Synthesis and herbicidal activity of novel pyrazolo[3,4-d]pyrimidin-4-one derivatives containing aryloxyphenoxypropionate moieties

Article abstract of DOI:10.1016/j.bmcl.2007.01.083

The 6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio(alkylsulfonyl)-1-phenyl-5-(substituted phenyl)pyrazolo[3,4-d]pyrimidin-4-ones 6 and 7 have been synthesized via the tandem aza-Wittig and annulation reactions of the corresponding iminophosphoranes 4, arom

Full text of DOI:10.1016/j.bmcl.2007.01.083

Bioorganic & Medicinal Chemistry Letters 17 (2007) 2203–2209
Synthesis and herbicidal activity of novel pyrazolo[3,4-d]pyrimidin-
4-one derivatives containing aryloxyphenoxypropionate moieties
Hui Liu,a Hong-Qing Wangb and Zhao-Jie Liua,*
aKey Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, 152 Luoyu Road, Wuhan, Hubei 430079, China
bCollege of Chemistry and Chemical Engineering, Nanhua University, Hengyang, Hunan 421001, China
Received 2 August 2006; revised 4 January 2007; accepted 23 January 2007
Available online 1 February 2007
Abstract—The 6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio(alkylsulfonyl)-1-phenyl-5-(substituted phenyl)pyrazolo[3,4-d]pyr-
imidin-4-ones 6 and 7 have been synthesized via the tandem aza-Wittig and annulation reactions of the corresponding iminophos-
phoranes 4, aromatic isocyanates, and substituted phenols 2 in 52–98% yields. Their structures were clearly verified by spectroscopic
1
data (IR, H NMR, 13C NMR, MS, and elemental analysis or X-ray diffraction crystallography). And the results of preliminary
bioassay indicated that these title compounds possess potential herbicidal activity against the root of rape and barnyard grass.
Ó 2007 Elsevier Ltd. All rights reserved.
The derivatives of fused pyrimidinones have been the fo-
cus of great interest over many years due to the fact that
many compounds containing a fused pyrimidinone ring
play an important role in the biochemistry of the living
cell.1 Pyrazolo[3,4-d]pyrimidin-4-one derivatives also
have extremely rich biological activities because of their
structural similarity with purines,2 they exhibit excellent
antibacterial, antiphlogistic, and antitumor activities,3
and they are employed in the treatment of erectile dys-
function in male animals.4 In previous reports, various
synthetic procedures have been devised for the conversion
of o-aminonitriles and o-aminoesters bearing pyrazole
ring to pyrazolopyrimindinone derivatives.5 However,
3-substituted-6-(4-alkoxycarb-onylalkoxy)phenoxy pyr-
azolo[3,4-d]pyrimidin-4-ones are not easily accessible by
these existing methods.
carbonates are of good fungicidal activity and anti-can-
cer activity.8
Aza-Wittig reactions of iminophosphoranes have re-
ceived increasing attention in view of their utility in
the synthesis of nitrogen-containing heterocyclic com-
pounds.9 Recently, aza-Wittig reactions of isocyanates
were used to synthesize carbodiimides, which, in turn,
were able to undergo a plethora of cyclization reactions,
leading to the preparation of thienodipyrimidinones,10
quinazolines,11 imidazolinones,12 pteridinones,13 and
fused pyrimidines.14 As the continuing work of our
search for new herbicidal active heterocycles,15 we
designed the structures which contain both pyrazolo-
[3,4-d]pyrimidin-4-one and aryloxyphenoxypropionate
(APP) moieties based on biochemical reasoning, and
developed a new annulation process (Scheme 1), which
proceeded smoothly via a tandem aza-Wittig and
cyclization reaction to afford the novel title compounds
6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio(alkylsulfo-
nyl)-1-phenyl-5-(substituted phenyl)pyrazolo[3,4-d]pyrimi-
din-4-ones 6 and 7, in order to obtain better herbicidal
activity.
Aryloxyphenoxypropionate (APP) derivatives are a very
important class of herbicides in the international mar-
ket.6 In recent years, heterocycles were introduced to
the structures of APP, which lead to the development
of a new series of highly efficient herbicides, such as
whip, fenthiaprop-ethyl, quizalofop-ethyl, and heloxy-
fop-methyl.7 Furthermore, some heteroaryloxo-phenoxy
The iminophosphorane 4, which was prepared from
3-alkylthio-5-amino-4-ethoxycarbonyl-1-phenylpyrazole 3,
reacted with aromatic isocyanate to afford carbodiimide
5. Then reaction of 2-(4-hydroxyphenoxy)-carboxylate 2
with 5 provides intermediate guanidine 8. In the
presence of catalytic amount of potassium carbonate,
Keywords: Pyrazolo[3,4-d]pyrimidin-4-one; Aza-Wittig reaction; Syn-
thesis; Herbicide.
*
Corresponding author. E-mail: zhjliu@mail.ccnu.edu.cn
0960-894X/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2007.01.083

2204
H. Liu et al. / Bioorg. Med. Chem. Lett. 17 (2007) 2203–2209
O
Br
R1
O
O
HO
O
R1
R2
HO
OH
O
R2
a
1
2
R3S
R3S
R3S
COOEt
NH2
Ph
3
COOEt
COOEt
N C NAr
5
PPh3/Br2
b
ArNCO
c
N
N
N
PPh
N
3
N
N
N
Ph
Ph
4
O
R3S
N
O
N
O
O
O
O
R3
S
K2CO3
d
[O]
e
R1
Ar
N
O
R1
Ar
O
O
+
5 2
N
O
R2
N
R2
N
N
O
N
O
Ph
Ph
6
7
Scheme 1. Synthesis of the title compounds 6 and 7. Reagents and conditions: (a) R1ONa, R1OH, 0–35 °C, 6 h, yields 57–66%; (b) Et3N, CH2Cl2,
0 °C for 30 min then 25 °C for 26 h, yields 84%; (c) CH2Cl2, rt, 2–5 h; (d) K2CO3, CH3CN, reflux, 5 h, yields 52–84%; (e) Na2WO4ÆH2O, AcOH, 30%
H2O2, 50 °C, 5 h, yields 75–98%.
O
R3S
R3S
COOEt
Et
O
NAr
N C
N
N
N C NAr
N
R3S
N
O
N
O
N
Ar
O
O
R1
O
-EtOH
Ph
K2CO3
Ph
N
O
5
R2
N
O
HO
O
R1
Ph
O
6
O
R2
R2
O
2
O R1
8
Scheme 2. The cyclization of carbodiimide 5 to synthesize the title compounds 6.
the reaction took place to give 6 in moderate to good
yields after recrystallization. This process can be ratio-
nalized in Scheme 2.
Cl) or electron-donating group (Me). R1, R2, and R3
also could be various alkyl groups. Satisfactory yields
of 6 were obtained when polar solvent acetonitrile was
used;16 furthermore, compounds 6 could be oxidized
by hydrogen peroxide (H2O2) using sodium wolframate
(Na2WO4) as catalyst to give the corresponding
compounds 7 at about 40 °C. The results are listed in
Table 1.
