Catalytic C-H activation of arylacetylenes: A fast assembly of 3-(arylethynyl)-3-hydroxyindolin-2-ones using CuI/DBU

Article abstract of DOI:10.1055/s-0033-1338563

A highly efficient and atom-economic methodology has been developed for the synthesis of 3-(arylethynyl)-3-hydroxyindolin-2-ones from isatins by C-H activation of arylacetylenes using a catalytic quantity of copper(I) iodide (5 mol%) and DBU (20 mol%) at 25°C, affording the products in excellent yields in very short reaction time (5 min).

Full text of DOI:10.1055/s-0033-1338563

PAPER
▌195
paper
Catalytic C–H Activation of Arylacetylenes: A Fast Assembly of
3-(Arylethynyl)-3-hydroxyindolin-2-ones Using CuI/DBU
Assembly of 3-(Arylethynyl)-3-hydroxyindolin-2-ones Using CuI/DBU
Mangilal Chouhan, Kishna Ram Senwar, Kapil Kumar, Ratnesh Sharma, Vipin A. Nair*
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, Mohali, Punjab 160062, India
E-mail: vn74nr@yahoo.com
Received: 27.08.2013; Accepted after revision: 29.10.2013
isatins catalyzed by activation of alkyne C–H bond in wa-
Abstract: A highly efficient and atom-economic methodology has
ter, mediated by N-heterocyclic carbene–silver complex-
been developed for the synthesis of 3-(arylethynyl)-3-hydroxyindo-
es was efficient for the synthesis of 3-ethynyl-3-
lin-2-ones from isatins by C–H activation of arylacetylenes using a
catalytic quantity of copper(I) iodide (5 mol%) and DBU (20 mol%)
hydroxyindolin-2-ones;14c a rate enhancement by water
at 25 °C, affording the products in excellent yields in very short re- was observed in the heterogeneous system. Despite the
action time (5 min).
wide applicability, the available methods have limitations
such as: pre-synthesis of metal acetylides; the use of sub-
stoichiometric (and not catalytic) amount of strongly ba-
sic reagents; air and moisture sensitivity; costly reagents,
catalysts, and ligands; long reaction times; and moderate
yields. These limitations provide sufficient scope for the
development of newer catalysts.
Key words: catalysis, C–H activation, copper(I) iodide, arylalkyne
addition, 3-hydroxyindolin-2-ones
The C–H bond activation of relatively inert organic com-
pounds has been an area of the intense research and mech-
anistic studies.1 It continues to attract the attention of
synthetic chemists due to the challenges encountered in
C–C bond formation in the synthesis of complex organic
molecules.2 An interesting example that has wide signifi-
cance is the synthesis of propargylic alcohols3 from metal
acetylides via activation of the C–H bond of the terminal
alkyne and subsequent addition to carbonyl substrates.
These compounds are versatile building blocks for com-
plex natural products.4 The available reports for direct al-
kynylation of aldehydes or ketones include use of metal
acetylides like alkynylmagnesium,5 alkynyllithium,5 bo-
ryl acetylide,6 and zinc alkynilide.7 Gold(I) was an effec-
tive catalyst in water for the three-component coupling
reactions of α-oxyaldehydes, alkynes, and amines to af-
ford propargylamines in good yields and moderate diaste-
reoselectivities.8 Cesium hydroxide monohydrate
catalytically activates the C–H bond of alkynes to afford
propargylic alcohols from aliphatic aldehydes or ketones.9
Microwave-assisted copper(I)-catalyzed coupling of a ke-
tone, an alkyne, and a primary amine, leading to second-
ary alkylpropargylamines is also reported.10 Chiral
variants of the reaction have been successfully attempted
by reacting terminal alkynes with aldehydes in procedures
involving catalytic quantities of zinc(II) metal and the chi-
ral ligand N-methylephedrine with triethylamine.11 The
solvent-free alkynilide addition reaction furnishes chiral
propargyl alcohols with good enantioselectivities.12 Cam-
phorsulfonamide–titanium complex was found to be an-
other catalyst of choice for the enantioselective addition
of phenylacetylene to aldehydes.13 Addition reactions of
phenylacetylene to isatin and its N-substituted derivatives
are also well documented.14 The direct alkynylation of
Natural products containing the 3-substituted 3-hydroxy-
