A facile synthesis of novel thiazolo[4,5-d]pyrimidin-7-ones

Article abstract of DOI:10.1002/jhet.515

Sixteen 5-alkylamino-3,6-diaryl-2-thioxo-2,3,6,7-tetrahydrothiazolo[4,5-d] pyrimidin-7-ones 4a-4p were designed and easily synthesized via a tandem aza-Wittig reaction. The iminophosphorane 2, obtained from reaction of 1 with triphenylphosphine, hexachloroethane and Et₃N, reacted with aromatic isocyanate to give carbodiimide 3. carbodiimide 3 reacted with alkylamines to provide the title compounds in 45-61% isolated yields in presence of catalytic amount of ethoxide. The structures of compounds 4 were confirmed by ¹H NMR, IR, MS, and elemental analysis.

Full text of DOI:10.1002/jhet.515

88
A Facile Synthesis of Novel Thiazolo[4,5-d]pyrimidin-7-ones
Ying Liang,a,b* Hong-Wu He,b and Zi-Wen Yanga
Vol 48
aLaboratory of Green Chemistry & Synthesis, Hubei Biopesticide Engineering Research Center,
Hubei Academy of Agricultural Science,
Wuhan 430064, People’s Republic of China
bKey Laboratory of Pesticide and Chemical Biology, Ministry of Education,
Central China Normal University, Wuhan 430079, People’s Republic of China
*E-mail: ly.liang8@gmail.com
Received February 2, 2010
DOI 10.1002/jhet.515
Published online 2 September 2010 in Wiley Online Library (wileyonlinelibrary.com).
Sixteen 5-alkylamino-3,6-diaryl-2-thioxo-2,3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-ones 4a–4p
were designed and easily synthesized via a tandem aza-Wittig reaction. The iminophosphorane 2,
obtained from reaction of 1 with triphenylphosphine, hexachloroethane and Et3N, reacted with aromatic
isocyanate to give carbodiimide 3. carbodiimide 3 reacted with alkylamines to provide the title com-
pounds in 45–61% isolated yields in presence of catalytic amount of ethoxide. The structures of com-
1
pounds 4 were confirmed by H NMR, IR, MS, and elemental analysis.
J. Heterocyclic Chem., 48, 88 (2011).
INTRODUCTION
RESULTS AND DISCUSSION
Thiazolo[4,5-d]pyrimidines are widely recognized as
pharmaceutically and biologically useful heterocycles
because of their structural similarities to purine bases.
As such, thiazolo[4,5-d]pyrimidines have been found to
possess anti-HIV [1], anticancer [2], anti-inflammatory
[3], and antimicrobial activities [4,5]. An important syn-
thetic route for thiazolo[4,5-d]pyrimidines in previous
reports is the condensation reaction of 4-aminothiazole-
5-carboxylate and isothiocyanate. However, this method
is characterized as a long reaction time and low yield
[6].
The iminophosphorane 2, which was prepared in a
satisfactory yield by the reaction of 1 with triphenyl-
phosphine, hexachloroethane and Et3N [9,10], reacted
with aryl isocyanate to give carbodiimide 3. In refluxing
toluene, 3 did not react with alkylamines to provide the
target compounds. However, in CH2Cl2 and in the pres-
ence of a catalytic amount of EtONa, compounds 3
were converted smoothly to the 5-alkylamino-3,6-diaryl-
2-thioxo-2,3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-
ones 4 in satisfactory yields at room temperature
(Scheme 1). Irrespective of the fact whether primary
or secondary amines were used, and whether the sub-
stitutes on the amines were bulky or small groups, the
cyclization proceeded very smoothly in the same
regioselectivity. Thin layer chromatography was used
to follow the progress of every above reaction. Most
of the compounds 4 were readily soluble in polar or-
ganic solvents. The results are listed in Table 1.
Recently, we have been interested in the synthesis of
fused pyrimidinones via aza-Wittig reaction of b-ethoxy-
carbonyl iminophosphorane with aromatic isocyanate
and subsequent reaction with various nucleophile under
mild condition [7]. As a continuation of our research for
new biologically active heterocycles [8], here we wish
to report an efficient synthesis of 5-alkylamino-3,6-dia-
ryl-2-thioxo-2,3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-
7-ones, a series of compounds which have not been
reported before.
