Synthesis of N-pyrimidin[1,3,4]oxadiazoles and N-pyrimidin[1,3,4]-thiadiazoles from 1,3,4-oxadiazol-2-amines and 1,3,4-thiadiazol-2-amines via Pd-catalyzed heteroarylamination

Article abstract of DOI:10.1016/j.tetlet.2019.04.022

An efficient and practical procedure was developed to prepare various N-pyrimidin[1,3,4]oxadiazole and thiadiazole scaffolds using a Buchwald-type coupling. The products of this reaction are otherwise difficult to access and could be used as building bloc

Full text of DOI:10.1016/j.tetlet.2019.04.022

Accepted Manuscript
Synthesis of N-pyrimidin[1,3,4]oxadiazoles and N-pyrimidin[1,3,4]-thiadia-
zoles from 1,3,4-oxadiazol-2-amines and 1,3,4-thiadiazol-2-amines via Pd-
catalyzed heteroarylamination
Longjia Yan, Minggao Deng, Anchao Chen, Yongliang Li, Wanzheng Zhang,
Zhi-yun Du, Chang-zhi Dong, Bernard Meunier, Huixiong Chen
PII:
S0040-4039(19)30360-0
https://doi.org/10.1016/j.tetlet.2019.04.022
TETL 50737
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
6 March 2019
9 April 2019
12 April 2019
Please cite this article as: Yan, L., Deng, M., Chen, A., Li, Y., Zhang, W., Du, Z-y., Dong, C-z., Meunier, B., Chen,
H., Synthesis of N-pyrimidin[1,3,4]oxadiazoles and N-pyrimidin[1,3,4]-thiadiazoles from 1,3,4-oxadiazol-2-amines
and 1,3,4-thiadiazol-2-amines via Pd-catalyzed heteroarylamination, Tetrahedron Letters (2019), doi: https://
doi.org/10.1016/j.tetlet.2019.04.022
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Synthesis of N-pyrimidin[1,3,4]oxadiazoles and N-
pyrimidin[1,3,4]-thiadiazoles from 1,3,4-oxadiazol-
2-amines and 1,3,4-thiadiazol-2-amines via Pd-
catalyzed heteroaryl-amination
Leave this area blank for abstract info.
Longjia Yana, Minggao Denga, Anchao Chena, Yongliang Lia, Wanzheng Zhanga, Zhi-yun Dua, Chang-zhi Donga,c, Bernard
Meuniera,d and Huixiong Chena,b,
*

