Facile method for the synthesis of pyrazolo[3,4-b]-pyrido[4,3-d]- pyrimidine-4-ones via a tandem aza-wittig reaction

Article abstract of DOI:10.1080/00397910902730895

Fifteen novel pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7a-o) were designed and have been successfully synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 5, phenylisocyanate, and substituted phenols in 60-77% isolated yields. Their structures were clearly verified by infrared (IR), 1H NMR, electron impact-mass spectrometry (EI-MS), and elemental analysis. The results of a preliminary bioassay indicated that some compounds possess inhibition activities against the root of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100mg/L and 10mg/L.

Full text of DOI:10.1080/00397910902730895

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Facile Method for the Synthesis
of Pyrazolo[3,4-b]-pyrido[4,3-
d]-pyrimidine-4-ones via a
Tandem Aza-Wittig Reaction
Tao Wang a , Cai Hua Zheng a , Shu Liu a & Hong Wu
He b
a College of Chemistry and Chemical Engineering,
Jiangxi Normal University , Nanchang, China
b Key Laboratory of Pesticide and Chemical Biology,
Ministry of Education of China, Institute of Organic
Synthesis, Central China Normal University , Wuhan,
China
Published online: 04 Sep 2009.
To cite this article: Tao Wang , Cai Hua Zheng , Shu Liu & Hong Wu He (2009) Facile
Method for the Synthesis of Pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones via a
Tandem Aza-Wittig Reaction, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:19, 3386-3398, DOI:
10.1080/00397910902730895
To link to this article: http://dx.doi.org/10.1080/00397910902730895
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Synthetic Communications1, 39: 3386–3398, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902730895
Facile Method for the Synthesis of
Pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones
via a Tandem Aza-Wittig Reaction
Tao Wang,1 Cai Hua Zheng,1 Shu Liu,1 and Hong Wu He2
1College of Chemistry and Chemical Engineering, Jiangxi Normal
University, Nanchang, China
2Key Laboratory of Pesticide and Chemical Biology, Ministry of Education
of China, Institute of Organic Synthesis, Central China
Normal University, Wuhan, China
Abstract: Fifteen novel pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7a–o)
were designed and have been successfully synthesized via tandem aza-Wittig
and annulation reactions of the corresponding iminophosphorances 5, phenyliso-
cyanate, and substituted phenols in 60–77% isolated yields. Their structures were
1
clearly verified by infrared (IR), H NMR, electron impact–mass spectrometry
(EI-MS), and elemental analysis. The results of a preliminary bioassay indicated
that some compounds possess inhibition activities against the root of Brassica
napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg=L
L and 10 mg=L.
Keywords: aza-Wittig reaction, herbicidal activity, pyrazolo[3,4-b]-pyrido[4,3-d]-
pyrimidine-4-ones, synthesis
INTRODUCTION
The derivatives of pyridopyrimidines have been the focus of great interest
over many years. This is due to the wide range of biological activities
associated with this heterocyclic scaffold. Some of their derivatives have
Received October 6, 2008.
Address correspondence to Tao Wang, College of Chemistry and Chemical
Engineering, Jiangxi Normal University, Nanchang 330022, China. E-mail:
wangtao1962@sohu.com
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Pyrazolo-Pyridopyrimidine Synthesis
3387
shown remarkable biological properties such as antitumor, antiviral,
antibacterial, antihypertensive, antibronchitis, antiallergic, antiarthritic,
and anti-HIV activities,[1–12] whereas others exhibited good insecticidal,
growth regulatory, herbicidal, and fungicidal activities.[13–15] On the other
hand, heterocycles containing the pyrazole nucleus exhibit various biolo-
gical activities; several of them have been used as fungicidal, bactericidal,
and insecticidal agents[16–18]. The introduction of a pyrazole ring to the
pyrido[4,3-d]-pyrimidine-4-one system is expected to significantly influ-
ence the biological activities. However, this heterocyclic scaffold system
has been much less investigated, and there is no report on the synthesis
of pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones.
The aza-Wittig reactions of iminophosphoranes have received increa-
sing attention in view of their utility in the synthesis of N-heterocyclic
compounds.[19–23] Recently, we have become interested in the synthesis
of new bioactive heterocycles such as pyrido[4,3-d]-pyrimidine from
various iminophosphoranes, with the aim of evaluating their biological
activities. Herein, we describe a facile synthesis of 2-(substituted
phenoxy)-3,7-dihydro-3,7-diphenyl-5-methyl-9-methylthio-pyrazolo[3,4-
b]pyrido[4,3-d]pyrimidine-4-ones via the tandem aza-Wittig and cycliza-
tion reaction. The results of bioassay indicated that these title compounds
possess herbicidal activity against the roots of Brassica napus (rape) and
Echinochloa crusgalli (barnyard grass).
RESULTS AND DISCUSSION
Synthesis
5-Amino-4-cyano-3-methylthio-1-phenylpyrazole 3[24] was converted to
pyrazolo[3,4-b]pyridine derivative 4 via reaction with acetoacetic ester and
tin tetrachloride under heating. The iminophosphorane 5 was subsequen-
tly obtained in satisfactory yield when 4 was treated with triphenylpho-
sphine, hexachloroethane, and Et3N. Iminophosphorane 5 reacted with
phenylisocyanate to give carbodiimide 6. The direct reaction of carbodii-
mide 6 with substituted phenols did not produce 2-(substituted phenoxy)-
3,7-dihydro-3,7-diphenyl-5-methyl-9-methylthio-pyrazolo[3,4-b]pyrido[4,
3-d]pyrimidine-4-ones 7. However, the reaction took place to give 7a–o in
good yields with heating for 12–14 h in the presence of a catalytic amount
of K2CO3 (Table 1). The formation of 7 can be rationalized in terms of an
initial nucleophilic addition of phenoxides to the carbodiimides 6 to give
the intermediate 8, which cyclizes to give 7a–o (Scheme 1). Regardless of
whether the substituents on the phenols were electron-withdrawing or
electron-releasing groups, the cyclization was completed smoothly.