All products 4 were obtained as yellow crystals after
recrystallization from CH2Cl2/petroleum ether and were
confirmed by their elemental analysis and spectral data.
C
V
2010 HeteroCorporation

January 2011
A Facile Synthesis of Novel Thiazolo[4,5-d]pyrimidin-7-ones
89
Scheme 1
1
EXPERIMENTAL
For example, the H NMR spectra data of 4m showed
the signals of NH at d 4.72 as triplet, which were not
the same as the proton of PhNH, the chemical shift of
which is greater than d 7.0. Its methylene protons dis-
played a doublet also, which strongly suggested the ex-
istence of an NHCH2-group. In IR spectral of 4m–4p,
the relatively strong absorption of NAH appeared at
3336–3431 cmꢀ1, which was only one peak. The
stretching resonance of C¼¼O showed strong absorption
at about 1675–1697 cmꢀ1. The MS spectrum of 4m dis-
played strong molecule ion peaks. The structure of 4
was also established on the basis of elemental analysis
data. The difference between found value and calculated
value of elemental analysis of all compounds was under
0.5%.
Melting points were determined with a WRS-1B Digital
melting point apparatus and are uncorrected. EI-MS were
measured on a Finnigan Trace MS spectrometer. IR were
recorded on a PE-983 infrared spectrometer as KBr pellets
1
with absorption in cmꢀ1. H NMR were recorded in CDCl3 on
a Varian Mercury 400 spectrometer and resonances are given
in ppm (d) relative to TMS. Elementary analyses were taken
on a Perkin-Elmer CHN 2400 elementary analysis instrument.
All the solvent and materials are reagent grades and purified
before use.
Thiazolecarboxylate derivatives 1 was prepared according to
the literature procedures in 68.8% yield [11]. Yellow crystal,
mp 221.8–222.4ꢁC, 1H NMR (400 MHz CDCl3): d (ppm):
7.63–7.32 (m, 5H, Ph-H), 5.63 (s, 2H, ANH2), 4.28(q, 2H, J
¼ 7.2 Hz, ACH2), 0.97(t, 3H, J ¼ 6.8 Hz, ACH3).
Table 1
Reaction conditions of the target compounds.
Compds
Ar1
Ar2
R1R2N
r.t. (h)
Yield (%)a
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
Ph
Ph
Ph
Ph
Et2N
(i-Pr)2N
3
3
2
3
2
2
3
3
2
3
3
2
3
3
3
3
54
58
56
58
60
59
58
61
56
54
55
45
57
55
54
52
Ph
Ph
Ph
(n-Amyl)2N
Et2N
(i-Pr)2N
(n-Amyl)2N
Et2N
(i-Pr)2N
4-ClPh
4-ClPh
4-ClPh
4-FPh
4-FPh
4-FPh
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
(n-Amyl)2N
Et2N
(i-Bu)2N
4-FPh
4-FPh
4-FPh
Ph
(n-Amyl)2N
2-MePhCH2NH
3-MePhCH2NH
2-MePhCH2NH
3-MePhCH2NH
Ph
Ph
4-ClPh
4-ClPh
Ph
a Yields of isolated products based on iminophosphosphorane 2.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

90
Y. Liang, H.-W. He, and Z.-W. Yang
Vol 48
Preparation of iminophosphorane 2. A solution of 1 (14.0
6-(4-Chlorophenyl)-5-di(i-propyl)amino-3-phenyl-2-thioxo-2,
3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4e). Yellow
g, 0.05 mol) in CH3CN (150 mL) was added triphenylphos-
phine (26.5 g, 0.1 mol) and C2Cl6 (24.0 g, 0.1 mol). The mix-
ture was treated with triethylamine (28.0 mL, 0.2 mol), then
stirred for 4–5 h at 20ꢁC, the solution was condensed and the
residue was recrystallized from CH3CH2OH to give imino-
phosphorane 2 in yield 98.5%. Yellow crystal, m.p. 224.1–
1
crystals, m.p. > 270ꢁC. H NMR (400 MHz CDCl3) d (ppm):
0.85 (d, J ¼ 6.4 Hz, 12H, 4CH3), 3.47 (m, 2H, 2CH), 7.22–
7.60 (m, 9H, Ph-H); IR (KBr) t (cmꢀ1): 2981 (CAH), 1675
(C¼¼O), 1570, 1529 (Ph); Elemental Anal. Calcd. for
C23H23ClN4OS2 (471.0): C, 58.65; H, 4.92; N, 11.89; S, 13.61;
Found: C, 57.13; H, 4.87; N, 11.44; S, 13.24.