1
Tetrahedron Letters
Synthesis of N-pyrimidin[1,3,4]oxadiazoles and N-pyrimidin[1,3,4]-thiadiazoles from
1,3,4-oxadiazol-2-amines
heteroarylamination
and
1,3,4-thiadiazol-2-amines
via
Pd-catalyzed
Longjia Yana, Minggao Denga, Anchao Chena, Yongliang Lia, Wanzheng Zhanga, Zhi-yun Dua, Chang-zhi
Donga,c, Bernard Meuniera,d and Huixiong Chena,b,
aFaculty of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou, Guang Dong 510006
bCNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité,
UFR Biomédicale, 75006 Paris, France.
c
, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Cedex 13 Paris, France
d Laboratoire, de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077 Cedex Toulouse, France
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient and practical procedure was developed to prepare various N-pyrimidin[1,3,4]
oxadiazole and thiadiazole scaffolds using a Buchwald-type coupling. The products of this
reaction are otherwise difficult to access and could be used as building blocks in drug design.
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
1,3,4-oxadiazole
1,3,4-thiadiazole
pyrimidine
C-N cross-coupling
Introduction
Rosuvastatin (Crestor, 9).21 However, the synthesis of pyrimidine
derivatives containing
a 1,3,4-oxadiazole ring or 1,3,4-
Five-membered aromatic rings with three heteroatoms are a
type of aromatic compound in which the various heteroatoms
contribute very differently to the formation of aromatic
conjugation.1 Among them, 1,3,4-oxadiazole and 1,3,4-
thiadiazole scaffolds constitute an important core structure in
chemotherapeutic agents and have attracted significant attention
due to their interesting biological activities and medicinal
properties (Fig. 1),2-5 including as a melanin-concentrating
hormone receptor 1 (MCHr1) antagonist (1: AZD1979),6-7
sphingosine kinase (SK) inhibitor (2: SKI-II),8 5-HT4 receptor
partial agonists (3),9 glucocorticoid receptor modulator (4: BMS-
341),10 and FMS-like tyrosine kinase 3 (FLT3) inhibitor (5).11 In
addition, these compounds also play a fundamental role in
bioorganic chemistry and material science.12-15
thiadiazole ring, as well as their biological activities are seldom
described in the literature.22-23
1,3,4-oxadiazoles:
O
N
N
O
H
N
N
O
N
O
N
O
N
I
O
N
N
O
N
OH
O
N
N
1: AZD1979
2: SKI-II
3
1,3,4-thiadiazoles:
F
O
N
H
O
N
OH
O
O
N
S
N
O
S
HN
N
O
S
N
O
N
H
NH
N
N
N
4: MS-341
5
Pyrimidines:
H
F
N
N
N
N
NH
N
2
N
Pyrimidine, a six membered heterocyclic compound bearing
two N-atoms in the ring, constitutes an important component of
nucleic acid and is widespread in Nature.16-17 The pyrimidine
system is an important pharmacophore endowed with druglike
properties (Fig. 1), which is present in the BCRABL tyrosine
O
N
N
N
O
N
O
N
N
N
OH
COOH
N
N
HN
O
S
H
N
O
2
O
O
OH
N
O
9: Crestor
8: Buspar
6: Gleevec
7: Triprim
Figure 1. Representative bioactive skeletons containing 1,3,4-
oxadiazole, 1,3,4-thiadiazole or pyrimidine frameworks.
kinase inhibitor
imatinib (Gleevec, 6),18 a dihydrofolate
reductase inhibitor (Trimethoprim, 7),19 a 5-HT 1A receptor
agonist (Buspirone, 8),20 and the HMG-CoA reductase inhibitor
———
 Corresponding author. Tel.: +33-1-42864085; fax: +33-1-42864082; e-mail: huixiong.chen@parisdescartes.fr

