Please Gd roe en no tC ha ed mj u iss tt r my argins
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COMMUNICATION
Journal Name
O
O
Br
Conflicts of interest
The authors declare no competing financial interests.
DOI: 10.1039/D0GC00757A
K2CO3 (3.0 equiv)
DMF, 95 oC, 6 h
O
O
.
H2N OH HCl(1.2 equiv)
HO
HO
O
O
+
.
HCl DMPU( 1.0 equiv)
MeCN, 60 oC, 5 h
O
8
6
7
O
O
N
O
O
O
O
CN
Acknowledgements
O
O
N
NH
9, 98%
We are grateful to the National Institutes of Health for financial
support (R01GM121660). We are grateful to Dr. Ricardo A.
Angnes (University of São Paulo, Brazil) for scientific support
and discussions.
1
0
Erlotinib
OH
N
N
CF3
Cl
CF3
References:
.
F
F
NH2OH HCl (1.2 equiv)
O
.
F
HCl DMPU (1.0 equiv)
MeCN,60 oC, 5 h
CN
1.
J. S. Miller and J. L. Manson, Acc. Chem. Res., 2001, 34, 563-
70.
Cl
S
5
11
12, 98%
13
2
3
4
.
.
.
F. F. Fleming, L. Yao, P. C. Ravikumar, L. Funk and B. C.
Shook, J. Med. Chem., 2010, 53, 7902-7917.
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cyano compounds, Wiley, 1983.
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J. W. F. Wasley, J. Med. Chem., 2000, 43, 2488-2488.
A. Khan, Expert Opinion on Investigational Drugs, 2009, 18,
Fluanxol
HO
Br
HO
Br
Br
O
NH2OH.HCl (1.2 equiv)
.
5.
6.
HCl DMPU, (1.0 equiv)
K2CO3, DMF
95 oC, 4 h
CN
Br
CN
16, 91%
MeCN,60 oC,5 h
O
14
15, 95%
1
753-1764.
A. J. Lees, CNS Neuroscience & Therapeutics, 2008, 14, 83-
3.
H. G. Johnson and A. Q. Sheridan, Agents and Actions,
986, 18, 301-305.
7
8
9
1
1
.
9
.
O
1
O
S
.
E. Pascual, F. Sivera, U. Yasothan and P. Kirkpatrick, Nat.
Rev. Drug Discov., 2009, 8, 191-192.
N
N
OH
17
0.
1.
T. Sandmeyer, Berichte der deutschen chemischen
Gesellschaft, 1884, 17, 2650-2653.
K. W. Rosenmund and E. Struck, Berichte der deutschen
chemischen Gesellschaft (A and B Series), 1919, 52, 1749-
Febuxostat
We also performed a gram-scale synthesis of tris-(4-
cyanophenyl)amine (19) from 4,4',4''-nitrilotribenzaldehyde
18) in 91% yield (Scheme 3). Since compound (18) contains
three aldehyde groups, the stoichiometry of the reagents were
1
756.
(
1
2.
A. Pradal and G. Evano, Chem. Commun., 2014, 50, 11907-
11910.
modified accordingly. 4-Cyanophenyl)amine (19) is utilized in 13.
K. Hyodo, K. Togashi, N. Oishi, G. Hasegawa and K. Uchida,
Org. Lett., 2017, 19, 3005-3008.
L. Friedman and H. Shechter, J. Org. Chem., 1960, 25, 877-
the preparation of metal-organic frameworks for high-intensity
light emission and other applications.
4
1
14.
5.
16.
8
79.
X. Zhang, A. Xia, H. Chen and Y. Liu, Org. Lett., 2017, 19,
118-2121.
1
2
Scheme 3. Gram scale synthesis of tris-(4-cyanophenyl)amine:
NC
CN
M. Sundermeier, A. Zapf, S. Mutyala, W. Baumann, J. Sans,
S. Weiss and M. Beller, Chemistry (Weinheim an der
Bergstrasse, Germany), 2003, 9, 1828-1836.
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2011, 40, 5049-5067.
OHC
CHO
N
N
.
HCl DMPU (1.0equiv)
MeCN, 4h, 60 o
.
NH2OH HCl (3.0 equiv)
C
1
7.
CN
CHO
18
19, 91%
18.
Q. Wu, Y. Luo, A. Lei and J. You, J. Am. Chem. Soc., 2016,
1
38, 2885-2888.
S. Laulhé, S. S. Gori and M. H. Nantz, J. Org. Chem., 2012,
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1
2
2
2
9.
0.
1.
2.
Conclusions
7
We have successfully developed a practical, and efficient one-
pot conversion of aldehydes to nitriles with inexpensive and
readily available reagents that are compatible with diverse
functional groups, providing rapid access to 40 diverse nitriles
in good to excellent yields. Furthermore, this one-pot process
5
1
D. J. Quinn, G. J. Haun and G. Moura-Letts, Tetrahedron
Letters, 2016, 57, 3844-3847.
was found to be applicable to the synthesis of key precursors 23.
for various drug molecules in excellent yields.
W.-Y. Fang and H.-L. Qin, J. Org. Chem, 2019, 84, 5803-
5812.
4
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