1
225.0ꢁC H NMR (400 MHz CDCl3): d (ppm): 7.50–7.27 (m,
6-(4-Chlorophenyl)-5-di(n-amyl)amino-3-phenyl-2-thioxo-2,3,
6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4f). Yellow crys-
20H, Ph-H), 3.75 (q, 2H, J ¼ 6.8 Hz, ACH2), 0.97 (t, 3H, J ¼
7.2 Hz, ACH3); EI-MS (70 eV, m/z) (relative intensity %):
(m/z) 540 (Mþ, 100), 512(28), 262(99), 183(90), 107(54).
Preparation of carbodiimides 3. To a solution of imino-
phosphorane 2 (0.54 g, 1 mmol) in anhyd CH2Cl2 (10 mL)
was added aromatic isocyanate (1.1 mmol) under N2 at r.t. Af-
ter the reaction mixture was left unstirred for 5–12 h, the sol-
vent was removed off under reduced pressure and Et2O/petro-
leum ether was added to precipitate triphenylphosphine oxide.
Removal of the solvent gave carbodiimides 3, which were
used directly without further purification partly because they
easily decomposed.
1
tals, m.p. 177.2–178.7ꢁC. H NMR (400 MHz CDCl3) d (ppm):
0.79–0.86 (m, 10H, 2CH2CH3), 1.08–1.14 (m, 8H, 2CH2CH2),
2.83 (t, J ¼ 8.0 Hz, 4H, 2CH2), 7.22–7.57 (m, 9H, Ph-H); IR
(KBr) t (cmꢀ1): 2957(CAH), 1682 (C¼¼O), 1571, 1532(Ph);
Elemental Anal. Calcd. for C27H31ClN4OS2 (527.1): C, 61.52;
H, 5.93; N, 10.63; S, 12.17; Found: C, 60.77; H, 5.85; N,
10.84; S, 11.84.
5-Diethylamino-6-(4-fluorophenyl)-3-phenyl-2-thioxo-2,3,6,
7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4g). Yellow crys-
1
tals, m.p. 219.5–220.4ꢁC. H NMR(400 MHz CDCl3) d (ppm):
General procedure for the preparation of compounds
4a–4p. To the solution of carbodiimides 3 prepared above in
ethanol (15 mL) was added alkylamine (1.1 mmol) and a cata-
lytic amount of sodium ethoxide in ethanol. After the mixture
had been stirred for 2–3 h at 303 K, the solution was concen-
trated and the residue was recrystallized from CH3CN to give
0.72 (t, J ¼ 7.2 Hz, 6H, 2CH3), 2.95 (q, J ¼ 7.2 Hz, 4H,
2CH2), 7.20–7.57 (m, 9H, Ph-H); IR (KBr) t (cmꢀ1): 2976
(CAH), 1684 (C¼¼O), 1571, 1526(Ph); Elemental Anal. Calcd.
for C21H19FN4OS2 (426.5): C, 59.13; H, 4.49; N, 13.14; S,
15.04; Found: C, 59.28; H, 4.91; N, 12.79; S, 15.51 .
5-Di(i-propyl)amino-6-(4-fluorophenyl)-3-phenyl-2-thioxo-2,
3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4h). Yellow
crystals, m.p. 265.1–265.4ꢁC. 1H NMR(400 MHz CDCl3) d
(ppm): 0.85 (d, J ¼ 6.8 Hz, 12H, 4CH3), 3.47 (m, 2H, 2CH),
7.15–7.60 (m, 9H, Ph-H); IR (KBr) t (cmꢀ1): 2977 (CAH),
1679 (C¼¼O), 1573, 1529(Ph); Elemental Anal. Calcd. for
C23H23FN4OS2 (454.6): C, 60.77; H, 5.10; N, 13232; S, 14.11;
Found: C, 60.43; H, 4.81; N, 12.85; S, 14.54.
