4-aryl-pyrimidin-2-yl tosylates as efficient reaction partners: Application to the synthesis of pyrimidines functionalised with propargyloxy and 1,2,3-triazolo groups

Article abstract of DOI:10.3184/174751915X14242834761170

The 4-arylated pyrimidin-2-yl tosylate derivatives, easily prepared from cheap commercial materials, reacted efficiently with propargyl alcohol/NaOBu^t to give the corresponding 4-arylated 2-propargyloxy-pyrimidine derivatives which, in a onepot

Full text of DOI:10.3184/174751915X14242834761170

170 RESEARCH PAPER
VOL. 39 MARCH, 170–173
JOURNAL OF CHEMICAL RESEARCH 2015
4-Aryl-pyrimidin-2-yl tosylates as efficient reaction partners: application
to the synthesis of pyrimidines functionalised with propargyloxy and
1,2,3-triazolo groups
Zheng-Jun Quan, Shao-Wei Fang, Yu-Xia Da, Zhang Zhang and Xi-Cun Wang*
College of Chemistry and Chemical Engineering, Northwest Normal University, Anning East Road 967, Lanzhou, Gansu 730070, P.R. China
The 4‑arylated pyrimidin‑2‑yl tosylate derivatives, easily prepared from cheap commercial materials, reacted efficiently
with propargyl alcohol/NaOBut to give the corresponding 4‑arylated 2‑propargyloxy‑pyrimidine derivatives which, in a one‑
pot reaction catalysed by CuSO4·5H2O/sodium ascorbate, reacted with NaN3 and hexyl or benzyl bromide to give a series of
2‑(1‑hexyl‑ or 1‑benzyl‑1,2,3‑triazol‑4‑yl)methoxy‑pyrimidine derivatives in good yields.
Keywords: 1,2,3-triazoles, Cu (I)-catalysed click reaction, C2-substituted pyrimidines, three-component reaction
3,4-Dihydropyrimidinone (DHPM) is a simple heterocyclic
scaffoldexhibitingawiderangeofpharmacologicalproperties.1,2
Among the DHPM derivatives, most of the pharmacologically
importantderivativesareN3-substituted-andC2-functionalised
analogues.3–8 Only a few methods have been developed to
efficiently convert DHPM to 2-substituted pyrimidines.9–15
In 2010, we reported the synthesis of 4-aryl-pyrimidin-2-yl
tosylates and their utilisation in the formation of C2-substituted
pyrimidines.16 The 4-aryl-pyrimidin-2-yl tosylates were easily
available from Biginelli 3,4-dihydropyrimidine-2(1H)-ones
via oxidation and esterification under very mild conditions.16
It has been shown that 4-aryl-pyrimidin-2-yl tosylates can
be useful synthetic building blocks for important pyrimidine
derivatives (Scheme 1). For example, they coupled with
arylboronic acids and alkynes to deliver C–C coupling
products17 and reacted with phenols and anilines to construct
C–O and C–N bonds.18 We recently reported a multicomponent
reaction (MCR) of 4-aryl-pyrimidin-2-yl tosylates with NaN3
and alkynes19 or active methylene ketones20 for the synthesis of
C2-(1,2,3-triazolo-subsituted)pyrimidines. In this context, we
became interested in combining click chemistry (azide-alkyne
cycloadditions) with MCR strategies. Here, we report the use of
4-aryl-pyrimidin-2-yl tosylates in the synthesis of pyrimidines
functionalised with propargyloxy and 1,2,3-triazolo groups
(Schemes 2 and 3).
reactions of alkyl or aryl halides, terminal alkynes and safe-
to-use sodium azide have been developed by several groups to
produce 1,2,3-triazole derivatives.24–29 We have also employed
sodium azide in the work reported here.