indolin-2-one scaffold, such as convolutamydines, dia-
zonamide A, leptosin D, 3′-hydroxyglucoisatisin,
witindolinone C, and dioxibrassinine have gained consid-
erable attention because of their diverse biological activi-
ty.15 In particular, 3-alkynyl-3-hydroxyindolin-2-ones
showed excellent biological activity on Echinococcus
multilocularis metacestodes.5a 3-(Cyclopropylethynyl)-3-
hydroxy-5-methylindolin-2-one A was reported to exhibit
activity greater than efavirenz against HIV-1 replication
without significant cytotoxicity16 (Figure 1). Develop-
ment of cost-effective and atom-economic approaches for
the synthesis of these templates is highly desirable, which
defines our keen interest.17 Herein we report a highly effi-
cient synthesis of 3-(arylethynyl)-3-hydroxyindolin-2-
ones from isatins. Though the use of zinc complexes has
demonstrated promising results in the synthesis of these
scaffolds, the use of stoichiometric amounts of the re-
agents, long reaction times, and moderate yields are of
concern.14b Our efforts resulted in a simple one-pot proto-
col employing catalytic amount of copper(I) iodide in
combination with 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) for in situ generation of copper alkynilide, and its
subsequent reaction with isatin to afford 3-(arylethynyl)-
3-hydroxyindolin-2-ones. The reagent system is highly
convenient, both in terms of cost as well as in ease of han-
HO
CF3
O
R
Cl
O
N
N
O
H
Me
A
Efavirenz
SYNTHESIS 2014, 46, 0195–0202
R = Me, Br
Advanced online publication: 28.11.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338563; Art ID: SS-2013-N0587-OP
© Georg Thieme Verlag Stuttgart · New York
Figure 1 Efavirenz and a 3-alkynyl-3-hydroxy bioactive mimetic

196
M. Chouhan et al.
PAPER
dling. The products were obtained in high yields within a these observations we inferred that reacting 1.0 equivalent
reaction time of five minutes.
of the N-benzylisatin 1a with 1.05 equivalents of phenyl-
acetylene (2a), 0.05 equivalents of copper(I) iodide, 0.2
equivalents of 1,8-diazabicyclo[5.4.0]undec-7-ene in tol-
uene at 25 °C under a nitrogen atmosphere would be the
ideal conditions for the reaction. The reactions of isatins
with a free NH group did not afford the desired products
under the experimental conditions.
To carry out a detailed investigation, a model reaction of
phenylacetylene (2a) and 1-benzylisatin (1a) (Scheme 1)
was performed in presence of different copper salts and
bases using toluene as the solvent at room temperature
(25 °C) under a nitrogen atmosphere (Table 1). Proton ab-
straction by the base from the alkyne terminus results in
the formation of copper acetylide, which reacts with the
isatin to afford 3-hydroxy-3-(phenylethynyl)indolin-2-
one 3aa. From the different copper salts examined, it was
inferred that copper(I) iodide provided maximum yields
of 3aa in a short span of five minutes, at an optimum cat-
alyst concentration of 5 mol% (entry 5) compared with
copper(I) chloride and copper(I) bromide, which showed
inferior results (entries 7 and 8). Examination of the effect
of different bases on the outcome of the reaction indicated
that 50 mol% of triethylamine and N,N-diisopropylethyl-
amine afforded yields of 37% and 40%, respectively, after
one hour (entries 2 and 3) while 50 mol% of DBU provid-
ed a maximum yield of 98% within five minutes (entry 5).
In a separate study we observed that 20 mol% of DBU is
sufficient to catalyze the reaction (entry 6).
Table 1 Effect of Various Copper Catalysts on the Alkynylation of
Isatinsa
Entry
Catalyst
(mol%)
Base
(mol%)
Time
(min)
Yieldb
(%)
1
2
–
Et3N (50)
Et3N (50)
DIPEA (50)
DBU (50)
DBU (50)
DBU (20)
DBU (50)
DBU (50)
DBU (50)
DBU (50)
60
60
60
5
trace
37
CuI (10)
CuI (10)
CuI (10)
CuI (5)
3
40
4
98
5
5
97
6
CuI (5)
5
97
7
CuCl (10)
CuBr (10)
CuO (10)
Cu(OAc)2 (10)
60
60
120
120
30
8
65
c
9
–
catalyst
O
HO
c
10
–
base
+
O
a 1-Benzylisatin (1a, 1.0 equiv), phenylacetylene (2a, 1.05 equiv), tol-
uene (2 mL), N2 atmosphere, 25 °C.
b Isolated yield.
O
solvent, 25 °C
N
N
Bn
Bn
c Not determined.
