Green approach to the synthesis of polyfunctionalized pyrazolo[4',3':5,6] pyrido[2,3-d]pyrimidines via microwave-assisted multicomponent reactions in water without catalyst

Article abstract of DOI:10.1080/00397910902962860

A green approach to the synthesis of polyfunctionalized pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidines was successfully realized via multicomponent reactions of aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5-amine, and 1-methylbarbituric acid in water under microwave irradiation without catalyst. This protocol has the prominent advantages of environmental friendliness, short reaction time, excellent yields, low cost, easy operation, and broad scope of applicability.

Full text of DOI:10.1080/00397910902962860

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Green Approach to the
Synthesis of Polyfunctionalized
Pyrazolo[4′,3′:5,6]pyrido[2,3-
d]pyrimidines via Microwave-Assisted
Multicomponent Reactions in Water
Without Catalyst
Feng Shi a , Ning Ma a , Dianxiang Zhou a , Ge Zhang a , Rongshun
Chen a , Yajie Zhang a & Shujiang Tu a
a School of Chemistry and Chemical Engineering, Xuzhou Normal
University, Key Laboratory of Biotechnology for Medicinal Plant,
Xuzhou, Jiangsu, China
Version of record first published: 09 Dec 2009
To cite this article: Feng Shi, Ning Ma, Dianxiang Zhou, Ge Zhang, Rongshun Chen, Yajie
Zhang & Shujiang Tu (2009): Green Approach to the Synthesis of Polyfunctionalized
Pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines via Microwave-Assisted Multicomponent Reactions
in Water Without Catalyst, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:1, 135-143
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Synthetic Communications1, 40: 135–143, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902962860
GREEN APPROACH TO THE SYNTHESIS OF
POLYFUNCTIONALIZED PYRAZOLO[40,30:5,6]
PYRIDO[2,3-d]PYRIMIDINES VIA MICROWAVE-ASSISTED
MULTICOMPONENT REACTIONS IN WATER
WITHOUT CATALYST
Feng Shi, Ning Ma, Dianxiang Zhou, Ge Zhang, Rongshun Chen,
Yajie Zhang, and Shujiang Tu
School of Chemistry and Chemical Engineering, Xuzhou Normal University,
Key Laboratory of Biotechnology for Medicinal Plant, Xuzhou,
Jiangsu, China
A green approach to the synthesis of polyfunctionalized pyrazolo[40,30:5,6]pyrido[2,3-
d]pyrimidines was successfully realized via multicomponent reactions of aldehydes,
3-methyl-1-phenyl-1H-pyrazol-5-amine, and 1-methylbarbituric acid in water under
microwave irradiation without catalyst. This protocol has the prominent advantages of
environmental friendliness, short reaction time, excellent yields, low cost, easy operation,
and broad scope of applicability.
Keywords: Green synthesis; microwave irradiation; pyrazolopyridopyrimidine; water
INTRODUCTION
Pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidines, which contain three fused hetero-
cyclic skeletons in one molecule, have wide applications in medicinal and chemical
industry, acting as anticonvulsant agents,[1] colorants,[2] heat=moisture-resistant
and thermal transfer printing agents,[3] as well as photographic couplers.[4] There-
fore, much attention has been paid to the synthesis of this class of polyfunctionalized
compounds.[5] For example, Hussein and El-Emary[6] disclosed that the condensation
of 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde with cyanoacetamide in
refluxing ethanol=piperidine yielded the intermediate compounds of aminocarboxa-
mide derivatives in moderate yields, which then reacted with urea derivatives to yield
the pyrazolopyridopyrimidine derivatives. Recently, Jachak and coworkers[7]
reported the synthesis of pyrazolopyridopyrimidine derivatives by a three-step reac-
tion in organic solvents from 5-aminopyrazole-4-carbaldehyde. However, these
methods suffer from the disadvantage of complicated multistep reactions and are
Received December 17, 2008.
Address correspondence to Shujiang Tu, School of Chemistry and Chemical Engineering, Xuzhou
Normal University, Xuzhou 221116, China. E-mail: laotu2001@263.net
135

136
F. SHI ET AL.
Scheme 1. The synthesis of pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidines.
environmentally unfriendly because volatile or toxic organic solvents are used. As a
result, developing a green and facile approach to the synthesis of pyrazo-
lo[40,30:5,6]pyrido[2,3-d]pyrimidines is of great significance.
