Sequential C-C, C-O, and C-N bond-forming reaction of methyl (-)-3-dehydroshikimate, malononitrile, and bromoalkanes: Simple synthesis of 2-(alkylamino)-3-cyanobenzofurans from a biomass-derived substrate

Article abstract of DOI:10.1055/s-0035-1560582

An interesting and simple method was developed for the synthesis of 2-(alkylamino)-3-cyanobenzofurans by consecutive C-C, C-O, and C-N coupling reaction of methyl (-)-3-dehydroshikimate with malononitrile and a bromoalkane or dibromoalkane under microwave

Full text of DOI:10.1055/s-0035-1560582

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Sequential C–C, C–O, and C–N Bond-Forming Reaction of Methyl
(–)-3-Dehydroshikimate, Malononitrile, and Bromoalkanes:
Simple Synthesis of 2-(Alkylamino)-3-cyanobenzofurans from a
Biomass-Derived Substrate
Dejian Wangb,c
Ensheng Zhangd
Tianlong Xub,c
Jianfei Shenga
Yong Zou*a
a School of Pharmaceutical Sciences, Sun Yat-sen University,
Guangzhou, 510006, P. R. of China
zou_jinan@163.com
b Guangzhou Institute of Chemistry, Chinese Academy of
Sciences, Guangzhou, 510650, P. R. of China
c University of Chinese Academy of Sciences, Beijing
100039, P. R. of China
d School of Chemistry and Chemical Engineering, Yan’an
University, Yan’an 716000, P. R. of China
Received: 25.08.2015
OH
MeO
Accepted after revision: 18.09.2015
Published online: 28.10.2015
DOI: 10.1055/s-0035-1560582; Art ID: st-2015-w0666-l
HO
OH
OMe
OH
O
O
OMe
Et
Abstract An interesting and simple method was developed for the
synthesis of 2-(alkylamino)-3-cyanobenzofurans by consecutive C–C,
C–O, and C–N coupling reaction of methyl (–)-3-dehydroshikimate with
malononitrile and a bromoalkane or dibromoalkane under microwave
conditions. This process represents a metal-free sustainable strategy
for the construction of 2-(alkylamino)-3-cyanobenzofurans from a bio-
mass-derived starting material.
obovaten
ailanthoidol
O
O
N
H
N
O
S
O
Me
O
Key words benzofurans, coupling, nitriles, bromoalkanes, cascade re-
NC
action, green-chemistry
dronedarone
N
O
The benzofuran scaffold is an important privileged
structure that occurs in various natural products and syn-
thetic molecules that show interesting biological and phar-
maceutical activities.1 For instance, the antiviral and anti-
fungal agent ailanthoidol,2 the antitumor natural product
obovaten,3 the cardiac arrhythmia drug dronedarone, and
the H3 receptor antagonist ABT-239 are all characterized by
a benzofuran motif (Figure 1).4,5 Studies have also shown
that benzofurans can serve as protein phosphatase 1B in-
hibitors,6 5-lipoxygenase inhibitors,7 antimicrobial agents,8
ABT-239
Figure 1 Examples of biologically active benzofuran derivatives
The rapid progress in biological research on benzofu-
rans has stimulated recent interest in the synthesis of vari-
ous functionalized benzofuran derivatives.12 Wang, Ku-
maraswamy, and Sakai and their respective co-workers
used the coupling reaction of activated phenols with α-bro-
mo ketones to provide an array of 2-carbonylated benzofu-
rans in high yields.13 Liu, Hu, and Ragauskas and their re-
antioxidants,9
agents.10,11
antidepressants,
and
antidementia
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spective co-workers have reported consecutive coupling
and cyclization reactions of O-arylhydroxylamines, aryl tri-
flates, or catechols to give 3-carbonylated benzofurans in
good yields and excellent regioselectivities.14 Others have
developed cross-coupling strategies that exploit the reac-
tions of alkynes with o-substituted phenolics in the pres-
ence of transition metals and ligands to give various 2,3-
disubstituted benzofurans in moderate to good yields.15
More recently, several groups have demonstrated a hyper-
valent iodine-mediated oxidative dearomatization and pal-
ladium-catalyzed domino reaction to provide access to
multifunctionalized benzofurans from 2-alkynylphenols,
terminal alkenes, and aromatic amines in the presence of
(diacetoxyiodo)benzene and palladium(II) bromide.16 Al-
though these methods represent workable approaches to
syntheses of particular types of benzofurans and show con-
siderable potential for medicinal chemistry research, there
remains a need to expand the chemical diversity and range
of synthetic strategies for the benzofuran motif. As far as
we are aware, there have been no previous reports on the
synthesis and biological properties of 2-(alkylamino)-3-cy-
anobenzofurans, a novel group of multifunctionalized ben-
zofurans. As a part of our continuing efforts on biomass
conversion and the utilization of methyl 3-dehydroshi-
kimate (3-MDHS) as an interesting platform compound de-
rived from shikimic acid,17 we report a novel and efficient
method for the synthesis of 2-(alkylamino)-3-cyanobenzo-
furans by sequential C–C, C–O, and C–N coupling reactions,
starting from 3-MDHS.