Results and discussion
Initially, in order to optimise the first reaction of our proposed
two-step synthesis, the base-catalysed reaction between the
4-phenyl-pyrimidin-2-yl tosylate derivative 1a (Ar=Ph) and
propargyl alcohol 2 was chosen as a model (Scheme 2). After
several experiments we found that this reaction proceeded
smoothly in the presence of 2 equiv. of NaOBut and 1 equiv.
of K3PO4 at room temperature to form the desired 4-phenyl-2-
propargyloxy-pyrimidine derivative 3a (Ar=Ph) in a good yield
of 83%. Other combinations of bases, for example NaOBut with
K2CO3 or Et3N gave lower yields (72% and 76%, respectively).
Acetone, PEG-400 and dichloromethane (DCM) were tested as
solvents, but only the latter gave a satisfactory yield. Applying
these conditions to five other 4-aryl-pyrimidin-2-yl tosylate
derivatives 1, good yields (66–83%) of the desired products
3b–f were obtained (Scheme 2). The reaction tolerated both
electron-withdrawing group (Cl, Br and F) and electron-
donating group (Me, MeO) on the phenyl ring to deliver the
desired products.
For optimisation of the conditions for the second step of
the synthesis (Scheme 3), a three-component Cu-catalysed
reaction, the 4-phenyl-2-propargyloxy-pyrimidine derivative
3a and benzyl bromide 4a were chosen as model substrates
to react with NaN3. Recently, we reported that the Cu(I)
It is well known that copper (I)-catalysed click chemistry of
azide–alkyne cycloaddition proceed with high regioselectivity
to deliver 1,4-disubstituted 1,2,3-triazoles as the major
products.21–23 Essentially, copper-catalysed three-component
Ar
N
O
Ar
O
N
EtO
N
EtO
Me
Ar
Me
N
XR
ArB(OH)2
NuH
X = N-, O-, S
Ar
Ar
N
O
O
Ar
O
NaN3
R
N
EtO
R
N
EtO
N
EtO
R
Me
Me
N
N
N
Me
N
OTs
R
N
Scheme 1
* Correspondent. E-mail: wangxicun@nwnu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2015 171
Ar
O
Ar
N
O
Ar
N
O
tBuOOH
CuCl2
TsCl
NH
EtO
N
Ar
N
EtO
N
EtO
K
rt
2CO3
,
Me
N
H
O
Me
OH
N
Me
OTs
ref. 16
1
O
3a
Ar = C6H5, , 83%;
4-MeC6H4, , 68%;
3c
4-MeOC6H4, , 66%;
2-ClC6H4, , 72%;
4-BrC6H4, , 78%;
4-FC6H4, , 81%
OH
2 eq. NaOBut
3b
EtO
+
1
3d
3e
3f
1
K
3PO4
eq.
CH2Cl2
12 h
Me
O
,
rt,
2
3
Scheme 2
Ar
O
Ar
N
O
CuSO4 (0.2 eq.)
ascorbate (0.3 eq.)
N
EtO
Me
EtO
+
+
NaN3 RBr
K3PO4 1.2 eq.
