A new method for synthesizing asymmetric urea containing thiazolo[5,4-b]pyridine and applications in agriculture

Article abstract of DOI:10.1080/10426507.2010.497518

Chemical Equation Presented In this article, we describe the use of diphenyl carbonate (DPC) as a carbonyl source instead of isocyanate to synthesize asymmetric substituted urea derivatives. In a study aiming to discover new lead compounds with agricultur

Full text of DOI:10.1080/10426507.2010.497518

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A New Method for Synthesizing
Asymmetric Urea Containing
Thiazolo[5,4-b]pyridine And Applications
in Agriculture
Wenbin Chen a & Kejian Li a
a State Key Laboratory of Elemento-Organic Chemistry, Tianjin Key
Laboratory of Pesticide Science, Institute of Elemento-Organic
Chemistry, Nankai University, Tianjin, P.R. China
Version of record first published: 19 Feb 2011.
To cite this article: Wenbin Chen & Kejian Li (2011): A New Method for Synthesizing Asymmetric Urea
Containing Thiazolo[5,4-b]pyridine And Applications in Agriculture, Phosphorus, Sulfur, and Silicon and
the Related Elements, 186:2, 311-318
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Phosphorus, Sulfur, and Silicon, 186:311–318, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.497518
A NEW METHOD FOR SYNTHESIZING ASYMMETRIC
UREA CONTAINING THIAZOLO[5,4-b]PYRIDINE
AND APPLICATIONS IN AGRICULTURE
Wenbin Chen and Kejian Li
State Key Laboratory of Elemento-Organic Chemistry, Tianjin Key Laboratory
of Pesticide Science, Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin, P.R. China
GRAPHICAL ABSTRACT
Abstract In this article, we describe the use of diphenyl carbonate (DPC) as a carbonyl source
instead of isocyanate to synthesize asymmetric substituted urea derivatives. In a study aiming
to discover new lead compounds with agricultural activities, thiazole[5,4-b]pyridine ureas
were prepared by this method and characterized by mass spectrometry, elemental analysis, and
1H NMR spectroscopy. The biological activities show that the title compounds have moderate
activities on herbicide, fungicide, and plant growth regulation.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Biological activities; diphenyl carbonate; synthesis; thiazolopyridine; urea
INTRODUCTION
Asymmetric substituted ureas play a key role in agriculture and medicine. Although
there are many feasible routes for the synthesis of asymmetric urea derivatives, these
Received 9 April 2010; accepted 26 May 2010.
The authors are grateful to the National Natural Science Foundation of China (No. 20702027) and Natural
Science Foundation of Tianjin (No. 07JCYBJC00100) for the financial support.
Address correspondence to Wenbin Chen, State Key Laboratory of Elemento-Organic Chemistry, Tianjin
Key Laboratory of Pesticide Science, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071,
P.R. China. E-mail: wbchen@nankai.edu.cn
311

312
W. CHEN AND K. LI
methods are generally limited to the addition of substituted amines to isocyanate from
phosgene.1,2 Because of their high toxicity and reactivity, phosgene and isocyanates are
difficult to handle in the laboratory. Although alternatives for phosgene, such as triphos-
gene, have been developed during the last few decades,3 it itself is prepared from phosgene.
Other methods such as carbonyldiimidazole,4 selenium-catalyzed carbonylation,5,6 and S,S-
dimethyl dithiocarbonate2,7,8 also suffer from drawbacks, such as reagents prepared from
phosgene, human carcinogens, unstable intermediates, or high pressure conditions. Alter-
native methods involve drastic reaction conditions, such as direct reactions of amines with
dialkyl carbonates at high temperature9 and the reaction of amines with N,Nꢁ-diphenylurea
in the presence of Et3N in refluxing DMF,10 but only symmetric ureas can be obtained by
these methods. So the development of a facile and safe procedure to synthesize asymmetric
ureas is of importance and has practical application.
Heterocyclic compounds also play a key role in the research and development of new
pesticides because of their special chemical structures and physical properties, and now
they have become important for new pesticides. There are a lot of commercial pesticides
containing heterocyclic structures: for example, neonicotinoid insecticides imidacoprid and
acetamiprid, super-high efficient herbicide sulfonylurea, triazolopyrimidine and imidazoli-
none, and the fungicides Triadimefon and Triadimenol.