Initially, we chose the reaction of 3-MDHS (1), readily
obtained from renewably sourced shikimic acid as previ-
ously described,17 with malononitrile (2) and bromoethane
(3a) as a model reaction for the optimization of the reaction
conditions, the results are summarized in Table 1. Interest-
ingly, when 3-MDHS (1, 1 mmol) was treated with malono-
nitrile (2, 1.5 mmol) in water (10 mL) at 85 °C for ten min-
utes under catalyst-free microwave conditions, the novel
multifunctional intermediate methyl 2-amino-3-cyanoben-
zofuran-5-carboxylate (A) was precipitated and could be
isolated quantitatively by filtration of the reaction mixture
(step 1). The formation of intermediate A probably occurs
through highly consecutive and thermodynamically favor-
able processes that include Knoevenagel condensation, de-
hydrative aromatization, intramolecular addition, and
Table 1 Optimization of the Reaction Conditionsa
3a
COOMe
MeOOC
CN
MeOOC
H2O
Br
CN
NC
CN
solvent, base
T2, t2
T1 = 85 °C
t1 = 10 min
MW
NH2
O
OH
O
N
O
MW
H
OH
A
4a
1
2
step 1
step 2
Entry
Solvent
Base
K2CO3
T2 (°C)
t2b (min)
Yieldc (%)
1
2
DMF
90
78
6
15
10
10
15
5
62
trace
53
trace
–
EtOH
MeCN
K2CO3
3
K2CO3
80
4
1,4-dioxane
THF
K2CO3
100
66
5
K2CO3
6
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
K2CO3
110
110
110
110
110
90
77
64
75
81
60
54
82
78
74
65
7
Cs2CO3
Na2CO3
NaHCO3
Et3N
5
8
6
9
5
10
11
12
13
14
15
6
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
8
120
130
140
120d
5
5
5
300
a Reaction conditions (unless otherwise noted): Step1: 1 (1 mmol), 2 (1.5 mmol), H2O (10.0 mL), 85 °C, MW; Step 2: intermediate A (without further purifica-
tion); 3a (1 mmol), base (2 mmol), solvent (8 mL), 120 °C, MW, 5 min.
b The ramp time is included as part of the reaction time.
c Isolated yield.
d Oil bath.