5-Di(n-amyl)amino-6-(4-fluorophenyl)-3-phenyl-2-thioxo-2,
3,6,7-tetra hydrothiazolo[4,5-d]pyrimidin-7-one (4i). Yellow
crystals, m.p. 153.5–154.1ꢁC. 1H NMR(400 MHz CDCl3) d
(ppm): 0.79–0.87 (m, 10H, 2CH2CH3), 1.08–1.13 (m, 8H,
2CH2CH2), 2.83 (t, J ¼ 8.0 Hz, 4H, 2CH2), 7.19–7.56 (m, 9H,
Ph-H); IR (KBr) t (cmꢀ1): 2958 (CAH), 1681 (C¼¼O), 1572,
1532(Ph); Elemental Anal. Calcd. for C27H31FN4OS2 (510.7):
C, 63.50; H, 6.12; N, 10.97; S, 12.56; Found: C, 63.45; H,
6.65; N, 10.46; S, 12.91.
5-Diethylamino-3-(4-fluorophenyl)-6-phenyl-2-thioxo-2,
3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4j). Yellow
crystals, m.p. 172.6–173.2ꢁC. 1H NMR (400 MHz CDCl3)
d (ppm): 0.71 (t, J ¼ 7.2 Hz, 6H, 2CH3), 2.96 (q, J ¼ 7.2 Hz, 4H,
2CH2), 7.25–7.50 (m, 9H, Ph-H); IR (KBr) t (cmꢀ1): 2976
(CAH), 1689 (C¼¼O), 1573, 1528(Ph); Elemental Anal. Calcd. for
C21H19FN4OS2 (426.5): C, 59.13; H, 4.49; N, 13.14; S, 15.04;
Found: C, 59.36; H, 4.58; N, 12.89; S, 15.59.
pure
5-alkylamino-3,6-diaryl-2-thioxo-2,3,6,7-tetrahydrothia-
zolo[4,5-d]pyrimidin-7-ones 4a–4p.
5-Diethylamino-3,6-diphenyl-2-thioxo-2,3,6,7-tetrahydro-
thiazolo[4,5-d]pyrimidin-7-one (4a). Yellow crystals, m.p.
1
206.2–207.1ꢁC. H NMR(400 MHz CDCl3) d (ppm): 0.68 (t, J
¼ 7.2 Hz, 6H, 2CH3), 3.09 (q, J ¼ 7.2 Hz, 4H, 2CH2), 7.28–
7.59 (m, 10H, Ph-H); IR (KBr) t (cmꢀ1): 2974 (CAH), 1687
(C¼¼O), 1573, 1528(Ph); Elemental Anal. Calcd. for
C21H20N4OS2 (408.5): C, 61.74; H, 4.93; N, 13.71; S, 15.70;
Found: C, 61.31; H, 5.01; N, 13.50; S, 15.23.
5-Di(i-propyl)amino-3,6-diphenyl-2-thioxo-2,3,6,7-tetrahydro-
thiazolo[4,5-d]pyrimidin-7-one (4b). Yellow crystals, m.p.
1
254.1–255.6ꢁC. H NMR(400 MHz CDCl3) d (ppm): 0.82 (d, J
¼ 6.4 Hz, 12H, 4CH3), 3.49 (m, 2H, 2CH), 7.25–7.58 (m, 10H,
Ph-H); IR (KBr) t (cmꢀ1): 2962 (CAH), 1689 (C¼¼O), 1571,
1525 (Ph); Elemental Anal. Calcd. for C23H24N4OS2 (436.6):
C, 63.27; H, 5.54; N, 12.83; S, 14.69; Found: C, 63.37; H,
5.33; N, 12.69; S, 14.15.
5-Di(n-amyl)amino-3,6-diphenyl-2-thioxo-2,3,6,7-tetrahydro-
thiazolo[4,5-d]pyrimidin-7-one (4c). Yellow crystals, m.p.
151.1–151.7ꢁC. 1H NMR(400 MHz CDCl3) d (ppm): 0.77–
0.85 (m, 10H, 2CH2CH3), 1.06–1.10 (m, 8H, 2CH2CH2), 2.82
(t, J ¼ 8.0 Hz, 4H, 2CH2), 7.29–7.57 (m, 10H, Ph-H); IR
(KBr) t (cmꢀ1): 2953 (CAH), 1684 (C¼¼O), 1573, 1530(Ph);
Elemental Anal. Calcd. for C27H32N4OS2 (492.7): C, 65.22; H,
6.55; N, 11.37; S, 13.02; Found: C, 65.73; H, 6.50; N, 11.26;
S, 12.53.