In this reaction, a variety of substituents can be tolerat-
ed in Ar group, such as electron-withdrawing groups (F,
Table 1. Yields of compounds 6 and 7
Compounds
R3 R2 R1
Yields Yields
of 6 (%) of 7 (%)
R
NCO
R =
6a, 7a
6b, 7b
6c, 7c
6d, 7d
6e, 7e
6f, 7f
H
Me Me Me 80
Me Me Me 73
Me Me Me 80
Me Me Me 65
75
78
91
85
98
83
86
77
90
82
78
95
77
o-Cl
m-Me
o-F
H
Me Me Et
Me Me Et
Me Me Et
84
71
78
82
52
66
o-Cl
m-Me
m-Me
m-Me
m-Me
H
6g, 7g
6h, 7h
6i, 7i
Me
Bn Me Et
Bn Et
H
Et
6j, 7j
H
6k, 7k
6l, 7l
6m, 7m
Me Me n-Pr 82
Me Me n-Pr 72
Me Me n-Pr 74
o-Cl
m-Me
Figure 1. View and atom labeling of 6h.

H. Liu et al. / Bioorg. Med. Chem. Lett. 17 (2007) 2203–2209
Table 2. The herbicidal activity of compounds 6 and 7
2205
Compound
Relative inhibition (root%/stalk%)
Rape (100 mg/L)
Rape (10 mg/L)
Barnyard grass (100 mg/L)
Barnyard grass (10 mg/L)
6a
6b
6c
6d
6e
6f
96.1/76.9
84.3/56.4
52.2/17.8
27.2/0.0
86.1/46.2
93.1/63.5
97.0/63.5
100/100
40.2/20.5
27.5/7.7
3.3/6.7
93.5/68.9
97.8/68.9
66.7/À7.3
62.2/0.0
63.0/44.8
63.0/62.1
35.5/À5.3
51.1/À31.6
57.7/12.9
75.0/À25.8
59.6/À12.9
59.6/À6.5
33.3/À6.4
66.7/5.3
19.6/6.7
57.4/12.9
61.4/26.9
46.5/9.6
60.4/25.0
24.4/À2.1
20.6/20.0
21.1/À2.1
5.5/10.6
30.0/31.9
25.0/13.3
14.1/2.2
19.6/13.3
16.3/0.0
42.2/15.4
29.4/5.1
51.0/17.9
50.0/28.2
9.8/6.7
88.5/32.3
92.3/35.5
88.5/0.0
6g
6h
6i
98.1/77.4
61.9/À6.4
75.5/À10.5
71.4/35.5
64.3/25.8
57.1/35.5
93.3/31.6
46.7/15.8
86.7/15.8
53.3/À21.0
89.1/34.5
89.1/47.9
95.6/51.7
95.6/37.9
72.5/16.7
62.2/0.0
32.2/10.6
64.1/24.0
44.4/14.9
36.7/8.5
35.5/4.3
80.4/48.9
21.7/4.4
72.8/26.7
28.0/0.0
89.2/58.9
81.4/48.7
98.0/74.4
94.1/71.8
34.8/6.7
51.1/6.7
27.2/6.7
67.4/42.2
63.0/31.1
99.0/91.2
6j
6k
6l
57.1/25.8
53.4/25.8
30.9/41.9
66.7/5.3
6m
7a
7b
7c
7d
7e
7f
42.2/À5.3
44.4/À15.8
33.3/10.5
50.0/31.0
63.0/37.9
54.3/3.4
7g
7h
7i
58.7/À3.4
50.0/13.3
35.5/À5.3
32.5/13.3
50.0/16.7
35.0/13.3
97.5/30.8
7j
21.7/15.5
3.3/2.2
7k
7l
62.5/13.3
80.0/23.3
80.0/20.0
97.5/33.3
17.4/À17.8
14.1/13.3
98.1/91.2
7m
2,4-D
The structures of compounds 6 and 7 were deduced from
their spectra data (IR, 1H NMR, 13C NMR, MS, and ele-
mental analysis).17 Compound 6h was recrystallized by
slow evaporation from CH2Cl2, and its single crystal
was analyzed by X-ray diffraction crystallography.18
The corresponding structure is shown in Figure 1. X-ray
structure analysis further confirmed the proposed struc-
ture and showed that ring atoms in pyrazolo[3,4-d]pyrim-
idin-4-one moiety are essentially planar. The bond lengths
of C(8)@N(1), C(9)@C(10), and C(12)@N(4) are 1.313(5),
cidal activity than the corresponding methyl ester and
n-propyl ester in general, the reason may be the hydro-
lysis of the products.20 The investigations on R and S
isomers of products are going on further.
In summary, we have developed a novel synthesis of
6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio(alkylsulfo-
nyl)-1-phenyl-5-(substituted phenyl)pyrazolo[3,4-d]pyr-
imidin-4-one derivatives via tandem aza-Wittig and
annulation reactions smoothly in moderate to good
yields. The structure of the title compounds has both
the skeletons of pyrazolo[3,4-d]pyrimidin-4-one and
aryloxyphenoxypropionate (APP). The herbicidal tests
showed that these title compounds possess herbicidal
activity and could be further used as potential
herbicides.
´
˚
1.371(5), and 1.283(4) A, respectively, which are longer
´
˚
than the lengths of the typical C@N (1.28 A) and C@C
(1.34 A), while the single bond lengths of C(10)–N(2),
C(8)–C(9), C(9)–C(11), C(12)–N(3), and C(10)–N(4),
´
˚
´
˚
are 1.345(5), 1.409(5), 1.432(5), 1.375(4), and 1.377(4) A,
respectively, which are significantly shorter than
´
2
the lengths of typical C(sp )–N (1.426 A) and C–C
˚
´
˚
(1.53 A). These results show some degree of delocaliza-
tion in 6h.
Acknowledgment
The herbicidal activity of all compounds 6 and 7 against
brassica napus (rape) and echinochloa crus-galli (barn-
yard grass) has been investigated at the dosage of 100
and 10 mg/L using the reported procedure,19 compared
with distilled water and 2,4-dichlorophenoxyl acetic acid
(2,4-D), a commercially available herbicide in the mar-
ket. The results of preliminary bioassay showed that
some of them exhibit good herbicidal activities (the inhi-
bition rates are listed in Table 2). For example, 6a, 6f,
6h, 7g, and 7h showed more than 90% inhibitory rate
to root of rape and barnyard grass at 100 mg/L. It is also
interesting to note that ethyl ester showed higher herbi-
We are grateful to the National Natural Science Foun-
dation of China (No. 20101001).
References and notes
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carboxylate 2 was prepared according to literature
procedures.17a,7b Compound 3-Alkylthio-5-amino-4-eth-
oxycarbonyl-1-phenylpyrazole 3 was prepared according
to literature procedures.17c Iminophosphorane 4 was
prepared according to the reported procedures.17d Melting
points were uncorrected. IR was recorded on a Perkin-
Elmer PE-983 infrared spectrometer as KBr film with
1
absorption in cmÀ1. H NMR spectra were recorded on
Mercury Plus-400 (400 MHz) spectrophotometers. Chem-
ical shifts are reported in ppm from TMS with the solvent
resonance as the internal standard (CDCl3: d 7.26). 13C
NMR spectra were recorded on Mercury Plus-400
(100 MHz) spectrophotometers with complete proton
decoupling spectrophotometers (CDCl3: 77.2). Mass spec-
tra were measured on a Finnigan Trace MS spectrometer.