2
Tetrahedron
Table 1. Optimization of the heteroarylamination reaction.a
O
N
Cl
N
O
Cl
H2N
O
O
N
O
[Pd]/Ligand
N
N
+
N
N
O
Base/Solvent
N
H
N
Cl
1a
2a
3a
Entry
1
2
3
4
5
6
7
8
[Pd]
Ligand
BINAP
dppf
xphos
P(t-Bu)3
Sphos
xantphos
xantphos
xantphos
xantphos
xantphos
xantphos
xantphos
xantphos
xantphos
xantphos
xantphos
xantphos
Base
Solvent
T(oC)
100
100
100
100
100
100
100
100
100
100
100
100
100
80
Yield 3a (%)b
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2dba3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
LiHMDS
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Toluene
THF
36
24
trace
15
trace
45
44
26
40
56
14
9
10
11
12
13
14
15
16
17
46
68
34
71
DMF
DME
DMF
DMF
110
120
110
68
DMF
65c
a Reagents and conditions: 1a (0.2 mmol), 2a (0.3 mmol), [Pd] (0.02 mmol), ligand (0.04 mmol), base (0.3 mmol), solvent (2 mL), 36 h. b Isolated yield.
c
microwave (MW) irradiation, 1 h.
During the course of a medicinal chemistry program, the
synthesis of a pyrimidine intermediate containing a 1,3,4-
oxadiazole ring 3a (Table 1) became important for further
transformations. Despite the simple structural features of this
compound, our synthetic efforts towards 3a were met with
significant setbacks, due to the low reactivity of the five-
membered ring. Herein, we report optimized conditions, substrate
scope, and applications of the Pd-catalyzed C-N cross-coupling
of 4-chloro-2-methylpyrimidines and 1,3,4-oxadiazol-2-amines
or 1,3,4-thiadiazol-2-amines, which provide facile access to these
compounds and their derivatives.
temperatures led to partial decomposition (Table 1, entry 16).
Various studies have indicated that microwave irradiation (MW)
could accelerate the Pd-catalyzed C-N reaction.26-27 However,
attempts to increase the yield of 3a by performing the reaction
under MW condition were not successful (Table 1, entry 17).
Table 2. Preparation of N-pyrimidin[1,3,4]oxadiazoles 3a-f.a
R1
N
R1
CO2Et
N
H2N
Pd(OAc)2/xantphos
N
O
O
N
+
CO2Et
NaOtBu/ DMF
110 oC, 36 h
N
N
N
H
N
Cl
N
1
2
3
Results and Discussion
Entry
R1
Product
3a
Yield (%)b
For this study, we chose 4,6-dichloro-2-methylpyrimidine
1a and ethyl 5-amino-1,3,4-oxadiazole-2-carboxylate 2a as
model starting materials. Compound 2a can be prepared via
oxidative cyclization from the corresponding acyhydrazone in
good yields.24-25 We first examined the reaction of 2a with 4,6-
dichloro-2-methylpyrimidine in the presence of different bases
(Cs2CO3, NaH, NaOtBu and LiHMDS) in 1,4-dioxane under
conventional thermal heating conditions, which failed to
effectively produce product 3a. In order to access 3a, we next
1
2
3
4
5
6
7
Cl
71
70
61
66
55
36
20
Ph
3b
3-NO2Ph
4-NO2Ph
3c
3d
N-methylpiperazine
N-acetylpiperazine
3e
3f
examined
the
Pd-catalyzed
Buchwald–Hartwig-type
N-(2-hydroxyethyl)piperazine
3g
heteroarylamination procedure. Under classical conditions using
10 mol% Pd(OAc)2, 20 mol% BINAP and 1.5 equiv. of Cs2CO3
in 1,4-dioxane, the reaction proceeded and product 3a was
obtained in 36% yield (Table 1, entry 1). We subsequently
investigated the effect of various ligands on the yield. Xantphos
ligand gave better results (Table 1, entry 6). A similar yield was
obtained when Xantphos ligand was replaced by Pd2dba3 (Table
1, entry 7). Replacement of Cs2CO3 by K2CO3 or LiHMDS led to
lower yields and NaOtBu gave a satisfactory yield (Table 1,
entries 8–10). Next, we screened different organic solvents and
identified DMF as the most effective solvent (Table 1, entry 13),
while toluene resulted in a poor yield (Table 1, entry 11). The
yield could be further improved by increasing the temperature to
a
Reagents and conditions: 1 (0.2 mmol), 2 (0.3 mmol), Pd(OAc)2 (0.02
mmol), xantphos (0.04 mmol), NaOtBu (0.3 mmol), DMF (2 mL), 36 h.
Isolated yield.
b
Having determined the optimal reaction conditions (Table 1,
entry 15), the scope of the reaction was explored with different
substituted pyrimidine derivatives 1 (Table 2), which were
prepared by the reaction of 4,6-dichloro-2-methylpyrimidine 1a
with arylamines or substituted piperazines, to afford various
functionalized N-pyrimidin[1,3,4]oxadiazoles 3. 4-Chloro-2-
methylpyrimidine substituted by a phenyl group provided the
desired product in good yield (Table 2, entry 2). 4-Chloro-2-
methylpyrimidine substituted by phenyl groups with electron
withdrawing NO2 substituents were also tolerated, leading to the
o
a maximum of 110 C (Table 1, entry 15), whereas higher