In recent years, microwave-assisted synthesis in water as solvent has become a
hot spot of investigation because it combines the two prominent green chemistry
principles of ‘‘safer solvents’’ and ‘‘energy efficiency.’’[8] Besides the general advan-
tages of water and microwave irradiation (MWI),[9] several important benefits are
expected when they are combined with each other.[10] On the other hand, multicom-
ponent reactions (MCRs) occupy an outstanding position in organic and medicinal
chemistry by virtue of the intrinsic atom economy and selectivity, simpler procedures
and equipment, time and energy savings, as well as environmental friendliness.[11]
Thus, it goes without saying that the use of water as a nontoxic reaction medium
together with the employment of energy-efficient microwave heating and
atom-economical MCRs must be considered to be a synergistic and effective green
synthesis strategy in the sense that the combination in itself offers greater potential
than the three parts in isolation.
Very recently, we have synthesized a series of pyrazolo[40,30:5,6]pyrido[2,3-
d]pyrimidine derivatives by a pot, atom, and step economical method under MWI
in the presence of p-toluene sulfonic acid in water.[12] However, in this method,
p-toluene sulfonic acid (a corrosive and irritant organic catalyst) was used, which
is harmful to health and the environment. Hence, to some extent, this approach
was still not a green one and should be improved toward the goal of environmental
friendliness. Herein, we report an improved green and facile approach to the syn-
thesis of another series of novel pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidines 4 via
microwave-assisted three-component reactions of aldehydes 1, 3-methyl-1-phenyl-
1H-pyrazol-5-amine 2, and 1-methylbarbituric acid 3 in water without catalyst
(Scheme 1).
RESULTS AND DISCUSSION
Initially, we screened various conditions for the three-component reaction
of 4-bromobenaldehyde 1e, 3-methyl-1-phenyl-1H-pyrazol-5-amine 2, and 1-
methylbarbituric acid 3 in different solvents at 100ꢀC under MWI (Table 1,
entries 1–5). Of the various polar solvents tested, water and glycol gave the great
yields of the expected products within the shortest reaction time (Table 1, entries
4 and 5). Considering environmental friendliness and avoidance of organic
solvents, water was preferred as solvent for all further microwave-assisted
reactions.

GREEN SYNTHESIS OF PYRAZOLOPYRIDOPYRIMIDINES
137
Table 1. Reaction condition optimization for the synthesis of 4e
Entry
Solvent
T (ꢀC)
Time (min)
Yield (%)
1
2
EtOH
DMF
HOAc
Glycol
Water
Water
Water
Water
Water
Water
100
100
100
100
100
80
15
14
15
10
8
58
65
72
83
81
72
78
86
85
85
3
4
5
6
12
10
5
7
90
8
110
120
130
9
10
6
5
To further optimize the reaction conditions, the reaction was carried out under
MWI using water as solvent at temperatures ranging from 80 to 130ꢀC, with an
increment of 10ꢀC each time (Table 1, entries 5–10). The yield of product 4e was
improved and the reaction time was shortened as the temperature increased from
80ꢀC to 110ꢀC (Table 1, entries 5–8). However, the yield was decreased when
temperature was further increased to 120 and 130ꢀC (Table 1, entries 9 and 10).
Therefore, 110ꢀC was choosen as the most suitable reaction temperature.
Moreover, we found that the yield of this reaction was affected by the volume
of water. The synthesis of 4e was tested in different volumes of water at 110ꢀC.
The results show that 1.5 mL of water was optimal as solvent because it generated
the most yield of 4e.