dioxane, 80 oC, 12 h
4
N
N
O
Me
N
O
N
3
5
N
5a
5c
5e
5b
:
: Ar = C6H5, R = Bn, 66%;
Ar = 4-MeC6H4, R = Bn, 60%;
R
5d
: Ar = 2-ClC6H4, R = Bn, 64%;
:
Ar = 4-BrC6H4, R = Bn, 62%;
5f
: Ar = C6H5, R = hexyl, 47%;
:
Ar = 4-FC6H4, R = Bn, 68%;
5g
5h
:
Ar = 4-MeC6H4, R = hexyl 41%;
: Ar = 2-ClC6H4, R = hexyl 44%;
5j
: Ar = 4-FC6H4, R = hexyl 46%;
5i
:
Ar = 4-BrC6H4, R = hexyl 44%;
Scheme 3
species generated in situ from CuSO4·5H2O (or Cu(OAc)2·H2O)
with sodium ascorbate (NaAsc) catalysed the reaction of an
azide with an acetylene30 and the amination of aryl halides
with amines or amides.31,32 So we tested the CuSO4·5H2O
(20 mol%)/NaAsc (30 mol%) and Cu(OAc)2·H2O (20 mol%)/
NaAsc (30 mol%) catalyst systems in the three-component
model reaction. The results are shown in Table 1. We found
that both catalyst systems gave a good yield of the product 5a
(Ar=Ph, R=Bn) in the presence of K3PO4 as a base (entries 1
and 2). The reaction was significantly affected by the base
used. Although the inorganic bases K3PO4, K2CO3, and Cs2CO3
all delivered the desired product in 50–60% yield, Na2CO3
gave only a 30% yield and Et3N resulted in only a trace of the
product (entries 3–6). Among the solvents tested, acetone,
DMSO, DMF, and dioxane gave satisfactory yields, the latter
the best yield of 63% (entries 7–10). Cu (I) salts, for example,
CuCl, CuBr, and CuI at 10 mol% also gave good yields in
dioxane (entries 9–11). The best yield (63%) was realised using
CuSO4·5H2O/NaAsc in the presence of K3PO4 at 80 °C for 12 h
in dioxane.
To test the scope of the second step of the synthesis, the
4-aryl-2-propargyloxypyrimidine derivatives 3a–b, 3d–f were
reacted with sodium azide and benzyl bromide 4a or hexyl
bromide 4b under the optimised conditions and the yields of
the products obtained are shown in Scheme 3. In general, good
yields (60–68%) of the desired products 5a–e were obtained
from benzyl bromide when the aryl group contained either an
electron-withdrawing or an electron-donating group on the
benzene ring. However, only moderate yields (41–47%) of the
desired 1,2,3-triazole derivatives 5f–j were obtained employing
Table 1 Optimisation of the reaction conditions (catalyst, base and solvent) for the one‑pot reaction of 3a with
NaN3 and benzyl bromide 4a to form 5a (Ar=Ph, R=Bn) (Scheme 3)a
Entry
Catalysis (mol %)
Solvent
Base
Yield/%b
1
2
3
4
5
6
7
8
9
10
9
10
11
Cu(OAc)2·H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuSO4·5H2O (20)/NaAsc (30)
CuI (10)
EA
EA
EA
EA
EA
EA
Acetone
Dioxane
DMSO
DMF
Dioxane
Dioxane
Dioxane
K3PO4
K3PO4
K2CO3
Na2CO3
Cs2CO3
Et3N
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
60
59
52
30
55
Trace
47
63
40
35
60
60
52
CuBr (10)
CuCl (10)
aReaction conditions: 3a (0.5 mmol), NaN3 (0.75 mmol), 4a (R=Bn) (0.6 mmol), base (0.6 mmol) and catalyst (10
or 30 mol%) were stirred in solvent (3 mL) at 80 °C for 12 h.
bIsolated yield.

172 JOURNAL OF CHEMICAL RESEARCH 2015
129.4, 126.5, 120.9, 77.9, 74.8, 61.3, 55.3, 23.6, 13.3; ESI-MS: 331.05
[M+1]+. Anal. calcd for C17H15ClN2O3: C, 61.73; H, 4.57; N, 8.47; found
C, 61.91; H, 4.52; N, 8.55%.
Ethyl 4‑(4‑bromophenyl)‑6‑methyl‑2‑(prop‑2‑ynyloxy)pyrimidine‑5‑
carboxylate (3e): Yellow oil; 1H NMR: δ 7.58 (d, J=8.0 Hz, 2H), 7.54
(d, J=8.0 Hz, 2H), 5.08 (s, 2H), 4.20 (q, J=8.0 Hz, 2H), 2.58 (s, 3H),
1.12 (t, J=8.0 Hz, 3H); 13C NMR: δ 169.2, 167.8, 165.0, 163.0, 136.3,
131.6, 129.9, 124.9, 120.3, 78.1, 74.8, 61.8, 55.2, 22.7, 13.7; ESI-MS:
376.13 [M+1]+. Anal. calcd for C17H15BrN2O3: C, 54.42; H, 4.03; N,
7.47; found C, 54.63; H, 4.09; N, 7.55%.
hexyl bromide 4b, again the yields not notably influenced by
the nature of the aromatic substituent.
