DOI: 10.1002/ejoc.

201601234 Full Paper

Heterocyclic Chemistry
Efficient Synthesis of (1,2,3-Triazol-1-yl)methylpyrimidines from
5-Bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one
Estefania da C. Aquino,[a] Marcio M. Lobo,[a] Guilherme Leonel,[a] Marcos A. P. Martins,[a]
Helio G. Bonacorso,[a] and Nilo Zanatta*[a]

Abstract: 5-Bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one the key intermediate 5-[4-alkyl(aryl)-1H-1,2,3-triazol-1-yl]-1,1,1-

was used as an efficient precursor for the synthesis of a new
series of (1,2,3-triazol-1-yl)methyl-pyrimidine biheterocycles. For
this stepwise synthesis, the 5-bromo-1,1,1-trifluoro-4-methoxy-
pent-3-en-2-one was first converted into 5-azido-1,1,1-trifluoro-
4-methoxypent-3-en-2-one through a nucleophilic substitution
of the bromine by an azide group. This was then followed by
an azidealkyne cycloaddition reaction (click chemistry) to give
trifluoro-4-methoxypent-3-en-2-ones. These were cyclocon-
densed with 2-methylisothiourea sulfate to give a series of 2-
(methylthio)-4-(1,2,3-triazol-1-yl)methyl-6-(trifluoromethyl)pyr-
imidines. Additionally, the 2-methylthiopyrimidine products
were used to prepare a new series of 2-amino-4-(1,2,3-triazol-1-
yl)methyl-6-(trifluoromethyl)pyrimidines.

Introduction The synthetic versatility of brominated enone 1, in relation

to its reaction centers, is summarized in Scheme 1. For example,
There have been extensive studies on the applications of 4-
enone 1 can be converted into 5-azido-enone I by nucleophilic
alkoxy-1,1,1-trifluoroalk-3-en-2-ones (enones) in heterocyclic
substitution of the bromine with an azide group.[2a,3] Enone 1
chemistry.[1] One such enone, 1,1,1-trifluoro-4-methoxypent-3-
reacts with alcohols to give compound II through a transetheri-
en-2-one, can be converted through a bromination reaction
fication reaction,[3] and it reacts with amines to give enamino-
into the derivative 5-bromo-4-methoxy-1,1,1-trifluoropent-3-en-
nes III.[4] Furthermore, phosphorylated enones IV were ob-
2-one (1),[2] whose utility in organic synthesis has been much
tained through the addition of secondary amines at the -car-
less explored.[2a,37] Brominated enone 1 is a versatile building
bon atom of enone 1 followed by the elimination of methanol,
block as it is a highly functionalized structure with diverse react-
ive sites, as shown in Figure 1. The carbon atoms shown in red
(i.e., A, B, and C) are electrophilic centers. Carbon atom A is
suitable for nucleophilic substitution, while carbon atom B can
undergo Michael type reactions through either nucleophilic ad-
dition, or nucleophilic addition followed by elimination of a
methanol molecule. Carbon atom C is a highly electrophilic cen-
ter; it is a carbonyl carbon atom, and is also attached to a
strongly electron-withdrawing CF3 group. Carbon atom D and
oxygen atom E are nucleophilic centers.

Figure 1. Reaction sites of brominated enone 1.

[a] Ncleo de Qumica de Heterociclos (NUQUIMHE), Departamento de

Qumica, Universidade Federal de Santa Maria,
97105-900 Santa Maria, Brazil
E-mail: nilo.zanatta@ufsm.br
http://www.ufsm.br/nuquimhe
Supporting information for this article is available on the WWW under Scheme 1. Conversion of enone 1 into a second generation of reaction inter-
http://dx.doi.org/10.1002/ejoc.201601234. mediates IIV.

Eur. J. Org. Chem. 2017, 306312 306 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