3
under these conditions, providing the corresponding products in
lower yields (3t-w).
desired products 3c-d (Table 2, entries 3-4). Conversely, 4-
chloro-2-methylpyrimidine substituted by piperazine groups,
resulted in decreased yields (Table 2, entries 5-7), especially for
2-(4-(6-chloro-2-methylpyrimidin-4-yl)piperazin-1-yl)ethan-1-ol
(Table 2, entry 7).
Table 4. Preparation of N-pyrimidin[1,3,4]thiadiazoles 5a-g.a
R1
R1
R2
N
H2N
Pd(OAc)2/xantphos
N
S
S
N
4
N
R2
+
NaOtBu/ DMF
110 oC, 36 h
Table 3. Preparation of N-pyrimidin[1,3,4]oxadiazoles 3h-w.a
N
N
N
N
H
N
Cl
1
1
5
1
R
2
R
R
Entry
R1
Cl
Cl
Cl
R2
COOEt
Me
Product
5a
Yield (%)b
H N
2
N
O
Pd(OAc) /xantphos
2
O
N
2
N
+
R
t
NaO Bu/ DMF
N
N
N
N
H
1
2
3
4
5
6
50
38
35
41
33
25
16
N
Cl
N
o
110 C, 36 h
1
2
3
5b
i-Pr
5c
CH
3
Cl
N
Cl
N
Cl
N
Ph
CH
3
N
O
N
O
N-methylpiperazine
N-methylpiperazine
N-methylpiperazine
N-methylpiperazine
Ph
5d
N
O
N
N
N
N
N
N
N
N
N
COOEt
Me
5e
H
H
H
3j, 60%
3h, 73%
3i, 53%
5f
F
OCH
CH
3
3
7
i-Pr
5g
Cl
Cl
Cl
a
N
O
Reagents and conditions: 1 (0.2 mmol), 4 (0.3 mmol), Pd(OAc)2 (0.02
mmol), xantphos (0.04 mmol), NaOtBu (0.3 mmol), DMF (2 mL), 36 h.
b Isolated yields.
N
N
O
N
O
N
N
N
N
N
H
N
N
N
N
N
N
H
H
3m, 72%
3l, 75%
3k, 72%
NO
2
Finally, this procedure was applied to the preparation of N-
pyrimidin[1,3,4]thiadiazoles 5. As shown in Table 4, the
Buchwald-Hartwig reaction could be used for the
functionalization of 5-substituted 1,3,4-thiadiazol-2-amines by
Cl
Cl
N
Cl
N
Bn
N
CH
3
Cl
N
O
O
N
O
N
N
N
N
O
N
N
N
N
N
N
N
N
H
H
H
N
N
N
using 4-chloropyrimidine derivative
1
to provide the
H
3o, 58%
3p, 41%
3q, 68%
3n, 50%
corresponding N-pyrimidin[1,3,4]thiadiazoles. Compared to the
synthesis of N-pyrimidine[1,3,4]oxadiazoles, the decrease in
yield may be due to poisoning of the Pd-catalyst by the S-atom in
the 1,3,4-thiadiazole ring, which is consistent with other
Buchwald–Hartwig amine arylation reactions with sulfur-
containing reagents, using a (NHC)Pd(R-allyl)Cl complex as the
catalyst.28
N
N
Cl
N
N
Bn
N
Ph
N
N
O
N
O
N
O
N
N
N
N
N
N
N
N
H
N
N
H
H
3t, 52%
3r, 66%
3s, 56%
Conclusion
OH
N
OH
We have successfully developed an efficient Buchwald-type
coupling method for the synthesis of novel N-
pyrimidin[1,3,4]oxadiazoles and N-pyrimidin[1,3,4]thiadiazoles
using Pd(OAc)2 as the catalyst and xantphos as the ligand. The
method employs readily available reagents and possesses broad
scope and good functional group tolerance. Further efforts to
utilize these compounds as versatile building blocks for
assembling interesting heterocyclic molecules which can be
applied in medicinal chemistry research are currently underway
in our laboratories.
N
N
N
N
N
Ph
Bn
N
N
O
N
O
N
O
N
N
N
N
N
N
N
N
N
N
N
H
H
H
3u, 50%
3v, 23%
3w, 18%
a
Reagents and conditions: 1 (0.2 mmol), 2 (0.3 mmol), Pd(OAc)2 (0.02
mmol), xantphos (0.04 mmol), NaOtBu (0.3 mmol), DMF (2 mL), 36 h.
Next, we extended the Pd-catalyzed heteroarylamination to
1,3,4-oxadiazol-2-amines bearing various substituents at the 5-
position (Table 3). The reaction conditions were compatible with
phenyl (3h), benzyl (3q) and electron-donating substituents at the
aryl moieties, such as methyl and methoxy groups (3k-l). In
addition to electron-donating substitution, halogens such as F
were also tolerated (3m). However, aryl groups with an electron
deficient substituent led to a modest yield (3n). Additionally,
aliphatic groups afforded the corresponding products with
reduced yields (3o-p). On the other hand, and similar to the
results observed in Table 2, 1,3,4-oxadiazol-2-amines bearing
phenyl and benzyl groups did not react well with 4-chloro-2-
methyl-6-(4-methylpiperazin-1-yl)pyrimidine 1e and 2-(4-(6-
Acknowledgments
This project is supported by China Science Foundation (Grant
No. 21672043).
References and notes
1. Majumdar, P.; Pati, A.; Patra, M.; Behera, R. K.; Behera, A. K. Chem.
Rev. 2014, 114, 2942-2977.
2. Hamdy, R.; Ziedan, N. I.; Ali, S.; Bordoni, C.; EI-Sadek, M.; Lashin, E.;
Brancale, A.; Jones, A. T.; Westwell, A. D. Bioorg. Med. Chem. Lett.
2017, 27, 1037-1040.
3. Bajaj, S.; Roy, P. P.; Singh, J. Anticancer Agents Med. Chem. 2018, 17,
1869-1883.
4. Aliabadi, A. Anticancer Agents Med. Chem. 2016, 16, 1301-1314.
chloro-2-methylpyrimidin-4-yl)piperazin-1-yl)ethan-1-ol
1g