The newly synthesised products 3a–f and 5a–j were fully
characterised by their 1H NMR, 13C NMR spectra and elemental
analyses. Some selected NMR data is discussed below. The
formation of product 3a was confirmed by observing two
singlets at δ 5.09 and 2.48, which were assigned to methylene
and alkyl protons of the prop-2-ynyloxy group. Formation of
product 3a was further confirmed by the 13C NMR spectra
showing singlets at δ 78.2, 74.7 and 55.1, which were assigned
to methylene and alkyne carbons of the prop-2-ynyloxy group.
Ethyl 4‑(4‑fluorophenyl)‑6‑methyl‑2‑(prop‑2‑ynyloxy)pyrimidine‑5‑
1
carboxylate (3f): Yellow oil; H NMR: δ 7.67 (q, J=4.0 2H), 7.13 (t,
1
The H NMR spectrum of product 5a exhibited a singlet at δ
J=8.0 Hz, 2H), 5.07 (s, 2H), 4.19 (q, J=8.0 Hz, 2H), 2.57 (s, 3H), 1.10
(t, J=8.0 Hz, 3H); 13C NMR: δ 168.9, 167.9, 165.3, 164.9, 162.9, 162.8,
133.5, 130.5, 130.4, 120.3, 115.6, 115.4, 78.2, 74.723, 61.8, 55.1, 22.7,
13.7; ESI-MS: 315.21 [M+1]+. Anal. calcd for C17H15FN2O3: C, 64.96;
H, 4.81; N, 8.91; found C, 65.12; H, 4.87; N, 8.80%.
5.50 attributed as the CH2 of Bn group. This CH2 appeared
as a singlet at δ 61 in the 13C NMR spectrum. Meanwhile the
absence of alkyne protons and carbons in the 1H NMR and 13
C
NMR spectra confirmed the formation of 5a.
Experimental
Synthesis of C2‑triazolomethoxypyrimidines 5; general procedure
A mixture of 2-propargyloxy pyrimidine derivatives 3 (0.5 mmol),
NaN3 (0.6 mmol), benzyl or hexyl bromide 4a,b (0.6 mmol),
CuSO4·5H2O (0.1 mmol), sodium ascorbate (0.15 mmol) and dioxane
(3 mL) was stirred at 80 °C for 12 h. After completion (monitored by
TLC), the reaction mixture was quenched into saturated aqueous
NH4Cl solution (10 mL). The aqueous phase was extracted with
3×15 mL of ethyl acetate and the combined organic phases were dried
over MgSO4 and evaporated. The products were separated by silica
gel column chromatography eluting with EtOAc/petroleum ether
(V/V=1:3).
Ethyl 4‑methyl‑6‑phenyl‑2‑[(1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)methoxy]‑
pyrimidine‑5‑carboxylate (5a): Yellow oil; 1H NMR: δ 7.62 (d,
J=8.0 Hz, 3H), 7.43 (q, J=8.0 Hz, 3H), 7.33 (d, J=8.0 Hz, 3H), 7.24
(d, J=4.0 Hz, 2H), 5.62 (s, 2H), 5.50 (s, 2H), 4.15 (q, J=8.0 Hz, 2H),
2.56 (s, 3H), 1.03 (t, J=8.0 Hz, 3H); 13C NMR: δ 168.6, 167.8, 166.2,
163.3, 143.5, 137.3, 134.2, 129.9, 128.9, 128.5, 128.2, 128.0, 127.9,
123.0, 120.1, 61.5, 61.1, 53.9, 22.5, 13.4. ESI-MS: 430.11 [M+1]+. Anal.
calcd for C24H23N5O3: C, 67.12; H, 5.40; N, 16.31; found C, 67.33; H,
5.46; N, 16.41%.