1a
2a
3aa
Scheme 1 One-pot alkynylation of isatin by C–H activation
Table 2 Effect of Solvents on the Alkynylation of Isatinsa
Entry
Solvent
Time (min)
Yieldb (%)
Further, the effect of the solvents as a reaction parameter
was also evaluated (Table 2). In the case of polar protic
solvents like ethanol and water (entries 4 and 5), the start-
ing material remained as such even after two hours, while
an improvement was observed with polar aprotic solvents
(entries 1–3). Nonpolar solvents like toluene exhibited an
enhancement in the reaction rate (entry 6), providing ex-
cellent yields of the desired product in a very short period
of time. The reason for the high output in toluene could be
attributed to the hydrophobic environment provided by
the solvent which assists in the generation of the copper
acetylide and drives its subsequent reaction with the elec-
trophilic carbonyl carbon. The longer reaction time and
low yield in polar aprotic solvent such as tetrahydrofuran,
N,N-dimethylformamide, and acetonitrile might be due to
coordination ability of these solvent molecules with the in
situ generated nucleophile and stabilization of the polar
transition state. A competing protonation of the generated
nucleophile in polar protic solvents can be reasoned for
the failure of the reaction in water and ethanol. In the ab-
sence of a nitrogen atmosphere the reaction was sluggish
(8 h) and afforded only a moderate yield (55%). From
1
2
3
4
5
6
THF
120
120
120
120
120
5
30
45
25
DMF
MeCN
EtOH
H2O
c
–
c
–
toluene
98
a 1-Benzylisatin (1a, 1.0 equiv), phenylacetylene (2a, 1.05 equiv),
CuI (5 mol%), DBU (20 mol%), N2 atmosphere, 25 °C.
b Isolated yield.
c Not determined.
Under the standardized conditions, the reaction was gen-
eralized on substituted arylacetylenes 2a–f and N-alkyli-
satins 1a–h to afford 3-(arylethynyl)-3-hydroxyindolin-2-
one derivatives 3aa–ef in excellent yields (Table 3). The
operationally simple one-pot procedure, utilizes reactants
without prior preparation and works well irrespective of
Synthesis 2014, 46, 195–202
© Georg Thieme Verlag Stuttgart · New York

PAPER
Assembly of 3-(Arylethynyl)-3-hydroxyindolin-2-ones Using CuI/DBU
197
the substituents on the arylacetylene. The scope of the re- reaction condition to simple aldehydes and unactivated
action was also examined by carrying out the model reac- ketones, as electrophiles, failed. Similarly, the reactions
tion on a 10-gram scale, which afforded the product in of N-alkylisatins with alkylacetylenes were also unsuc-
good yield (85%), though the reaction took a longer time cessful.
to go to completion (1 h). However, attempts to extend the
Table 3 Synthesis of 3-(Arylethynyl)-3-hydroxyindolin-2-onesa
X
R3
CuI (5 mol%)
O
HO
R1
R1
DBU (20 mol%)
O
+
O
X
N
R2
N
R2
toluene, 25 °C
5 min
R3
1a–h
2a–e, X = CH
2f, X = N
3aa–ef
Entry
R1
R2
R3
Product
Yielda (%)
1
2
H
F
Bn
Bn
Bn
Bn
Me
Me
Me
Me
Bn
Bn
Bn
Bn
Me
Me
Me
Me
Bn
Bn
Bn
Bn
Me
Me
Me
Me
Bn
Me
Bn
Me
Bn
Me
H
H
H
H
H
H
H
H
3aa
3ba
3ca
3da
3ea
3fa
97
94
96
97
98
95
97
95
96
97
95
96
97
94
96
97
96
95
97
96
98
95
96
95
95
93
96
93
95
96
3
Cl
Br
H
F
4
5
6
7
Cl
Br
H
F
3ga
3ha
3ab
3bb
3cb
3db
3eb
3fb
3gb
3hb
3ac
3bc
3cc
3dc
3ec
3fc
8
9
4-Br
4-Br
4-Br
4-Br
4-Br
4-Br
4-Br
4-Br
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
2-OMe
2-OMe
2-CF3
2-CF3
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Cl
Br
H
F
Cl
Br
H
F
Cl
Br
H
F
Cl
Br
H
H
H
H
H
H
3gc
3hc
3ad
3ed
3ae
3ee
3af
H
3ef
a Isatin 1 (1.0 equiv), arylacetylene 2 (1.05 equiv).
b Isolated yield.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 195–202

198
M. Chouhan et al.
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1H and 13C NMR spectra were recorded at 400 and 100 MHz, re-
spectively on a Bruker Avance DPX 400 (400 MHz) spectrometer
in CDCl3 using TMS as the internal standard and the residual signal
of the solvents. HRMS spectra were recorded on Bruker Maxix
TOF spectrometer. The reactions were monitored using TLC silica
gel 60 F254 (Merck). Evaporation of solvents was performed under
reduced pressure. Melting points were recorded and uncorrected.