Elementary analyses were taken on a Vario EL III
elementary analysis instrument. X-ray diffraction crystal-
lography was measured on Bruker Smart Apex Area
CCD.
General procedure for the preparation of 6-(4-
alkoxycarbonylalkoxy)phenoxy-3-alkylthio-1-phenyl-5-(substi-
tuted phenyl)pyrazolo[3,4-d]pyrimidin-4-ones (6a–6m). To
a solution of iminophosphorane 4 (2 mmol) in dry
dichloromethane (25 mL), aromatic isocyanate (2 mmol)
was added under nitrogen at room temperature. After the
reaction mixture was stirred for 2–5 h, the solvent was
removed off under reduced pressure, then 25 mL anhy-
drous accetonitrile, 2.0 mmol 2-(4-hydroxyphenoxy)-car-
boxylate 2, and 0.05 g anhydrous potassium carbonate
were added to the mixture. Stirring for another 5 h
at refluxing and filtering, the solution was condensed
under reduced pressure, the residue was recrystallized with
ethanol to give pure 6-(4-alkoxycarbonylalkoxy)phenoxy-
3-alkylthio-1-phenyl-5-(substituted phenyl)pyrazolo[3,4-
d]pyrimidin-4-ones 6a–6m.
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1563.
6-[4-(1-Methoxycarbonylethoxy)]phenoxy-3-methylthio-
1,5-diphenylpyrazolo[3,4-d]pyrimidin-4-one (6a). White
crystals, mp 238–240 °C; yield, 80%; IR (KBr) t (cmÀ1):
2990, 2926, 1753, 1704, 1604, 1574, 1547, 1516, 1500, 1347,
1
1204, 1136, 895, 769, 688; H NMR (CDCl3, 400 MHz) d
7.91 (d, 2H, J = 7.6 Hz, Ph), 7.26–7.52 (m, 7H, Ph), 7.20
(t, 1H, J = 8.0 Hz, Ar), 7.08 (dd, 2H, J = 2.0 and 7.2 Hz,
OC6H4O), 6.90 (dd, 2H, J = 2.0 and 8.0 Hz, OC6H4O),
4.77 (q, 1H, J = 6.8 Hz, OCHC@O), 3.75 (s, 3H, OCH3),
2.67 (s, 3H, SCH3), 1.65 (d, 3H, J = 6.8 Hz, CH3CHO);
EI-MS (70 eV, m/z): 528 (M+À1), 530 (M++2); Elemental
Anal. Calcd for C28H24N4O5S: C, 63.62; H, 4.58; N, 10.60.
Found: C, 63.49; H, 4.67; N, 10.42.
5-(2-Chlorophenyl)-6-[4-(1-methoxycarbonylethoxy)]phen-
oxy-3-methylthio-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(6b). White crystals, mp 182–183 °C; yield, 73%; IR (KBr)
t (cmÀ1): 2989, 2955, 1754, 1718, 1591, 1573, 1545, 1352,
1190, 1099, 896, 824, 762, 689; 1H NMR (CDCl3,
400 MHz) d 7.91 (d, 2H, J = 8.0 Hz, Ph), 7.18–7.71 (m,
8H, Ar), 7.11 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90 (d, 2H,
J = 9.2 Hz, OC6H4O), 4.77 (q, 1H, J = 6.8 Hz,
OCHC@O), 3.76 (s, 3H, OCH3), 2.68 (s, 3H, SCH3),
1.65 (d, 3H, J = 6.4 Hz, CH3CHO); EI-MS (70 eV, m/z):
562 (M+À1), 563 (M+); Elemental Anal. Calcd for
C28H23ClN4O5S: C, 57.93; H, 4.12; N, 9.95. Found: C,
60.00; H, 4.01; N, 10.12.
16. Ding, M.-W.; Zeng, G.-P.; Wu, T.-J. Synth. Commun.
1999, 29, 1171.
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G.-X.; Liu, Y.-X.; Yang, X.-F.; Yang, H.-Z. Chin. J. Appl.
6-[4-(1-Methoxycarbonylethoxy)]phenoxy-5-(3-methyl-
phenyl)-3-methylthio-1-phenylpyrazolo[3,4-d]pyrimidin-
4-one (6c). White crystals, mp 239–241 °C; yield, 80%; IR

H. Liu et al. / Bioorg. Med. Chem. Lett. 17 (2007) 2203–2209
2207
(KBr) t (cmÀ1): 2989, 2927, 1753, 1701, 1602, 1573, 1548,
1501, 1349, 1195, 1135, 830, 755, 686; H NMR (CDCl3,
J = 7.6 Hz, Ar), 7.15–7.35 (m, 6H, Ar), 7.08 (d, 2H,
J = 8.8 Hz, OC6H4O), 6.90 (d, 2H, J = 8.8 Hz, OC6H4O),
4.74 (q, 1H, J = 7.2 Hz, CHC@O), 4.21 (q, 2H, J = 7.6 Hz,
OCH2), 2.67 (s, 3H, SCH3), 2.43 (s, 3H, m-CH3Ph), 1.65
(d, 3H, J = 8.4 Hz, CHCH3), 1.23 (t, 3H, J = 7.2 Hz,
CH2CH3); EI-MS (70 eV, m/z): 556 (M+), 557(M++1);
Elemental Anal. Calcd for C30H28N4O5S: C, 64.73; H,
5.07; N, 10.0. Found: C, 64.87; H, 4.82; N, 10.04.
6-(4-Ethoxycarbonylmethoxy)phenoxy-5-(3-methylphenyl)-
3-methylthio-1-phenylpyrazolo[3,4-d]pyrimidin-4-one (6h).
White crystals, mp 202–204 °C; yield, 82%; IR (KBr) t
(cmÀ1): 2974, 2930, 1751, 1701, 1603, 1573, 1549, 1502,
1349, 1186, 1077, 911, 830, 779, 684; 1H NMR (CDCl3,
400 MHz) d 7.91 (d, 2H, J = 8.0 Hz, Ar), 7.43 (t, 1H,
J = 7.8 Hz, Ar), 7.15–7.34 (m, 6H, Ar), 7.10 (d, 2H,
J = 8.8 Hz, OC6H4O), 6.94 (d, 2H, J = 9.2 Hz, OC6H4O),
4.64 (s, 2H, J = 7.2 Hz, OCH2C@O), 4.28 (q, 2H,
J = 7.2 Hz, OCH2), 2.67 (s, 3H, SCH3), 1.30 (t, 3H,
J = 7.2 Hz, OCH2CH3); EI-MS (70 eV, m/z): 542 (M+),
543 (M++1); Elemental Anal. Calcd for C29H26N4O5S: C,
64.19; H, 4.83; N, 10.33. Found: C, 64.32; H, 4.64; N,
10.37.