Fused systems containing a pyridine ring, in particular thiazolopyridines, are widely
used as base structures in the design of various biologically active compounds possess-
ing antiviral, anticarcinogenic, antiphlogistic, and antispasmodic properties.11–14 There are
six isomeric thiazolopyridine systems reported in the literature (Scheme 1).15 Depending
on the fusion of the thiazole moiety to the pyridine ring, thiazolopyridines can be clas-
sified into the following classes: thiazolo[3,2-a]pyridine (I), thiazolo[3,4-a]pyridine (II),
thiazolo[5,4-b]pyridine (III), thiazolo[5,4-c]pyridine (IV), thiazolo[4,5-c]pyridine (V), and
thiazolo[4,5-b]pyridine (VI). Several thiazolo[5,4-b]pyridines have been evaluated as an-
tibacterials,16–20 antibiotics,21,22 antivirals,23 bronchospasmolytics,24 leukotriene antiago-
nists,25 antiulcer agents,26,27 and as azo dyes.28
S
N
N
S
N
N
S
Thiazole[3, 2-a]pyridine Thiazole[3, 4-a]pyridine
(I) (II)
Thiazole[5,4-b]pyridine
(III)
N
N
N
N
N
N
S
S
S
Thiazole[4, 5-b]pyridine
Thiazole[5, 4-c]pyridine Thiazole[4, 5-c]pyridine
(IV) (V)
(VI)
Scheme 1 Structures of six thiazolopyridines.
To develop a convenient method to synthesize asymmetric ureas, obtain the multifunc-
tional libraries of 1,3-disubstituted asymmetric urea derivatives, and optimize the structure
of urea derivative to find a new lead compound, in this article we report another asymmet-
ric urea derivative, thiazolo[5,4-b]pyridine urea, from substituted amino compounds, and

SYNTHESIS OF ASYMMETRIC UREA
313
phenyl thiazolo[5,4-b]pyridine-2-yl carbamate under refluxing in toluene, as well as their
biological activities.
RESULTS AND DISCUSSION
We used diphenyl carbonate (DPC) as a carbonyl source to synthesize the title com-
pounds. Diphenyl carbonate, a key raw material utilized in the phosgene-free polycarbonate
manufacturing process, has been one of the foci of research in chemistry and chemical en-
gineering in recent decades. It is also used as a solvent and chemical intermediate, and it
is easy and safe to handle in the laboratory as a carbonyl source, instead of phosgene. The
synthetic route to the title compounds 5 is outlined in Scheme 2.
O
H
N
H
N
NH2
Cl
Reflux
CH3ONa
Cl
+
+
NH4SCN
NMP,120 0C
S
O
N
N
Cl
1
O
N
S
O
C
O
N
S
N
S
70% H2SO4
PhOCOPh
NH2
NH
NH
C
O
N
NaH
N
N
2
4
3
O
C
RNH2
Toluene, 120oC
N
NH
NHR
S
N
5
Scheme 2 Synthetic route for the preparation of compounds 5.
The key intermediate thiazolo[5,4-b]pyridin-2-yl amine 3, which was obtained from
2-chloropyridinyl-3-amine in three steps according to a modified literature procedure,29 was
treated with diphenyl carbonate and NaH in anhydrous THF to give phenyl thiazolo[5,4-
b]pyridin-2-yl carbamate 4 in an acceptable yield. The title compounds 5 were produced
by aminolysis of compound 4 and diversified amine in refluxing toluene for about 20 h in
good yield. They were easy to isolate by filtration or recrystallization and seldom needed
silica gel column chromatography.
As a control, the synthesis of phenyl carbamate 4 was attempted from 3 by treatment
with phenyl chloroformate and Et3N in THF. However, this procedure did not work well,
and no desired product was monitored from TLC. It is possible that phenyl chloroformate
is so active that many side products were formed under these conditions. In this article, the
benzothiazole amine 3 was first converted to the sodium salt and then treated with diphenyl
carbonate to give moderate yield of the desired phenyl carbamate.