3388

Pyrazolo-Pyridopyrimidine Synthesis
3389
Scheme 1. Synthesis of the title compounds 7a–o.
Herbicidal Activity
The herbicidal activity of all compounds 7 against Brassica napus (rape)
and Echinochloa crusgalli (barnyard grass) has been investigated at the
dosage of 100 mg=L and 10 mg=L using known procedure[25] compared
with distilled water. The results of bioassay showed that many of them
exhibit good herbicidal activity when the pyrazole ring is introduced.
The inhibition rates are listed in Table 2. They showed that most of com-
pounds 7 in Table 2 exhibit good inhibition rates (80–100%) against the
root of barnyard grass at a dose of 10 mg=L. For example, 7d, 7e, 7f, 7g,
7j, 7k, 7l, 7m, and 7o showed >90% inhibition rate to roots of barnyard
grass. Most of compounds 7 in Table 2 exhibit good inhibition rates (97–
100%) against the roots of rape and barnyard grass at 100 mg=L. For
example, 7a, 7b, 7c, 7e, 7g, 7h, 7i, 7j, 7k, 7l, 7m, 7n, and 7o showed
>97% inhibition rate to roots of rape and barnyard grass.
EXPERIMENTAL
Melting points were measured on an electrothermal melting-point appa-
ratus and are uncorrected. Mass spectra were measured on a Finnigan
Trace MS 2000 spectrometer. Infrared (IR) spectra were recorded on
an FTS-185 IR spectrometer as KBr pellets with absorption in cen-
1
timetersꢀ1. H NMR were recorded in dimethyl sulfoxide (DMSO)-d6
or CDCl3 as solvent on a Bruker AC-P400 spectrometer, and resonances

