One-step synthesis of tetrazolo[1,5-a]pyrimidines by cyclization reaction of dihydropyrimidine-2-thiones with sodium azide

Article abstract of DOI:10.3987/COM-11-12351

An novel, versatile and cost-effective approach for tetrazolo[1,5-a] pyrimidines and tetrazolo[1,5-a]quinazolines from cyclization reaction of dihydropyrimidinethiones with sodium azide in the presence of mercuric acetate is described. To compare this pro

Full text of DOI:10.3987/COM-11-12351

HETEROCYCLES, Vol. 83, No. 12, 2011
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HETEROCYCLES, Vol. 83, No. 12, 2011, pp. 2811 - 2822. © 2011 The Japan Institute of Heterocyclic Chemistry
Received, 31st August, 2011, Accepted, 30th September, 2011, Published online, 7th October, 2011
DOI: 10.3987/COM-11-12351
ONE-STEP SYNTHESIS OF TETRAZOLO[1,5-a]PYRIMIDINES BY
CYCLIZATION REACTION OF DIHYDROPYRIMIDINE-2-THIONES
WITH SODIUM AZIDE
Xi-Cun Wang,* Ying Wei, Yu-Xia Da, Zhang Zhang, and Zheng-Jun Quan
Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of
Education, China; Gansu Key Laboratory of Polymer Materials, College of
Chemistry and Chemical Engineering, Northwest Normal University, Anning East
Road 967#, Lanzhou, Gansu 730070, China
E-mail: wangxicun@nwnu.edu.cn, Fax: +086-931-7971971
Abstract
–
An novel, versatile and cost-effective approach for
tetrazolo[1,5-a]pyrimidines and tetrazolo[1,5-a]quinazolines from cyclization
reaction of dihydropyrimidinethiones with sodium azide in the presence of
mercuric acetate is described. To compare this procedure with the conventional
method, we carried out the cyclization reactions through direct functionalization
of
the
pyrimidinethione
core,
which
obtained
from
Biginelli
3,4-dihydropyrimidine-2-thiones or 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-
octahydroquinazoline-2-thiones.
INTRODUCTION
3,4-Dihydropyrimidine-2-thiones,1 as a core unit in most organic compounds, are chemical precursors of
multifunctionalized pyrimidines in a broad range of medicinal agents. These complex heterocyclic
scaffolds is assigned as one of the most fertile areas for both organic chemistry, medicinal chemistry and
biochemistry, which display interesting pharmacological and biological properties such as calcium

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HETEROCYCLES, Vol. 83, No. 12, 2011
channel modulators, α1a-adrenergic receptor antagonists, mitotic kinesin inhibitors and hepatitis B virus
replication inhibitors.2 Several marine alkaloids containing the pyrimidine core unit were found to show
interesting biological activities such as antiviral, antibacterial and anti-inflammatory activity.3 Over the
past decades, research interest in multifunctionalized pyrimidines, has surged rapidly, owing to the
pharmacological properties associated with many derivatives of this privileged heterocyclic core.
Compounds containing the tetrazolo[1,5-a]pyrimidine scaffold have been reported to have more
biological activities, there is considerable interest in the medicinal and biological applications of
tetrazoles, such as antimicrobial activity,4 farnesyl transferase inhibitory,5 fungicidal activity,6
antihypertensive,7 KATP channel opening,8 central nervous system stimulating,9 etc.
However, after a detailed literature survey, we found that there were only limited publications devoted to
the preparation of tetrazolopyrimidines. In general, these compounds were prepared by the
multicomponent reaction between aminotetrazole, aldehyde and β-oxo carbonyl compounds or α,
β-unsaturated carbonyl compounds using sulfamic acid,10-12 iodine,13 treating with HCl subsequently with
p-toluenesulfonic acid,14 or in the absence of catalysis at 130-170 ºC,15 or using a base triethylamine in
ethanol refluxing for 15 h.16 However, most of the synthetic protocols reported so far have some flaws,
such as high temperatures, poor yields or prolonged reaction time.
Recently, structures change associated with mercury-promoted desulfurization reactions, including
hydrolysis, cyclizations and eliminations, have been reported.17-21 Because of the strong thiophilic affinity
of Hg2+, mercuric acetate was used in the design of formation for HgS. We devised a strategy in which the
azido group would be formed by desulfurization of 3,4-dihydropyrimidine-2-thiones using Hg2+ ion. The
-
addition of the Hg2+ ion induced the N3 to attack the 2-C atom of pyrimidine, followed by the removal of
HgS and the formation of intramolecular guanylation. Finally, a stable cyclic product
tetrazolo[1,5-a]pyrimidine 2 was formed through an irreversible desulfurization reaction, as depicted in
Scheme 1. To the best of our knowledge, elaboration of tetrazolo[1,5-a]pyrimidines through reactions of
3,4-dihydropyrimine-2-thiones with sodium azide was unprecedented. In the context of our interest in the
synthesis of functionalized DHPM derivatives, we became interested in combining tetrazole with the
DHPM core. In this paper, we would like to describe a general and comprehensive strategy for the