All the starting isatins (isatin, 5-fluoroisatin, 5-chloroisatin, 5-bro-
moisatin), copper salts [CuCl, CuBr, CuI, Cu(OAc)2, CuO] and sol-
vents (MeCN, DMF, THF, EtOH, toluene) were purchased from
commercial sources and used as such without further purification.
Based on these observations, a plausible reaction mecha-
nism for the product formation can be envisaged (Scheme
2). It can fairly be assumed that initially copper(I) iodide
coordinates with the arylacetylene weakening the termi-
nal C–H bond. This facilitates the abstraction of the termi-
nal proton by DBU and generates the copper acetylide
nucleophile, which attacks the electrophilic carbonyl car-
bon to afford the addition product. Electrophilic activation
by coordination between the metal center of the in situ
generated copper acetylide and the carbonyl group of isa-
tin can also be expected to account for the fast reaction ki-
netics.
1-Benzyl-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-2H-indol-
2-one (3aa); Typical Procedure
To a stirred mixture of 1-benzyl-1H-indole-2,3-dione (1a, 0.25 g,
1.05 mmol), CuI (0.01 g, 0.05 mmol, 0.05 equiv), and phenylacety-
lene (2a, 0.11 g, 1.11 mmol, 1.05 equiv) in anhyd toluene (2 mL),
DBU (0.032 g, 0.21 mmol, 0.2 equiv) was added at 25 °C under a
N2 atmosphere. Stirring was continued at this temperature until the
starting material was completely consumed (TLC monitoring). Af-
ter completion, the mixture was quenched with sat. aq NH4Cl (2
mL) and extracted with EtOAc (2 × 5 mL). The combined organic
layers were dried (anhyd Na2SO4) and evaporated under reduced
pressure to dryness. The crude product thus obtained was purified
by column chromatography (activated silica gel, 60–120 mesh, hex-
ane–EtOAc) to afford pure 3aa as a white solid; yield: 0.35 g (97%);
mp 177–179 °C.
O
R1
O
HO
N
R2
R1
CuI, DBU
O
N
toluene
R2
DBU + CuI
DBU·HI
IR (KBr): 3292, 2839, 2223, 1707, 1616, 1494, 1466, 1456, 1375,
1271, 1123, 1071, 1018, 976, 760, 749, 625, 600, 494 cm–1.
CuI
DBU
1H NMR (400 MHz, CDCl3): δ = 3.88 (br s, 1 H), 4.93 (s, 2 H), 6.72
(d, J = 7.8 Hz, 1 H), 7.12 (dt, J = 0.7, 7.6 Hz, 1 H), 7.22–7.35 (m, 9
H), 7.44–7.46 (m, 2 H), 7.62 (dd, J = 0.8, 7.4 Hz, 1 H).
CuO
R1
H
O
13C NMR (100 MHz, CDCl3): δ = 44.1, 69.6, 85.5, 86.6, 110.0,
121.6, 123.8, 124.8, 127.2, 127.8, 128.2, 128.9, 129.0, 129.1, 130.4,
132.1, 135.0, 142.1, 174.2.
N
R2
DBU·HI
Cu
HRMS (ESI): m/z [M + Na]+ calcd for C23H17NO2Na: 362.1157;
found: 362.1157.
1-Benzyl-5-fluoro-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-
2H-indol-2-one (3ba)
White solid; yield: 0.33 g (94%); mp 156–158 °C.
O
R1
IR (KBr): 3377, 3055, 2936, 2233, 1883, 1701, 1610, 1491, 1349,
1262, 1106, 1049, 825, 816, 684, 600, 477 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.16 (br s, 1 H), 4.92 (s, 2 H),
6.61–6.65 (m, 1 H), 6.92–6.97 (m, 1 H), 7.26–7.38 (m, 9 H), 7.44–
7.46 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 44.3, 69.7, 84.9, 87.0, 110.6,
110.7, 112.8, 113.1, 116.6, 116.8, 121.4, 127.1, 127.9, 128.3, 129.0,
130.4, 132.1, 134.7, 138.0, 158.5, 160.9, 174.0.
O
O
N
R2
R1
O
N
R2
Scheme 2 Plausible mechanism
HRMS (ESI): m/z [M + Na]+ calcd for C23H16FNO2Na: 380.1063;
found: 380.1061.