5-Di(i-butyl)amino-3-(4-fluorophenyl)-6-phenyl-2-thioxo-2,
3,6,7-tetra hydrothiazolo[4,5-d]pyrimidin-7-one (4k). Yellow
crystals, m.p. 193.6–195.1ꢁC. 1H NMR (400 MHz CDCl3) d
(ppm): 0.67 (d, J ¼ 6.4 Hz, 12H, 4CH3), 1.62–1.73 (m, 2H,
2CH), 7.25–7.51 (m, 9H, Ph-H); IR (KBr) t (cmꢀ1): 2964
(CAH), 1681 (C¼¼O), 1574, 1529(Ph); Elemental Anal. Calcd.
for C25H27FN4OS2 (482.6): C, 62.21; H, 5.64; N, 11.61; S,
13.29; Found: C, 62.58; H, 5.87; N, 12.03; S, 13.57.
6-(4-Chlorophenyl)-5-diethylamino-3-phenyl-2-thioxo-2,3,6,
7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4d). Yellow crys-
1
tals, m.p. 246.1–247.3ꢁC. H NMR(400 MHz CDCl3) d (ppm):
0.73 (t, J ¼ 7.2 Hz, 6H, 2CH3), 2.95 (q, J ¼ 7.2 Hz, 4H,
2CH2), 7.24–7.57 (m, 9H, Ph-H); IR (KBr) t (cmꢀ1): 2965
(CAH), 1683 (C¼¼O), 1572, 1525(Ph); Elemental Anal. Calcd.
for C21H19ClN4OS2 (443.0): C, 56.94; H, 4.32; N, 12.65; S,
14.48; Found: C, 56.28; H, 4.31; N, 12.38; S, 14.15.
5-Di(n-amyl)amino-3-(4-fluorophenyl)-6-phenyl-2-thioxo-2,
3,6,7-tetra hydrothiazolo[4,5-d]pyrimidin-7-one (4l). Yellow
crystals, m.p. 173.6–174.2ꢁC. 1H NMR (400 MHz CDCl3) d
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2011
A Facile Synthesis of Novel Thiazolo[4,5-d]pyrimidin-7-ones
91
(ppm): 0.78–0.88 (m, 10H, 2CH2CH3), 1.08–1.14 (m, 8H,
2CH2CH2), 2.84 (t, J ¼ 8.0 Hz, 4H, 2CH2), 7.22–7.49
(m, 9H, Ph-H); IR (KBr) t (cmꢀ1): 2957 (CAH), 1682
(ppm): 2.27 (s, 3H,CH3), 4.15 (d, J ¼ 6.0 Hz, 2H, CH2), 4.81
(s, 1H, NH), 6.65–7.61 (m, 13H, Ph-H); IR (KBr) t (cmꢀ1):
3303 (NAH), 2931 (CAH), 1678 (C¼¼O), 1544 (Ph); Elemen-
tal Anal. Calcd. For C25H19ClN4OS2 (491.0): C, 61.15; H,
3.90; N, 11.41; S, 13.06; Found: C, 61.52; H, 3.76; N, 11.01;
S, 13.02.
(C¼¼O),1571,1532(Ph);
Elemental
Anal.
Calcd.
for
C27H31FN4OS2 (510.7): C, 63.50; H, 6.12; N, 10.97; S, 12.56;
Found: C, 63.37; H, 5.95; N, 10.88; S, 12.14.
3,6-diphenyl-5-(2-methylbenzylamino)-2-thioxo-2,3,6,7-tet-
rahydrothiazolo[4,5-d]pyrimidin-7-one (4m). Yellow crystals,
m.p. 271.2–273.2ꢁC. 1H NMR (400 MHz CDCl3) d (ppm):
1.98 (s, 3H,CH3), 4.19 (d, J ¼ 6.0 Hz, 2H, CH2), 4.72 (s, 1H,
NH), 6.69–7.63 (m, 14H, Ph-H); EI-MS (70eV, m/z)(relative
intensity %) 456 (Mþ, 100), 351(47), 336(7), 181(48),
105(93), 91(43), 77(99); IR (KBr) t (cmꢀ1): 3426 (NAH),
2923 (CAH), 1697 (C¼¼O), 1545(Ph); Elemental Anal. Calcd.
for C25H20N4OS2 (456.6): C, 65.76; H, 4.42; N, 12.27; S,
14.05; Found: C, 64.71; H, 3.80; N, 11.74; S, 14.51.