HETEROCYCLES, Vol. 83, No. 12, 2011
2813
preparation of ethyl 5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylates and
6,6-dimethyl-9-aryl-5,6,7,9-tetrahydrotetrazolo[1,5-a]quinazolin-8(4H)-ones through direct cyclization
reactions from 3,4-dihydropyrimidine-2(1H)-thiones and 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-
octahydroquinazoline-2-thiones with sodium azide.
O
Ar
O
Ar
O
Ar
O
Ar
Hg2+
HgS
N
N
EtO
NH
EtO
NH
EtO
N
EtO
N
N
Hg2+
Me
N
H
S
Me
N
H
S
Me
N
H
N3
Me
N
H
1
2
-
N3
Scheme 1. Hg2+-induced desulfurization and cyclization of DHPM
RESULTS AND DISCUSSIONS
Table 1. Optimization of reaction conditions for product 2a
O
Ph
O
Ph
conditions
N
N
NaN
EtO
Me
NH +
EtO
Me
N
3
N
N
S
N
H
H 2a
1a
Equiv
of
Desulfurization
reagent
Entry
Solvent
Temp (ºC)
Time (h)
Yield (%)a
1a/NaN3/reagent
1:2:1
1
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
DMF
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
Hg(OAc)2
HgCl2
25
24
6
-
2
1:2:1
80
70
92
92
45
56
75
80
80
66
85
3
1:2:1
100
110
100
100
100
80
6
4
1:2:1
6
5
1:2:0.5
1:1:1
6
6
6
7
1:2:1
6
8
1:2:1
EtOH
HOAc
DMF
6
9
1:2:1
100
25
6
10
11
12
1:2:1
HgCl2
12
6
1:2:1
DMF
HgCl2
100
100
b
1:2:1
HOAc
Zn(OAc)2
6
-

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HETEROCYCLES, Vol. 83, No. 12, 2011
13
14
15
16
17
18
19
1:2:1
1:2:1
1:2:1
1:2:1
1:2:1
1:2:1
1:2:1
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
ZnCl2
NiCl2
CoCl2
Cu(OAc)2
CuCl2
FeCl3
-
100
100
100
100
100
100
100
6
6
6
6
6
6
6
-
-
-
-
-
-
-
c
a Isolated yields.
b No product was isolated or detected by TLC.
c The 3,4-dihydropyrimidine-2-thione (C=S) was transferred to 3,4-dihydropyrimidine-2-one (C=O).
Initially, we chose the reaction of 3,4-dihydropyrimidine-2(1H)-thione 1a and sodium azide as a model
reaction to optimize the reaction conditions. A series of experiments was performed to evaluate the
feasibility of the formation of tetrazolo[1,5-a]pyrimidine and to identify the best cyclic agents. The results
are shown in Table 1. By analogy with the mercury-promoted desulfurization reactions,17-21 the mixture
of 1 equivalent of NaN3 and Hg(OAc)2 in acetic acid was heated at 100 ºC to give the cyclization product
2a in 56% yield (entry 6). It was found that Hg(OAc)2 and a stoichiometric amount of NaN3 are essential
for the success of the reaction (entries 3-10) and 2 equivalent of NaN3 obtained the best result (entry 3).
Another source of mercuric catalyst HgCl2 was used, but the reaction yield was slightly slower (entries
9-11). However, when using other catalysts Zn(OAc)2, ZnCl2, NiCl2, CoCl2, CuCl2, FeCl3, Cu(OAc)2,
compound 2a was not detected by GC-Mass (or TLC), and starting DHPM 1a was recovered. After
experimentation with different catalysts, solvents and reaction temperatures, it was found that the optimal
proportion of the reaction between 3,4-dihydropyrimidine-2(1H)-thione 1a, sodium azide and mercuric
acetate could be achieved 1: 2: 1 in acetic acid at 100 ºC within 6 h.
Under the optimized conditions, the substrate scope of the reaction was examined (Table 2). A variety
dihydrotetrazolo[1,5-a]pyrimidines (2a-i) were regioselectively prepared through this method. The
electronics of the aromatic groups of DHPMs did not appear to influence the process, as substrates
substituted with methoxy or nitro groups gave comparable product yields. However,
3,4-dihydropyrimidine-2-thione with an o-nitro group on the phenyl ring do not give the desired product.
We speculated that one possible reason is the big steric of nitro group.