3-Benzylsulfanyl-6-[4-(1-ethoxycarbonylethoxy)]phenoxy-
5-(3-methylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(6i). White crystals, mp 117–120 °C; yield, 52%; IR (KBr)
t (cmÀ1): 2986, 2921, 1728, 1705, 1598, 1572, 1555, 1502,
1271, 1197, 1089, 1047, 911, 828, 762, 698; 1H NMR
(CDCl3, 400 MHz) d 7.89 (d, 2H, J = 8.8 Hz, Ar), 7.08–
7.49 (m, 12H, Ar), 7.05 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90
(d, 2H, J = 9.2 Hz, OC6H4O), 4.74 (q, 1H, J = 7.2 Hz,
OCHC@O), 4.49 (s, 2H, PhCH2), 4.21 (q, 2H, J = 6.8 Hz,
OCH2), 2.43 (s, 3H, PhCH3), 1.65 (d, 3H, J = 6.8 Hz,
CHCH3), 1.24 (t, 3H, J = 7.2 Hz, CH2CH3); 13C NMR
(100 MHz, CDCl3): d 14.3, 18.6, 21.5, 35.2, 61.5, 73.2,
102.6, 115.9, 120.3, 122.7, 125.4, 126.1, 127.3, 128.5, 128.9,
129.0, 129.3, 130.1, 134.3, 137.7, 138.7, 139.6, 145.9, 146.2,
151.2, 155.7, 156.4, 157.5, 171.9; EI-MS (70 eV, m/z): 633
(M+), 634 (M++1); Elemental Anal. Calcd for
C36H32N4O5S: C, 68.34; H, 5.10; N, 8.85. Found: C,
68.32; H, 4.94; N, 8.77.
1
400 MHz) d 7.91 (d, 2H, J = 8.0 Hz, Ar), 7.17–7.42 (m,
7H, Ar), 7.08 (d, 2H, J = 9.2 Hz, OC6H4O), 6.90 (d, 2H,
J = 8.8 Hz, OC6H4O), 4.77 (q, 1H, J = 6.4 Hz,
OCHC@O), 3.76 (s, 3H, OCH3), 2.68 (s, 3H, SCH3),
2.43 (s, 3H, m-CH3C6H4), 1.65 (d, 3H, J = 6.4 Hz,
CH3CHO); 13C NMR (100 MHz, CDCl3): d 13.6, 18.7,
21.5, 52.5, 73.3, 102.4, 116.0, 120.3, 122.8, 125.4, 126.1,
129.0, 129.4, 130.2, 134.4, 138.8, 139.7, 146.0, 147.5, 151.3,
155.7, 156.4, 157.7, 172.5; EI-MS (70 eV, m/z): 542 (M+);
Elemental Anal. Calcd for C29H26N4O5S: C, 64.19; H,
4.83; N, 10.33. Found: C, 64.35; H, 5.01; N, 10.22.
6-[4-(1-Methoxycarbonylethoxy)]phenoxy-5-(2-fluorophe-
nyl)-3-methylthio-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(6d). White crystals, mp 205–206 °C; yield, 65%; IR (KBr)
t (cmÀ1): 2991, 2951, 1748, 1709, 1601, 1576, 1546, 1501,
1350, 1201, 1136, 896, 829, 756, 680; 1H NMR (CDCl3,
400 MHz) d 7.90 (d, 2H, J = 8.4 Hz, Ar), 7.20–7.44 (m,
7H, Ar), 7.07 (dd, 2H, J = 2.0 and 8.8 Hz, OC6H4O), 6.90
(dd, 2H, J = 2.0 and 7.2 Hz, OC6H4O), 4.78 (q, 1H,
J = 7.2 Hz, OCHC@O), 3.76 (s, 3H, OCH3), 2.68 (s, 3H,
SCH3), 1.65 (d, 3H, J = 6.8 Hz, CH3CHO); 13C NMR
(100 MHz, CDCl3): d 13.5, 18.6, 52.5, 73.2, 102.1, 116.0,
116.6, 116.8, 120.4, 122.2, 122.7, 124.8, 126.2, 128.9, 130.6,
131.2, 131.3, 138.7, 145.9, 147.5, 151.3, 155.7, 156.0, 156.6,
156.8, 159.1, 172.4; EI-MS (70 eV, m/z): 546 (M+À1), 547
(M+); Elemental Anal. Calcd for C28H23FN4O5S: C,
61.53; H, 4.24; N, 10.25. Found: C, 61.24; H, 4.36; N,
10.38.
6-[4-(1-Ethoxycarbonylethoxy)]phenoxy-3-methylthio-
1,5-diphenylpyrazolo[3,4-d]pyrimidin-4-one (6e). White
crystals, mp 213–214 °C, yield, 84%; IR (KBr) t (cmÀ1):
2991, 2924, 1743, 1703, 1604, 1573, 1548, 1501, 1348, 1192,
1
1135, 1093, 896, 830, 688; H NMR (CDCl3, 400 MHz) d
7.91 (d, 2H, J = 8.0 Hz, Ph), 7.54 (d, 2H, J = 7.6 Hz, Ph),
7.49 (d, 1H, J = 7.2 Hz, Ph), 7.31–7.37 (m, 4H, Ph), 7.20
(t, 1H, J = 7.2 Hz, Ph), 7.07 (d, 2H, J = 9.2 Hz, OC6H4O),
6.90 (d, 2H, J = 8.8 Hz, OC6H4O), 4.74 (q, 1H, J = 6.8 Hz,
OCH), 4.21 (q, 2H, J = 7.2 Hz, OCH2), 2.67 (s, 3H,
SCH3), 1.64 (d, 3H, J = 6.8 Hz, CH3CH), 1.23 (t, 3H,
J = 6.4 Hz, CH2CH3); EI-MS (70 eV, m/z): 542 (M+), 543
(M++1); Elemental Anal. Calcd for C29H26N4O5S: C,
64.19; H, 4.83; N, 10.33. Found: C, 64.35; H, 4.67; N,
10.54.
3-Benzylsulfanyl-6-(4-ethoxycarbonylmethoxy)phenoxy-5-
(3-methylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(6j). White crystals, mp 130–131 °C; yield, 66%; IR (KBr)
t (cmÀ1): 2980, 2919, 1759, 1701, 1598, 1572, 1544, 1503,
1
1193, 1085, 778, 690; H NMR (CDCl3, 400 MHz) d 7.86
5-(2-Chlorophenyl)-6-[4-(1-ethoxycarbonylethoxy)phen-
oxy-3-methylthio-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(6f). White crystals, mp 192–194 °C, yield, 71%; IR (KBr)
t (cmÀ1): 2985, 2932, 1747, 1714, 1594, 1575, 1551, 1503,
1350, 1205, 1188, 1130, 895, 825, 778, 759; 1H NMR
(CDCl3, 400 MHz) d 7.91 (d, 2H, J = 8.4 Hz, Ar), 7.59 (d,
1H, J = 2.8 Hz, Ar), 7.46 (d, 3H, J = 3.2 Hz, Ar), 7.33 (t,
2H, J = 7.8 Hz, Ar), 7.20 (t, 1H, J = 7.2 Hz, Ar), 7.10 (d,
2H, J = 8.8 Hz, OC6H4O), 6.91 (d, 2H, J = 8.8 Hz,
OC6H4O), 4.75 (q, 1H, J = 6.8 Hz, OCH), 4.21 (q, 2H,
J = 7.2 Hz, OCH2), 2.68 (s, 3H, SCH3), 1.65 (d, 3H,
J = 6.8 Hz, CH3CH), 1.24 (t, 3H, J = 7.2 Hz, CH2CH3);
13C NMR (100 MHz, CDCl3): d 13.5, 14.3, 18.6, 61.5,
73.3, 102.2, 115.9, 120.4, 122.7, 126.2, 128.0, 128.9, 130.5,
130.8, 132.5, 138.7, 145.8, 147.6, 151.4, 155.8, 156.0, 156.7,
171.9; EI-MS (70 eV, m/z): 576 (M+), 578 (M++2);
Elemental Anal. Calcd for C29H25ClN4O5S: C, 60.36; H,
4.37; N, 9.71. Found: C, 60.57; H, 4.20; N, 9.69.