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isomerization, leading to the construction of the new C–C
and C–O bonds in A. Note that water was the optimal sol-
vent for step 1; other solvents such as ethanol, acetonitrile,
or tetrahydrofuran gave A in much lower yields (see Sup-
porting Information). Subsequent N-alkylation of A with
bromoethane (3a) in the presence of potassium carbonate
in N,N-dimethylformamide under microwave conditions
gave benzofuran 4a in 62% yield. When other solvents were
screened, dimethyl sulfoxide gave the best result (77% yield;
Table 1, entries 1–6). We also explored the effect of the
Table 2 Scope of the Reactiona,b
COOMe
CN
MeOOC
MeOOC
CN
CN
H2O, 85 °C,10 min, MW
R1Br
R1
R1
or
then NaHCO3, 120 °C, 5 min
DMSO, MW
CN
N
N
O
OH
O
O
H
R1
OH
5
3
1
2
4
MeOOC
MeOOC
CN
MeOOC
CN
CN
N
N
N
O
O
O
O
O
O
O
O
O
H
H
H
4a (82%)
4b (70%)
4c (78%)
MeOOC
MeOOC
CN
MeOOC
CN
CN
N
H
N
N
O
H
H
4d (85%)
4e (83%)
4f (87%)
MeOOC
MeOOC
MeOOC
CN
CN
CN
N
N
N
H
O
H
H
4g (85%)
4i (89%)
4h (81%)
MeOOC
MeOOC
CN
MeOOC
CN
CN
OH
N
N
N
O
H
O
H
H
4j (60%)
4k (not obtained)
4l (not obtained)
MeOOC
MeOOC
MeOOC
CN
CN
CN
F
N
N
N
O
O
H
H
H
4m (80%)c
4n (61%)c
4o (70%)c
MeOOC
MeOOC
CN
MeOOC
CN
CN
F
N
N
O
O
N
NO2
O
F
O2N
5n (83%)d
5o (78%)d
5p (73%)d
MeOOC
CN
MeOOC
CN
N
O
N
O
5q (75%)d
5r (72%)d
a Reaction conditions: Step1: 1 (1 mmol), 2 (1.5mmol), H2O (10.0 mL), 85 °C, MW, 10 min; Step2: 3 (1 mmol), NaHCO3 (2 mmol), DMSO (8 mL), 120 °C, MW, 5
min.18
b All yields are isolated yields.
c Step 2: 3 (1 mmol), NaHCO3 (2 mmol), MeCN (8 mL), 80 °C (conventional heating), 18 h.
d Step 2: 3 (2.4 mmol), NaHCO3 (4 mmol), MeCN (8 mL), 80 °C (conventional heating), 18 h.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 287–293

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base. Whereas inorganic bases (such as potassium, cesium,
or sodium carbonate or sodium bicarbonate) and the organ-
ic base triethylamine were all suitable for this N-alkylation
process (entries 6–10), sodium bicarbonate proved to be
the optimal base, affording the desired product in 82% yield.
In addition, a study on the reaction temperature showed
that 120 °C was most favorable for step 2; lower or higher
temperatures gave lower yields (entries 11–14). In contrast
to microwave heating, when the reaction was performed
with conventional heating, a prolonged reaction time (300
min) was needed to give a 65% yield of 4a (entry 15).
Therefore, the optimal conditions for the synthesis of 2-
(alkylamino)-3-cyanobenzofurans are as follows: 3-
MDHS (1, 1 mmol) and malononitrile (2, 1.5 mmol) in wa-
ter (10 mL) at 85 °C for 10 minutes (step 1), then A, 3a (1
mmol), and sodium bicarbonate (2.0 mmol) in dimethyl
sulfoxide (8 mL) at 120 °C for 5 minutes (step 2). Both steps
are performed under microwave conditions (entry 12).
Having established the optimal reaction conditions, we
screened a variety of bromoalkanes 3 to explore the gener-
ality and limitations of this cascade process. As shown in
Table 2, the coupling reactions of intermediate A with vari-
ous linear or branched saturated bromoalkanes proceeded
under the optimized conditions to give the corresponding
2-(alkylamino)-3-cyanobenzofurans in satisfactory yield
(70–89%). The hydroxylated alkyl bromide 3j also gave the
expected product 4j in 60% yield (Table 2). We were disap-
pointed to note that the desired products (4k, 4l) were not
detected when bromocyclopentane 3k or bromocyclohex-
ane 3l was used as the reactant, indicating that the steric
hindrance in 3 has a significant effect on the course of step
2. Interestingly, the reaction worked well under the stan-
dard reaction conditions when reactive benzylated bro-
mides 3m–o were used, affording the corresponding prod-
ucts 4m–o in 61–80% yield. Note that when an excess (2.4
equiv) of a reactive bromoalkane, such as the benzylated
bromides 3n–p, allyl bromide (3q), or propargyl bromide
(3r), was used as the reactant, the corresponding N,N-(dial-
kylamino)-3-cyanobenzofuran 5n–r was obtained in good
to high yield.