Under these optimized reaction conditions (1.5 mL of water, 110ꢀC), a series of
novel pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidines 4 was synthesized under MWI, and
the results are summarized in Table 2. To test the efficiency and applicability of this
green synthetic approach, different aldehydes were employed in the reactions. As
illustrated in Table 2, this protocol could be applied not only to the aromatic
aldehydes with either electron-withdrawing groups such as nitro or halide groups
or electron-donating groups such as an alkoxyl group but also to heterocyclic
Table 2. Synthesis of 4 under microwave irradiation
Entry
4
R
Time (min)
Yield (%)
Mp (ꢀC)
1
2
4a
4b
4c
4d
4e
4f
4-FC6H4
4-ClC6H4
2,4-Cl2C6H3
7
6
86
85
88
84
86
87
80
82
84
83
81
83
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
>300
3
5
4
C6H5
4-BrC6H4
10
5
5
6
3-NO2C6H4
Thien-2-yl
7
7
4g
4h
4i
9
8
4-CH3OC6H4
3,4-(CH3O)2C6H3
Benzo[d][1,3]dioxol-5-yl
3,4,5-(CH3O)3C6H2
4-NO2C6H4
8
9
10
8
10
11
12
4j
4k
4l
10
6

138
F. SHI ET AL.
Scheme 2. The reasonable mechanism for the formation of product 4.
aldehydes with excellent yields. So, it was concluded that the electronic nature of the
substituents on aldehydes has no significant effect on this reaction.
The structures of all the synthesized compounds were established on the basis
of their spectroscopic data and high-resolution mass spectrometry (HRMS).
A reasonable mechanism for the formation of product 4 is outlined in
Scheme 2. The formation of 4 is expected to proceed via initial condensation of alde-
hyde 1 with 1-methylbarbituric acid 3 to give an intermediate 5. Then, it undergoes
Michael addition with 2 to give an open-chain intermediate 6, which is subsequently
cyclized, dehydrated, and dehydrogenated to afford the aromatized product 4.
CONCLUSION
In brief, we have realized a green and facile approach to the synthesis
of polyfunctionalized pyrazolo[40,30:5,6]pyrido[2,3-d]pyrimidines via microwave-
assisted multicomponent reactions of aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5-
amine, and 1-methylbarbituric acid in water without catalyst. This protocol has the
prominent advantages of environmental friendliness, short reaction time, excellent
yields, low cost, easy operation, and broad scope of applicability. At the same time,
this efficient synthesis cannot only offer a green synthetic strategy to highly fused
heterocyclic compounds but also enrich the investigations on microwave-assisted
multicomponent reactions in water.
EXPERIMENTAL
MWI was carried out in a monomodal Emrys Creator from Personal Chemis-
try, Uppsala, Sweden. Melting points were determined on an XT5 apparatus and are
uncorrected. Infrared (IR) spectra were recorded on an Fourier transform (FT)–IR
1
Tensor 27 spectrometer. H NMR and 13C NMR spectra were measured on a DPX
400 spectrometer operating at 400 MHz and 100 MHz, respectively, using dimethyl-
sulfoxide (DMSO-d6) as solvent and tetramethylsilane (TMS) as an internal stan-
dard. HRMS (ESI) was determined on a microtof-QII HRMS=MS instrument
(Bruker).

GREEN SYNTHESIS OF PYRAZOLOPYRIDOPYRIMIDINES
139
General Procedure for the Synthesis of Compounds 4 Under
Microwave Irradiation
Typically, in a 10-mL Emrys reaction vial, aldehyde 1 (1 mmol), 3-methyl-1-
phenyl-1H-pyrazol-5-amine 2 (1 mmol), 1-methylbarbituric acid 3 (1 mmol), and
water (1.5 mL) were mixed, and then the vial was capped. The mixture was irradiated
at 200 W and 110ꢀC for a given time. The reaction mixture was cooled to room
temperature, poured into water, and filtered to give the crude product, which was
further purified by recrystallization from ethanol (EtOH) to give pure pyrazo-
lo[40,30:5,6]pyrido[2,3-d]pyrimidines 4.