(d, 2H, J = 7.6 Hz, Ar), 7.07–7.49 (m, 12H, Ar), 7.08 (d,
2H, J = 8.8 Hz, OC6H4O), 6.90 (d, 2H, J = 9.2 Hz,
OC6H4O), 4.63 (3, 2H, OCH2C@O), 4.50 (s, 2H, PhCH2),
4.28 (q, 2H, J = 7.2 Hz, OCH2), 2.43 (s, 3H, PhCH3), 1.28
(t, 3H, J = 7.2 Hz, CH2CH3); 13C NMR (100 MHz,
CDCl3): d 14.3, 21.6, 60.5, 61.7, 65.9, 101.5, 115.5, 121.7,
122.6, 125.2, 126.8, 128.0, 128.8, 128.9, 129.0, 129.1, 129.7,
130.7, 131.5, 133.9, 137.6, 140.1, 145.8, 146.5, 151.9, 156.2,
156.6, 157.0, 168.6; EI-MS (70 eV, m/z): 618 (M+À1),
619(M+); Elemental Anal. Calcd for C35H30N4O5S: C,
67.94; H, 4.89; N, 9.06. Found: C, 68.02; H, 4.94; N, 8.98.
3-Methylthio-1,5-diphenyl-6-[4-(1-propoxycarbonyleth-
oxy)]phenoxy pyrazolo[3,4-d]pyrimidin-4-one (6k). White
crystals, mp 195–197 °C; yield, 82%; IR (KBr) t (cmÀ1):
2974, 2919, 1746, 1701, 1604, 1573, 1548, 1500, 1347, 1191,
1
1134, 895, 757, 687; H NMR (CDCl3, 400 MHz) d 7.91
(d, 2H, J = 8.0 Hz, Ar), 7.20–7.57 (m, 8H, Ph), 7.08 (dd,
2H, J = 7.2 and 2.0 Hz, OC6H4O), 6.90 (dd, 2H, J = 7.2
and 2.0 Hz, OC6H4O), 4.75 (q, 1H, J = 7.2 Hz, CHC@O),
4.11 (m, 2H, OCH2Et), 2.68 (s, 3H, SCH3), 1.60–1.66 (m,
5H, CH3CHO and CH2CH2CH3), 0.87 (t, 3H, J = 7.2 Hz,
CH3); EI-MS (70 eV, m/z): 557 (M+); Elemental Anal.
Calcd for C30H28N4O5S: C, 64.73; H, 5.07; N, 10.07.
Found: C, 64.92; H, 5.16; N, 9.96.
6-[4-(1-Ethoxycarbonylethoxy)]phenoxy-5-(3-methylphe-
nyl)-3-methylthio-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(6g). White crystals, mp 223–225 °C; yield, 78%; IR (KBr)
t (cmÀ1): 2989, 2924, 1744, 1701, 1601, 1573, 1549, 1501,
1
1349, 1194, 1134, 1093, 831, 779, 755; H NMR (CDCl3,
400 MHz) d 7.91 (d, 2H, J = 8.0 Hz, Ar), 7.42 (t, 1H,

2208
H. Liu et al. / Bioorg. Med. Chem. Lett. 17 (2007) 2203–2209
5-(2-Chlorophenyl)-3-methylthio-1-phenyl-6-[4-(1-propoxy-
6-[4-(1-Methoxycarbonylethoxy)]phenoxy-5-(3-methyl-
phenyl)-3-methylsulfonyl-1-phenylpyrazolo[3,4-d]pyrimi-
din-4-one (7c). White crystals, mp 227–228 °C; yield, 91%;
IR (KBr) t (cmÀ1): 3012, 2928, 1753, 1723, 1598, 1574,
1545, 1501, 1324, 1202, 1140, 1096, 774, 696; 1H NMR
(CDCl3, 400 MHz) d 7.89 (d, 2H, J = 8.4 Hz, Ar), 7.46 (t,
2H, J = 7.6 Hz, Ar), 7.27–7.40 (m, 3H, Ar), 7.18 (d, 2H,
J = 8.0 Hz, Ar), 7.06 (d, 2H, J = 9.2 Hz, OC6H4O), 6.90
(d, 2H, J = 8.8 Hz, OC6H4O), 4.77 (q, 1H, J = 6.8 Hz,
OCHC@O), 3.76 (s, 3H, OCH3), 3.51 (s, 3H, S(O2)CH3),
2.47 (s, 3H, m-CH3C6H4), 1.65 (d, 3H, J = 6.8 Hz,
CH3CHO); 13C NMR (100 MHz, CDCl3): d 18.7, 21.5,
42.7, 52.5, 73.2, 101.0, 116.0, 121.7, 122.6, 125.2, 128.0,
128.8, 129.2, 129.7, 130.6, 133.9, 137.7, 140.0, 145.7, 147.6,
151.9, 155.9, 156.5, 157.1, 172.4; EI-MS (70 eV, m/z): 574
(M+), 576 (M++2); Elemental Anal. Calcd for
C29H26N4O7S: C, 60.62; H, 4.56; N, 9.75. Found: C,
60.52; H, 4.77; N, 9.89.
carbonylethoxy)]phenoxypyrazolo[3,4-d]pyrimidin-4-one
(6l). White crystals, mp 168–170 °C; yield, 72%; IR (KBr)
t (cmÀ1): 2974, 1751, 1716, 1594, 1574, 1503, 1399,
1351, 1191, 896, 758; 1H NMR (CDCl3, 400 MHz) d
7.91 (d, 2H, J = 7.6 Hz, Ar), 7.20–7.61 (m, 7H, Ar),
7.10 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90 (dd, 2H,
J = 9.2 Hz, OC6H4O), 4.76 (q, 1H, J = 6.8 Hz, CHC@O),
4.12 (t, 2H, J = 6.8 Hz, OCH2Et), 2.69 (s, 3H, SCH3),
1.61–1.66 (m, 5H, CH3CHO and CH2CH2CH3), 0.88 (t,
3H, J = 7.6 Hz, CH3); EI-MS (70 eV, m/z): 590 (M+À1),
591 (M+); Elemental Anal. Calcd for C30H27ClN4O5S:
C, 60.69; H, 4.60; N, 9.48. Found: C, 60.48; H, 4.53; N,
9.57.