and subsequent substitution of the bromine with triethyl phos-
phite.[4b] All these compounds represented by structures IIV
are important chemical intermediates that can be useful for
the construction of various classes of heterocyclic compounds.
Thus, brominated enone 1 has been used by our research group
to prepare series of heterocyclic compounds, including pyraz-
oles,[5,2a] pyrroles,[3] thiopyrimidines,[6] and pyrazolinium cat-
ions.[7] Another research group used brominated enone 1 as
the starting material for the synthesis of pyrazole, isoxazole,
and oxy- and thiopyrimidines,[4b] thus demonstrating its great
synthetic potential.
The aim of this study was to demonstrate the use of 5-
bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one as an efficient
building block for the synthesis of a new series of (1,2,3-triazol-
1-yl)methylpyrimidine biheterocycles, which can be considered
to be triazolo acyclic nucleosides (Figure 2).[8] Compounds simi-
lar to the ones prepared in this study, such as 5-chloro-6-[1-(2-
iminopyrrolidinyl)methyl]uracil hydrochloride (V) and its ana-
logues VI and VII, have been shown to act as potent thymidine-
phosphorylase inhibitors (Figure 2).[911] These TPase inhibitors
were developed in an attempt to improve the potency of the
antitumor effects of 2-deoxy-5-(trifluoromethyl)uridine (VIII),
which is currently being used clinically.[9] In 2011, a series of
5-[(1H-1,2,3-triazol-1-yl)]-2-deoxyuridines IX were prepared by
using the Huisgen reaction, from 5-ethynyl-2-deoxyuridine and
a series of aryl azides.[12] In the same year, Jansa et al. reported
the synthesis of a new series of 6-[(1H-1,2,3-triazol-1-yl)methyl]-
uracils X by using a click protocol, from the reaction of 6-azido-
methyluracil with a series of alkynes (Figure 2).[13] To the best
of our knowledge, 5-bromo-1,1,1-trifluoro-4-methoxypent-3-en-
2-one has never been used as building block for the synthesis
of biheterocyclic compounds such as (1H-1,2,3-triazol-1-yl)-
methylpyrimidines. As an extension of this study, the utility of
the 2-thiomethoxy group of the pyrimidines 5 was demon-
strated by the synthesis of a series of 2-amino-substituted pyr-
imidine analogues (Scheme 2).
Figure 2. Structure of known potent thymidine phosphorylase inhibitors.
Scheme 2 shows an overview of the synthetic strategy for
obtaining all the compounds proposed in this study.
Eur. J. Org. Chem. 2017, 306312 www.eurjoc.org
Full Paper
Scheme 2. General synthetic strategy for obtaining all compounds proposed
in this study.
Results and Discussion
The starting material for this work was brominated enone 1,
which was prepared through the bromination of the parent
compound 1,1,1-trifluoro-4-methoxypent-3-en-2-one, following
the procedure described in the literature.[2] The reaction of
brominated enone 1 with sodium azide gave the key intermedi-
ate 5-azido-1,1,1-trifluoro-4-methoxypent-3-en-2-one (2).[2a,3]
From key intermediate 2, the reaction followed two different
paths. In path 1, intermediate 2 reacted with alkynes through
a click chemistry protocol to give a series of new 1,1,1-tri-
fluoro-4-methoxy-5-(4-substituted-1H-1,2,3-triazol-1-yl)pent-3-
en-2-ones 3a3d in very good yields.[14] Two methods were
tested for the synthesis of compounds 3a3d. The first method
used a solution of copper acetate [Cu(OAc)2H2O; 3 mol-%] and
sodium ascorbate (6 mol-%) as the catalyst, in a solvent mixture
of dichloromethane and water (1:1), for 12 h at room tempera-
ture, and this led to a 70 % yield. The second method differed
from the first in that the catalyst was changed from copper
acetate to copper sulfate pentahydrate (CuSO45H2O). The best
yield of 89 % was obtained for compound 3b by using the sec-
ond method, when the reaction was carried out at room tem-
perature for 12 h. Triazolyl enones 3a3d were characterized by
GCMS and 1H and 13C NMR spectroscopy. The structures of
compounds 3a3d showed an E configuration for the double
bond of the enone, and the triazole ring was 1,4-substituted, as
confirmed by the single-crystal X-ray structure of compound 3b
(Figure 3). Table 1 shows the optimized reaction conditions and
yields for the synthesis of compounds 3a3d.
The reaction of azide 2 with prop-2-yn-1-ol (propargylic alco-
hol) did not give the expected result. From this reaction, a com-
plex mixture of compounds was obtained, probably due to the
competitive reaction of the propargylic alcohol with the -car-
bon atom of enone 2 (transetherification reaction) and/or the
azido group (click chemistry). This problem was overcome by
firstly cyclocondensing intermediate 2 with 2-methylisothiourea
sulfate to give pyrimidine 4 in 75 % yield, and then, carrying
out the click reaction of 4-azidomethylpyrimidine 4 with the
307 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
 Full Paper

azoles 3a3d (dichloromethane/water at room temperature)

Figure 3. ORTEP structure of compound 3b. Thermal ellipsoids are shown at
the 50 % probability level.
with tBuOH/water at 7080 C.
Path 2 of Scheme 2 was used only to prepare pyrimidine 4.
All the other reactions for obtaining compounds 5a5d were
carried out by path 1, because this route gave better yields
for the synthesis of triazoles 3a3d than that achieved for the
conversion of compound 4 into compound 5e. However, the
cyclocondensation steps from intermediate 2 to pyrimidine 4
and from intermediates 3 to pyrimidines 5 gave similar yields.
Another reason for choosing path 1 was because when pyrimid-
ine 4 was prepared on a larger scale, its yield decreased from
75 to 50 %. The cyclocondensation reaction of intermediates 2
and 3a3d with 2-methythioisourea sulfate, which gave pyrim-
idines 4 and 5a5d, was carried out following a procedure de-
scribed in the literature for similar compounds.[6] Table 2 shows
the optimized reaction conditions and yields for obtaining
the 4-[(4-substituted-1H-1,2,3-triazol-1-yl)methyl]-6-(trifluoro-
methyl)-2-(methylthio)-pyrimidines 5a5d by path 1.

Table 1. Optimized reaction conditions and yields for the synthesis of com- Table 2. Optimized reaction conditions and yields for obtaining compounds
pounds 3a3d. 5a5d.

Entry Compd. R[a] Product Yield [%][b] Entry Compd.[a] R Product Yield [%][b]
1 2 Bu 3a 74 1 3a Bu 5a 76
2 2 C6H5 3b 89 2 3b C6H5 5b 79
3 2 4-OMeC6H4 3c 90 3 3c 4-MeOC6H4 5c 78
4 2 4-CNC6H4 3d 81 4 3d 4-CN C6H4 5d 72
[c]
5 2 CH2OH 3e
[a] Reaction conditions: 2-methylisothiourea sulfate (2 equiv.), Na2CO3 (1 M
[a] Reaction conditions: Enone 2 (1.0 equiv.), alkyne (1.1 equiv.), CuSO45H2O aq.; 2 equiv.), MeOH, 50 C, 1 h. [b] Yields of isolated products.
(3 mol-%), sodium ascorbate (6 mol-%), CH2Cl2/H2O (1:1), 25 C, 12 h.
[b] Yields of isolated products. [c] Compound 3e was obtained together with
a complex mixture of products.
As an extension of this study, and also to demonstrate the
versatility of pyrimidines 5 for the generation of new series of
propargylic alcohol. This gave 4-triazolmethyl-pyrimidine 5e in
compounds, 2-methylthiopyrimidines 5a and 5b were con-
74 % yield (Scheme 3). The reaction conditions for carrying out
verted into a series of 2-aminopyrimidines 8a8e and 9a9e.
the conversion of pyrimidine 4 into product 5e had to be
To carry out this conversion, 2-methylthiopyrimidines 5a and
adapted by replacing the solvent used for the synthesis of tri-
5b were first oxidized to the respective 2-methylsulfonylpyr-
imidines 6 and 7, by using m-chloroperoxybenzoic acid
(mCPBA)[15] or Oxone (2KHSO5KHSO4K2SO4).[16,17] The oxid-
ation carried out with Oxone was more efficient, as it gave com-
pounds 6 and 7 in better yields, with an easier work-up, and
with fewer by-products (Scheme 4).

Scheme 3. Synthetic strategy for obtaining compound 5e. Scheme 4. Oxidation of compounds 5a and 5b to give compounds 6 and 7.