In conclusion, a one-pot, atom-economic methodology
was developed for the syntheses of 3-(arylethynyl)-3-hy-
droxyindolin-2-ones by C–H activation of arylacetylenes
using copper(I) iodide (5 mol%) and DBU (20 mol%) in
toluene at 25 °C. The reaction afforded excellent yields of
the products in very short reaction time (5 min). The pro-
cedure has advantages over the previously reported meth-
ods such as use of catalytic amount of the readily available
and inexpensive reagents that could be handled easily, in
situ generation of the copper arylacetylide, employing
costly alkynes only in stoichiometric quantities and not in
1-Benzyl-5-chloro-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-
2H-indol-2-one (3ca)
White solid; yield: 0.33 g (96%); mp 176–178 °C.
IR (KBr): 3308, 2219, 1715, 1612, 1488, 1435, 1350, 1171, 1122,
1077, 1030, 986, 881, 811, 760, 740, 722, 691, 606 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.12 (br s, 1 H), 4.91 (s, 2 H), 6.62
(d, J = 8.4 Hz, 1 H), 7.20 (dd, J = 2.2, 8.4 Hz, 1 H), 7.25–7.36 (m,
8 H), 7.44–7.47 (m, 2 H), 7.59 (d, J = 2.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 44.2, 69.5, 84.8, 87.1, 111.0,
121.3, 125.4, 127.1, 128.0, 128.2, 128.3, 129.0, 129.2, 130.3, 130.4,
excess, and high reactivity with arylacetylenes bearing 132.1, 134.6, 140.6, 173.8.
HRMS (ESI): m/z [M + Na]+ calcd for C23H16ClNO2Na: 396.0767;
both electron-withdrawing and electron-donating groups.
found: 396.0767.
Synthesis 2014, 46, 195–202
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Assembly of 3-(Arylethynyl)-3-hydroxyindolin-2-ones Using CuI/DBU
199
1-Benzyl-5-bromo-3-hydroxy-3-(phenylethynyl)-1,3-dihydro-
2H-indol-2-one (3da)
13C NMR (100 MHz, CDCl3): δ = 26.7, 69.3, 84.8, 86.9, 110.3,
116.3, 121.3, 128.0, 128.2, 129.2, 130.7, 132.1, 133.3, 142.1, 173.5.
HRMS (ESI): m/z [M + Na]+ calcd for C17H12BrNO2Na: 363.9949;
found: 363.9952.
White solid; yield: 0.32 g (97%); mp 188–190 °C.
IR (KBr): 3303, 3081, 3066, 2927, 2228, 1925, 1705, 1619, 1494,
1348, 1262, 1143, 1064, 995, 882, 781, 636, 533 cm–1.
1-Benzyl-3-[(4-bromophenyl)ethynyl]-3-hydroxy-1,3-dihydro-
2H-indol-2-one (3ab)
1H NMR (400 MHz, CDCl3): δ = 3.94 (br s, 1 H), 4.90 (s, 2 H), 6.58
(dd, J = 3.2, 8.3 Hz, 1 H), 7.28–7.37 (m, 9 H), 7.46 (d, J = 7.6 Hz,
2 H), 7.73 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 44.2, 69.4, 84.7, 87.2, 111.4,
116.4, 121.3, 127.1, 128.0, 128.1, 128.3, 129.0, 129.2, 130.7, 132.1,
133.2, 134.5, 141.1, 173.6.
White solid; yield: 0.42 g (96%); mp 180–182 °C.
IR (KBr): 3421, 2923, 1615, 1376, 1178, 696 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.64 (br s, 1 H), 4.95 (s, 2 H), 6.75
(d, J = 8.0 Hz, 1 H), 7.14 (t, J = 7.4 Hz, 1 H), 7.26–7.34 (m, 8 H),
7.45 (d, J = 8.2 Hz, 2 H), 7.62 (d, J = 7.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 44.1, 69.6, 85.5, 86.6, 110.0,
120.5, 123.5, 123.8, 124.8, 127.2, 127.9, 128.6, 128.9, 130.5, 131.6,
133.5, 134.9, 142.2, 173.9.
HRMS (ESI): m/z [M + Na]+ calcd for C23H16BrNO2Na: 440.0262;
found: 440.0258.
3-Hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-2H-indol-
2-one (3ea)
White solid; yield: 0.40 g (98%); mp 164–166 °C.
HRMS (ESI ): m/z [M + Na]+ calcd for C23H16BrNO2Na: 440.0262;
found: 440.0256.