5-(2-Methylphenyl)-3-methylthio-1-phenyl-6-[4-(1-prop-
oxycarbonylethoxy)]phenoxypyrazolo[3,4-d]pyrimidin-4-one
(6m). White crystals, mp 187–188 °C; yield, 74%; IR (KBr)
t (cmÀ1): 2971, 2919, 1749, 1701, 1602, 1572, 1550, 1500,
1349, 1192, 1132, 779, 684; 1H NMR (CDCl3, 400 MHz) d
7.91 (d, 2H, J = 8.4 Hz, Ar), 7.15–7.44 (m, 7H, Ar), 7.08
(d, 2H, J = 8.8 Hz, OC6H4O), 6.90 (d, 2H, J = 9.2 Hz,
OC6H4O), 4.76 (q, 1H, J = 6.8 Hz, CHC@O), 4.11 (t, 2H,
J = 6.8 Hz, OCH2Et), 2.67 (s, 3H, SCH3), 2.43 (s, 3H, m-
CH3Ph), 1.60–1.66 (m, 5H, CH3CHO and CH2CH2CH3),
0.87 (t, 3H, J = 7.4 Hz, CH3); EI-MS (70 eV, m/z): 570
(M+À1), 571 (M+); Elemental Anal. Calcd for
C31H30N4O5S: C, 65.25; H, 5.30; N, 9.82. Found: C,
65.46; H, 5.41; N, 10.01.
General procedure for the preparation of 6-(4-alkoxy
carbonylalkoxy)phenoxy-3-alkylsulfonyl-1-phenyl-5-(substi-
tuted phenyl)pyrazolo[3,4-d]pyrimidin-4-ones (7a–7m). To
a 25 mL flask, 1.5 mmol 6 and 15 ml acetic acid were
added at room temperature, and 0.002 g (0.06 mmol)
Na2WO4ÆH2O was added with stirring. Then the reaction
mixture was heated to 40 °C with vigorous stirring. Under
this condition, 0.51 g (4.5 mmol) of 30% H2O2 was added
dropped slowly, when addition is complete, the mixture
was heated to 50 °C and stirred for another 5 h. The
reaction mixture was chilled to room temperature and
dumped to a solution that was dispensed by 0.25 g Na2SO3
and 20 mL water. A great deal white solid was precipitated
with stirring, after filtering, pure compounds 7 were
obtained after recrystallization with ethanol.
5-(2-Fluorophenyl)-6-[4-(1-methoxycarbonylethoxy)]phen-
oxy-3-methylsulfonyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-
one (7d). White crystals, mp 209–210 °C; yield, 85%; IR
(KBr) t (cmÀ1): 2999, 2954, 1755, 1727, 1601, 1574, 1546,
1502, 1327, 1197, 1135, 1093, 901, 828, 758, 692; 1H NMR
(CDCl3, 400 MHz) d 7.89 (d, 2H, J = 7.6 Hz, Ar), 7.30–
7.40 (m, 7H, Ar), 7.06 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90
(d, 2H, J = 9.2 Hz, OC6H4O), 4.77 (q, 1H, J = 6.8 Hz,
OCHC@O), 3.75 (s, 3H, OCH3), 3.51 (s, 3H, S(O2)CH3),
2.44 (s, 3H, m-CH3Ph), 1.65 (d, 3H, J = 6.8 Hz,
CH3CHO); 13C NMR (100 MHz, CDCl3): d 18.6, 21.4,
42.6, 52.5, 73.1, 101.0, 116.0, 121.6, 122.5, 127.9, 129.1,
130.5, 131.2, 137.6, 139.8, 145.7, 147.4, 151.8, 155.8, 156.5,
157.2, 172.3; EI-MS (70 eV, m/z): 574 (M+À4), 575
(M+À3); Elemental Anal. Calcd for C28H23FN4O7S: C,
58.13; H, 4.01; N, 9.68. Found: C, 58.24; H, 4.11; N, 9.79.
6-[4-(1-Ethoxycarbonylethoxy)]phenoxy-3-methylsulfo-
nyl-1,5-diphenylpyrazolo[3,4-d]pyrimidin-4-one (7e). White
crystals, mp 228–229 °C, yield, 98%; IR (KBr) t (cmÀ1):
2987, 2926, 1744, 1726, 1603, 1575, 1546, 1500, 1328, 1192,
1
1136, 1097, 904, 776, 699; H NMR (CDCl3, 400 MHz) d
7.89 (d, 2H, J = 8.0 Hz, Ph), 7.53–7.59 (m, 3H, Ph), 7.31–
7.40 (m, 5H, Ph), 7.06 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90
(d, 2H, J = 9.2 Hz, OC6H4O), 4.74 (q, 1H, J = 6.8 Hz,
OCH), 4.21 (q, 2H, J = 7.2 Hz, OCH2), 3.51 (s, 3H,
S(O2)CH3), 1.64 (d, 3H, J = 6.8 Hz, CH3CH), 1.23 (t, 3H,
J = 7.2 Hz, CH2CH3); EI-MS (70 eV, m/z): 574 (M+), 575
(M++1); Elemental Anal. Calcd for C29H26N4O7S: C,
60.62; H, 4.56; N, 9.75. Found: C, 60.53; H, 4.67; N, 9.54.
5-(2-Chlorophenyl)-6-[4-(1-ethoxycarbonylethoxy)phen-
oxy-3-methylsulfonyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-
one (7f). White crystals, mp 123–125 °C, yield, 83%; IR
(KBr) t (cmÀ1): 2988, 2924, 1747, 1719, 1594, 1575, 1545,
1501, 1321, 1196, 1144, 1098, 903, 828, 766, 670; 1H NMR
(CDCl3, 400 MHz) d 7.89 (d, 2H, J = 8.0 Hz, Ar), 7.29–
7.63 (m, 7H, Ar), 7.09 (d, 2H, J = 8.8 Hz, OC6H4O), 6.91
(d, 2H, J = 9.2 Hz, OC6H4O), 4.75 (q, 1H, J = 7.2 Hz,
OCH), 4.21 (q, 2H, J = 7.2 Hz, OCH2), 3.51 (s, 3H,
S(O2)CH3), 1.65 (d, 3H, J = 7.2 Hz, CH3CH), 1.24 (t, 3H,
J = 7.2 Hz, CH2CH3); 13C NMR (100 MHz, CDCl3): d
14.2, 18.6, 42.6, 61.5, 73.2, 100.7, 116.0, 121.7, 122.5,
128.0, 128.3, 129.1, 130.4, 130.6, 131.2, 131.9, 132.3, 137.5,
145.5, 147.6, 152.0, 155.4, 156.0, 156.7, 171.8; EI-MS
(70 eV, m/z): 608 (M+), 609 (M++2); Elemental Anal.
Calcd for C29H25ClN4O7S: C, 57.19; H, 4.14; N, 9.20.
Found: C, 57.31; H, 4.20; N, 9.09.