Eur. J. Org. Chem. 2017, 306312 www.eurjoc.org 308 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
 Full Paper

The reaction of 2-methylsulfonylpyrimidines 6 and 7 with a Experimental Section

series of amines, including morpholine, butylamine, benzyl-
General Remarks: Reagents were purchased and used without fur-
amine, phenethylamine, and 4-anisidine, gave a new series of ther purification. Flash chromatography was carried out by using
2-amino-4-[(4-substituted-1H-1,2,3-triazol-1-yl)methyl]-6-(tri- silica gel (230400 mesh) as the stationary phase. The procedure
fluoromethyl)pyrimidines 8a8e and 9a9e, in very good yields for obtaining 1,1,1-trifluoro-4-methoxy-3-penten-2-one is described
(Table 3). in ref.[18] The bromination method for obtaining 5-bromo-1,1,1-tri-
fluoro-4-methoxy-3-penten-2-one (1) is described in ref.[2] The reac-
Table 3. Optimized reaction conditions and yields for obtaining compounds
tion of the brominated enone 1 with sodium azide to give the
8 and 9.
key intermediate 5-azido-1,1,1-trifluoro-4-methoxy-3-penten-2-one
(2) is described in refs.[2a,3] Thin-layer chromatography (TLC) was
carried out by using F-254 silica gel plates with a thickness of
0.25 mm. For visualization, the TLC plates were either placed under
ultraviolet light or stained with iodine vapour or acidic vanillin. Most
reactions were monitored for the disappearance of the starting ma-
terial by using TLC. Acetone, acetonitrile, and dichloromethane were
dried and purified by distillation, as described by the Perrin proce-
dures.[19] Temperatures above room temperature were maintained
by using a vegetable-oil bath. Melting points were determined with
Compd. Amine (R1) Reaction Product Yield [%][b]
time [h][a] an MQAPF-301 apparatus. LCMS spectra were recorded with an
LCMS/MS Agilent 6460 instrument in ESI mode. GCMS spectra
6 Morpholine (a) 2 8a 80 were recorded with an Agilent 5975B GCMSD spectrometer in EI
6 Butylamine (b) 2 8b 94
mode. The GC was equipped with a split-splitless injector, auto-
6 Benzylamine (c) 2 8c 90
6 Phenethylamine (d) 2 8d 86
sampler, and a cross-linked HP-5 capillary column (30 m, 0.32 mm
6 4-Anisidine (e) 5 8e 70 internal diameter), and helium was used as the carrier gas. High-
7 Morpholine (a) 2 9a 79 resolution mass spectra were recorded with an ESI-TOF mass spec-
7 Butylamine (b) 2 9b 93 trometer. 1H and 13C NMR spectra and 2D NMR spectra were re-
7 Benzylamine (c) 2 9c 90 corded with a Bruker Avance III 600 spectrometer (1H at 600 MHz,
7 Phenethylamine (d) 2 9d 88 and 13C at 150 MHz) or a Bruker Avance III 400 (1H at 400 MHz, and
7 4-Anisidine (e) 5 9e 72 13
C at 100 MHz) in CDCl3 or [D6]DMSO, by using tetramethylsilane
[a] Reaction conditions: Amine (3 equiv.), acetonitrile, 100 C (temperature of (TMS) as an internal standard. Chemical shifts () are quoted in
the oil bath), 25 h. [b] Yields of isolated products. parts per million (ppm), and coupling constants (J) are given in
Hertz (Hz). CCDC 1510712 (for 3b) contains the supplementary crys-
The reaction conditions used for converting the 2-methyl- tallographic data for this paper. These data can be obtained free of
sulfonylpyrimidines 6 and 7 into the respective 2-aminopyrim- charge from The Cambridge Crystallographic Data Centre.
idines 8a8e and 9a9e were based on the procedure reported General Procedure for the Synthesis of Compounds 3a3d: The
by Swarbrick et al.[17] However, it was slightly modified by using alkyne (1.1 mmol) and a solution of sodium ascorbate (0.012 mg,
3 equiv. of the amine and a temperature of 100 C, instead of 6 mol-%) and CuSO45H2O (0.007 mg, 3 mol-%) in water (3 mL)
5 equiv. of the amine and 140 C as reported by those authors. were added to a solution of azide 2 (0.209 g, 1 mmol) in dichloro-
Most of the amines tested gave very good yields after 2 h at methane (3 mL), and the reaction was stirred at room temperature
100 C. However, for 4-anisidine, the reaction took 5 h to com- for 12 h. The reaction mixture was then washed with brine (15 mL)
plete, and for aniline and 4-chloroaniline, the reaction failed to and distilled water (2 15 mL). The remaining organic layer was
give the expected product, even under the conditions reported then dried with anhydrous sodium sulfate, and filtered. The solvent
was removed under reduced pressure. The solid compounds 3b
by Swarbrick et al., which was probably due to the lower react-
3d were purified by recrystallization from solutions in chloroform/
ivity of these amines.
hexane (50:50). Compound 3a, which was obtained as an oil, was
All the new intermediates and products were fully character- purified by column chromatography on silica gel, by using ethyl
ized by GCMS and 1H and 13C NMR spectroscopy, with 2D acetate/hexane (20:80) as the eluent.
HMBC NMR experiments for representative compounds. The pu- (E)-5-(4-Butyl-1H-1,2,3-triazol-1-yl)-1,1,1-trifluoro-4-methoxy-
rity of the compounds was confirmed by elemental analysis or pent-3-en-2-one (3a): Brown oil (215 mg, 74 %). 1H NMR (400 MHz,
by high-resolution mass spectrometry. CDCl3): = 7.40 (s, 1 H), 5.83 (s, 1 H), 5.64 (s, 2 H), 3.82 (s, 3 H), 2.71
(t, J = 7.8 Hz, 2 H), 1.691.62 (m, 2 H), 1.431.34 (m, 2 H), 0.92 (t,
J = 7.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): = 179.1 (q, 2JC,F =
Conclusions 35.0 Hz), 174.0, 149.0, 122.2, 116.3 (q, 1JC,F = 291.2 Hz), 93.0, 57.5,
50.23, 31.3, 25.2, 22.2, 13.6 ppm. GCMS (EI, 70 eV): m/z (%) = 291
We have shown that 5-bromo-1,1,1-trifluoro-4-methoxypent-3- (>5) [M] + , 248 (10), 166 (100), 139 (26). HRMS (ESI): calcd. for
en-2-one can be used as an efficient precursor for the synthesis C12H17F3N3O2 [M + H]+ 292.1273; found 292.1274.
of new series of biheterocycles such as 4-[(4-substituted-1H-
(E)-1,1,1-Trifluoro-4-methoxy-5-(4-phenyl-1H-1,2,3-triazol-1-
1,2,3-triazol-1-yl)methyl]-6-(trifluoromethyl)-2-(methylthio)- yl)pent-3-en-2-one (3b): Brown solid (276 mg, 89 %). m.p. 109
pyrimidines 5a5e and 2-amino-4-[(4-substituted-1H-1,2,3-tri- 111 C. 1H NMR (400 MHz, CDCl3): = 7.89 (s, 1 H), 7.83 (d, J =
azol-1-yl)methyl]-6-(trifluoromethyl) pyrimidines 8a8e and 9a 8.0 Hz, 2 H), 7.43 (t, J = 8.0 Hz, 2 H), 7.34 (t, J = 8.0 Hz, 1 H), 5.86
9e. The syntheses have low numbers of reaction steps and give (s, 1 H), 5.71 (s, 2 H), 3.82 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
the desired products 59 in high overall yields. = 179.1 (q, 2JC,F = 35.1 Hz), 173.7, 147.8, 130.3, 128.7, 128.2, 125.6,