HETEROCYCLES, Vol. 83, No. 12, 2011
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Table 2. Mercuric acetate catalyzed synthesis of dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylatesa
R
R
O
O
Hg(OAc)2
N
N
EtO
NH
EtO
N
+NaN3
HOAc,100 oC, 6 h
N
Me
N
H
Me
N
S
H
2
1
Entry
R
Product
2a
Yield (%)
92
1
2
3
4
5
6
7
8
9
H
2-Cl
74
2b
4-MeO
2-Me
4-Me
4-Cl
86
2c
85
2d
87
2e
79
2f
4-NO2
4-Br
73
2g
80
2h
3-NO2
76
2i
a Reaction conditions: DHPM 1 (1 mmol), NaN3 (2 mmol), Hg(OAc)2 (1 mmol) in 5 mL
acetic acid at 100 ºC for 6 h.
Extension of the reaction to 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones 3
was successful, and compounds tetrahydrotetrazolo[1,5-a]quinazolines 4a-4h were obtained in good
yields (Table 3). To our delight, further research suggested that the mercuric acetate catalyzed one-pot
synthesis of tetrazolo[1,5-a]pyrimidines proceeded smoothly.
All the compounds were characterized by 1H NMR, 13C NMR, MS, and elemental analyses. The 1H NMR
spectrum of product 2 and 4 exhibited a singlet around δ 6.7 as the C4-H, which confirmed the C2-N3
linked products tetrazolo[1,5-a]pyrimidines and tetrahydrotetrazolo[1,5-a]quinazolin-8(4H)-ones.
According to previous study, when the methyl or N-allyl groups were in the N1 position, two cross peaks
between the hydrogen atoms of the N-methyl or NCH2 groups of the allyl groups and C-2 and -6 were
observed.22

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Table 3. Mercuric acetate catalyzed synthesis of tetrahydrotetrazolo[1,5-a]quinazolin-8(4H)-onesa
R
R
O
O
Hg( OAc)2
N
N
+
NH
NaN3
N
HO Ac,100 oC, 6 h
N
N
H
S
N
H
3
4
Entry
R
Product
Yield (%)
1
2
3
4
5
6
7
8
H
76
68
72
67
65
70
69
71
4a
4b
4c
4d
4e
4f
4-Cl
4-MeO
4-NO2
3-NO2
2-MeO
4-Br
4g
4h
4-Me
a Reaction conditions: 3 (1 mmol), sodium azide (2 mmol), mercuric acetate (1 mmol) in
5 mL acetic acid at 100 ºC for 6h.
The single crystal X-ray crystallography of product 2a also confirmed the structures of obtained products
(Figure 1). Crystallographic data for the structure analysis have been deposited at the Cambridge
Crystallographic Data Centre as supplementary publication (for 2a CCDC No. CCDC 807622).
In conclusion, we have developed a novel and efficient synthetic method to prepare ethyl
5-methyl-7-aryl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylates and 6,6-dimethyl-9-aryl-5,6,7,9-
tetrahydrotetrazolo[1,5-a]quinazolin-8(4H)-ones
by
the
cyclization
reactions
between
3,4-dihydropyrimidine-2-thiones or 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-
2-thiones, sodium azide and mercuric acetate. Compared to previously known approaches, the simplicity
and higher efficiency make this method particularly attractive. These results provided, as well as other
reported studies, this cyclization reaction conditions could be potentially applicable to other
electron-deficient heterocylic or aromatic systems. The present study also provides a readily accessible
approach to construct multifunctionalized pyrimidine template for diversity-oriented synthesis.