6-[4-(1-Methoxycarbonylethoxy)]phenoxy-3-methylsulfonyl-
1,5-diphenylpyrazolo[3,4-d]pyrimidin-4-one (7a). White crys-
tals, mp 256–258 °C; yield, 75%; IR (KBr) t (cmÀ1): 2999,
2917, 1753, 1731, 1596, 1573, 1551, 1499, 1329, 1191, 1134,
1
1088, 901, 762, 690; H NMR (CDCl3, 400 MHz) d 7.89
(d, 2H, J = 8.4 Hz, Ph), 7.53–7.58 (m, 3H, Ph), 7.31–7.40
(m, 5H, Ph), 7.06 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90 (d,
2H, J = 9.2 Hz, OC6H4O), 4.77 (q, 1H, J = 6.8 Hz,
OCHC@O), 3.75 (s, 3H, OCH3), 3.51 (s, 3H, S(O2)CH3),
1.65 (d, 3H, J = 7.2 Hz, CH3CHO); EI-MS (70 eV, m/z):
560 (M+), 561 (M++1); Elemental Anal. Calcd for
C28H24N4O7S: C, 59.99; H, 4.32; N, 9.99. Found: C,
59.89; H, 4.45; N, 10.12.
5-(2-Chlorophenyl)-6-[4-(1-methoxycarbonylethoxy)]phen-
oxy-3-methylsulfonyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-
one (7b). White crystals, mp 153–158 °C; yield, 78%; IR
(KBr) t (cmÀ1): 3000, 2951, 1715, 1593, 1575, 1544, 1504,
1323, 1199, 1141, 1092, 903, 829, 764, 691; 1H NMR
(CDCl3, 400 MHz) d 7.89 (d, 2H, J = 7.6 Hz, Ph),
7.27–7.50 (m, 7H, Ar), 7.09 (d, 2H, J = 8.8 Hz, OC6H4O),
6.90 (d, 2H, J = 8.8 Hz, OC6H4O), 4.77 (q, 1H, J = 6.8 Hz,
OCHC@O), 3.76 (s, 3H, OCH3), 3.51 (s, 3H, S(O2)CH3),
1.65 (d, 3H, J = 6.8 Hz, CH3CHO); EI-MS (70 eV, m/z):
594 (M+), 595 (M++1); Elemental Anal. Calcd for
C28H23ClN4O7S: C, 56.52; H, 3.90; N, 9.42. Found: C,
56.50; H, 4.01; N, 9.32.
6-[4-(1-Ethoxycarbonylethoxy)]phenoxy-5-(3-methylphe-
nyl)-3-methylsulfonyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-
one (7g). White crystals, mp 215–216 °C; yield, 86%; IR
(KBr) t (cmÀ1): 2986, 2930, 1744, 1720, 1600, 1573, 1553,
1501, 1320, 1196, 1135, 1094, 917, 759, 690; 1H NMR

H. Liu et al. / Bioorg. Med. Chem. Lett. 17 (2007) 2203–2209
2209
(CDCl3, 400 MHz) d 7.89 (d, 2H, J = 8.0 Hz, Ar), 7.46 (t,
1H, J = 7.6 Hz, Ar), 7.29–7.40 (m, 5H, Ar), 7.18 (d, 1H,
J = 8.0 Hz, Ar), 7.06 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90
(d, 2H, J = 8.8 Hz, OC6H4O), 4.74 (q, 1H, J = 7.2 Hz,
CHC@O), 4.21 (q, 2H, J = 7.6 Hz, OCH2), 3.51 (s, 3H,
S(O2)CH3), 2.45 (s, 3H, m-CH3Ph), 1.65 (d, 3H,
J = 8.4 Hz, CHCH3), 1.23 (t, 3H, J = 7.2 Hz, CH2CH3);
EI-MS (70 eV, m/z): 588 (M+), 589(M++1); Elemental
Anal. Calcd for C30H28N4O7S: C, 61.21; H, 4.79; N, 9.52.
Found: C, 61.33; H, 4.82; N, 9.76.
6-(4-Ethoxycarbonylmethoxy)phenoxy-5-(3-methylphenyl)-
3-methylsulfonyl-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(7h). White crystals, mp 234–235 °C; yield, 77%; IR (KBr)
t (cmÀ1): 2976, 2924, 1748, 1709, 1601, 1574, 1502, 1446,
1320, 1188, 1144, 1075, 917, 833, 782, 687; 1H NMR
(CDCl3, 400 MHz) d 7.89 (d, 2H, J = 8.0 Hz, Ar), 7.44 (t,
1H, J = 7.8 Hz, Ar), 7.31–7.37 (m, 4H, Ar), 7.18–7.20 (m,
2H, Ar), 7.08 (d, 2H, J = 9.2 Hz, OC6H4O), 6.94 (d, 2H,
J = 9.2 Hz, OC6H4O), 4.64 (s, 2H, J = 7.2 Hz,
OCH2C@O), 4.28 (q, 2H, J = 7.2 Hz, OCH2), 3.51 (s,
3H, S(O2)CH3), 1.30 (t, 3H, J = 7.2 Hz, OCH2CH3); EI-
MS (70 eV, m/z): 574 (M+), 575 (M++1); Elemental Anal.
Calcd for C29H26N4O7S: C, 60.62; H, 4.56; N, 9.75.
Found: C, 60.53; H, 4.48; N, 9.87.
d 7.90 (d, 2H, J = 8.0 Hz, Ar), 7.26–7.58 (m, 8H, Ph), 7.06
(d, 2H, J = 8.8 Hz, OC6H4O), 6.90 (d, 2H, J = 8.8 Hz,
OC6H4O), 4.74 (q, 1H, J = 6.8 Hz, CHC@O), 4.11 (m, 2H,
OCH2Et), 3.51 (s, 3H, S(O2)CH3), 1.57–1.66 (m, 5H,
CH3CHO and CH2CH2CH3), 0.87 (t, 3H, J = 7.6 Hz,
CH3); EI-MS (70 eV, m/z): 589 (M+); Elemental Anal.
Calcd for C30H28N4O7S: C, 61.21; H, 4.79; N, 9.52. Found:
C, 61.18; H, 4.83; N, 9.44.
5-(2-Chlorophenyl)-3-methylsulfonyl-1-phenyl-6-[4-(1-
propoxycarbonylethoxy)]phenoxypyrazolo[3,4-d]pyrimi-
din-4-one (7l). White crystals, mp 148–150 °C; yield, 95%;
IR (KBr) t (cmÀ1): 2971, 1718, 1594, 1575, 1545, 1501, 1196,
1142, 1095, 903, 765; 1H NMR (CDCl3, 400 MHz) d 7.91 (d,
2H, J = 8.0 Hz, Ar), 7.26–7.63 (m, 8H, Ar), 7.06 (d, 2H,
J = 8.8 Hz, OC6H4O), 6.90 (dd, 2H, J = 9.2 Hz, OC6H4O),
4.75 (q, 1H, J = 6.8 Hz, CHC@O), 4.11 (t, 2H, J = 7.2 Hz,
OCH2Et), 3.51 (s, 3H, S (O2)CH3), 1.57–1.66 (m, 5H,
CH3CHO and CH2CH2CH3), 0.87 (t, 3H, J = 7.6 Hz, CH3);
EI-MS (70 eV, m/z): 624 (M+); Elemental Anal. Calcd for
C30H27ClN7O5S: C, 57.83; H, 4.37; N, 8.99. Found: C,
57.91; H, 4.43; N, 8.97.