To further investigate the applicability of our protocol,
we examined the coupling reactions of an array of dibro-
moalkanes 6a–h (Table 3). The reaction was found to ac-
commodate a variety of dibromoalkanes 6a–g, giving the
corresponding four- to seven-membered nitrogen-contain-
ing alicyclic-substituted benzofurans 7a–g in good to high
yields (68–90%), regardless of whether a linear or branched
dibromoalkane was used. Note that when 1,2-bis(bro-
momethyl)benzene (6g) was used, the reaction with inter-
mediate A led to the corresponding benzofuran 7g in excel-
lent yield, probably owing to the high reactivity of the ben-
zylic bromide groups in the substrate. Unfortunately, the
Table 3 Scope of Dibromoalkane Substratesa,b
COOMe
MeOOC
CN
R2
CN
CN
R2
H2O, 85 °C,10 min, MW
Br
n
Br
then K2CO3, 120 °C, 5 min
DMSO, MW
N
O
OH
O
OH
7
6
2
1
MeOOC
CN
MeOOC
CN
CN
MeOOC
N
O
N
N
O
O
O
7a (69%)
7c (81%)
7b (68%)
MeOOC
MeOOC
MeOOC
CN
CN
CN
N
N
N
O
O
7e (85%)
7f (87%)
7d (78%)
MeOOC
CN
MeOOC
CN
N
O
N
O
7h (not obtained)
7g (90%)c
a Reaction conditions: Step1: 1 (1 mmol), 2 (1.5 mmol), H2O (10.0 mL), 85 °C, MW, 10 min; Step 2: 6 (1.2 mmol), K2CO3 (2 mmol), DMSO (8 mL), 120 °C (MW).18
b All yields are isolated yields.
c Step 2: MeCN, 80 °C (conventional heating), 18 h.
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COOMe
COOMe
COOMe
CN
CN
CN
CN
–H2O
Knoevenagel
condensation
–H2O
HO
O
OH
intramolecular
addition
dehydration
aromatization
OH
OH CN
OH
N
B
1
C
MeOOC
MeOOC
CN
MeOOC
CN
CN
R1Br
isomerization
R1
NH
O
– HBr
N
NH2
O
O
H
D
A
4
R2
Br
n
2 R1Br
Br
– 2 HBr
– 2 HBr
MeOOC
MeOOC
CN
CN
R2
R1
N
R1
N
O
O
5
Scheme 1 Proposed reaction pathway for the formation of 2-(alkylamino)-3-cyanobenzofurans
use of 1,2-dibromoethane (6h) did not give the expected
benzofuran 7h, possibly due to the immense strain that has
to be overcome for the formation of the aziridine motif.
On the basis of our previous studies and the results dis-
cussed above, we propose a plausible reaction pathway for
the formation of the benzofurans (Scheme 1).17 The reac-
tion starts with the Knoevenagel condensation of 3-MDHS
(1) with malononitrile to generate the olefin B with loss of
water. Olefin B is then readily transformed by dehydrative
aromatization into intermediate C, which undergoes subse-
quent intramolecular cycloaddition to give imine D. The
driving force of forming a conjugated product then results
in isomerization of D to give intermediate A. Finally, nucleo-
philic substitution of A with various bromoalkanes or di-
bromoalkanes gives the corresponding 2-(alkylamino)-3-
cyanobenzofurans 4, 5, or 7.
Acknowledgment
We are grateful to the National Natural Science Foundation of China
(21272280), the Science and Technology Program of Guangdong Prov-
ince, Hunan Province and Guangzhou City (2011A081401002,
2015SK2075, 201505041557046), the Guangdong Natural Science
Foundation (S2013010014278), for their generous financial support
of this project. We are thankful to Prof. Albert S. C. Chan at Sun Yat-
sen University for guidance and help and also thankful to Guangxi
Wanshan Spice Co. Ltd. for giving high quality (–)-shikimic acid as a
gift.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560582.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
In summary, we have developed a novel and straightfor-
ward protocol for the assembly of multifunctional benzofu-
rans through a cascade reaction of 3-MDHS, malononitrile,
and a bromoalkane involving C–C, C–O, and C–N bond-
forming processes. Notable features of this strategy, such as
the use of a biomass-derived starting material, metal-free
reaction conditions, controllable selectivity, and operation-
al simplicity make the protocol synthetically useful. It is
worth mentioning that the presence in the benzofuran
products of readily transformable methoxycarbonyl, cyano,
and alkylamino functional groups should facilitate further
transformations and might be useful in medicinal chemis-
try research.