Eur. J. Org. Chem. 2017, 306312 www.eurjoc.org 309 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

121.0, 116.2 (q, 1JC,F = 291.2 Hz), 93.1, 57.6, 50.4 ppm. GCMS (EI,
70 eV): m/z (%) = 311 (20) [M]+, 283 (10), 255 (31), 214 (11), 186
(25), 167 (25), 116 (100). HRMS (ESI): calcd. for C14H13F3N3O2 [M +
H]+ 312.0960; found 312.0964.
(E)-1,1,1-Trifluoro-4-methoxy-5-[4-(4-methoxyphenyl)-1H-1,2,3-
triazol-1-yl]pent-3-en-2-one (3c): Pale yellow solid (306 mg, 90 %).
m.p. 114116 C. 1H NMR (400 MHz, CDCl3): = 7.80 (s, 1 H), 7.76
(d, J = 8.8 Hz, 2 H), 6.95 (d, J = 8.8 Hz, 2 H), 5.85 (s, 1 H), 5.70 (s, 2
H), 3.84 (s, 3 H), 3.83 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): =
179.1 (q, 2JC,F = 34.9 Hz), 173.8, 159.7, 147.7, 127.0, 123.0, 120.2,
116.3 (q, 1JC,F = 291.3 Hz), 114.2, 93.0, 57.6, 55.2, 50.4 ppm. GCMS
(EI, 70 eV): m/z (%) = 341 (20) [M]+, 285 (28), 216 (100), 207 (25),
146 (75). C15H14F3N3O3 (341.10): calcd. C 52.79, H 4.13, N 12.31;
found C 52.58, H 4.39, N 12.46.
(E)-4-[1-(5,5,5-Trifluoro-2-methoxy-4-oxopent-2-en-1-yl)-1H-
1,2,3-triazol-4-yl]benzonitrile (3d): Yellow solid (272 mg, 81 %).
m.p. 155157 C. 1H NMR (400 MHz, CDCl3): = 8.01 (s, 1 H), 7.96
(d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H), 5.89 (s, 1 H), 5.73 (s, 2
H), 3.86 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): = 179.5 (q, 2JC,F =
35.2 Hz), 173.3, 146.2, 134.8, 132.8, 126.2, 122.2, 118.7, 116.3 (q,
1 3
JC,F = 291.3 Hz), 111.7, 93.6, 57.8, 50.7 ppm. GCMS (EI, 70 eV): m/z
(%) = 336 (8) [ M] + , 28 0 ( 8) , 2 11 (1 0) , 1 67 (1 0) , 1 41 (1 00 ).
C 15 H 11 F 3 N 4 O 2 (336.08): calcd. C 53.58, H 3.30, N 16.66; found C
53.19, H 3.43, N 16.26.
General Procedure for the Synthesis of Compound 4: A solution
of Na2CO3 (1 M aq.; 4 mL) was added to a flask containing azide 2
(0.418 g, 2 mmol) and 2-methylisothiourea sulfate (1.113 g, 4 mmol)
at room temperature. The reaction mixture was vigorously stirred
for 3 h. Chloroform (20 mL) was then added to the reaction vessel,
and the organic layer was washed with a solution of HCl (3 % aq.;
20 mL) and water (3 20 mL). The organic layer was dried with
anhydrous sodium sulfate, filtered, and evaporated under reduced
pressure. The oily residue was purified by column chromatography
on silica gel (ethyl acetate/hexane 10:90 as eluent) to give com-
pound 4 as an oil.
4-(Azidomethyl)-2-(methylthio)-6-(trifluoromethyl)pyrimidine
(4): Orange oil (373 mg, 75 %). 1H NMR (400 MHz, CDCl3): = 7.31
(s, 1 H), 4.50 (s, 2 H), 2.61 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
= 174.6, 167.7, 156.6 (q, 2JC,F = 36.6 Hz), 120.2 (q, 1JC,F = 275.7 Hz),
109.0 (q, 3JC,F = 2.5 Hz), 54.3, 14.1 ppm. GCMS (EI, 70 eV): m/z
(%) = 249 (100) [M]+, 220 (32), 206 (26), 193 (32). HRMS (ESI): calcd.
for C7H7F3N5S [M + H]+ 250.0374; found 250.0375.
General Procedure for the Synthesis of Compounds 5a5d: 2-
Methylisothiourea sulfate (0.557 g, 2 mmol) and Na2CO3 (1 M aq.;
2 mL) were added to a solution of compounds 3a3d (1 mmol) in
methanol (5 mL). The reaction mixture was heated to 50 C, and
then vigorously stirred for 1 h. After the end of the reaction, the
solvent was evaporated. The residue was dissolved in chloroform
(30 mL), and the resulting solution was washed with a HCl (1 M aq.;
20 mL) and water (3 20 mL). The organic layer was dried with
anhydrous sodium sulfate, and filtered. The solvent was removed
under reduced pressure, and the products were purified by column
chromatography on silica gel, by using ethyl acetate/hexane (20:80)
as the eluent.
4-[(4-Butyl-1H-1,2,3-triazol-1-yl)methyl]-2-(methylthio)-6-(tri-
fluoromethyl)pyrimidine (5a): Orange solid (251 mg, 76 %). m.p.
6062 C. 1H NMR (400 MHz, CDCl3): = 7.45 (s, 1 H), 6.93 (s, 1 H),
5.61 (s, 2 H), 2.72 (t, J = 7.6 Hz, 2 H), 2.54 (s. 3 H), 1.671.63 (m, 2
H), 1.401.34 (m, 2 H), 0.90 (t, J = 7.3 Hz) ppm. 13C NMR (100 MHz,
CDCl3): = 174.8, 166.2, 156.8 (q, 2JC,F = 36.6 Hz), 149.3, 121.7, 119.9
(q, 1JC,F = 275.7 Hz), 108.9 (q, J = 2.5 Hz), 54.0, 31.3, 25.2, 22.1, 14.1,
Eur. J. Org. Chem. 2017, 306312 www.eurjoc.org 310
