-MS: m/z = 352 [MÀH] . Anal.
calcd for C13 : C, 44.18; H, 4.28; N, 19.82; found: C,
44.15; H, 4.20; N, 19.86.
À1
À
578 cm
;
ESI-MS: m/z = 460 [MÀH] . Anal. calcd for
15 5 3 2
H N O S
19 23 7 3 2
C H N O S : C, 49.44; H, 5.02; N, 21.24; found: C, 49.53; H,
5
.09; N, 21.13.
2.1.11. 5-(5-(N-Butyloxycarbonylaminosulfonyl)-3-thienyl)-1-
2
.1.8. 5-(2-(4-Methylpiperazinyl)-5-(4-
methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-
one (14) [33]
methylpiperazinylsulfonyl)-3-thienyl)-1-methyl-3-propyl-1,6-
dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (11) [32]
Compound 13 (65 mg, 0.18 mmol) was dissolved in pyridine
(4 mL) and 4-dimethylaminopyridine (44 mg, 0.36 mmol) was
added. The solution was cooled in ice bath and butyl
chloroformate (40 mL, 0.31 mmol) was added. After stirred at
room temperature overnight, the mixture was added by HCl
(1N, 50 mL) and extracted with ethyl acetate (2Â 50 mL). The
combined organic layers were washed with HCl (1N) and brine,
After compound 5 (65 mg, 0.13 mmol) was dissolved in DMF
(
5 mL), Pd(OAc)
.026 mmol), Cs CO
2
(3 mg, 0.013 mmol), DPPF (14 mg,
0
2
3
(42 mg, 0.13 mmol), and N-methylpiper-
azine (16 mg, 0.16 mmol) were added. The resulted mixture
was heated at 120 8C in nitrogen with stirring for 6 h, allowed
to cool to room temperature, poured into water, and extracted
with ethyl acetate (150 mL). The organic extract was washed
dried over Na
2
SO
4
, concentrated in vacuum, and then purified
:CH OH = 30:1).
with water for three times, dried over Na
concentrated in vacuum. The residue was purified by column
chromatography (eluted with CHCl :CH OH = 20:1). The
yielded compound in title was a white solid (55 mg, yield:
9%).
mp 187–188 8C; H NMR (300 MHz, CD
J = 7.2, 3H, CH ), 1.71–1.78 (m, 2H), 2.19 (s, 3H, NCH
NCH ), 2.43 (br s, 4H), 2.50 (br s, 4H), 2.77 (t, J = 7.2, 2H, CH
br s, 4H), 3.13 (br s, 4H), 4.14 (s, 3H, NCH ), 7.70 (s, 1H), 12.14 (s,
): d 13.82, 21.71, 27.05, 37.74,
2
SO
4
, and then
by column chromatography (eluted with CHCl
3
3
The yielded compound in title was a white solid (50 mg, yield:
3
3
61%).
1
mp 317–318 8C (dec.); H NMR (500 MHz, CD
3
SOCD
), 1.23–1.30 (m, 2H,
), 1.73–1.80 (m, 2H, CH ), 2.79 (t,
), 4.04 (t, J = 5.7, 2H, OCH ), 4.14 (s, 3H, NCH ),
8.30 (s, 1H), 8.78 (s, 1H), 12.55 (s, 1H); C NMR (125 MHz,
CD SOCD ): d 13.26, 13.69, 18.20, 21.46, 26.97, 29.91, 37.75, 65.75,
3
): d 0.83
7
(t, J = 7.2, 3H, CH
CH ), 1.49–1.54 (m, 2H, CH
J = 7.2, 2H, CH
3 3
), 0.95 (t, J = 6.9, 3H, CH
1
3
SOCD
3
): d 0.96 (t,
), 2.23 (s, 3H,
), 3.00
2
2
2
3
3
2
2
3
1
3
3
2
(
3
3
3
13
1
4
1
1
H); C NMR (75 MHz, CD
3
SOCD
3
124.3, 132.6, 133.8, 134.6, 137.3, 140.5, 144, 8, 144.9, 151.0, 154.2;
À1
5.05, 45.32, 45.63, 52.23, 53.25, 53.68, 117.4, 119.9, 124.0, 134.1,
37.2, 144.5, 145.5, 153.5, 163.1; IR (KBr): 3432, 2940, 1698,
IR (KBr): 3437, 2961, 1755, 1681, 1584 cm ; ESI-MS: m/z = 452
À
[MÀH] . Anal. calcd for C18
23 5 5 2
H N O S : C, 47.67; H, 5.11; N, 15.44;
À1
À
582 cm
;
ESI-MS: m/z = 533 [MÀH] . Anal. calcd for
found: C, 47.54; H, 5.17; N, 15.45.