4-(4-Fluorophenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
[2,3-d]pyrimidine-5,7(6H,8H)-dione (4a). 1H NMR (400 MHz, DMSO-d6) (d,
ppm): 12.12 (s, 1H, NH), 8.27 (d, 2H, J ¼ 8.4 Hz, ArH), 7.57 (t, 2H, J ¼ 8.0 Hz,
ArH), 7.38–7.42 (m, 3H, ArH), 7.35 (d, 2H, J ¼ 8.4 Hz, ArH), 3.12 (s, 3H, CH3),
1.81 (s, 3H, CH3). IR (KBr, n, cmꢁ1): 3109, 3043, 2950, 2833, 1719, 1667, 1589,
1568, 1512, 1443, 1412, 1379, 1351, 1222, 1159, 1039, 1015, 842, 811, 757, 734,
691, 659, 609. HRMS (ESI) m=z: calc. for C22H16FN5O2: 402.1361 [M þ H]þ:found:
found: 402.1352 [M þ H]þ.
4-(4-Chlorophenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
[2,3-d]pyrimidine-5,7(6H,8H)-dione (4b). 1H NMR (400 MHz, DMSO-d6) (d,
ppm): 12.11 (s, 1H, NH), 8.26 (d, 2H, J ¼ 8.0 Hz, ArH), 7.55–7.58 (m, 4H, ArH),
7.34–7.40 (m, 3H, ArH), 3.12 (s, 3H, CH3), 1.82 (s, 3H, CH3). 13C NMR
(100 MHz, DMSO-d6) (d, ppm): 163.3, 153.54 152.7, 152.2, 151.8, 151.7, 147.3,
140.9, 137.5, 135.1, 131.8, 131.6, 130.1, 128.4, 122.7, 122.6, 116.0, 114.7, 105.7,
29.4, 16.5. IR(KBr, n, cmꢁ1): 3107, 3036, 2949, 2834, 1717, 1667, 1589, 1567,
1494, 1439, 1411, 1379, 1350, 1315, 1271, 1210, 1088, 1038, 1016, 838, 810, 758,
734, 690, 608. HRMS (ESI) m=z: calc. for C22H16ClN5O2: 418.1066 [M þ H]þ,
found: 418.1061 [M þ H]þ.
4-(2,4-Dichlorophenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
1
[2,3-d]pyrimidine-5,7(6H,8H)-dione (4c). H NMR (400 MHz, DMSO-d6) (d, ppm):
12.25 (s, 1H, NH), 8.26 (d, 2H, J ¼ 8.4 Hz, ArH), 7.85 (s, 1H, ArH), 7.56–7.60 (m,
3H, ArH), 7.44 (d, 1H, J ¼ 8.0 Hz, ArH), 7.38 (t, 1H, J ¼ 7.6 Hz, ArH), 3.14 (s,
3H, CH3), 1.87 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 163.1,
153.5, 152.6, 152.4, 148.2, 146.8, 140.7, 136.6, 136.1, 134.3, 133.0, 131.6, 130.7,
129.5, 128.4, 122.7, 115.3, 105.7, 29.5, 15.7. IR (KBr, n, cmꢁ1): 3108, 3045, 2951,
2833, 1716, 1667, 1589, 1569, 1496, 1442, 1411, 1380, 1350, 1315, 1275, 1210,
1122, 1100, 1040, 860, 835, 790, 758, 690, 609. HRMS (ESI) m=z: calc. for
C22H16Cl2N5O2: 452.0676 [M þ H]þ, found: 452.0665 [M þ H]þ.
3,6-Dimethyl-1,4-diphenyl-1H-pyrazolo-[40,30:5,6]pyrido[2,3-d]pyrimidine-
1
5,7(6H,8H)-dione (4d). H NMR (400 MHz, DMSO-d6) (d, ppm): 12.10 (s, 1H,
NH), 8.27 (d, 2H, J ¼ 7.6 Hz, ArH), 7.57 (t, 2H, J ¼ 7.6 Hz, ArH), 7.48–7.50 (m,
3H, ArH), 7.33–7.38 (m, 3H, ArH), 3.12 (s, 3H, CH3), 1.74 (s, 3H, CH3). 13C
NMR (100 MHz, DMSO-d6) (d, ppm): 163.1, 153.4, 153.1, 152.7, 152.0, 147.3,
140.9, 138.5, 131.4, 130.1, 129.9, 129.8, 128.0, 122.4, 116.1, 105.4, 29.4, 16.1. IR
(KBr, n, cmꢁ1): 3105, 3055, 2946, 2830, 1716, 1663, 1589, 1565, 1503, 1443, 1411,

140
F. SHI ET AL.
1378, 1347, 1312, 1272, 1210, 1197, 1123, 1041, 810, 756, 690, 608. HRMS (ESI) m=z:
calc. for C22H17N5O2: 384.1460 [M þ H]þ, found: 384.1462 [M þ H]þ.