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13.6 ppm. GCMS (EI, 70 eV): m/z (%) = 331 (>5) [M]+, 288 (100),
260 (24), 208 (32). HRMS (ESI): calcd. for C 13 H 16 F 3 N 5 S [M + H] +
332.1157; found 332.1164.
2-(Methylthio)-4-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-6-(tri-
fluoromethyl)pyrimidine (5b): Brown solid (277 mg, 79 %). m.p.
9496 C. 1H NMR (400 MHz, CDCl3): = 7.93 (s, 1 H), 7.82 (d, J =
7.3 Hz, 2 H), 7.43 (t, J = 7.2 Hz, 2 H), 7.35 (t, J = 7.4 Hz, 1 H), 7.05
(s, 1 H), 5.67 (s, 2 H), 2.55 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
= 175.1, 165.7, 157.0 (q, 2JC,F = 36.7 Hz), 148.6, 130.0, 128.9, 128.5,
125.8, 120.6, 120.0 (q, 1JC,F = 275.7 Hz), 109.1 (q, 3JC,F = 2.6 Hz), 54.3,
14.2 ppm. GCMS (EI, 70 eV): m/z (%) = 351 (11) [M]+, 322 (28), 308
(100), 116 (82). HRMS (ESI): calcd. for C 1 5 H 1 2 F 3 N 5 S [M + H] +
352.0844; found 352.0848.
4-{[4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl]methyl}-2-(meth-
ylthio)-6-(trifluoromethyl)pyrimidine (5c): Pale yellow solid
(297 mg, 78 %). m.p. 103105 C. 1H NMR (400 MHz, CDCl3): =
7.79 (s, 1 H), 7.75 (d, J = 7.9 Hz, 2 H), 7.05 (s, 1 H), 6.96 (d, J = 7.9 Hz,
2 H), 5.65 (s, 2 H), 3.84 (s, 3 H), 2.57 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): = 175.0, 165.9, 159.9, 157.0 (q, 2JC,F = 36.7 Hz), 148.5,
127.1, 122.77, 120.0 (q, 1 J C,F = 275.5 Hz), 119.7, 114.4, 109.1 (q,
JC,F = 2.0 Hz), 55.3, 54.3, 14.2 ppm. GCMS (EI, 70 eV): m/z (%) =
381 (23) [M]+, 352 (15), 338 (100), 146 (100). C16H14F3N5OS (381.09):
calcd. C 50.39, H 3.70, N 18.36; found C 50.75, H 3.86, N 18.06.
4-(1-{[2-(Methylthio)-6-(trifluoromethyl)pyrimidin-4-yl]methyl}-
1H-1,2,3-triazol-4-yl)benzonitrile (5d): Pale brown solid (270 mg,
72 %). m.p. 152154 C. 1H NMR (400 MHz, CDCl3): = 8.08 (s, 1 H),
7.96 (d, J = 8.0 Hz, 2 H), 7.72 (d, J = 8.0 Hz, 2 H), 7.12 (s, 1 H), 5.72
(s, 2 H), 2.56 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): = 175.3,
165.2, 157.1 (q, 2JC,F = 36.7 Hz), 146.8, 134.5, 132.8, 126.3, 121.9,
120.0 (q, 1JC,F = 275.5 Hz), 118.6, 111.9, 109.3 (q, 3JC,F = 2.4 Hz),
54.4, 14.1 ppm.LCMS (ESI): m/z = 377.2 [M + H]+, 399.4 [M + Na]+.
C16H11F3N6S (376.07): calcd. C 51.06, H 2.95, N 22.33; found C 51.43,
H 3.31, N 22.17.
General Procedure for the Synthesis of Compound 5e: Proparg-
ylic alcohol (0.6 mL, 1.1 mmol) and a solution of sodium ascorbate
(0.012 g, 6 mol-%) and CuSO45H2O (0.007 g, 3 mol-%) in water
(3 mL), were added to a solution of azide 4 (0.249 g, 1 mmol), in
tert-butyl alcohol (3 mL). The reaction mixture was heated to 70
80 C, and stirred for 12 h. The solvent was then evaporated under
reduced pressure, and the residue was dissolved in ethyl acetate
(20 mL). The resulting solution was washed with brine (15 mL) and
water (2 15 mL). The organic layer was dried with anhydrous so-
dium sulfate, and filtered. The solvent was removed under reduced
pressure, and product 5e was purified by column chromatography
on silica gel, by using ethyl acetate/hexane (30:70) as the eluent.
(1-{[2-(Methylthio)-6-(trifluoromethyl)pyrimidin-4-yl]methyl}-
1H-1,2,3-triazol-4-yl)methanol (5e): Yellow solid (225 mg, 74 %).
m.p. 8386 C. 1H NMR (400 MHz, CDCl3): = 7.71 (s, 1 H), 7.02 (s,
1 H), 5.63 (s, 2 H), 4.83 (s, 2 H), 2.57 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): = 174.7, 165.6, 156.6 (q, 2JC,F = 36.6 Hz), 148.3, 123.4, 119.8
(q, 1JC,F = 275.8 Hz), 109.1 (q, 3JC,F = 2.6 Hz), 55.5, 54.0, 14.0 ppm.
LCMS (ESI): m/z = 306.1 [M + H] + . HRMS (ESI): calcd. for
C10H11F3N5OS [M + H]+ 306.0636; found 306.0639.
General Procedure for the Synthesis of Compounds 6 and 7: A
solution of Oxone (1.23 g, 2 mmol) in water (5 mL) was added to a
solution of 2-methylthio pyrimidine 5a or 5b (1 mmol) in methanol
(5 mL). The reaction mixture was stirred at room temperature for
16 h, and then the solvent was evaporated. Water (20 mL) was
added to the product and extracted with chloroform (3 20 mL).
The organic layer was dried with anhydrous sodium sulfate, and
filtered. The solvent was removed under reduced pressure, and the
2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