IR (KBr): 3285, 2917, 2218, 1706, 1614, 1464, 1376, 1178, 1068,
982, 759, 694, 641 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.84 (br s, 1 H), 6.86
(d, J = 7.8 Hz, 1 H), 7.16 (t, J = 7.5 Hz, 1 H), 7.24–7.33 (m, 3 H),
7.36–7.44 (m, 3 H), 7.62 (d, J = 7.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 26.6, 69.5, 85.4, 86.4, 108.9,
121.6, 123.8, 124.7, 128.2, 128.8, 129.0, 130.5, 132.1, 143.1, 173.9.
1-Benzyl-3-[(4-bromophenyl)ethynyl]-5-fluoro-3-hydroxy-1,3-
dihydro-2H-indol-2-one (3bb)
Pale brown solid; yield: 0.42 g (97%); mp 178–180 °C.
IR (KBr): 3304, 3066, 2228, 1705, 1620, 1494, 1347, 1262, 1176,
1143, 1011, 882, 810, 726, 696, 636, 532 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.94 (br s, 1 H), 4.91 (s, 2 H), 6.64
(dd, J = 4.0, 4.6 Hz, 1 H), 6.95 (dt, J = 2.6, 8.9 Hz, 1 H), 7.27–7.38
(m, 8 H), 7.42–7.45 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 44.3, 69.6, 85.9, 86.0, 110.7,
110.8, 112.9, 113.1, 116.8, 117.0, 120.3, 123.7, 127.1, 128.0, 129.0,
131.6, 133.5, 134.6, 138.0, 158.5, 160.9, 173.8.
HRMS (ESI): m/z [M + Na]+ calcd for C17H13NO2Na: 286.0844;
found: 286.0863.
5-Fluoro-3-hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-
2H-indol-2-one (3fa)
White solid; yield: 0.37 g (95%); mp 175–177 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C23H15BrFNO2Na: 458.0168;
found: 458.0171.
IR (KBr): 3315, 2230, 1715, 1613, 1488, 1435, 1350, 1171, 1122,
1077, 986, 881, 811, 760, 740, 691, 606 cm–1.
1-Benzyl-3-[(4-bromophenyl)ethynyl]-5-chloro-3-hydroxy-1,3-
dihydro-2H-indol-2-one (3cb)
1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.81 (br s, 1 H), 6.79
(dd, J = 4.0, 8.5 Hz, 1 H), 7.09 (dt, J = 2.6, 9.0 Hz, 1 H), 7.28–7.37
(m, 4 H), 7.44 (dd, J = 0.2, 7.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 26.8, 69.5, 84.8, 86.8, 109.5,
109.6, 112.8, 113.1, 116.7, 116.9, 121.3, 128.3, 129.2, 130.1, 130.2,
132.1, 139.0, 158.5, 161.0, 173.6.
White solid; yield: 0.40 g (95%); mp 181–182 °C.
IR (KBr): 3418, 2225, 1730, 1703, 1609, 1487, 1329, 1168, 1126,
983, 823, 692, 622 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.65 (br s, 1 H), 4.91 (d, J = 2.1
Hz, 2 H), 6.64 (d, J = 8.4 Hz, 1 H), 7.22 (dd, J = 2.2, 8.4 Hz, 1 H),
7.29–7.35 (m, 7 H), 7.44–7.47 (m, 2 H), 7.58 (d, J = 2.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 44.3, 69.4, 86.0, 90.7, 111.0,
120.2, 123.8, 125.4, 127.1, 128.0, 129.0, 129.3, 130.0, 130.4, 131.6,
133.5, 134.5, 140.6, 173.5.
HRMS (ESI): m/z [M + Na]+ calcd for C17H12FNO2Na: 304.0750;
found: 304.0774.
5-Chloro-3-hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-
2H-indol-2-one (3ga)
White solid; yield: 0.37 g (97%); mp 190–192 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C23H15BrClNO2Na:
473.9872; found: 473.9898.
IR (KBr): 3292, 2225, 1706, 1498, 1362, 1263, 1096, 995, 879, 813,
784, 760, 690 cm–1.
1-Benzyl-5-bromo-3-[(4-bromophenyl)ethynyl]-3-hydroxy-1,3-
dihydro-2H-indol-2-one (3db)
1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.79 (br s, 1 H), 6.79
(d, J = 8.2 Hz, 1 H), 7.28–7.37 (m, 4 H), 7.44 (d, J = 6.6 Hz, 2 H),
7.59 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 26.8, 69.3, 84.7, 86.9, 109.9,
121.2, 125.3, 128.3, 129.1, 129.2, 130.2, 130.4, 132.1, 141.6, 173.5.