All starting materials and reagents were obtained commercially and
used without further purification. Melting points were determined
on an XT-4 electrothermal micromelting point apparatus and
uncorrected. Mass-spectra were recorded on an Esquire 6000
instrument. NMR spectra were recorded at 400 (1H) and 100 (13C)
MHz, respectively, on a Varian Mercury plus-400 instrument in
CDCl3 or DMSO-d6 (for 13C NMR of compound 5b) and TMS as
internal standard. TLC was performed on 5×10 cm aluminium plates
coated with silica gel 60F-254 in an appropriate solvent. 4-Aryl-
pyrimidin-2-yl tosylate derivatives 3a–f were synthesised (Scheme 2)
in accordance with our previously reported methods.16
Synthesis of 2‑propargyloxy pyrimidines 3; general procedure
A mixture of pyrimidin-2-yl tosylate 1 (2 mmol), propargyl alcohol
2 (3 mmol), NaOBut (4 mmol), K3PO4 (2 mmol) in DCM (5 mL) was
stirred at room temperature for 12 h. After completion (monitored
by TLC), the reaction mixture was quenched into saturated aqueous
NH4Cl solution (15 mL). The aqueous phase was extracted with
3×15 mL of CH2Cl2 and the combined organic phases were dried
over MgSO4 and evaporated. The products were isolated by silica
gel column chromatography eluting with EtOAc/petroleum ether
(V/V=1:15).
Ethyl 4‑methyl‑6‑phenyl‑2‑(prop‑2‑ynyloxy)pyrimidine‑5‑carboxylate
(3a): Yellow oil; 1H NMR: δ 7.66 (d, J=8.0 Hz, 2H), 7.47–7.27 (m, 3H),
5.09 (s, 2H), 4.16 (q, J=8.0 Hz, 2H), 2.59 (s, 3H), 1.05 (t, J=8.0 Hz,
3H); 13C NMR: δ 168.9, 168.0, 166.3, 163.0, 137.5, 130.2, 128.4, 128.3,
120.5, 78.2, 74.7, 61.7, 55.1, 22.7, 13.6; ESI-MS: 297.15 [M+1]+. Anal.
calcd for C17H16N2O3: C, 68.91; H, 5.44; N, 9.45; found C, 69.21; H,
5.49; N, 9.60%.
Ethyl 4‑methyl‑2‑(prop‑2‑ynyloxy)‑6‑p‑tolylpyrimidine‑5‑carboxylate
(3b): Yellow oil; 1H NMR: δ 7.48 (d, J=8.0 Hz, 2H), 7.12 (d, J=8.0 Hz,
2H), 4.96 (s, 2H), 4.08 (q, J=8.0 Hz, 2H), 2.45 (s, 3H), 2.27 (s, 3H),
0.98 (t, J=8.0 Hz, 3H); 13C NMR: δ 168.3, 167.9, 165.8, 162.7, 140.3,
134.3, 128.8, 128.1, 120.0, 78.1, 74.5, 61.4, 54.8, 22.4, 21.1, 13.4; ESI-
MS: 311.11 [M+1]+. Anal. calcd for C18H18N2O3: C, 69.66; H, 5.85; N,
9.03; found C, 69.88; H, 5.90; N, 9.12%.
Ethyl 4‑methyl‑2‑[(1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)methoxy]‑6‑p‑tolyl‑
1
pyrimidine‑5‑carboxylate (5b): Yellow oil; H NMR: δ 7.59–7.53 (m,
3H), 7.35–7.34 (m, 3H), 7.27–7.22 (m, 4H), 5.61 (s, 2H), 5.50 (s, 2H),
4.19 (q, J=8.0 Hz, 2H), 2.54 (s, 3H), 2.40 (s, 3H), 1.09 (t, J=8.0 Hz,
3H); 13C NMR: δ 168.5, 168.2, 166.1, 163.3, 143.8, 140.4, 134.5, 134.3,
128.9, 128.9, 128.6, 128.1, 128.0, 122.9, 120.0, 77.3, 76.9, 76.7, 61.5,
61.2, 54.0, 22.5, 21.2, 13.6, 13.5. ESI-MS: 444.32 [M+1]+. Anal. calcd
for C25H25N5O3: C, 67.70; H, 5.68; N, 15.79; found C, 67.52; H, 5.74; N,
15.91%.