4
Tetrahedron
5. Haider, S.; Alam, M. S.; Hamid, H. Eur. J. Med. Chem. 2015, 92, 156-
177.
16. Seio, K.; Kanamori, T.; Masaki, Y. Tetrahedron Lett. 2018, 59, 1977-
1985.
6. Ploj, K.; Benthem, L.; Kakol-Palm, D.; Gennemark, P.; Anderesson, L.;
Bjursell, M.; Börjesson, J.; Kärrberg, L.; Månsson, M.; Antonsson, M.;
Johansson, A.; Iverson, S.; Carlsson, B.; Turnbull, A.; Lindén, D. Br. J.
Pharmacol. 2016, 173, 2739-2751.
7. Johansson, A.; Löfberg, C.; Antonsson, M.; Unge, von. S.; Hayes, M. A.;
Judkins, R.; Ploj, K.; Benthem, L.; Lindén, D.; Brodin, P.; Wennerberg,
M.; Fredenwall, M.; Li, L.; Persson, J.; Bergman, R.; Pettersen, A.;
Gennemark, P.; Hogner, A. J. Med. Chem. 2016, 59, 2497-2511.
8. Aurelio, L.; Scullino, C. V.; Pitman, M. R.; Sexton, A.; Oliver, V.;
Davies, L.; Rebello, R. J.; Furic, L.; Creek, D. J.; Pitson, S. M.; Flynn, B.
L. J. Med. Chem. 2016, 59, 865-984.
9. Niroqi, R.; Mohammed, A. R.; Shinde, A. K.; Gaqqinapally, S. R.;
Kancharla, D. M.; Middekadi, V. R.; Boqaraju, N.; Ravella, S. R.; Singh,
P.; Birangal, S. R.; Subramanian, R.; Palacharla, R. C.; Benade, V.;
Muddana, N.; Jayarajan, P. J. Med. Chem. 2018, 61, 4993-5008.
10. Yang, M. G.; Dhar, T. G.; Xiao, Z.; Xiao, H. Y.; Duan, J. J.; Jiang, B.;
Galella, M. A.; Cunningham, M.; Wang, J.; Habte, S.; Shuster, D.;
McIntyre, K. W.; Carman, J.; Holloway, D. A.; Somerville, J. E.; Nadler,
S. G.; Salter-Cid, L.; Barrish, J. C.; Weinstein, D. S. J. Med. Chem. 2015,
58, 4278-4290.
17. Prachayasittikul, S.; Pingaew, R.; Worachartcheewan, A.; Sinthupoom,
N.; Prachayasittikul, V.; Ruchirawat, S.; Prachayasittikul, V. Mini-Rev.
Med. Chem. 2017, 17, 869-901.
18. Campiotti, L.; Suter, M. B.; Guasti, L.; Piazza, R.; Gambacorti-Passerini,
C.; Grandi, A. M.; Squizzato, A. Eur. J. Cancer. 2017, 77, 48-56.
19. Palomino, J. C.; Martin, A. Future Microbiol. 2016, 11, 539-547.
20. Mula, M. Expert Opin. Pharmacother. 2018, 19, 1867-1874.
21. Leea, Y. H.; Vijia, M.; Leeb, E.; Joa, H.; Yoob, K.; Sima, J.; Leeb, S.;
Leec, K.; Leea, H.; Junga, J. K. Tetrahedron Lett. 2017, 58, 2614-2617.