HRMS (ESI): m/z [M + Na]+ calcd for C17H12ClNO2Na: 320.0454;
found: 320.0450.
Pale brown solid; yield: 0.38 g (96%); mp 189–191 °C.
IR (KBr): 3302, 2225, 1705, 1613, 1580, 1462, 1373, 1201, 1087,
1000, 781, 747, 696, 628, 609, 483 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.64 (br s, 1 H), 4.91 (s, 2 H), 6.59
(d, J = 8.2 Hz, 1 H), 7.26–7.38 (m, 8 H), 7.45 (d, J = 7.3 Hz, 2 H),
7.71 (s, 1 H).
5-Bromo-3-hydroxy-1-methyl-3-(phenylethynyl)-1,3-dihydro-
2H-indol-2-one (3ha)
White solid; yield: 0.34 g (95%); mp 188–190 °C.
13C NMR (100 MHz, CDCl3): δ = 44.2, 69.3, 85.8, 87.8, 111.5,
116.4, 123.8, 125.6, 127.1, 128.0, 128.1, 129.0, 130.3, 131.7, 133.3,
133.5, 134.4, 141.2, 173.5.
HRMS (ESI): m/z [M + Na]+ calcd for C23H15Br2NO2Na: 517.9367;
found: 517.9401.
IR (KBr): 3293, 2936, 2223, 1707, 1615, 1492, 1375, 1270, 1171,
1071, 976, 814, 761, 700, 647, 494 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.21 (s, 3 H), 3.99 (br s, 1 H), 6.72
(d, J = 8.3 Hz, 1 H), 7.24–7.34 (m, 3 H), 7.42–7.44 (m, 2 H), 7.49
(dd, J = 2.0, 8.3 Hz, 1 H), 7.72 (d, J = 2.0 Hz, 1 H).
3-[(4-Bromophenyl)ethynyl]-3-hydroxy-1-methyl-1,3-dihydro-
2H-indol-2-one (3eb)
White solid; yield: 0.52 g (97%); mp 176–177 °C.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 195–202

200
M. Chouhan et al.
PAPER
IR (KBr): 3313, 2230, 1707, 1607, 1492, 1461, 1350, 1261, 1178,
1142, 1105, 1050, 994, 956, 872, 815, 785, 683, 605, 531, 471 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.98 (br s, 1 H), 6.86
(d, J = 7.8 Hz, 1 H), 7.17 (dt, J = 0.8, 7.6 Hz, 1 H), 7.26–7.29 (m, 2
H), 7.36–7.41 (m, 3 H), 7.60 (dd, J = 0.7, 7.3 Hz, 1 H).
1-Benzyl-5-fluoro-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-
2H-indol-2-one (3bc)
White solid; yield: 0.35 g (95%); mp 182–184 °C.
IR (KBr): 3314, 2223, 1708, 1616, 1493, 1350, 1261, 1177, 1083,
994, 871, 813, 785, 721, 685, 605, 556, 530 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.84 (br s, 1 H), 4.91
(s, 2 H), 6.62 (dd, J = 4.0, 8.6 Hz, 1 H), 6.93 (dt, J = 2.6, 8.9 Hz, 1
H), 7.10 (d, J = 7.8 Hz, 2 H), 7.26–7.37 (m, 8 H).
13C NMR (100 MHz, CDCl3): δ = 21.5, 44.2, 69.6, 84.2, 87.3, 110.6,
110.7, 112.8, 113.1, 116.5, 116.8, 118.2, 127.1, 129.1, 130.5, 132.0,
134.7, 138.0, 139.5, 160.9, 174.0.
13C NMR (100 MHz, CDCl3): δ = 26.7, 69.5, 85.2, 86.6, 108.9,
120.5, 123.4, 123.8, 124.7, 128.6, 130.6, 131.5, 133.5, 143.0, 173.8.
HRMS (ESI): m/z [M + Na]+ calcd for C17H12BrNO2Na: 363.9949;
found: 363.9412.
3-[(4-Bromophenyl)ethynyl]-5-fluoro-3-hydroxy-1-methyl-1,3-
dihydro-2H-indol-2-one (3fb)
White solid; yield: 0.47 g (94%); mp 165–167 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C24H18FNO2Na: 394.1219;
found: 394.1219.