HETEROCYCLES, Vol. 83, No. 12, 2011
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Figure 1. The crystal structure of 2a
EXPERIMENTAL
Commercially available reagents were used without further purification. Solvents were treated prior to
use according to the standard methods. Melting points were determined on an XT-4 electrothermal
micromelting point apparatus and are uncorrected. NMR spectra were recorded at 400 (1H) and 100 (13C)
MHz, respectively, on a Varian Mercury plus-400 instrument using CDCl3 and DMSO-d6 as solvent and
TMS as an internal standard. Mass spectra were obtained on a Bruker Daltonics APEXII 47e FT-ICR
spectrometer. The Biginelli 3,4-dihydropyrimidine-2-thiones 1 and 4-aryl-7,7-dimethyl-5-oxo-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones 3 were readily prepared according to the procedures
reported.23,24
General procedure. The mixture of 3,4-dihydropyrimidine-2(1H)-thione (1 mmol), sodium azide (2
mmol) and mercuric acetate (1 mmol) in HOAc (5 mL) was stirred at 100 ºC for 6 h. After completion of
the reaction (monitored by thin layer chromatography), the black sediment (HgS) was filtrated. Then
water was added to the filtrate to give the crude product. It was recrystallization from EtOH to give the
pure products 2 and 4.
1
2a: Yield 92%, mp 213-215 ºC. H NMR (400 MHz, CDCl3): δ = 1.13 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.70 (s, 3H, 5-CH3), 4.05-4.14 (m, 2H, OCH2CH3), 6.73 (s, 1H, CH), 7.26-7.37 (m, 5H, ArH), 10.90 (s,
13
1H, NH). C NMR (100 MHz, CDCl3): δ = 14.01, 19.54, 59.59, 60.51, 99.35, 127.30, 128.86, 128.97,
139.68, 145.92, 148.68, 164.85. Anal. Calcd for C14H15N5O2: C, 58.94; H, 5.30; N, 24.55. Found: C,
58.85; H, 5.23; N, 24.45. ESI-MS: m/z = 285 ([M + H+]).
1
2b: Yield 74%, mp 221-223 ºC. H NMR (400 MHz, CDCl3): δ = 1.11 (t, J = 7.2 Hz, 3H, OCH2CH3),