23 34 8 3 2
C H N O S : C, 51.66; H, 6.41; N, 20.96; found: C, 51.76; H,
6
.38; N, 20.91.
2.1.12. 5-(5-(N-Propyloxycarbonylaminosulfonyl)-3-thienyl)-
-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-
1
2
.1.9. 5-(2-Ethoxy-5-(sulfamoyl)-3-thienyl)-1-methyl-3-
one (15)
propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (12)
Compound 12 was prepared by the same method for
compound 8 except for the replacement of methanol and
compound 5, respectively with ethanol and compound 6. It
Compound 15 was prepared from compound 13 by the
same procedure for compound 14, except for a replacement
of butyl chloroformate with propyl chloroformate. Yield:
65%.
1
was a white solid (56 mg, yield: 56%).
mp 312–313 8C (dec.); H NMR (300 MHz, CD
3
SOCD
), 1.52–1.59 (m, 2H,
), 2.79 (t, J = 6.6, 2H, CH ), 4.00 (t,
), 4.14 (s, 3H, NCH ), 8.31 (s, 1H), 8.79 (s, 1H),
12.57 (s, 1H); C NMR (125 MHz, CD SOCD ): d 9.84, 13.69, 21.31,
3
): d 0.84
1
mp 255–256 8C; H NMR (300 MHz, CD
3
SOCD
3
): d 0.94 (t,
), 2.76
), 7.69 (s,
), 11.37 (s, 1H); C NMR (75 MHz,
): d 13.79, 14.41, 21.59, 27.10, 37.79, 72.36, 113.7, 123.8,
28.5, 129.6, 137.4, 144.5, 144.6, 153.2, 166.3; IR (KBr): 3332, 3089,
(t, J = 6.9, 3H, CH
CH ), 1.72–1.79 (m, 2H, CH
J = 5.4, 2H, OCH
3 3
), 0.95 (t, J = 6.6, 3H, CH
J = 6.8, 3H, CH
3
), 1.46 (t, J = 6.3, 3H), 1.73–1.78 (m, 2H, CH
t, J = 7.0, 2H, CH ), 4.13 (s, 3H, NCH ), 4.34 (m, 2H, OCH
H), 7.69 (br s, 2H, SONH
SOCD
2
2
2
2
(
2
3
2
2
3
1
3
13
1
2
3
3
CD
3
3
21.47, 26.96, 37.74, 67.50, 124.3, 132.7, 133.8, 134.7, 137.3, 140.5,
144.8, 144.9, 151.0, 154.2; IR (KBr): 3429, 2963, 1748, 1681,
1
2
À1
À
À1
À
969, 1684, 1587 cm ; ESI-MS: m/z = 396 [MÀH] . Anal. calcd
: C, 45.33; H, 4.82; N, 17.62; found: C, 45.29; H,
1584 cm
;
ESI-MS: m/z = 438 [MÀH] . Anal. calcd for
for C15
H
N O
19 5 4
S
2
17 21 5 5 2
C H N O S : C, 46.46; H, 4.82; N, 15.93; found: C, 46.35; H,
4
.75; N, 17.70.
4.85; N, 15.87.