Ethyl 4‑(2‑chlorophenyl)‑6‑methyl‑2‑[(1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)
methoxy]pyrimidine‑5‑carboxylate (5c): Yellow oil; 1H NMR: δ
7.69–7.24 (m, 10H), 5.58 (s, 2H), 5.50 (s, 2H), 4.04 (q, J=8.0 Hz, 2H),
2.66 (s, 3H), 0.90 (t, J=8.0 Hz, 3H); 13C NMR: δ 170.2, 166.4, 165.9,
163.2, 143.38, 137.4, 134.2, 129.9, 129.5, 129.2, 128.9, 128.5, 128.3,
128.2, 127.9, 123.2, 120.5, 61.3, 61.1, 53.9, 23.4, 13.2; ESI-MS: 464.95
[M+1]+. Anal. calcd for C24H22ClN5O3: C, 62.14; H, 4.78; N, 15.10;
found C, 62.32; H, 4.72; N, 15.20%.
Ethyl 4‑(4‑methoxyphenyl)‑6‑methyl‑2‑(prop‑2‑ynyloxy)pyrimidine‑
5‑carboxylate (3c): Yellow oil; 1H NMR: δ 7.48 (d, J=8.0 Hz, 2H), 7.12
(d, J=8.0 Hz, 2H), 4.96 (s, 2H), 4.08 (q, J=7.2 Hz, 2H), 2.45 (s, 3H),
2.27 (s, 3H), 0.98 (t, J=7.2 Hz, 3H); 13C NMR: δ 168.3, 168.3, 165.1,
162.7, 161.36, 129.9, 129.4, 119.7, 113.6, 78.2, 74.5, 61.5, 55.1, 54.8,
22.5, 13.6; ESI-MS: 327.10 [M+1]+. Anal. calcd for C18H18N2O4: C,
66.25; H, 5.56; N, 8.58; found C, 66.40; H, 5.61; N, 8.49%.
Ethyl 4‑(4‑bromophenyl)‑6‑methyl‑2‑[(1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)
methoxy]pyrimidine‑5‑carboxylate (5d): Yellow oil; 1H NMR: δ
7.57–7.49 (m, 6H), 7.36–7.25 (m, 4H), 5.60 (s, 2H), 5.51 (s, 2H), 4.18 (q,
J=8.0 Hz, 2H), 2.55 (s, 3H), 1.10 (t, J=8.0 Hz, 3H); 13C NMR: δ 169.1,
167.8, 165.1, 163.5, 143.7, 136.4, 134.3, 131.6, 131.6, 129.9, 129.1, 128.8,
128.1, 124.8, 123.0, 120.1, 61.8, 61.4, 54.2, 22.7, 13.6; ESI-MS: 509.35
[M+1]+. Anal. calcd for C24H22BrN5O3: C, 56.70; H, 4.36; N, 13.78;
found C, 56.87; H, 4.40; N, 13.72%.