3390

Pyrazolo-Pyridopyrimidine Synthesis
3391
are given in parts per million (d) relative to tetramethylsilane (TMS).
Elementary analyses were taken on a Vario EL III elementary analysis
instrument. All of the solvents and materials were reagent grade and
purified as required.
Synthesis of 3-Methylthio-1-phenyl-4-amine-5-ethanoxy-6-methyl-1H-
pyrazolo[3,4-b]-pyridine 4
5-Amino-3-methylthio-1-phenyl-pyrazole-4-carbonitrile 3(0.92 g, 4 mmol)
and anhydrous SnCl4 (0.92 mL, 8 mmol) were added to a stirred solution
of ethyl acetoacetate (0.56 g, 4.3 mmol) in anhydrous toluene (15 mL).
The mixture was stirred at rt for 1 h, and then heated at reflux for 5 h.
The mixture was added to sat. aq. Na2CO3 solution (50 mL, pH 10),
and the resulting suspension was extracted with AcOEt (350 mL). The
combined extracts were dried (Na2SO4) and concentrated under reduced
pressure to afford 4 in 63.5% yield. Colorless crystals; mp 117–118ꢀC; 1H
NMR (400 MHz, CDCl3) d: 1.40 (t, 3H, J ¼ 7.2 Hz, CH3), 2.68 (s, 3H,
SCH3), 2.78 (s, 3H, CH3), 4.37 (q, 2H, J ¼ 7.2 Hz, OCH2CH3),
7.25–8.22 (m, 5H, C6H5), 7.32 (br, 2H, NH2). Elemental anal. calcd.
for C17H18N4O2S: C, 59.63; H, 5.30; N, 16.36. Found: C, 59.59; H,
5.23; N, 16.44.
Synthesis of Iminophosphorane 5
To a solution of 4 (5.13 g, 15 mmol) in CH3CN (60 mL), Ph3P (7.86 g,
30 mmol), C2Cl6(7.11 g, 30 mmol), and, in this order, Et3N (8.3 ml) were
added. The mixture was stirred for 6–7 h at rt Then, the solution was con-
centrated, and the residue was recrystallized from EtOH to give 5 in
94.3% yield. mp 152–153ꢀC. 1H NMR (400 MHz, CDCl3) d 1.39 (t,
3H, CH2CH3, J ¼ 6.8 Hz), 2.77 (s, 3H, SCH3), 3.05 (s, 3H, CH3), 4.67
(q, 2H, CH2CH3, J ¼ 7.2 Hz), 7.22–7.68 (m, 20H, Ar-H). Elemental anal.
calcd. for C35H31N4O2PS: C, 69.75; H, 5.18; N, 9.30. Found: C, 71.49; H,
5.28; N, 9.67. MS (EI, m=z, %): 602 (Mþ, 43.30%), 539 (21.71%), 463
(43.86%), 262 (58.26%), 201 (45.49%), 183 (100%), 108 (40.30%), and
77 (56.03 %).
General Procedure for the Preparation of 2-(Substituted Phenoxy)-
3,7-dihydro-3,7-diphenyl-5-methyl-9-methylthio-pyrazolo
[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones
Phenylisocyanate (3 mmol) was added to a solution of iminophosphorane
5 (3 mmol) in dry methylene chloride (10 mL), under nitrogen at room