4-(4-Bromophenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
[2,3-d]pyrimidine-5,7(6H,8H)-dione (4e). 1H NMR (400 MHz, DMSO-d6) (d,
ppm): 12.14 (s, 1H, NH), 8.26 (d, 2H, J ¼ 8.0 Hz, ArH), 7.70 (d, 2H, J ¼ 8.4 Hz,
ArH), 7.57 (d, 2H, J ¼ 8.0 Hz, ArH), 7.37 (d, 1H, J ¼ 8.0 Hz, ArH), 7.32 (d, 2H,
J ¼ 8.4 Hz, ArH), 3.12 (s, 3H, CH3), 1.82 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO-d6) (d, ppm): 161.2, 151.3, 150.6, 149.9, 149.6, 145.2, 138.5, 135.6, 130.8,
129.8, 129.4, 126.3, 121.4, 120.6, 113.7, 103.4, 27.2, 14.2. IR (KBr, n, cmꢀ1): 3113,
3045, 2953, 2831, 1719, 1667, 1598, 1584, 1493, 1444, 1408, 1353, 1314, 1270,
1213, 1196, 1124, 1079, 1037, 1011, 836, 811, 790, 765, 748, 693, 657, 609. HRMS
(ESI) m=z: calc. for C22H16BrN5O2: 462.0561 [M þ H]þ: found: 462.0553 [M þ H]þ.
3,6-Dimethyl-4-(3-nitrophenyl)-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
[2,3-d]pyrimidine-5,7(6H,8H)-dione (4f). 1H NMR (400 MHz, DMSO-d6) (d,
ppm): 12.16 (s, 1H, NH), 8.38 (d, 1H, J ¼ 8.0 Hz, ArH), 8.27 (s, 1H, ArH), 8.26
(d, 2H, J ¼ 8.0 Hz, ArH), 7.87 (d, 1H, J ¼ 7.6 Hz, ArH), 7.82 (t, 1H, J ¼ 7.6 Hz,
ArH), 7.57 (t, 2H, J ¼ 8.0 Hz, ArH), 7.36 (t, 1H, J ¼ 7.6 Hz, ArH), 3.11 (s, 3H,
CH3), 1.77 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 163.5, 153.5,
152.7, 152.3, 150.0, 149.6, 147.1, 140.8, 140.3, 136.7, 131.8, 131.6, 128.4, 125.3,
124.9, 122.7, 115.9, 114.7, 105.8, 29.5, 16.7. IR (KBr, n, cmꢀ1): 3239, 3079, 2960,
2926, 1735, 1663, 1590, 1571, 1530, 1507, 1444, 1412, 1378, 1347, 1208, 1178,
1125, 1044, 907, 884, 840, 810, 753, 728, 689, 609. HRMS (ESI) m=z: calc. for
C22H16N6O4: 429.1306 [M þ H]þ: found: 429.1292 [M þ H]þ.
3,6-Dimethyl-1-phenyl-4-thien-2-yl-1H-pyrazolo-[40,30:5,6]pyrido[2,3-d]
pyrimidine-5,7(6H,8H)-dione (4g). 1H NMR (400 MHz, DMSO-d6) (d, ppm):
12.11 (s, 1H, NH), 8.25 (d, 2H, J ¼ 8.0 Hz, ArH), 7.80 (d, 1H, J ¼ 4.4 Hz,
Thiophene-H), 7.57 (t, 2H, J ¼ 8.0 Hz, ArH), 7.36 (t, 1H, J ¼ 7.2 Hz, ArH), 7.21 (t,
1H, J ¼ 4.4 Hz, Thiophene-H), 7.13 (d, 1H, J ¼ 4.4 Hz, Thiophene-H), 3.15 (s, 3H,
CH3), 1.93 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 162.8, 153.5,
152.6, 151.9, 147.3, 146.0, 140.8, 137.4, 131.5, 129.8, 129.5, 129.0, 128.3, 122.6,
117.1, 106.9, 29.4, 15.6. IR (KBr, n, cmꢀ1): 3438, 3244, 3069, 2953, 1717, 1669,
1590, 1572, 1495, 1437, 1377, 1353, 1279, 1207, 1141, 1044, 854, 826, 805, 753, 707,
692, 657, 618. HRMS (ESI) m=z: calc. for C20H15N5O2S: 390.1020 [M þ H]þ: found:
390.1014 [M þ H]þ.