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HETEROCYCLES, Vol. 83, No. 12, 2011
2.70 (s, 3H, 5-CH3), 4.03-4.09 (m, 2H, OCH2CH3), 7.19 (s, 1H, CH), 7.23-7.42 (m, 4H, ArH), 10.98 (s,
13
1H, NH). C NMR (100 MHz, CDCl3): δ = 13.90, 19.49, 56.78, 60.51, 98.35, 127.41, 129.67, 130.18,
130.20, 133.41, 137.15, 146.65, 148.56, 164.60. Anal. Calcd for C14H14ClN5O2: C, 52.59; H, 4.41; N,
21.90. Found: C, 52.68; H, 4.49; N, 21.98. ESI-MS: m/z = 319 ([M + H+]).
1
2c: Yield 86%, mp 208-209 ºC. H NMR (400 MHz, CDCl3): δ = 1.15 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.68 (s, 3H, 5-CH3), 3.78 (s, 3H, OCH3), 4.06-4.14 (m, 2H, OCH2CH3), 6.70 (s, 1H, 7-CH), 6.85 (d, J = 8
Hz, 2H, ArH), 7.29 (d, J = 8.8 Hz, 2H, ArH), 11.09 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.05,
19.48, 55.27, 59.08, 60.46, 99.46, 114.13, 128.57, 132.05, 145.68, 148.63, 159.90, 164.95. Anal. Calcd
for C15H17N5O3: C, 57.13; H, 5.43; N, 22.21. Found: C, 57.05; H, 5.49; N, 22.30. ESI-MS: m/z = 315 ([M
+ H+]).
1
2d: Yield 85%, mp 250-252 ºC. H NMR (400 MHz, CDCl3): δ = 1.08 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.71 (s, 6H, 2CH3), 4.01-4.08 (m, 2H, OCH2CH3), 6.98 (s, 1H, 7-CH), 7.12-7.26 (m, 4H, ArH), 11.25 (s,
13
1H, NH). C NMR (100 MHz, CDCl3): δ = 13.90, 19.31, 19.40, 55.65, 60.39, 99.33, 126.75, 127.09,
128.80, 130.74, 136.09, 138.37, 146.16, 148.46, 164.85. Anal. Calcd for C15H17N5O2: C, 60.19; H, 5.72;
N, 23.40. Found: C, 60.07; H, 5.78; N, 23.49. ESI-MS: m/z = 299 ([M + H+]).
1
2e: Yield 87%, mp 209-211 ºC. H NMR (400 MHz, CDCl3): δ = 1.15 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.31 (s, 3H, CH3), 2.67 (s, 3H, CH3), 4.06-4.13 (m, 2H, OCH2CH3), 6.70 (s, 1H, 7-CH), 7.13 (d, J = 8 Hz,
13
2H, ArH), 7.24 (d, J = 7.6 Hz, 2H, ArH), 11.07 (s, 1H, NH). C NMR (100 MHz, CDCl3): δ = 14.03,
19.46, 21.14, 59.33, 60.45, 99.41, 127.17, 129.39, 136.88, 138.82, 145.79, 148.71, 164.94. Anal. Calcd
for C15H17N5O2: C, 60.19; H, 5.72; N, 23.40. Found: C, 60.07; H, 5.63; N, 23.52. ESI-MS: m/z = 299 ([M
+ H+]).
1
2f: Yield 79%, mp 244-246 ºC. H NMR (400 MHz, CDCl3): δ = 1.15 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.69 (s, 3H, 5-CH3), 4.08-4.13 (m, 2H, OCH2CH3), 6.71 (s, 1H, CH), 7.27 (d, J = 8.8 Hz, 2H, ArH), 7.29
(d, J = 8.8 Hz, 2H, ArH), 11.22 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.04, 19.53, 58.94, 60.62,
98.87, 128.71, 129.09, 134.94, 138.17, 146.27, 148.61, 164.67. Anal. Calcd for C14H14ClN5O2: C, 52.59;
H, 4.41; N, 21.90. Found: C, 52.65; H, 4.49; N, 21.98. ESI-MS: m/z = 319 ([M + H+]).
1
2g: Yield 73%, mp 225-227 ºC. H NMR (400 MHz, CDCl3): δ = 1.16 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.73 (s, 3H, 5-CH3), 4.09-4.15 (m, 2H, OCH2CH3), 6.84 (s, 1H, 7-CH), 7.57 (d, J = 9.2 Hz, 2H, ArH),
8.22 (d, J = 8.4 Hz, 2H, ArH), 11.35 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.05, 19.70, 58.82,
60.88, 98.27, 124.17, 128.44, 146.04, 146.91, 148.10, 148.58, 164.39. Anal. Calcd for C14H14N6O4: C,
50.91; H, 4.27; N, 25.44. Found: C, 50.98; H, 4.18; N, 25.53. ESI-MS: m/z = 330 ([M + H+]).