3392
T. Wang et al.
temperature. After the reaction mixture was left unstirred for 6–8 h, the
solvent was removed under vacuum, and anhydrous ethanol (10 mL)
was added to precipitate triphenylphosphineoxide. Removal of the sol-
1
vent gave carbodiimides 6 [mp 161–161.3ꢀC H NMR (TMS, CDCl3):
d 1.37 (t, 3H, CH2CH3, J ¼ 6.8 Hz), 2.77 (s, 3H, SCH3), 3.05 (s, 3H,
CH3), 4.67 (q, 2H, CH2CH3, J ¼ 7.2 Hz), 7.24–8.38 (m, 10H, Ar-H)],
which were used directly without further purification.
Substituted phenol (2 mmol) and cat. solid K2CO3 (0.024 g, 0.2 mmol)
were added to the solution of 6 prepared previously in CH3CN (20 mL).
The mixture was stirred for 12–14 h at 75ꢀC and filtered, the filtrate was con-
densed, and the residue was recrystallized from dichloromethane=petroleum
ether to give pure 2-(substituted phenoxy)-3,7-dihydro-3,7-diphenyl-5-
methyl-9-methylthio-pyrzolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones.
Data
2-Phenoxy-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7a)
Anal. calcd. (%) for C28H21N5O2S: C, 68.41; H, 4.31; N, 14.25. Found: C,
68.20; H, 4.64; N, 14.47. IR (KBr, n=cmꢁ1): 3265 (Ph-H), 2919 (C-H), 1725
1
(C¼O), 1674 (C¼C), 1563 (N¼C); H NMR (DMSO-d6, 400MHz): 2.80
(s, 3H, SCH3), 3.03 (s, 3H, CH3), 7.27–8.28 (m, 15H, Ar-H); MS (EI, m=z,
%): 491 (Mþ þ 1, 2.08), 490 (Mþ, 6.59), 489 (Mþ ꢁ 1, 16.01), 415 (23.94),
368 (35.05), 323 (53.66), 268 (28.44), 119 (32.13), 93 (52.28), 77 (100).
2-[(2-Chlorophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-9-
methylthio-pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7b)
Anal. calcd. (%) for C28H20ClN5O2S: C, 63.93; H, 3.83; N, 13.31. Found:
C, 63.61; H, 3.64; N, 13.48; IR (KBr, n=cmꢁ1): 3272 (Ph-H), 2911 (C-H),
1720 (C¼O), 1663 (C¼C), 1561 (N¼C); 1H NMR (DMSO-d6, 400 MHz):
2.68 (s, 3H, SCH3), 2.83 (s, 3H, CH3), 7.17–8.29 (m, 14H, Ar-H); MS (EI,
m=z, %): 526 (Mþ þ 1, 2.22), 525 (Mþ, 4.92), 415 (82.31), 382 (59.74), 368
(7.57), 323 (3.66), 268 (27.92), 119 (37.31), 93 (11.17), 77 (100).
2-[(4-Chlorophenyl)oxy]- 3,7-dihydro-3,7-diphenyl-5-methyl-9-
methylthio-pyrazolo [3,4-B]-pyrido[4,3-d]-pyrimidine-4-ones (7c)
Anal. calcd. (%) for C28H20ClN5O2S: C, 63.93; H, 3.83; N, 13.31. Found:
C, 63.73; H, 3.62; N, 13.46; IR (KBr, n=cmꢁ1): 3272 (Ph-H), 2912 (C-H),