products were obtained as solids. Compound 6 was purified by
column chromatography on silica gel (ethyl acetate/hexane, 50:50);
compound 7 was recrystallized from a mixture of chloroform/
hexane (50:50).
4-[(4-Butyl-1H-1,2,3-triazol-1-yl)methyl]-2-(methylsulfonyl)-6-
(trifluoromethyl)pyrimidine (6): Pale brown solid (286 mg, 79 %).
m.p. 8486 C. 1H NMR (400 MHz, CDCl3): = 7.53 (s, 1 H), 7.48 (s,
1 H), 5.85 (s, 2 H), 3.41 (s, 3 H), 2.77 (t, J = 7.7 Hz, 2 H), 1.731.65
(m, 2 H), 1.431.37 (m, 2 H), 0.95 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): = 170.0, 166.4, 158.0 (q, 2JC,F = 38.0 Hz), 149.7,
122.0, 119.4 (q, 1JC,F = 276.0 Hz), 117.4, 53.8, 39.0, 31.3, 25.2, 22.1,
13.6 ppm. LCMS (ESI): m/z = 364.2 [M + H]+, 386.2 [M + Na]+.
C13H16F3N5O2S (363.10): calcd. C 42.97, H 4.44, N 19.27; found C
42.68, H 4.65, N 19.03.
2-(Methylsulfonyl)-4-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-6-
(trifluoromethyl)pyrimidine (7): Beige solid (314 mg, 82 %). m.p.
140141 C. 1H NMR (400 MHz, [D6]DMSO/TMS): = 8.66 (s, 1 H),
8.32 (s, 1 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.46 (t, J = 8.0 Hz, 2 H), 7.36
(t, J = 8.0 Hz, 1 H), 6.13 (s, 2 H), 3.36 (s, 3 H) ppm. 13C NMR (100 MHz,
[D6]DMSO/TMS): = 169.8, 165.7, 155.5 (q, 2JC,F = 37.1 Hz), 146.7,
130.5, 128.9, 128.0, 125.2, 122.9, 119.9 (q, 1JC,F = 275.7 Hz), 119.1,
53.2, 38.9 ppm. LCMS (ESI): m/z = 406.1[M + Na+, 422.1 [M + K]+.
C15H12F3N5O2S (383.07): calcd. C 47.00, H 3.16, N 18.27; found C
47.40, H 3.55, N 18.51.
General Procedure for the Synthesis of Compounds 8a8e and
9a9e: The appropriate amine (3 mmol) was added to a solution
of 2-(methylsulfonyl)pyrimidine 6 or 7 (1 mmol) in acetonitrile
(12 mL). The reaction mixture was heated at 100 C for 25 h, de-
pending on the amine (see Table 3 for details). The solvent was
evaporated. The product was dissolved in chloroform, and the re-
sulting solution was washed with HCl (1 M aq.; 20 mL) and water
(3 20 mL). The organic layer was dried with anhydrous sodium
sulfate, and filtered, and the solvent was removed under reduced
pressure. Compounds 8a8e were purified by column chromatogra-
phy on silica gel, by using ethyl acetate/hexane (30:70) as the elu-
ent. Compounds 9a9e were purified by recrystallization from a
solution of chloroform/hexane (50:50).
4-{4-[(4-Butyl-1H-1,2,3-triazol-1-yl)methyl]-6-(trifluoromethyl)-
pyrimidin-2-yl}morpholine (8a): Pale brown solid (296 mg, 80 %).
m.p. 8485 C. 1H NMR (400 MHz, CDCl3): = 7.36 (s, 1 H), 6.49 (s,
1 H), 5.46 (s, 2 H), 3.81 (t, J = 4.7 Hz, 4 H), 3.74 (d, J = 4.7 Hz, 4 H),
2.75 (t, J = 7.6 Hz, 2 H), 1.701.65 (m, 2 H), 1.431.34 (m, 2 H), 0.94
(d, J = 7.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): = 166.6,
161.2, 157.5 (q, 2 J C,F = 35.5 Hz), 149.0, 121.8, 120.3 (q, 1 J C,F =
275.7 Hz), 101.9 (q, 3JC,F = 2.4 Hz), 66.5, 54.3, 44.0, 31.4, 25.2, 22.1,
13.7 ppm. GCMS (EI, 70 eV): m/z (%) = 370 (22) [M]+, 285 (51), 245
(100). HRMS (ESI): calcd. for C16H22F3N6O [M + H]+ 371.1807; found
371.1809.
N-Butyl-4-[(4-butyl-1H-1,2,3-triazol-1-yl)methyl]-6-(trifluoro-
methyl)pyrimidin-2-amine (8b): Yellow oil (334 mg, 94 %). 1H NMR
(400 MHz, CDCl3): = 7.43 (br. s, 1 H), 6.49 (s, 1 H), 5.56 (br. s, 1 H),
5.48 (br. s, 2 H), 3.43 (br. s, 2 H), 2.77 (t, J = 7.6 Hz, 2 H), 1.721.64
(m, 2 H), 1.611.54 (m, 2 H), 1.441.35 (m, 4 H), 0.970.92 (m, 6 H)
ppm. 13C NMR (100 MHz, CDCl3): = 167.0, 162.4, 157.8 (q, 2JC,F =
35.4 Hz), 149.2, 121.8, 120.3 (q, 1JC,F = 275.5 Hz), 102.3, 54.4, 41.2,
31.5, 31.4, 25.4, 22.3, 20.0, 13.82, 13.8 ppm. LCMS (ESI): m/z = 357.3
[M + H]+, 379.3 [M + Na]+. HRMS (ESI): calcd. for C16H24F3N6 [M +
H]+ 357.2014; found 357.2005.
N-Benzyl-4-[(4-butyl-1H-1,2,3-triazol-1-yl)methyl]-6-(trifluoro-
methyl)pyrimidin-2-amine (8c): Yellow oil (351 mg, 90 %). 1H NMR
(400 MHz, CDCl3): = 7.337.29 (m, 6 H), 6.55 (s, 1 H), 5.93 (br. s, 1
Eur. J. Org. Chem. 2017, 306312 www.eurjoc.org 311
Full Paper
H), 5.44 (s, 2 H), 4.62 (d, J = 6.0 Hz, 2 H), 2.72 (t, J = 7.7 Hz, 2 H),
1.671.61 (m, 2 H), 1.401.35 (m, 2 H), 0.91 (d, J = 7.4 Hz, 3 H) ppm.