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1H NMR (400 MHz, DMSO-d6): δ = 8.93 (t, J = 5.60 Hz, 1 H), 7.74
(d, J = 1.60 Hz, 1 H), 7.71 (dd, J1 = 8.40 Hz, J2 = 1.60 Hz, 1 H), 7.49
(d, J = 8.40 Hz, 1 H), 3.86 (s, 3 H), 3.47 (m, 2 H), 1.25 (t, J = 4.00
Hz, 3 H). 13C NMR (100 MHz, DMSO-d6): δ = 165.9, 164.6, 150.4,
128.9, 125.8, 123.2, 116.5, 115.1, 110.0, 59.3, 52.1, 37.1, 14.8.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13N2O3: 245.0921;
found: 245.0923.
Methyl 3-Cyano-2-(propylamino)-1-benzofuran-5-carboxyl-
ate (4c)
White solid; yield: 70%; mp 168–169 °C. IR (KBr): 3435, 3288,
3047, 2980, 2200, 1703, 1628, 1531, 1450, 1288, 1250, 1176,
1165, 1101, 976, 766, 731, 644, 600 cm–1 1H NMR (400 MHz,
.
DMSO-d6): δ = 8.89 (d, J = 8.40 Hz, 1 H), 7.75 (s, 1 H), 7.71 (dd,
J1 = 8.40 Hz, J2 = 1.20 Hz, 1 H), 7.50 (d, J = 8.40 Hz, 1 H), 4.05 (m,
1 H), 3.86 (s, 3 H), 1.27 (d, J = 8.00 Hz, 6 H). 13C NMR (100 MHz,
DMSO-d6): δ = 166.0, 163.9, 150.5, 129.0, 125.9, 123.3, 116.5,
115.2, 110.0, 59.3, 52.2, 45.0, 22.6. HRMS (ESI-TOF): m/z [M +
H]+ calcd for C14H15N2O3: 259.1077; found: 259.1074.
Methyl 2-(sec-Butylamino)-3-cyano-1-benzofuran-5-carbox-
ylate (4e)
White needles; yield: 83%; mp 142–143 °C. IR (KBr): 3427,
3278, 3224, 3095, 2964, 2214, 1714, 1649, 1460, 1298, 1246,
1184, 1082, 991, 899, 822, 764, 656 cm–1 1H NMR (400 MHz,
.
DMSO-d6): δ = 8.86 (d, J = 8.80 Hz, 1 H), 7.74 (d, J = 1.60 Hz, 1 H),
7.71 (dd, J1 = 8.80 Hz, J2 = 2.00 Hz, 1 H), 7.49 (d, J = 8.40 Hz, 1 H),
3.86 (s, 3 H), 3.82 (m, 1 H), 1.61 (m, 2 H), 1.25 (d, J = 6.40 Hz, 3
H), 0.92 (t, J = 7.60 Hz, 3 H). 13C NMR (100 MHz, DMSO-d6): δ =
166.0, 164.2, 150.4, 129.1, 125.9, 123.3, 116.5, 115.3, 110.0,
59.1, 52.2, 50.6, 29.0, 20.4, 10.3. HRMS (ESI-TOF): m/z [M + H]+
calcd for C15H17N2O3: 273.1234; found: 273.1236.
Methyl 3-Cyano-2-[(3-methylbutyl)amino]-1-benzofuran-5-
carboxylate (4h)
White needles; yield: 81%; mp 136–137 °C. IR (KBr): 3429,
3224, 3086, 2951, 2879, 2214, 1718, 1662, 1460, 1369, 1294,
1248, 1190, 1119, 1101, 991, 957, 895, 822, 764, 669, 623 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 8.94 (t, J = 6.00 Hz, 1 H), 7.74
(d, J = 1.20 Hz, 1 H), 7.70 (dd, J1 = 8.40 Hz, J2 = 1.60 Hz, 1 H), 7.49
(d, J = 8.40 Hz, 1 H), 3.86 (s, 3 H), 3.44 (m, 2 H), 1.69 (m, 1 H),
1.52 (m, 2 H), 0.92 (d, J = 6.40 Hz, 6 H). 13C NMR (100 MHz,
DMSO-d6): δ = 166.0, 164.7, 150.5, 129.0, 125.9, 123.3, 116.5,
115.2, 110.0, 59.3, 52.2, 40.7, 37.9, 25.1, 22.3. HRMS (ESI-TOF):
m/z [M + H]+ calcd for C16H19N2O3: 287.1396; found: 287.1397.