Pyrazolo-Pyridopyrimidine Synthesis
3393
1722 (C¼O), 1671 (C¼C), 1562 (N¼C); 1H NMR (DMSO-d6, 400 MHz):
2.66 (s, 3H, SCH3), 2.82 (s, 3H, CH3), 7.19–8.30 (m, 14H, Ar-H); MS (EI,
m=z, %): 526 (Mþ þ 1, 1.02), 415 (86.36), 382 (50.94), 368 (4.59), 323
(4.69), 268 (21.02), 119 (47.30), 93 (10.11), 77 (100).
2-[(2-Methylphenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7d)
Anal. calcd. (%) for C29H23N5O2S: C, 68.89; H, 4.59; N, 13.85. Found: C,
68.71; H, 4.72; N, 13.66, IR (KBr, n=cmꢁ1): 3266 (Ph-H), 2914 (C-H),
1724 (C¼O), 1666 (C¼C), 1562 (N¼C), 1H NMR (DMSO-d6,
400 MHz): 1.58 (s, CH3Ph), 2.76 (s, 3H, SCH3), 2.92 (s, 3H, CH3),
7.18–8.32 (m, 14H, Ar-H); MS (EI, m=z, %): 506 (Mþ þ 1, 1.92), 505
(Mþ 4.02), 415 (81.32), 382 (53.93), 368 (4.39), 323 (4.62), 268 (35.03),
119 (42.33), 93 (13.21), 77 (100).
2-[(4-Methylphenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7e)
Anal. calcd. (%) for C29H23N5O2S: C, 68.89; H, 4.59; N, 13.85. Found: C,
68.71; H, 4.72; N, 13.66; IR (KBr, n=cmꢁ1): 3262 (Ph-H), 2913 (C-H),
1721 (C¼O), 1670 (C¼C), 1558 (N¼C), 1H NMR (DMSO-d6,
400 MHz): 1.58 (s, CH3Ph), 2.76 (s, 3H, SCH3), 2.92 (s, 3H, CH3),
7.22–8.34 (m, 14H, Ar-H); MS (EI, m=z, %): 506 (Mþ þ 1, 1.32), 505
(Mþ, 3.32), 415 (82.22), 382 (51.33), 368 (11.19), 323 (4.32), 268
(31.43), 119 (48.43), 93 (12.24), 77 (100).
2-[(2-Nitrophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7f)
Anal. calcd. (%) for C28H20N6O4S: C, 62.68; H, 3.76; N, 15.66. Found: C,
62.43; H, 3.56; N, 15.87, IR (KBr, n=cmꢁ1): 3258 (Ph-H), 2927 (C-H), 1726
(C¼O), 1670 (C¼C), 1561 (N¼C), 1H NMR (DMSO-d6, 400 MHz): 2.68
(s, 3H, SCH3), 2.88 (s, 3H, CH3), 7.08–8.29 (m, 14H, Ar-H); MS (EI,
m=z, %): 537 (Mþ þ 1, 3.12), 536 (Mþ, 6.59), 535 (Mþ ꢁ1, 16.01), 415
(76.39), 382 (56.74), 219 (32.29), 119 (22.76), 93(16.76), 77 (100).
2-[(4-Nitrophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7g)
Anal. calcd. (%) for C28H20N6O4S: C, 62.68; H, 3.76; N, 15.66. Found: C,
62.43; H, 3.56; N, 15.87, IR (KBr, n=cmꢁ1): 3264 (Ph-H), 2919 (C-H), 1723