13
C NMR (100 MHz, CDCl 3 ): = 167.0, 162.3, 158.0 (q, 2 J C,F =
35.8 Hz), 149.2, 138.2, 128.7, 127.6, 121.6, 120.3 (q, 1JC,F = 275.2 Hz),
103.2, 54.4, 45.6, 31.5, 25.4, 22.3, 13.8 ppm. LCMS (ESI): m/z = 391.3
[M + H]+, 413.3 [M + Na+. HRMS (ESI): calcd. for C19H22F3N6 [M +
H]+ 391.1858; found 391.1862.
4-[(4-Butyl-1H-1,2,3-triazol-1-yl)methyl]-N-phenethyl-6-(tri-
fluoromethyl)pyrimidin-2-amine (8d): Yellow solid (347 mg,
86 %). m.p. 6970 C. 1H NMR (400 MHz, CDCl3): = 7.37 (s, 1 H),
7.31 (t, J = 7.2 Hz, 2 H), 7.237.20 (m, 3 H), 6.51 (s, 1 H), 5.44 (br. s,
3 H), 3.70 (q, J = 6.4 Hz, 2 H), 2.89 (t, J = 6.8 Hz, 2 H), 2.74 (t, J =
7.6 Hz, 2 H), 1.691.63 (m, 2 H), 1.411.36 (m, 2 H), 0.93 (t, J = 7.3 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): = 167.0, 162.4, 158.0 (q,
2
JC,F = 35.9 Hz), 149.3, 138.7, 128.8, 128.7, 124.1, 121.6, 120.3 (q,
1
JC,F = 274.4 Hz), 102.9, 54.4, 42.8, 35.5, 31.5, 25.4, 22.3, 13.8 ppm.
LCMS (ESI): m/z = 405.3 [M + H]+, 427.3 [M + Na+. HRMS (ESI):
calcd. for C20H25F3N6 [M + H]+ 405.2014; found 405.2009.
4-[(4-Butyl-1H-1,2,3-triazol-1-yl)methyl]-N-(4-methoxyphenyl)-
6-(trifluoromethyl)pyrimidin-2-amine (8e): Brown solid (284 mg,
70 %). m.p. 9799 C. 1H NMR (400 MHz, CDCl3): = 7.41 (d, J =
8.7 Hz, 2 H), 7.39 (s, 1 H), 7.27 (br. s, 1 H), 6.89 (d, J = 8.9 Hz, 2 H),
6.67 (s, 1 H), 5.51 (s, 2 H), 3.81 (s, 3 H), 2.76 (t, J = 7.7 Hz, 2 H), 1.71
1.64 (m, 2 H), 1.441.35 (m, 2 H), 0.94 (t, J = 7.3 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): = 167.1, 160.3, 157.9 (q, 2JC,F = 35.9 Hz),
156.3, 149.3, 131.3, 121.8, 120.3 (q, 1JC,F = 275.4 Hz), 114.3, 104.3 (q,
3
JC,F = 2.2 Hz), 55.5, 54.2, 31.5, 25.4, 22.3, 13.8 ppm. LCMS (ESI):
m/z = 407.2 [M + H] + , 429.2 [M + Na] + . HRMS (ESI): calcd. for
C19H22F3N6O [M + H]+ 407.1807; found 407.1803.
4-{4-[(4-Phenyl-1H-1,2,3-triazol-1-yl)methyl]-6-(trifluoro-
methyl)pyrimidin-2-yl}morpholine (9a): White solid (308 mg,
79 %). m.p. 178180 C. 1H NMR (400 MHz, CDCl3): = 7.86 (s, 1 H),
7.83 (d, J = 8.0 Hz, 2 H), 7.43 (t, J = 8.0 Hz, 2 H), 7.35 (t, J = 8.0 Hz,
1 H), 6.59 (s, 1 H), 5.54 (s, 2 H), 3.83 (t, J = 4.4 Hz, 4 H), 3.73 (t, J =
4.4 Hz, 4 H) ppm. 13C NMR (100 MHz, CDCl3): = 166.2, 161.4, 157.9
(q, 2JC,F = 35.9 Hz), 148.5, 130.3, 128.9, 128.4, 125.8, 120.4, 120.3 (q,
1
JC,F = 275.5 Hz), 102.1 (q, 3JC,F = 2.5 Hz), 66.6, 54.7, 44.2 ppm. GC-
MS (EI, 70 eV): m/z (%) = 390 (28) [M]+, 361 (53), 246 (40), 116 (100).
C18H17F3N6O (390.14): calcd. C 55.38, H 4.39, N 21.53; found C 55.28,
H 4.73, N 21.70.
N-Butyl-4-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-6-(trifluoro-
methyl)pyrimidin-2-amine (9b): Pale brown solid (349 mg, 93 %).
m.p. 176178 C. 1H NMR (400 MHz, CDCl3): = 7.89 (s, 1 H), 7.84
(d, J = 8.0 Hz, 2 H), 7.41 (t, J = 8.0 Hz, 2 H), 7.34 (t, J = 8.0 Hz, 1 H),
6.61 (s, 1 H), 5.52 (s, 2 H), 5.47 (br. s, 1 H), 3.41 (t, J = 6.4 Hz, 2 H),
1.591.53 (m, 2 H), 1.401.34 (m, 2 H), 0.91 (d, J = 7.2 Hz, 3 H) ppm.
13
C NMR (100 MHz, CDCl 3 ): = 166.3, 162.6, 158.0 (q, 2 J C,F =
35.8 Hz), 148.4, 130.4, 128.9, 128.4, 125.9, 120.7, 120.4 (q, 1JC,F =
275.8 Hz), 102.6 (q, 3JC,F = 2.2 Hz), 54.6, 41.3, 31.4, 20.0, 13.7 ppm.
GCMS (EI, 70 eV): m/z (%) = 376 (30) [M]+, 347 (30), 319 (26), 305
(40), 189 (28), 116 (100). C18H19F3N6 (376.16): calcd. C 57.44, H 5.09,
N 22.33; found C 57.10, H 4.90, N 22.26.
N-Benzyl-4-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-6-(trifluoro-
methyl)pyrimidin-2-amine (9c): White solid (369 mg, 90 %). m.p.
144145 C. 1H NMR (400 MHz, CDCl3): = 7.817.79 (m, 3 H), 7.40
(t, J = 7.7 Hz, 2 H), 7.34 (d, J = 7.4 Hz, 1 H), 7.287.25 (m, 5 H), 6.68
(s, 1 H), 5.84 (br. s, 1 H), 5.51 (s, 2 H), 4.61 (d, J = 6.0 Hz, 2 H) ppm.
13
C NMR (100 MHz, CDCl 3 ): = 166.5, 162.4, 158.2 (q, 2 J C,F =
35.7 Hz), 148.5, 138.1, 130.4, 128.9, 128.8, 128.4, 127.6, 125.9, 120.6,
120.3 (q, 1JC,F = 275.2 Hz), 103.4 (q, 3JC,F = 2.4 Hz), 54.5, 45.7 ppm.
LCMS (ESI): m/z = 433.2 [M + Na]+, 449.2 [M + K]+. C21H17F3N6
2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