To evaluate the biological activity of the title compounds, we tested the insectici-
dal, herbicidal, fungicidal, and plant growth regulation activities. The results show that
the title compounds have no insecticidal activities against Oriental armyworm and Culex
pipiens pallens. Most compounds possess moderate herbicidal activities against Amaran-
thus tricolor L at post-emergence and very lower activities against Echinochloa crusgalli,
Brassica napus L., Medicago sativa L., and Digitaria sanguinalis(Linn)Scop., but have
some fungicidal inhibition against Fusarium graminearum, Alternaria solani, Cercospora
arachidicol, Botryosphaeria berengeriama, and Fusarium oxysporum. Most compounds

314
W. CHEN AND K. LI
have inhibition on rooting of cucumber cotyledon, while compound 5n has plant growth
regulation activities on rooting of cucumber cotyledon at 101.5%. The detailed biological
results are listed in Tables S1 and S 2 (see the Supplemental Materials, available online).
CONCLUSIONS
In summary, we have described the novel phosgene-free synthesis of asymmetric
urea containing thiazole[5,4-b]pyridine with agricultural activities (herbicide, fungicide,
and plant growth regulation). This method is safe, convenient, and easy to scale up in
laboratory. The final synthesized compounds were characterized by spectral data (1H NMR,
ESI-MS, and elemental analysis). Further investigations of these compounds are in progress.
EXPERIMENTAL
Melting points were determined using an X-4 Digital Microscope Melting Point
Apparatus (Beijing Taike Co. Ltd.) and were uncorrected. Nuclear magnetic resonance
spectra were recorded on Varian Mecury Plus 400 NMR or Bruker Avance-300 NMR
instrument in CDCl3 or (CD3)2SO. Chemical shifts (δH) are reported in parts per million
(ppm), relative to TMS as internal standard. Elemental analyses were carried out on an
MF-3 automatic analyzer instrument. Flash-column chromatography was performed using
commercial grades of silica gel 200∼300 meshes. Analytical thin layer chromatography
(TLC) was performed on precoated silica gel 60 F254 plates, and spot visualization was
accomplished by UV light (254 nm) or phosphomolybdic acid solution.
Solvents were obtained from commercial sources and purified according to the liter-
ature30 if necessary.
Preparation of Phenyl Thiazolo[5,4-b]pyridin-2-ylcarbamate 429
To the mixture of ammonium isothiocyanate (8.9 g, 116.68 mmol, 1.0 eq) and benzoyl
chloride (16.4 g, 116.68 mmol, 1.0 eq) in acetone (100 mL), 2-chloropyridin-3-amine (10 g,
77.78 mmol, 0.5 eq) in acetone (50 mL) was added with a mechanical stirrer and then heated
to reflux for 8 h. After cooling to room temperature, the solvent was removed under reduced
pressure, and the residue was dissolved in hot ethanol and filtered. The solid was washed
with water and diethyl ether successively, and dried at room temperature to obtain the
1
desired compound 1, mp 152–154◦C, yield 85%, H NMR [DMSO, 400MHz] δ/ppm:
8.51–8.52 (m, 1H), 8.16–8.18 (m, 1H), 8.11–8.13 (m, 2H), 7.63–7.67 (m,1H), 7.51–7.58
(m, 3H), 5.32 (brs, 2H, 2×NH).
In a 100 mL of flask, the above compound 1 (2.20 g, 7.5 mmol, 1.0 eq) and NaOCH3
(0.81 g, 15 mmol, 2.0 eq) were placed in N-methyl-2-pyrrolidone) (NMP, 15 mL). After
refluxing for 8 h, the mixture was poured into cool water (30 mL). The precipitate was
filtered and washed with water and diethyl ether successively, and dried at room temperature
to give the intermediate 2, yield 75%. 1H NMR [DMSO, 300MHz] δ/ppm: 13.00 (brs, 1H,
NH), 8.49–8.51 (m, 1H), 8.13–8.16 (m, 3H), 7.65–7.71 (m, 1H), 7.49–7.60 (m, 3H).
The above intermediate 2 (10 g, 40 mmol) in 70% sulfuric acid (50 mL) was heated
to reflux for 3–4 h. After cooling to room temperature, the mixture was poured into water
(125mL), and neutralized with 30% NaOH. The precipitate was filtered and washed with
water and diethyl ether to give the desired product, yield 56%, mp 241–243◦C (lit.31

315

316
W. CHEN AND K. LI
Table 2 Characteristic ESI-MS and 1H NMR data of thiazole[5,4-b]pyridine ureas 5
Compound
ESI-MS (M-1)− (%)
270 (100)
1H NMR (DMSO, 300MHz or 400MHz, δ/ppm)
5a
(300M Hz): 12.36(s, 1H, NH), 10.07(s, 1H, NH), 8.43(t, J = 2.0Hz,
1H), 8.07(d, J = 3.9Hz, 1H), 8.07(d, J = 8.1Hz, 1H), 7.87–7.82(m,
1H), 7.57(d, J = 7.8Hz, 1H), 7.48–7.45(m, 1H), 7.13(t, J =
11.7Hz, 1H)
5b
5c
5d
5e
284 (100)
284 (100)
284 (100)
283 (100)
(300M Hz): 12.42(s, 1H, NH), 10.04(s, 1H, NH), 8.43(t, J = 4.8Hz,
1H), 8.08(d, J = 8.1Hz, 1H), 7.72(t, J = 7.8Hz, 1H), 7.48–7.44(m,
1H), 7.35(t, J = 3.6Hz, 1H), 7.00(d, J = 7.5Hz, 1H), 2.48(s, 3H)
(300M Hz): 12.30(s, 1H, NH), 9.96(s, 1H, NH), 8.42(s, 1H), 8.18(s,
1H), 8.07(s, 1H), 7.66(d, J = 2.7Hz, 1H), 7.47(d, J = 1.0Hz, 2H),
2.26(s, 3H)
(300M Hz): 12.49(s, 1H, NH), 10.04(s, 1H, NH), 8.43(d, J = 3.3Hz,
1H), 8.23(d, J = 5.1Hz, 1H), 8.07(d, J = 8.1Hz, 1H), 7.49–7.45(m,
1H), 7.36(s, 1H), 6.98(d, J = 4.8Hz, 1H), 2.34(s, 3H)
(300M Hz): 10.90(s, 1H, NH), 9.08(s, 1H, NH), 8.39(d, J = 5.1Hz,
1H), 8.01(d, J = 6.9Hz, 1H), 7.40(d, J = 8.1Hz, 3H), 7.15(d, J =
7.5Hz, 2H), 2.27(s, 3H)
5f
348 (100), 350 (95)
304 (100)
(300M Hz): 11.65(s, 1H, NH), 9.98(s, 1H, NH), 8.45(t, J = 8.4Hz,
2H), 8.07–8.05(m, 2H), 7.76–7.74(m, 1H), 7.49–7.45(m, 1H)
(300M Hz): 11.64(s, 1H, NH), 9.99(s, 1H, NH), 8.43(t, J = 3.9Hz,
2H), 8.06(t, J = 2.4Hz, 1H), 7.96(t, J = 2.1Hz, 1H), 7.83–7.81(m,
1H), 7.47(t, J = 3.0Hz, 1H)
5g
5h
270 (100) (M-Cl)−
(300M Hz): 12.36(s, 1H, NH), 10.07(s, 1H, NH), 8.42(d, J = 3.3Hz,
1H), 8.37(s, 1H), 8.06(d, J = 7.5Hz, 1H), 7.84(t, J = 6.6Hz, 1H),
7.56(d, J = 6.9Hz, 1H), 7.47(d, J = 4.5Hz, 1H), 7.14(d, J = 4.2Hz,
1H)
5i
371 (100), 373 (80)
348 (100)
(300M Hz): 11.66(s, 1H, NH), 9.19(s, 1H, NH), 8.40(d, J = 15.4Hz,
2H), 8.02(d, J = 7.2Hz, 1H), 7.89(s, 1H), 7.43(d, J = 3.2Hz, 1H)
(400M Hz): 10.98(s, 1H, NH), 9.31(s, 1H, NH), 8.37–8.36(t, J =
2.2Hz, 1H), 7.98(d, J = 3.2Hz, 1H), 7.48(s, 4H), 7.43–7.40(m, 1H)
(300M Hz): 11.06(s, 1H, NH), 9.34(d, J = 1.6Hz, 1H), 8.45–8.39(m,
1H), 8.01–7.99(t, J = 8.8Hz, 1H), 7.57–7.37(m, 4H)
(300M Hz): 8.46(d, J = 3.9Hz, 2H), 8.06–8.04(t, J = 3.8Hz, 2H),
7.49–7.47(t, J = 3.8Hz, 2H)
5j
5k
5l
303 (100)
315 (100)
5m
5n
5o
283 (50)
(300M Hz): 8.23(s, 1H, NH), 7.79(d, J = 8.4Hz, 2H), 7.18–7.13(m,
3H), 6.96(d, J = 7.2Hz, 1H), 2.26(s, 3H)
285 (100)
(400M Hz): 10.96(s, 1H, NH), 8.33(d, J = 4.4Hz, 1H), 7.93(d, J =
8.0Hz, 1H), 7.39–7.24(m, 6H), 4.35(d, J = 5.6Hz, 2H)
(400M Hz): 10.76(s, 1H, NH), 8.31(d, J = 3.6Hz, 1H), 7.92(d, J =
8.0Hz, 1H), 7.38–7.35(m, 1H), 6.75(s, 1H), 3.16–3.11(m, 2H),
1.46–1.38(m, 2H), 1.33–1.23(m, 2H), 0.88–0.85(t, J = 7.2Hz, 3H)
(400M Hz): 10.76(s, 1H, NH), 8.32(d, J = 4.4Hz, 1H), 7.92(d, J =
8.0Hz, 1H), 7.38–7.35(m, 1H), 6.77(s, 1H), 3.12–3.07(m, 2H),
1.48–1.42(m, 2H), 0.86–0.83(t, J = 7.2Hz, 3H)
249 (100)
5p
5q
235 (100)
235 (100)
(400M Hz): 10.57(s, 1H, NH), 8.31(d, J = 4.4Hz, 1H), 7.92(d, J =
8.0Hz, 1H), 7.38–7.35(m, 1H), 6.63(d, J = 7.2Hz, 1H),
3.83–3.75(m, 1H), 1.11(d, J = 6.8Hz, 6H)
5r
5s
5t
270 (90) 271 (20)
287 (100)
(400M Hz): 8.76(d, J = 4.4Hz, 1H), 8.43–8.39(m, 2H), 8.03–8.01(m,
1H), 7.46–7.42(m, 2H)
(400M Hz): 8.40–8.39(t, J = 2.2Hz, 2H), 8.43–8.39(d, J = 8.0Hz,
1H), 7.46–7.42(m, 2H)
314 (100)
(400M Hz): 12.24(s, 1H, NH), 8.38(s, 2H), 8.23–8.19(m, 1H),
8.03–7.99(t, J = 7.6Hz, 1H), 7.769(s, 1H), 7.45–7.40(m, 2H)

SYNTHESIS OF ASYMMETRIC UREA
317
1
240–242◦C). H NMR [DMSO, 300MHz] δ/ppm: 8.06 (m, 1H), 7.61 (m, 1H), 7.25 (m,
1H).
To dry THF (50 mL), NaH (2.30 g, 0.10 mol, 6.0 eq) was added under an ice-water
bath and stirred for 30 min. Then thiazolo[5,4-b]pyridin-2-amine (2.52 g, 16.7 mmol,
1.0 eq) in 50 mL dry THF was added dropwise to the above mixture. After stirring for 1.5 h,
diphenyl carbonate (4.2 g, 20.0 mmol, 1.2 eq) was added and stirred overnight. The solvent
was removed under reduced pressure, and the residue was diluted with ethyl acetate (100
mL), washed with brine (50 mL × 3), and dried over Na2SO4. The solvent was evaporated,
and the residue was separated by flash silica gel column chromatograph to give white solid
2.4 g, yield 54%, 1H NMR [DMSO, 300MHz] δ/ppm: 12.81 (brs, 1H, NH), 8.44–8.47 (m,
1H), 8.10–8.13 (m, 1H), 7.45–7.51 (m, 3H), 7.30–7.35 (m, 3H).
Preparation of Title Compounds 5
A mixture of phenyl thiazolo[5,4-b]pyridin-2-ylcarbamate 4 (1.0 eq) and aliphatic or
aromatic amine (1∼1.5 eq) in toluene (40 mL) was refluxed for 20 h. When the solution
was cooled, the precipitate from the reactant was filtered and washed with ethanol to yield
one part of the desired product. The filtrate was concentrated and recrystallized from the
appropriate solvents or purified by flash silica gel column chromatography (hexane and
ethyl acetate as eluent) to yield another part of product. All physical constants and spectral
data are outlined in Tables 1 and 2.
REFERENCES
1. Ozaki, S. J. Synth. Org. Chem Jpn. 1982, 40, 285–295.
2. Leung, M. K.; Lai, J. L.; Lau, K. H.; Yu, H. H.; Hsiao, H. J. J. Org. Chem. 1996, 61, 4175–4179.
3. Eckert, H.; Forster, B. Angew. Chem., Int. Ed. Engl. 1987, 26, 894–895.
4. Batey, R. A.; Santhakumar, V.; Yoshina-Ishii, C.; Taylor, S. D. Tetrahedron Lett. 1998, 39,
6267–6270.
5. Yang, Y.; Lu, S. W. Tetrahedron Lett. 1999, 40, 4845–4846.
6. Mei, J. T.; Yang, Y.; Xue, Y.; Lu, S. W. J. Mol. Catal. A: Chem. 2003, 191, 135–139.
7. Artuso, E.; Degani, L.; Fochi, R.; Magistris, C. Synthesis 2007, 3497–3506.
8. Degani, I.; Fochi, R.; Magistris, C.; Migliaccio, M. Synthesis 2009, 801–808.
9. Fyles, T. M.; James, T. D.; Pryhitka, A.; Zojaji, M. J. Org. Chem. 1993, 58, 7456–7468.
10. Ramadas, K. Org. Prep. Proced. Int. 1993, 25, 711–711.
11. Mylari, B. L.; Larson, E. R.; Beyer, T. A.; Zembrowski, W. J.; Aldinger, C. E.; Dee, M. F.; Siegel,
T. W.; Singleton, D. H. J. Med. Chem. 1991, 34, 108–122.
12. Borthwick, A. D.; Davies, D. E.; Ertl, P. F.; Exall, A. M.; Haley, T. M.; Hart, G. J.; Jackson, D.
L.; Parry, N. R.; Patikis, A.; Trivedi, N.; Weingarten, G. G.; Woolven, J. M. J. Med. Chem. 2003,
46, 4428–4449.
13. Ternansky, R. J.; Draheim, S. E.; Pike, A. J.; Bell, F. W.; West, S. J.; Jordan, C. L.; Wu, C. Y. E.;
Preston, D. A.; Alborn, W.; Kasher, J. S.; Hawkins, B. L. J. Med. Chem. 1993, 36, 1971–1976.
14. AlvarezIbarra, C.; FernandezGranda, R.; Quiroga, M. L.; Carbonell, A.; Cardenas, F.; Giralt, E.
J. Med. Chem. 1997, 40, 668–676.
15. El-Gaby, M. S. A.; Al-Sehemi, A. G.; Mohamed, Y. A.; Ammar, Y. A. Phosphorus, Sulfur Silicon
Relat. Elem. 2006, 181, 631–674.
16. Stolle, A.; Habich, D.; Riedl, B.; Ruppelt, M.; Bartel, S.; Guarnieri, W.; Wild, H.; Endermann,
R.; Kroll, H. Eur. Pat. EP 785, 201 (Cl. Co7D513/04), 23 July 1997, DE Appl. 19, 601, 627, 18
Jan. 1996; Chem. Abstr. 1997, 127, 176421t.

318
W. CHEN AND K. LI
17. Blizzard, T. A.; Ratcliffe, R. W.; Waddell, S. T.; Szumiloski, S. P.; Wilkening, R. R.; Wildonger,
K. J. U.S. US 5, 496, 816 (Cl. 514–210; A61 K31/40), 5 Mar. 1996, us Appl. 213, 314, 14 Mar.
1994; Chem. Abstr. 1996, 125, 10478a.
18. Cama, L. D.; Hammond, M. L.; Sasor, M. F. U.S. US 5, 538, 964 (Cl. 514–210; Co7D487/04),
23 July 1996, US Appl. 391, 857, 22 Feb. 1995; Chem. Abstr. 1996, 125, 195285b.
19. Cama, L. D.; Hammond, M. L.; Sasor, M. F. U.S. US, 5, 565, 445 (Cl. 514–210; A61 K31/395),
15 Oct. 1996, Appl. 391, 857, 22 Feb. 1995; Chem. Abstr. 1996, 125, 328386j.
20. Brooks, G.; Davies, D. T.; Jones, G. E.; Markwell, R. E.; Pearson, N. D. PCT Int. Appl. WO 03
87, 098 (Cl. Co7D471/04), 23 Oct. 2003, GB Appl. 2001/12, 834, 25 May 2001; Chem. Abstr.
2003, 139, 337959q.
21. Ternansky, R. J. E. P. 495, 584. A. E., 584 (Cl. Co7D501/59), 22 July 1992, US Appl. 642, 959,
18 Jan. 1991; Chem. Abstr. 1992, 117, 191587p.
22. Ternansky, R. J. U. S. US, 077, 287 (Cl. 514-210; Co7D487/04), 31 Dec. 1991, Appl. 643, 244,
18 Jan. 1991; Chem. Abstr. 1992, 116, 128508c.
23. Borthwick, A. D.; Davies, D. E.; Exall, A. M.; Jackson, D. L.; Mason, A. M.; Pennell, A. M. K.;
Rahim, S. G.; Trivedi, N.; Weingarten, G. G. PCT Int. Appl. WO 98 43, 975 (Cl. Co7D487/04),
8 Oct. 1998, GB Appl. 97/91, 189, 9 Sept. 1997; Chem. Abstr. 1998, 129, 302643y.
24. Eisenburger, R. F. R.; Schemainda, I.; Seibel, K. Ger. Offen. DE 19, 618, 970 (Cl. Co7D 513/04),
13 Nov. 1997, Appl. 19, 618, 970, 10 May 1996; Chem. Abstr. 1998, 128, 34760z.
25. Young, R. N.; Labelle, M.; Leblanc, Y.; Xiang, Y. B.; Lau, C. K.; Dufresne, C.; Gareau, Y. US 5,
472, 964 (Cl. 514–243; A61K31/435), 5 Dec. 1995, US Appl. 994, 869, 22 Dec. 1992; Chem.
Abstr. 1996, 124, 232429d.
26. Yoshiyama, Y.; Nanba, R.; Endo, I.; Koyama, S. Jpn. Kokai Tokkyo Koho JP 03, 284, 684 [91,
284, 684] (Cl. Co7D513/04), 16 Dec. 1991, Appl. 90/81, 047, 30 Mar. 1990; Chem. Abstr. 1992,
116, 235621f.
27. Shikata, Y.; Endo, I.; Koyama, S. Eur. Pat. Appl. EP 426, 574 (Cl. Co7D513/04), 08 May 1991,
JP Appl. 89/284, 911, 02 Nov. 1989; Chem. Abstr. 1991, 115, 71591x.
28. Kaneko, M.; Kurose, Y.; Yutaka, H.; Hosogai, H. Jpn. Kokai Tokkyo Koho JP 0517, 699 [93 17,
699] (Cl. Co9B29/039), 26 Jan. 1993, Appl. 91/199, 860, 16 July 1991; Chem. Abstr. 1990, 119,
74601u.
29. Jouve, K.; Bergman, J. J. Heterocycl. Chem. 2003, 40(2), 261–268.
30. Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, 5th ed.; Butterworth-
Heinemann: Burlington, MA, 2003.
31. Altland, H. W.; Molander, G. A. J. Heterocycl. Chem. 1977, 14(1), 129–134.