HETEROCYCLES, Vol. 83, No. 12, 2011
2819
1
2h: Yield 80%, mp 242-244 ºC. H NMR (400 MHz, CDCl3): δ = 1.16 (t, J = 7.2 Hz, 3H, OCH2CH3),
2.67 (s, 3H, 5-CH3), 4.06-4.13 (m, 2H, OCH2CH3), 6.69 (s, 1H, CH), 7.25 (d, J = 8.8 Hz, 2H, ArH), 7.47
(d, J = 8.8 Hz, 2H, ArH), 10.98 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.07, 19.56, 59.01, 60.65,
98.83, 123.15, 129.01, 132.07, 138.69, 146.24, 148.60, 164.67. Anal. Calcd for C14H14BrN5O2: C, 46.17;
H, 3.87; N, 19.23. Found: C, 46.05; H, 3.80; N, 19.31. ESI-MS: m/z = 363 ([M + H+]).
2i: Yield 76%, mp 219-221 ºC. 1H NMR (400 MHz, CDCl3): δ = 1.17 (t, J = 7.2 Hz, 3H, OCH2CH3), 2.74
(s, 3H, 5-CH3), 4.09-4.15 (m, 2H, OCH2CH3), 6.85 (s, 1H, 7-CH), 7.57 (t, J = 8.8 Hz, 1H, ArH), 7.74 (d,
J = 8 Hz, 1H, ArH), 8.20-8.22 (m, 2H, ArH), 11.28 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 14.05,
19.78, 58.96, 60.88, 98.35, 122.38, 124.03, 130.03, 133.53, 141.73, 146.92, 148.48, 148.58, 164.39. Anal.
Calcd for C14H14N6O4: C, 50.91; H, 4.27; N, 25.44. Found: C, 50.99; H, 4.19; N, 25.51. ESI-MS: m/z =
330 ([M + H+]).
4a: Yield 76%, mp 326-327 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 1.00 (s, 3H, CH3), 1.06 (s, 3H,
CH3), 2.12-2.26 (m, 2H, CH2), 2.60 (s, 2H, CH2), 6.60 (s, 1H, 9-CH), 7.26-7.35 (m, 5H, ArH), 11.63 (s,
13
1H, NH). C NMR (100 MHz, d6-DMSO/TMS): δ = 26.99, 28.27, 32.32, 49.80, 57.44, 57.46, 105.65,
127.16, 128.34, 128.60, 140.46, 148.45, 150.50, 193.03. Anal. Calcd for C16H17N5O: C, 65.07; H, 5.80; N,
23.71. Found: C, 65.15; H, 5.73; N, 23.82. ESI-MS: m/z = 295 ([M + H+]).
4b: Yield 68%, mp 272-274 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 1.00 (s, 3H, CH3), 1.06 (s, 3H,
CH3), 2.12-2.25 (m, 2H, CH2), 2.60 (s, 2H, CH2), 6.63 (s, 1H, 9-CH), 7.33 (d, J = 8.4 Hz, 2H, ArH), 7.40
13
(d, J = 8.8 Hz, 2H, ArH), 11.67 (s, 1H, NH). C NMR (100 MHz, d6-DMSO/TMS): δ = 27.09, 28.15,
32.34, 49.77, 56.85, 105.28, 128.60, 129.19, 132.95, 139.41, 148.38, 150.68, 193.07. Anal. Calcd for
C16H16ClN5O: C, 58.27; H, 4.89; N, 21.24. Found: C, 58.18; H, 4.94; N, 21.31. ESI-MS: m/z = 329 ([M +
H+]).
1
4c: Yield 72%, mp 270-272 ºC. H NMR (400 MHz, CDCl3): δ = 1.12 (s, 3H, CH3), 1.16 (s, 3H, CH3),
2.26-2.35 (m, 2H, CH2), 2.65-2.75 (m, 2H, CH2), 3.77 (s, 3H, OCH3), 6.70 (s, 1H, 9-CH), 6.84 (d, J = 8.8
Hz, 2H, ArH), 7.26 (d, J = 8.8 Hz, 2H, ArH), 11.36 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 27.56,
28.87, 32.88, 40.82, 50.50, 53.37, 57.77, 107.62, 114.09, 128.40, 131.57, 135.38, 148.79, 153.40, 193.74.
Anal. Calcd for C17H19N5O2: C, 62.75; H, 5.89; N, 21.52. Found: C, 62.66; H, 5.83; N, 21.43. ESI-MS:
m/z = 325 ([M + H+]).
4d: Yield 67%, mp 248-249 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 0.99 (s, 3H, CH3), 1.06 (s, 3H,
CH3), 2.12-2.26 (m, 2H, CH2), 2.61 (s, 2H, CH2), 6.78 (s, 1H, 9-CH), 7.62 (d, J = 8.8 Hz, 2H, ArH), 8.19
13
(d, J = 8.8 Hz, 2H, ArH), 11.78 (s, 1H, NH). C NMR (100 MHz, d6-DMSO/TMS): δ = 17.12, 18.05,