4-(4-Methoxyphenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
[2,3-d]pyrimidine-5,7(6H,8H)-dione (4h). 1H NMR (400 MHz, DMSO-d6) (d,
ppm): 12.07 (s, 1H, NH), 8.27 (d, 2H, J ¼ 8.4 Hz, ArH), 7.56 (t, 2H, J ¼ 7.6 Hz,
ArH), 7.35 (t, 1H, J ¼ 7.6 Hz, ArH), 7.26 (d, 2H, J ¼ 8.4 Hz, ArH), 7.05 (d, 2H,
J ¼ 8.4 Hz, ArH), 3.86 (s, 3H, OCH3), 3.12 (s, 3H, CH3), 1.83 (s, 3H, CH3). 13C
NMR (100 MHz, DMSO-d6) (d, ppm): 163.2, 161.4, 153.6, 153.4, 152.7, 152.1,
147.5, 141.0, 131.5, 131.3, 130.4, 128.2, 122.6, 116.5, 115.4, 105.8, 57.5, 29.4, 16.6.
IR (KBr, n, cmꢀ1): 3106, 2998, 2954, 2836, 1716, 1668, 1589, 1566, 1514, 1440,
1412, 1380, 1351, 1246, 1176, 1036, 836, 812, 760, 692, 609. HRMS (ESI) m=z: calc.
for C23H19N5O3: 414.1561 [M þ H]þ: found: 414.1566 [M þ H]þ.

GREEN SYNTHESIS OF PYRAZOLOPYRIDOPYRIMIDINES
141
4-(3,4-Dimethoxyphenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[40,30:5,6]
pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione (4i). 1H NMR (400 MHz, DMSO-d6)
(d, ppm): 12.05 (s, 1H, NH), 8.26 (d, 2H, J ¼ 7.6 Hz, ArH), 7.56 (t, 2H, J ¼ 7.6 Hz,
ArH), 7.35 (t, 1H, J ¼ 7.6 Hz, ArH), 7.06 (d, 1H, J ¼ 8.0 Hz, ArH), 6.94 (s, 1H, ArH),
6.84 (d, 1H, J ¼ 8.0 Hz, ArH), 3.85 (s, 3H, OCH3), 3.73 (s, 3H, OCH3), 3.13 (s, 3H,
CH3), 1.86 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 160.9, 151.3,
151.2, 150.5, 149.9, 148.7, 148.2, 145.4, 138.7, 129.3, 128.5, 126.0, 120.4, 120.0,
114.3, 111.9, 111.1, 103.6, 55.8, 55.7, 27.2, 14.2. IR (KBr, n, cmꢀ1): 3113, 3045,
2953, 2831, 1719, 1667, 1584, 1493, 1444, 1408, 1353, 1314, 1270, 1124, 1037,
1011, 836, 811, 765, 748, 693, 609. HRMS (ESI) m=z: calc. for C24H21N5O4:
444.1667 [M þ H]þ: found: 444.1660 [M þ H]þ.