Ethyl 4‑(2‑chlorophenyl)‑6‑methyl‑2‑(prop‑2‑ynyloxy)pyrimidine‑
5‑carboxylate (3d): White solid, m.p. 113–114 °C (EtOH–H2O
Ethyl 4‑(4‑fluorophenyl)‑6‑methyl‑2‑[(1‑phenyl‑1H‑1,2,3‑triazol‑4‑yl)
1
1
(V/V=10:1); H NMR: δ 7.43 (d, J=8.0 Hz, 1H), 7.38–7.32 (m, 3H),
methoxy]pyrimidine‑5‑carboxylate (5e): Yellow oil; H NMR: δ 7.56
5.06 (s, 2H), 4.05 (q, J=8.0 Hz, 2H), 2.68 (s, 3H), 0.91 (t, J=8.0 Hz,
3H); 13C NMR: δ 170.3, 166.6, 166.1, 162.9, 137.5, 131.9, 130.1, 129.9,
(q, J=4.0 Hz, 3H), 7.26 (d, J=4.0 Hz, 3H), 7.18 (q, J=4.0 Hz, 2H),
7.03 (t, J=8.0 Hz, 2H), 5.53 (s, 2H), 5.42 (s, 2H), 4.10 (q, J=8.0 Hz,

JOURNAL OF CHEMICAL RESEARCH 2015 173
2H), 2.47 (s, 3H), 1.01 (t, J=8.0 Hz, 3H); 13C NMR: δ 168.8, 167.9,
165.0, 163.3, 143.6, 134.2, 130.3, 130.3, 128.9, 128.7, 128.0, 123.0,
115.5, 115.3, 61.7, 61.3, 54.1, 22.6, 13.6; ESI-MS: 448.35 [M+1]+. Anal.
calcd for C24H22FN5O3: C, 64.42; H, 4.96; N, 15.65; found C, 64.60; H,
5.01; N, 15.58%.
We are thankful for financial support from the National Nature
Science Foundation of China (nos 21362032, and 21362031),
Gansu Provincial Department of Finance, Natural Science
Foundation of Gansu Province (no. 1308RJZA299).
Ethyl 2‑[(1‑hexyl‑1H‑1,2,3‑triazol‑4‑yl)methoxy]‑4‑methyl‑6‑phenyl‑
pyrimidine‑5‑carboxylate (5f): Yellow oil; 1H NMR: δ 7.66 (t,
J=8.0 Hz, 3H), 7.46 (d, J=8.0 Hz, 3H), 5.66 (s, 2H), 4.34 (q,
J=4.0 Hz, 2H), 4.15 (q, J=8.0 Hz, 2H), 2.60 (s, 3H), 1.87 (d,
J=4.0 Hz, 2H), 1.30 (s, 6H), 1.04 (t, J=8.0 Hz, 3H), 0.88 (s, 3H);
13C NMR: δ 168.8, 168.1, 166.5, 163.5, 143.4, 137.6, 130.1, 128.4, 128.3,
122.8, 120.3, 61.7, 61.5, 50.3, 31.1, 30.2, 26.1, 22.7, 22.3, 13.9, 13.6; ESI-
MS: 424.18 [M+1]+. Anal. calcd for C23H29N5O3: C, 65.23; H, 6.90; N,
16.54; found C, 65.41; H, 6.97; N, 16.63%.
Received 13 January 2015; accepted 12 February 2015
Paper 1503140 doi: 10.3184/174751915X14242834761170
Published online: 18 March 2015
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Ethyl 4‑methyl‑2‑[(1‑hexyl‑1H‑1,2,3‑triazol‑4‑yl)methoxy]‑6‑p‑tolyl‑
1
pyrimidine‑5‑carboxylate (5g): Yellow oil; H NMR: δ 7.58 (s, 1H),
7.51 (d, J=8.0 Hz, 2H), 7.18 (d, J=8.0 Hz, 2H), 5.59 (s, 2H), 4.27
(t, J=8.0 Hz, 2H), 4.12 (t, J=8.0 Hz, 2H), 2.50 (s, 3H), 2.37 (s, 3H),
1.81 (t, J=4.0 Hz, 2H), 1.23 (s, 6H), 1.04 (t, J=8.0 Hz, 3H), 0.81 (t,
J=4.0 Hz, 3H); 13C NMR: δ 168.6, 168.3, 166.2, 163.5, 143.5, 140.5,
134.6, 129.1, 128.3, 122.8, 120.1, 61.6, 61.4, 50.3, 31.1, 30.1, 26.1,
22.7, 22.3, 21.3, 13.8, 13.6; ESI-MS: 438.32 [M+1]+. Anal. calcd for
C24H31N5O3: C, 65.88; H, 7.14; N, 16.01; found C, 65.99; H, 7.10; N,
16.06%.