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18.60, 22.33, 39.69, 46.90, 94.89, 113.69, 117.57, 118.80, 137.03, 138.41, 141.09, 183.04. Anal. Calcd
for C16H16N6O3: C, 56.47; H, 4.74; N, 24.69. Found: C, 56.52; H, 4.79; N, 24.77. ESI-MS: m/z = 340 ([M
+ H+]).
1
4e: Yield 65%, mp 281-283 ºC. H NMR (400 MHz, CDCl3): δ = 1.15 (s, 3H, CH3), 1.19 (s, 3H, CH3),
2.29-2.39 (m, 2H, CH2), 2.73-2.84 (m, 2H, CH2), 6.84 (s, 1H, 9-CH), 7.58 (t, J = 8 Hz, 1H, ArH), 7.84 (d,
J = 8 Hz, 1H, ArH), 8.09-8.21(m, 2H, ArH), 11.49 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 27.62,
28.77, 33.04, 40.92, 50.35, 57.69, 106.46, 121.93, 124.04, 130.03, 133.95, 140.92, 148.57, 148.62, 149.83,
193.71. Anal. Calcd for C16H16N6O3: C, 56.47; H, 4.74; N, 24.69. Found: C, 56.56; H, 4.82; N, 24.75.
ESI-MS: m/z = 340 ([M + H+]).
1
4f: Yield 70%, mp 296-298 ºC. H NMR (400 MHz, CDCl3): δ = 1.06 (s, 3H, CH3), 1.15 (s, 3H, CH3),
2.21-2.32 (m, 2H, CH2), 2.63-2.72 (m, 2H, CH2), 3.67 (s, 3H, OCH3), 6.84 (s, 1H, 9-CH), 6.95-7.54 (m,
4H, ArH), 11.23 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ = 26.84, 29.09, 32.81, 40.91, 50.50, 55.36,
56.29, 106.40, 111.20, 120.68, 126.35, 130.38, 130.68, 149.45, 149.59, 157.22. 193.71. Anal. Calcd for
C17H19N5O2: C, 62.75; H, 5.89; N, 21.52. Found: C, 62.68; H, 5.82; N, 21.63. ESI-MS: m/z = 325 ([M +
H+]).
4g: Yield 69%, mp 326-328 ºC. 1H NMR (400 MHz, d6-DMSO/TMS): δ = 0.87 (s, 3H, CH3), 1.01 (s, 3H,
CH3), 2.00-2.21 (m, 2H, CH2), 2.24-2.43 (m, 2H, CH2), 7.18 (d, J = 8.4 Hz, 2H, ArH), 7.52 (d, J = 8.4 Hz,
2H, ArH), 7.81 (s, 1H, 9-CH), 9.53 (s, 1H, NH). 13C NMR (100 MHz, d6-DMSO/TMS): δ = 26.83, 28.66,
32.26, 49.74, 51.53, 106.94, 128.47, 129.46, 131.19, 143.98, 151.69, 152.54, 192.85. Anal. Calcd for
C16H16BrN5O: C, 51.35; H, 4.31; N, 18.71. Found: C, 51.28; H, 4.39; N, 18.63. ESI-MS: m/z = 373 ([M +
H+]).
1
4h: Yield 71%, mp 304-305 ºC. H NMR (400 MHz, CDCl3): δ = 1.12 (s, 3H, CH3), 1.16 (s, 3H, CH3),
2.30 (s, 3H, CH3), 2.31 (s, 2H, CH2), 2.67-2.78 (m, 2H, CH2), 6.71 (s, 1H, 9-CH), 7.13 (d, J = 8 Hz, 2H,
13
ArH), 7.23 (d, J = 8 Hz, 2H, ArH), 11.47 (s, 1H, NH). C NMR (100 MHz, CDCl3): δ = 21.15, 27.54,
28.84, 32.90, 40.80, 50.49, 58.03, 107.60, 127.02, 129.58, 136.34, 138.84, 148.80, 149.05, 193.75. Anal.
Calcd for C17H19N5O: C, 66.00; H, 6.19; N, 22.64. Found: C, 66.12; H, 6.26; N, 22.71. ESI-MS: m/z =
309 ([M + H+]).
ACKNOWLEDGMENTS
We are thankful for the financial support from the National Nature Science Foundation of China (No.
20902073 and 21062017), the Natural Science Foundation of Gansu Province (No. 096RJZA116), and

HETEROCYCLES, Vol. 83, No. 12, 2011
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Scientific and Technological Innovation Engineering program of Northwest Normal University
(nwnu-kjcxgc-03-64, nwnu-lkqn-10-15).
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