3394
T. Wang et al.
(C¼O), 1664 (C¼C), 1553 (N¼C), 1H NMR (DMSO-d6, 400 MHz): 2.68
(s, 3H, SCH3), 2.86 (s, 3H, CH3), 7.16–8.28 (m, 14H, Ar-H); MS (EI,
m=z, %): 537 (Mþ þ 1, 3.72), 536 (Mþ, 10.50), 535(Mþ, ꢁ1 19.11), 415
(78.38), 382 (55.64), 219 (31.22), 119 (25.26), 93(19.79), 77 (100).
2-[(3-Fluorophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7h)
Anal. calcd. (%) for C28H20FN5O2S: C, 66.00; H, 3.96; N, 13.74. Found: C,
66.23; H, 4.03; N, 13.57, IR (KBr, n=cmꢁ1): 3262 (Ph-H), 2925 (C-H), 1724
(C¼O), 1677 (C¼C), 1566 (N¼C), 1H NMR (DMSO-d6, 400 MHz): 2.72 (s,
3H, SCH3), 2.99 (s, 3H, CH3), 7.07–8.30 (m, 14H, Ar-H); MS (EI, m=z, %):
512 (Mþ þ 3, 4.32), 511 (Mþ þ 2, 7.87), 510 (Mþ þ 1, 43.32), 494 (32.69), 474
(38.05), 398 (15.68), 219 (32.12), 119 (24.72), 101 (49.80), 93 (6.41), 77 (100).
2-[(2,4-Difluorophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7i)
Anal. calcd. (%) for C28H19F2N5O2S: C, 63.75; H, 3.63; N, 13.28. Found:
C, 63.54; H, 3.46; N, 13.10, IR (KBr, n=cmꢁ1): 3265 (Ph-H), 2926 (C-H),
1730 (C¼O), 1680 (C¼C), 1568 (N¼C), 1H NMR (DMSO-d6, 400 MHz):
2.58 (s, 3H, SCH3), 3.07 (s, 3H, CH3), 6.97–8.32 (m, 13H, Ar-H); MS (EI,
m=z, %): 529 (Mþ þ 3, 7.19), 528 (Mþ þ 2, 24.12), 527 (Mþ þ 1, 55.11),
494 (38.27), 474 (31.08), 398 (19.62), 219 (34.09), 119 (21.77), 101
(44.00), 93 (6.32), 77 (100).
2-[(4-Bromophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7j)
Anal. calcd. (%) for C28H20BrN5O2S: C, 58.95; H, 3.53; N, 12.28. Found:
C, 58.78; H, 3.34; N, 12.02, IR (KBr, n=cmꢁ1): 3263 (Ph-H), 2924 (C-H),
1728 (C¼O), 1675 (C¼C), 1565 (N¼C), 1H NMR (DMSO-d6, 400 MHz):
2.68 (s, 3H, SCH3), 3.00 (s, 3H, CH3), 6.98–8.22 (m, 14H, Ar-H); MS (EI,
m=z, %): 570 (Mþ þ 1, 5.62), 415 (67.76), 382 (72.90), 368 (5.56), 323
(4.06), 268 (26.21), 119 (52.33), 93 (11.12), 77 (100).
2-[(2-Chloro-4-fluorophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-ones (7k)
Anal. calcd. (%) for C28H19FClN5O2S: C, 61.82; H, 3.52; N, 12.87.
Found: C, 61.69; H, 3.33; N, 12.69, IR (KBr, n=cmꢁ1): 3268 (Ph-H),

Pyrazolo-Pyridopyrimidine Synthesis
3395
1
2924 (C-H), 1729 (C¼O), 1678 (C¼C), 1566 (N¼C), H NMR (DMSO-
d6, 400 MHz): 2.56 (s, 3H, SCH3), 2.97 (s, 3H, CH3), 6.98–8.23 (m, 13H,
Ar-H); MS (EI, m=z, %): 544 (Mþ þ 1, 2.72), 543 (Mþ 6.59), 415 (54.73),
382 (63.60), 368 (7.58), 323 (8.16), 268 (21.25), 119 (72.35), 93 (14.22),
77 (100).
2-[(3-Chloro-4-fluorophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-
methyl-9-methylthio-pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-
ones (7l)
Anal. calcd. (%) for C28H19FClN5O2S: C, 61.82; H, 3.52; N, 12.87.
Found: C, 61.66; H, 3.31; N, 12.73, IR (KBr, n=cmꢁ1): 3266 (Ph-H),
2922 (C-H), 1726 (C¼O), 1675 (C¼C), 1564 (N¼C), 1H NMR
(DMSO-d6, 400 MHz): 2.56 (s, 3H, SCH3), 3.02 (s, 3H, CH3),
6.97–8.24(m, 13H, Ar-H); MS (EI, m=z, %): 544 (Mþ þ 1, 3.79), 543
(Mþ, 9.74), 415 (59.61), 382 (62.63), 368 (6.98), 323 (7.31), 268 (22.45),
119 (79.25), 93 (12.52), 77 (100).
2-[(2-Chloro-5-methylphenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-
methyl-9-methylthio-pyrazolo[3,4-b]-pyrido[4,3-d]-pyrimidine-4-
ones (7m)
Anal. calcd. (%) for C29H22ClN5O2S: C, 64.50; H, 4.11; N, 12.97. Found:
C, 64.46; H, 4.30; N, 13.16, IR (KBr, n=cmꢁ1): 3266 (Ph-H), 2926 (C-H),
1728 (C¼O), 1677 (C¼C), 1565 (N¼C), 1H NMR (DMSO-d6, 400 MHz):
1.60 (s, CH3Ph), 2.78 (s, 3H, SCH3), 3.02 (s, 3H, CH3), 7.17–8.35 (m,
13H, Ar-H); MS (EI, m=z, %): 539 (Mþ þ 1, 2.72), 443 (100), 410
(71.21), 382 (48.62), 368 (7.77), 323 (6.16), 268 (16.65), 219 (14.65), 119
(24.76), 93 (13.45), 77 (98.38).
2-[(4-Chloro-3-methylphenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-
methyl-9-methylthio-pyrzolo [3,4-b]-pyrido[4,3-d]-pyrimidine-4-
ones (7n)
Anal. calcd. (%) for C29H22ClN5O2S: C, 64.50; H, 4.11; N, 12.97. Found:
C, 64.30; H, 4.34; N, 13.19, IR (KBr, n=cmꢁ1): 3262 (Ph-H), 2921 (C-H),
1729 (C¼O), 1674 (C¼C), 1562 (N¼C), 1H NMR (DMSO-d6, 400 MHz):
1.60 (s, CH3Ph), 2.77 (s, 3H, SCH3), 3.04 (s, 3H, CH3), 7.24–8.37 (m,
13H, Ar-H); MS (EI, m=z, %): 539 (Mþ þ 1, 1.82), 443 (100), 410
(62.69), 382 (52.85), 368 (8.89), 323 (6.10), 268 (11.48), 219 (10.25), 119
(20.79), 93 (10.86), 77 (92.53).