(410.15): calcd. C 61.46, H 4.18, N 20.48; found C 61.16, H 3.97, N
20.62.
N-Phenethyl-4-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-6-(tri-
fluoromethyl)pyrimidin-2-amine (9d): Yellow solid (373 mg,
88 %). m.p. 149150 C. 1H NMR (400 MHz, CDCl3): = 7.87 (s, 1 H),
7.82 (d, J = 8.0 Hz, 2 H), 7.41 (t, J = 8.0 Hz, 2 H), 7.33 (t, J = 8.0 Hz,
1 H), 7.277.24 (m, 2 H), 7.217.16 (m, 3 H), 6.61 (s, 1 H), 5.59 (br. s,
1 H), 5.49 (s, 2 H), 3.67 (q, J = 6.5 Hz, 2 H), 2.87 (t, J = 6.8 Hz, 2 H)
ppm. 13C NMR (100 MHz, CDCl3): = 166.4, 162.4, 158.0 (q, 2JC,F =
35.8 Hz), 148.4, 138.7, 130.3, 128.93, 128.8, 128.7, 128.4, 126.6, 125.8,
120.7, 120.3 (q, 1JC,F = 275.8 Hz), 102.9, 54.5, 42.8, 35.5 ppm. LCMS
(ESI): m/z = 425.3 [M + H]+, 447.3 [M + Na]+, 463.3 [M + K]+. HRMS
(ESI): calcd. for C22H19F3N6 [M + H]+ 425.1701; found 425.1695.
N-(4-Methoxyphenyl)-4-[(4-phenyl-1H-1,2,3-triazol-1-yl)-
methyl]-6-(trifluoromethyl)pyrimidin-2-amine (9e): Brown solid
(306 mg, 72 %). m.p. 176178 C. 1H NMR (400 MHz, [D6]DMSO): =
9.94 (s, 1 H), 8.65 (s, 1 H), 7.90 (d, J = 8.0 Hz, 2 H), 7.48 (t, J = 8.0 Hz,
2 H), 7.407.33 (m, 3 H), 7.16 (s, 1 H), 6.65 (d, J = 8.0 Hz, 2 H), 5.84
(s, 2 H), 3.57 (s, 3 H) ppm. 13C NMR (100 MHz, [D6]DMSO): = 167.9,
159.8, 155.5 (q, 2JC,F = 34.9 Hz), 154.8, 146.6, 132.2, 130.8, 128.9,
127.9, 125.2, 123.1, 120.9, 120.5 (q, 1JC,F = 275.4 Hz), 113.5, 103.9,
54.9, 53.2 ppm. LCMS (ESI): m/z = 427.3 [M + H]+, 465.2 [M + K]+.
C21H17F3N6O (426.14): calcd. C 59.15, H 4.02, N 19.71; found C 59.19,
H 4.20, N 19.55.
Acknowledgments
The authors are grateful for financial support from the Conselho
Nacional de Desenvolvimento Cientifco e Tecnolgico (CNPq;
Universal Grant No. 476341/2013-2) and fellowships from Coor-
denao de Aperfeioamento de Pessoal de Nvel Superior
(CAPES) (to E. d. C. A.) and CNPq (to M. M. L. and G. L.).
Keywords: Nitrogen heterocycles Pyrimidines 1,2,3-
Triazoles Trifluoromethyl enones Cyclization Click chemistry
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Received: September 30, 2016
Published Online: December 19, 2016
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