22. Li, C.; Rosenau, A. Tetrahedron Lett. 2009, 50, 5888-5893.
23. Stewart, A.O.; Bhatia, P. A.; McCarty, C. M.; Patel, M. V.; Staeger, M.
A.; Arendsen, D. L.; Gunawardana, I. W.; Melcher, L. M.; Zhu, G. D.;
Boyd, S. A.; Fry, D. G.; Cool, B. L.; Kifle, L.; Lartey, K.; Marsh, K. C.;
Kempf-Grote, A. J.; Kilgannon, P.; Wisdom, W.; Meyer, J.; Gallatin, W.
M.; Okasinski, G. F. J. Med. Chem. 2001, 44, 988-1002.
24. Reddy, G. D.; Mo, C. H.; Euy, L. M. RSC Advances. 2013, 3, 7684-7687.
25. Niu, P. F.; Kang, J. F.; Tian, X. H.; Song, L. N.; Liu, H. X.; Wu, J.; Yu,
W. Q.; Chang, J. B. J. Org. Chem. 2015, 80, 1018-1024.
26. Yang, J.; Li, P. H.; Zhang, Y. C.; Wang, L. J. Organomet. Chem. 2014,
766, 73-79.
11. Li, W. W.; Wang, X. Y.; Zheng, R. L.; Yan, H. X.; Cao, Z. X.; Zhong, L.;
Wang, Z. R.; Ji, P.; Yang, L. L.; Wang, L. J.; Xu, Y.; Liu, J. J.; Yang, J.;
Zhang, C. H.; Ma, S.; Feng, S.; Sun, Q. Z.; Wei, Y. Q.; Yang, S. Y. J.
Med. Chem. 2012, 55, 3852-3866.
27. Farard, J.; Loge, C.; Pferffer, B.; Lesur, B.; Duflos, M. Tetrahedron Lett.
2009, 50, 5729-5732.
28. Cawley, M. J.; Cloke, F. G. N.; Fitzmaurice, R. J.; Pearson, S. E.; Scott, J.
S.; Caddick, S. Org. Biomol. Chem. 2008, 6, 2820-2825.
12. Khalilullah, H.; Ahsan, M. J.; Hedaitullah, M.; Khan, S.; Ahmed, B.
Mini-Rev. Med. Chem. 2012, 12, 789-801.
13. Li, Z.; Zhan, P.; Liu, X. Mini-Rev. Med. Chem. 2011, 11, 1130-1142.
14. Guin, S.; Ghosh, T.; Rout, S. K.; Banerjee, A.; Patel, B. K. Org. Lett.
2011, 13, 5976-5979.
Supplementary Material
Experimental details and NMR spectra for all reported
compounds can be found in supplementary material.
15. Hu, Y.; Li, C. Y.; Wang, X. M.; Yang, Y. H.; Zhu, H. L. Chem. Rev.
2014, 114, 5572-5610.

5
HIGHLIGHTS

An
efficient
synthesis
of
N-
pyrimidin[1,3,4]oxadiazol
scaffolds.
and
thiadiazol



The products of this reaction could be used as
the building blocks in drug design..
The method has broad scope and good
functional group tolerance.
The reaction occurred generally in good yields.