Methyl 3-Cyano-2-[(3-hydroxypropyl)amino]-1-benzofuran-
5-carboxylate (4j)
(18) Methyl 2-(Alkylamino)-3-cyanobenzofuran-5-carboxylates
4a–j and 7a–g; General Procedure
A 25 mL round-bottomed flask was charged with 3-MDHS (1;
0.19 g, 1 mmol), malononitrile (2; 1.5 mmol), and H2O (10 mL).
The flask was placed in a microwave synthesizer, and the
mixture was irradiated (240 W) at 85 °C for 10 min. The mixture
was then filtered under reduced pressure to give the crude
intermediate A, which was used in step 2 without further puri-
fication.
Brown solid; yield: 60%; mp 150–151 °C. IR (KBr): 3469, 3286,
3242, 3084, 2947, 2881, 2202, 1713, 1651, 1456, 1363, 1302,
1244, 1190, 1144, 1099, 1063, 978, 885, 829, 760, 698, 658, 590
cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 8.89 (t, J = 5.60 Hz, 1 H),
7.74 (d, J = 1.20 Hz, 1 H), 7.70 (dd, J1 = 8.40 Hz, J2 = 2.00 Hz, 1 H),
7.49 (d, J = 8.40 Hz, 1 H), 4.59 (s, 1 H), 3.86 (s, 3 H), 3.50 (m, 4 H),
1.78 (m, 2 H). 13C NMR (100 MHz, DMSO-d6): δ = 166.0, 164.8,
Intermediate A, inorganic base [NaHCO3 (2 mmol) for 4a–j;
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Synlett
150.5, 129.0, 125.9, 123.2, 116.5, 115.2, 110.0, 59.4, 57.8, 52.2,
32.2. HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H15N2O4
: 275.1032; found: 275.1031.
Methyl 3-Cyano-2-pyrrolidin-1-yl-1-benzofuran-5-carboxyl-
ate (7c)
(ESI-TOF): m/z [M + H]+ calcd for C15H15N2O3: 271.1083; found:
271.1085.
Methyl 3-Cyano-2-piperidin-1-yl-1-benzofuran-5-carboxyl-
ate (7e)
White crystals; yield: 87%; mp 147–148 °C. IR (KBr): 3448,
3425, 3107, 2939, 2856, 2197, 1724, 1610, 1585, 1450, 1383,
1363, 1302, 1234, 1186, 1142, 1097, 962, 851, 800, 760, 665,
609 cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 7.76 (d, J = 1.20 Hz,
1 H), 7.73 (dd, J1 = 8.40 Hz, J2 = 1.60 Hz, 1 H), 7.50 (d, J = 8.40 Hz,
1 H), 3.87 (s, 3 H), 3.73 (s, 4 H), 1.67 (s, 6 H). 13C NMR (100 MHz,
DMSO-d6): δ = 165.9, 162.8, 150.2, 129.2, 126.0, 123.7, 116.7,
115.6, 110.2, 61.0, 52.2, 47.0, 24.8, 23.1. HRMS (ESI-TOF): m/z
[M + H]+ calcd for C16H17N2O3: 285.1239; found: 285.1238.
White needles; yield: 81%; mp 185–186 °C. IR (KBr): 3431,
3064, 2960, 2879, 2191, 1724, 1637, 1450, 1352, 1300, 1246,
1178, 1097, 960, 881, 858, 818, 764, 733, 662, 517 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 7.71 (d, J = 1.20 Hz, 1 H), 7.69
(dd, J1 = 8.40 Hz, J2 = 2.00 Hz, 1 H), 7.48 (d, J = 8.40 Hz, 1 H), 3.87
(s, 3 H), 3.68 (t, J = 6.00 Hz, 4 H), 2.00 (t, J = 6.40 Hz, 4 H).
13C NMR (100 MHz, DMSO-d6): δ = 166.0, 161.8, 150.7, 129.3,
126.0, 123.3, 116.6, 115.8, 110.1, 60.2, 52.2, 48.1, 24.9. HRMS
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 287–293