4-(1,3-Benzodioxol-5-yl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
[2,3-d]pyrimidine-5,7(6H,8H)-dione (4j). 1H NMR (400 MHz, DMSO-d6) (d,
ppm): 12.08 (s, 1H, NH), 8.26 (d, 2H, J ¼ 8.0 Hz, ArH), 7.56 (t, 2H, J ¼ 8.0 Hz,
ArH), 7.35 (t, 1H, J ¼ 7.6 Hz, ArH), 7.03 (d, 1H, J ¼ 8.0 Hz, ArH), 6.94 (s, 1H,
ArH), 6.78 (d, 1H, J ¼ 8.0 Hz, ArH), 6.14 (d, 2H, J ¼ 5.6 Hz, CH2), 3.14 (s, 3H,
CH3), 1.91 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 163.0, 161.1,
151.4, 151.1, 150.6, 150.0, 145.3, 144.5, 138.8, 136.4, 129.5, 129.4, 128.0, 127.8,
127.5, 126.2, 120.6, 118.8, 114.7, 114.0, 103.5, 27.2, 14.0. IR (KBr, n, cmꢀ1): 3308,
3064, 2987, 2895, 1727, 1674, 1588, 1571, 1494, 1440, 1377, 1351, 1235, 1117,
1037, 933, 804, 751, 691, 662, 646, 624, 582. HRMS (ESI) m=z: calc. for
C23H17N5O4: 428.1354 [M þ H]þ: found: 428.1347 [M þ H]þ.
3,6-Dimethyl-1-phenyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrazolo-[40,30:5,6]
1
pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione (4k). H NMR (400MHz, DMSO-d6)
(d, ppm): 12.08 (s, 1H, NH), 8.25 (d, 2H, J ¼ 7.2Hz, ArH), 7.56 (t, 2H, J ¼ 7.2 Hz,
ArH), 7.33–7.37 (m, 1H, ArH), 6.65 (s, 2H, ArH), 3.76 (s, 9H, OCH3), 3.15 (s, 3H,
CH3), 1.89 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6) (d, ppm): 163.0, 154.8,
153.5, 153.1, 152.7, 152.1, 147.7, 140.9, 139.4, 134.0, 131.5, 128.3, 122.7, 116.3, 107.6,
105.6, 62.7, 58.5, 29.4, 16.1. IR (KBr, n, cmꢀ1): 3105, 3062, 3041, 2940, 2829, 1720,
1668, 1587, 1567, 1506, 1462, 1411, 1380, 1355, 1317, 1236,1127, 1040, 1013, 860, 814,
788, 751, 688, 667, 651, 585. HRMS (ESI) m=z: calc. for C25H23N5O5: 474.1772
[M þ H]þ: found: 474.1770 [M þ H]þ.
3,6-Dimethyl-4-(4-nitrophenyl)-1-phenyl-1H-pyrazolo-[40,30:5,6]pyrido
[2,3-d]pyrimidine-5,7(6H,8H)-dione 4l. 1H NMR (400 MHz, DMSO-d6) (d,
ppm): 12.18 (s, 1H, NH), 8.37 (d, 2H, J ¼ 8.4 Hz, ArH), 8.26 (d, 2H, J ¼ 8.0 Hz,
ArH), 7.68 (d, 2H, J ¼ 8.4 Hz, ArH), 7.58 (t, 2H, J ¼ 8.0 Hz, ArH), 7.37 (t, 1H,
J ¼ 8.0 Hz, ArH), 3.12 (s, 3H, CH3), 1.80 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO-d6) (d, ppm): 161.2, 151.3, 150.5, 150.1, 148.3, 147.4, 144.8, 143.8, 138.6,
129.4, 129.3, 129.3, 126.3, 123.0, 120.6, 120.5, 114.7, 113.2, 103.4, 27.2, 14.3. IR
(KBr, n, cmꢀ1): 3109, 3057, 2955, 2839, 1720, 1668, 1587, 1570, 1517, 1496, 1445,
1408, 1343, 1271, 1211, 1124, 1037, 858, 843, 811, 761, 694, 608. HRMS (ESI)
m=z: calc. for C22H16N6O4: 429.1306 [M þ H]þ: found: 429.1302 [M þ H]þ.

142
F. SHI ET AL.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China (No. 20672090
and 20810102050), the Key Item of Natural Science Foundation of Xuzhou Normal
University (No. 07XLA04), the Preliminary Item of Xuzhou Normal University on
National Natural Science Foundation of China (No. 08XLY04), the Science
and Technology Foundation of Xuzhou (No. XM08C027), the Natural Science
Foundation (09KJB150011) and Qing Lan Project (08QL001) of Jiangsu Education
Committee, and the Open Foundation of Jiangsu Key Laboratory for Chemistry
and Low-Dimensional Materials (JSKC07035) for financial support.
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