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A.R. Gholap, K.S. Toti, F. Shirazi, M.V. Deshpande and K.V. Srinivasan,
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Ethyl 4‑(2‑chlorophenyl)‑2‑[(1‑hexyl‑1H‑1,2,3‑triazol‑4‑yl)methoxy]‑
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6‑methylpyrimidine‑5‑carboxylate (5h): Yellow oil; H NMR: δ 7.67
(s, 1H), 7.45 (d, J=7.2 Hz, 1H), 7.36 (d, J=7.2 Hz, 3H), 5.62 (s, 2H),
4.34 (t, J=7.2 Hz, 2H), 4.05 (q, J=7.2 Hz, 2H), 2.69 (s, 3H), 1.88
(s, 2H), 1.28 (s, 6H), 1.06 (t, J=8.0 Hz, 3H), 0.90 (d, 7.2 Hz, 3H);
13C NMR: δ 170.4, 166.7, 166.2, 163.5, 143.2, 137.7, 131.9, 130.1, 129.8,
129.4, 126.6, 123.1, 120.8, 61.7, 61.3, 50.4, 31.1, 30.2, 26.1, 23.7, 22.4,
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60.32; H, 6.16; N, 15.29; found C, 60.11; H, 6.20; N, 15.41%.
Ethyl 4‑(4‑bromophenyl)‑2‑[(1‑hexyl‑1H‑1,2,3‑triazol‑4‑yl)methoxy]‑
6‑methylpyrimidine‑5‑carboxylate (5i): Yellow oil; 1H NMR: δ
7.58 (s, 1H), 7.51 (d, J=8.0 Hz, 2H), 7.47 (d, J=8.0 Hz, 2H), 5.57 (s,
2H), 4.27 (t, J=8.0 Hz, 2H), 4.12 (q, J=8.0 Hz, 2H), 2.51 (s, 3H),
1.81 (t, J=8.0 Hz, 2H), 1.22 (s, 6H), 1.04 (t, J=8.0 Hz, 3H), 0.80
(d, J=4.0 Hz, 3H); 13C NMR: δ 169.0, 167.8, 165.1, 163.5, 143.2,
136.4, 131.6, 129.9, 124.8, 122.8, 120.1, 61.8, 61.4, 50.3, 31.0, 30.1,
26.0, 22.7, 22.3, 13.8, 13.6; ESI-MS: 503.22 [M+1]+. Anal. calcd for
C23H28BrN5O3: C, 54.99; H, 5.62; N, 13.94; found C, 55.19; H, 5.68; N,
14.04%.
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Ethyl 4‑(4‑fluorophenyl)‑2‑[(1‑hexyl‑1H‑1,2,3‑triazol‑4‑yl)methoxy]‑
1
6‑methylpyrimidine‑5‑carboxylate (5j): Yellow oil; H NMR: δ 7.66
(s, 2H), 7.27 (d, J=8.0 Hz, 2H), 7.14 (d, J=8.0 Hz, 2H), 5.66 (s, 2H),
4.35 (s, 2H), 4.20 (q, J=8.0 Hz, 2H), 2.59 (s, 3H), 1.89 (s, 2H), 1.31 (s,
6H), 1.11 (t, J=8.0 Hz, 3H), 0.88 (d, J=4.0 Hz, 3H); 13C NMR: δ 168.9,
168.1, 165.2, 163.5, 162.8, 143.4, 133.7, 130.5, 130.4, 122.8, 120.2,
115.7, 115.4, 61.8, 61.5, 50.4, 31.1, 30.2, 26.1, 22.8, 22.4, 13.9; ESI-MS:
442.17 [M+1]+. Anal. calcd for C23H28FN5O3: C, 62.57; H, 6.39; N,
15.86; found C, 62.72; H, 6.44; N, 15.77%.
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