3396
T. Wang et al.
2-[(2,4-Dichlorophenyl)oxy]-3,7-dihydro-3,7-diphenyl-5-methyl-
9-methylthio-pyrazolo [3,4-b]-pyrido[4,3-b]-pyrimidine-4-ones (7o)
Anal. calcd. (%) for C28H19Cl2N5O2S: C, 60.00; H, 3.42; N, 12.50.
Found: C, 60.22; H, 3.64; N, 12.77, IR (KBr, n=cmꢁ1): 3266 (Ph-H),
2926 (CꢁH), 1727 (C¼O), 1674 (C¼C), 1562 (N¼C), 1H NMR
(DMSO-d6, 400 MHz): 2.82 (s, 3H, SCH3), 3.02 (s, 3H, CH3),
7.14–8.36 (m, 13H, Ar-H); MS (EI, m=z, %): 561 (Mþ þ 2, 11.32), 560
(Mþ þ 1, 32.16), 494 (29.29), 474 (57.85), 398 (21.22), 219 (37.49), 119
(27.76), 101 (47.66), 93 (4.36), 77 (100).
Herbicidal Testing
Herbicidal testing of the newly synthesized compounds 7 was carried out
in a plant growth room (temperature 23 ꢂ 1ꢀC, RH 60 ꢂ 5%, light inten-
sity 10 Klux, photoperiod 8 h=day). Twenty seeds of each weed species
including rape and barnyard grass were chosen for testing. Seedlings were
grown in the 9-cm-diameter test plate of containing two pieces of filter
paper and 9 mL solution of the tested compound (100 mg=L and 10 mg=L,
respectively). Distilled water and 2,4-dichlorophenoxyl acetic acid
(2,4-D), a commercially available herbicide in the market, were used as
comparison compounds. The herbicidal activity was assessed as the inhi-
bition rate in comparison with the distilled water. The herbicidal rating
score was based on visual observation, ranging from 0% to 100%: 0%
means no effect, 100% means complete killing.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(No. 20862007) and the Natural Science Foundation of Jiangxi Province
in China (No. 2007GZH1399) for financial support.
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