Acknowledgments. The authors gratefully acknowledge the fi-
nancial support of this work by the National Basic Research Pro-
gram of China (No: 2003CB114400) and the National Natural
Science Foundation of China (No: 20372023).
REFERENCES AND NOTES
[1] Bekhit, A. A.; Fahmy, H. T. Y.; Rostom, S. A. F.; Baraka.
A. M. Eur J Med Chem 2003, 38, 27.
3,6-diphenyl-5-(3-methylbenzylamino)-2-thioxo-2,3,6,7-tet-
rahydrothiazolo[4,5-d]pyrimidin-7-one (4n). Yellow crystals,
[2] Kini, G. D.; Anderson, J. D.; Sanghvi, Y. S.; Lewis, A. F.;
Smee, D. F.; Revankar, G. R.; Robins, R. K.; Cottam, H. B. J Med
Chem 1991, 34, 3006.
1
m.p. 221.8–222.3ꢁC. H NMR(400 MHz CDCl3) d (ppm): 2.29
(s, 3H, CH3), 4.17 (d, J ¼ 5.6 Hz, 2H, CH2), 4.87 (s, 1H, NH),
6.86–7.52 (m, 14H, Ph-H); IR (KBr) t (cmꢀ1): 3370 (NAH),
2976 (CAH), 1689 (C¼¼O), 1544 (Ph); Elemental Anal. Calcd.
for C25H20N4OS2 (456.6): C, 65.76; H, 4.42; N, 12.27; S,
14.05; Found: C, 65.38; H, 4.40; N, 12.38; S, 13.89.
6-(4-chlorophenyl)-5-(2-methylbenzylamino)-3-phenyl-2-thioxo-
2,3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4o). Yellow
crystals, m.p. 263.4–265.1ꢁC. 1H NMR(400 MHz CDCl3) d
(ppm): 2.00 (s, 3H,CH3), 4.20 (d, J ¼ 5.6 Hz, 2H, CH2), 4.69
(s, 1H, NH), 6.70–7.59 (m, 13H, Ph-H); IR (KBr) t (cmꢀ1):
3360 (NAH), 2935 (CAH), 1675 (C¼¼O), 1542(Ph); Elemental
Anal. Calcd. For C25H19ClN4OS2 (491.0): C, 61.15; H, 3.90; N,
11.41; S, 13.06; Found: C, 61.68; H, 4.22; N, 11.25; S, 13.47.
6-(4-Chlorophenyl)-5-(3-methylbenzylamino)-3-phenyl-2-thi-
oxo-2,3,6,7-tetrahydrothiazolo[4,5-d]pyrimidin-7-one (4p). Yellow
crystals, m.p. 251.5–253.1ꢁC. 1H NMR(400 MHz CDCl3) d
[3] Tozkoparan, B.; Ertan, M.; Kelicen, P.; Demirdamar, R. Il
Farmaco 1999, 54, 588.
[4] Balkan, A.; Urgan, H.; Ozalp, M. Arzneim-Forsch 2001, 51, 839.
[5] Habin, N. S.; Rida, S. M.; Badaway, E. A. M.; Fahwy, H.
T. Y.; Ghozlan, H. A. Eur J Med Chem 1997, 32, 759.
[6] Balkan, A.; Goren, Z.; and Goren, H. Arzneim-Forsch
2002, 52, 462.
[7] Ding, M. W.; Yang, S. J.; Zhu, J. Synthesis 2004, 36, 75.
[8] Liu, J. C.; He, H. W.; Ren, Q. Y.; Ding, M. W. J Hetero-
cycl Chem 2006, 43, 803.
[9] Liu, J. C.; He, H. W.; Ren, Q. Y.; Ding, M. W. Helv Chim
Acta 2006, 89, 1337.
[10] Ding, M. W.; Xu, S. Z.; and Zhao, J. F. J Org Chem 2004,
69, 8366.
[11] Wamhoff, H.; Herrmann, S.; Stolben, S. Tetrahedron 1993,
49, 581.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet