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desired C-H arylation of selenopyrano[2,3-c]pyrazol-4(1H)-ones
derivatives. The well-known reaction path for palladium-
catalyzed direct C-H activation catalyzed by Palladium catalyst
heterocyclic systems is currently under-way in our laboratory
and will be reported in due course.
is similar to earlier reports3,6
.
Funding Information
Once the established reaction condition is in hand, we began
to investigate various aryl bromides with electron-donating
groups (EDG) present on the aromatic ring are important for
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the same in the acknowledgment.
(sPLA
IIA). activity7 and
Acknowledgment
group II secretory phospholipaseA
2
2
electron-withdrawing groups (EWG) as mentioned in scheme 3.
Both electron donating and electron withdrawing substituent
containing aryl bromide underwent direct C-H activation with
established reaction conditions. Both electronic functionalities
provided desired C-H activation product with moderate to good
yields (1a-h). On average, the activity of EDG and EWG looks
similar, but a slight higher yield was found in case of electron-
donating groups (EDG, Me group) present on 3rd position of
pyrazole (1a) ring provided better yield compared to phenyl
substituent (1m). In addition, it was observed that the
comparatively higher yields were obtained in case of ethyl,
isopropyl, cyclopropyl group (1j-l) when it was subject to react
with bromobenzene under the established conditions. The
presence of electron rich alkyl groups on adjacent carbon may
be weakening the electron withdrawing nature of carbonyl bond
which could participate as a mild co-ordination in the catalysis
process. This method can easily provide C-H arylation products
of various selenopyrano[2,3-c]pyrazol-4(1H)-ones with various
aryl bromides (Scheme 3).
This work was carried out as a co-operation project of “Enhancement of
Korea Chemical Bank (SI1807) supported by Korea Research Institute of
Chemical Technology (KRICT) and Yonsei Institute of Pharmaceutical
Sciences for financial support.
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References and Notes
(1) (a) Srivastava, P. C.; Robins, R. K. J. Med. Chem. 1983, 26, 445. (b)
Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004, 104,
6
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K.; Manna, D.; Minoura, M.; Mugesh, G. J. Am. Chem. Soc. 2010, 132,
5
364. (h) Bhabak, K. P.; Mugesh, G. Acc. Chem. Res. 2010, 43, 1408.
R1
O
R
1
O
(i) Koketsu, M.; Ishihara, H.; Wu, W.; Murakami, K.; Saiki, I. Eur. J.
Br
Pd(OAc)2, XPhos, Cs
2
CO
3
N
N
Pharm. Sci. 1999, 9, 157. (j) Takahashi, H.; Nishina, A.; Fukumoto,
R.-h.; Kimura, H.; Koketsu, M.; Ishihara, H. Eur. J. Pharm. Sci. 2005,
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D.; Schwartz, J. C. Proc. Natl. Acad. Sci. 1992, 89, 2649. (l) van der
Goot, H.; Eriks, J. C.; Leurs, R.; Timmerman, H. Bioorg. Med. Chem.
Lett. 1994, 4, 1913−1916. (m) Sekiguchi, A.; Nishina, A.; Kimura,
H.; Fukumoto, R. H.; Kanoh, K.; Ishihara, H.; Koketsu, M. Chem.
Pharm. Bull. 2005, 53, 1439. (n) Nam, K. N.; Koketsu, M.; Lee, E. H.
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+
3
N
N
R
Se
Se
3HBF4
R3
PivOH, P(t-Bu)
2
1
R2
O
R2
O
O
O
N
N
N
N
O
N
O
N
O
O
N
N
Se
Se
Se
Se
O
1
d 25%
1
a 75%
1b 64%
1c 23%
O
O
O
O
O
(
2) (a) Karabanovich, G.; Roh, J.; Pade
̌lková, Z.; Novák, Z.; Vávrová, K.;
N
N
N
N
N
N
Hrabalek, A. Tetrahedron 2013, 69, 8798. (b) Pizzo, C., Mahler, S.
́
Se
N
N
Se
Se
Se
O
Cl
NO
2
G. J. Org. Chem. 2014, 79, 1856. (c) Choi, Y.-S., Kim, D.-M., Kim, Y.-
J. Yang, S., Lee, K.-T., Ryu, J.-H., Jeong, J.-H. Int. J. Mol. Sci. 2015, 16,
29574.
1
e 59%
1h 30%
1f 58%
1g 37%
O
O
O
O
O
N
N
N
(
3) Yang, W.-R., Choi, Y.-S., Jeong, J.-H. Org. Biomol. Chem., 2017, 15,
N
N
Se
N
N
Se
Se
N
Se
l 85%
3074.
1i 49%
1j 82%
1
k 73%
(4) Klayman, D. L., Griffin, T. S. J. Am. Chem. Soc. 1973, 95, 197.
1
(
5) MacLean, M. A., Cecilia, E. D., Lavery, C. B., Reed, M. A., Wang, Y.,
Weaver, D. F., Stradiotto, M. Bioorg. Med. Chem. Lett., 2016, 26,
100.
O
N
N
Se
(
6) Lee, P.-H., Lee, K.-Y. Tetrahedron Lett. 2008, 49, 4302.
7) Chen, J.-J., Chang, H. W., Kim, H. P., Park, H.-I. Bioorg. Med. Chem.
Lett., 2006, 16, 2373.
(
1
m 43%
Scheme 3: C-H activation of selenopyrano[2,3-c]pyrazol-4(1H)-ones
(8) General procedure for Vilsmeier-Haack formylation
Phosphoryl chloride (0.12 mol, 11.27mL) was added dropwise to
an ice-cold dimethylformamide (0.52 mol, 4 mL) then cooling was
removed to reflux system, the mixture was treated with 3-methyl-
In conclusion, we have developed a multi-step synthetic
protocol for new selenopyrano[2,3-c]pyrazol-4(1H)-ones and
their direct C-H arylation using palladium catalyst. We have also
modified the oxidation and cyclization part compared to our
previous method and the products were obtained with
moderate to higher yields duly confirmed by NMR and HRMS
analysis. In general, we attempted to prepare various analogs of
this novel scaffold for further biological screenings. Further
work on the development of selenium containing other
5
-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (3.0 g, 17.22
mmol) and the mixture compound was heated at 120℃ for 20
min. After cooling, the reaction mixture was poured into ice-cold
water (200 mL) and stirred for 1h. Then extracted with Ethyl
acetate, Organics was washed with water and dried over Sodium
sulfate, and concentrated under vacuum. The product was
purified by column chromatography on silica gel.
5
-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (5a)
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