5-(3-Methylphenyl)-3-methysulfonyl-1-phenyl-6-[4-(1-prop-
oxycarbonylethoxy)]phenoxypyrazolo[3,4-d]pyrimidin-4-
one (7m). White crystals, mp 179–181 °C; yield, 77%; IR
(KBr) t (cmÀ1): 2969, 2923, 1751, 1717, 1601, 1577, 1553,
1502, 1199, 1147, 1093, 1046, 769, 573; 1H NMR (CDCl3,
400 MHz) d 7.90 (d, 2H, J = 8.0 Hz, Ar), 7.17–7.48 (m, 8H,
Ar), 7.06 (d, 2H, J = 8.8 Hz, OC6H4O), 6.90 (d, 2H,
J = 9.2 Hz, OC6H4O), 4.75 (q, 1H, J = 6.8 Hz, CHC@O),
4.11 (t, 2H, J = 7.6 Hz, OCH2Et), 3.51 (s, 3H, S(O2)CH3),
2.48 (s, 3H, m-CH3Ph), 1.57–1.66 (m, 5H, CH3CHO and
CH2CH2CH3), 0.87 (t, 3H, J = 7.4 Hz, CH3); EI-MS
(70 eV, m/z): 602 (M+À1), 603 (M+); Elemental Anal. Calcd
for C31H30N4O7S: C, 61.78; H, 5.02; N, 9.30. Found: C,
61.85; H, 5.14; N, 9.29.
3-Benzylsulfonyl-6-[4-(1-ethoxycarbonylethoxy)]phenoxy-
5-(3-methylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidin-4-
one (7i). White crystals, mp 208–210 °C; yield, 90%; IR
(KBr) t (cmÀ1): 2984, 2930, 1721, 1599, 1574, 1502, 1197,
1
1095, 1047, 918, 781, 688; H NMR (CDCl3, 400 MHz) d
7.85 (d, 2H, J = 8.2 Hz, Ar), 7.21–7.51 (m, 12H, Ar), 7.08
(d, 2H, J = 8.8 Hz, OC6H4O), 6.90 (d, 2H, J = 8.8 Hz,
OC6H4O), 5.00 (s, 2H, PhCH2S(O2)), 4.74 (q, 1H,
J = 6.8 Hz, OCHC@O), 4.21 (q, 2H, J = 6.8 Hz, OCH2),
2.47 (s, 3H, PhCH3), 1.66 (d, 3H, J = 6.4 Hz, CHCH3),
1.23 (t, 3H, J = 7.2 Hz, CH2CH3); 13C NMR (100 MHz,
CDCl3): d 14.3, 18.6, 21.6, 60.5, 61.5, 73.2, 101.4, 116.0,
121.7, 122.5, 125.2, 126.8, 127.9, 128.8, 128.9, 129.0,
129.1, 129.7, 130.6, 131.5, 133.9, 137.6, 140.1, 145.7, 146.4,
156.0, 156.6, 157.1, 171.9; EI-MS (70 eV, m/z): 665
(M+), 666 (M++1); Elemental Anal. Calcd for
C36H32N4O7S: C, 65.05; H, 4.85; N, 8.43. Found: C,
65.14; H, 4.92; N, 8.57.
3-Benzylsulfonyll-6-(4-ethoxycarbonylmethoxy)phenoxy-5-
(3-methylphenyl)-1-phenylpyrazolo[3,4-d]pyrimidin-4-one
(7j). White crystals, mp 230–231 °C; yield, 82%; IR (KBr) t
(cmÀ1): 2952, 2913, 1762, 1705, 1598, 1574, 1549, 1504,
1197, 1084, 1045, 699; 1H NMR (CDCl3, 400 MHz) d 7.85
(d, 2H, J = 6.8 Hz, Ar), 7.21–7.42 (m, 12H, Ar), 7.10 (d, 2H,
J = 9.2 Hz, OC6H4O), 6.94 (d, 2H, J = 8.8 Hz, OC6H4O),
5.00 (s, 2H, PhCH2 S(O2)), 4.64 (3, 2H, OCH2C@O), 4.28
(q, 2H, J = 7.2 Hz, OCH2), 2.48 (s, 3H, PhCH3), 1.30 (t, 3H,
J = 7.2 Hz, CH2CH3); 13C NMR (100 MHz, CDCl3): d
14.3, 21.5, 35.3, 61.6, 66.0, 102.6, 115.4, 120.3, 120.9, 122.3,
122.7, 125.4, 126.2, 127.3, 128.5, 128.9, 129.4, 130.2, 134.3,
137.7, 138.7, 139.7, 146.1, 146.2, 151.2, 156.0, 156.4, 157.6,
168.7; EI-MS (70 eV, m/z): 649 (M+À1), 650(M+); Elemen-
tal Anal. Calcd for C35H30N4O7S: C, 64.60; H, 4.65; N, 8.61.
Found: C, 64.75; H, 4.81; N, 8.68.
18. Single crystal X-ray diffraction data for 6h at 292 K on a
Bruker Smart Apex Area CCD equipped with Mo Ka
´
˚
radiation (k = 0.71073 A). Crystallographic data (exclud-
ing structure factors) for the structures in this paper have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication No. CCDC-606703.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (fax: +44 1223 336033 or email:
deposit@ccdc.cam.ac.uk).
19. (a) Yang, G.-F.; Xu, L.; Lu, A.-H. Heteroat. Chem.
2001, 12, 491; (b) Yang, F.-L.; Liu, Z.-J.; Huang, X.-B.;
Ding, M.-W. Heterocycl. Chem. 2004, 41, 77; Herbicidal
testing of the newly synthesized compounds 6 and 7 was
carried out in
a plant growth room. Temperature
23 1 °C, RH 60 5%, light intensity 10 Klux, and
photoperiod 8 h/day. Twenty seeds of each one of weed
species including rape and barnyard grass were chosen
for testing. Seedlings were grown in the test plate of
9 cm diameter containing two pieces of filter paper and
9 mL solution of the tested compound (100 and 10 mg/
L, respectively). Distilled water was used as comparison
compound. The herbicidal activity was assessed as the
inhibition rate in comparison with the distilled water.
The herbicidal rating score based on visual observation.
Range from 0% to 100%, 0% means no effect, 100%
means complete killing.
3-Methylsulfonyl-1,5-diphenyl-6-[4-(1-propoxycarbonyleth-
oxy)]phenoxy pyrazolo[3,4-d]pyrimidin-4-one (7k). White
crystals, mp 198–199 °C; yield, 78%; IR (KBr) t (cmÀ1):
2969, 2923, 1751, 1719, 1605, 1577, 1560, 1501, 1196, 1147,
1093, 1032, 900, 765, 571; 1H NMR (CDCl3, 400 MHz)
20. Bewick, D. W. Pestic. Sci. 1986, 17, 349.