IR (KBr): 3274, 2940, 2229, 1713, 1621, 1497, 1362, 1263, 1147,
1096, 996, 872, 813, 785, 698, 634, 555, 531 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.95 (br s, 1 H),
6.78–6.81 (m, 1 H), 7.07–7.12 (m, 1 H), 7.29 (d, J = 13.7 Hz, 2 H),
7.32–7.37 (m, 1 H), 7.42 (d, J = 8.5 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 26.8, 69.5, 85.7, 86.0, 109.6,
109.7, 112.9, 113.1, 116.8, 117.0, 120.3, 123.6, 131.6, 133.5, 138.9,
173.6.
1-Benzyl-5-chloro-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-
2H-indol-2-one (3cc)
White solid; yield: 0.35 g (97%); mp 199–200 °C.
IR (KBr): 3302, 3030, 2933, 2221, 1708, 1614, 1489, 1366, 1345,
1271, 1169, 1121, 1077, 985, 816, 683, 642, 532, 475 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.35 (s, 3 H), 3.70 (br s, 1 H), 4.91
(s, 2 H), 6.62 (d, J = 8.3 Hz, 1 H), 7.11 (d, J = 7.2 Hz, 2 H), 7.20 (d,
J = 8.16 Hz, 1 H), 7.19–7.37 (m, 7 H), 7.58 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 21.5, 44.2, 69.5, 84.1, 87.4, 110.9,
118.2, 125.3, 127.1, 128.0, 129.0, 129.1, 129.2, 130.2, 130.4, 132.0,
134.6, 139.5, 140.6, 173.3.
HRMS (ESI): m/z [M + Na]+ calcd for C17H11BrFNO2Na: 381.9855;
found: 381.9851.
3-[(4-Bromophenyl)ethynyl]-5-chloro-3-hydroxy-1-methyl-1,3-
dihydro-2H-indol-2-one (3gb)
White solid; yield: 0.46 g (96%); mp 212–214 °C.
HRMS (ESI): m/z [M + Na]+ calcd for C24H18ClNO2Na: 410.0924;
found: 410.0919.
IR (KBr): 3313, 2225, 1730, 1703, 1609, 1487, 1329, 1253, 1168,
1079, 983, 822, 692 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.57 (br s, 1 H), 6.80
(d, J = 8.3 Hz, 1 H), 7.31 (d, J = 8.3 Hz, 2 H), 7.36 (d, J = 8.3 Hz, 1
H), 7.44 (d, J = 8.1 Hz, 2 H), 7.57 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 26.8, 68.3, 86.5, 88.7, 109.8,
116.0, 120.4, 122.8, 128.6, 130.1, 131.7, 132.6, 133.1, 141.6, 173.1.
1-Benzyl-5-bromo-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-
2H-indol-2-one (3dc)
White solid; yield: 0.33 g (96%); mp 200–202 °C.
IR (KBr): 3303, 3066, 2927, 2228, 1926, 1705, 1620, 1494, 1348,
1262, 1176, 1143, 1064, 957, 882, 810, 726, 695, 636, 603, 533, 495
cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.81 (br s, 1 H), 4.90
(s, 2 H), 6.57 (d, J = 8.4 Hz, 1 H), 7.11 (d, J = 7.9 Hz, 2 H), 7.25–
7.36 (m, 8 H), 7.72 (d, J = 2.0 Hz, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C17H11BrClNO2Na:
397.9559; found: 397.9559.
5-Bromo-3-[(4-bromophenyl)ethynyl]-3-hydroxy-1-methyl-1,3-
dihydro-2H-indol-2-one (3hb)
White solid; yield: 0.43 g (97%); mp 218–220 °C.
13C NMR (100 MHz, CDCl3): δ = 21.5, 44.2, 69.4, 84.1, 87.4, 111.4,
116.4, 118.2, 127.1, 127.9, 128.1, 129.0, 129.1, 130.8, 132.0, 133.1,
134.6, 139.5, 141.1, 173.7.
HRMS (ESI): m/z [M + Na]+ calcd for C24H18BrNO2Na: 454.0419;
found: 454.0414.
IR (KBr): 3381, 2235, 1700, 1607, 1488, 1349, 1259, 1105, 1049,
826, 816, 714, 530 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.23 (s, 3 H), 3.84 (br s, 1 H), 6.75
(d, J = 8.3 Hz, 1 H), 7.30 (d, J = 8.6 Hz, 2 H), 7.43 (d, J = 8.5 Hz, 2
H), 7.51 (dd, J = 2.0, 8.3 Hz, 1 H), 7.70 (d, J = 2.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 26.8, 69.2, 85.8, 85.9, 110.4,
116.4, 120.2, 123.7, 128.0, 130.3, 131.6, 133.4, 133.5, 142.1, 173.2.
3-Hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-
2-one (3ec)
White solid; yield: 0.42 g (98%); mp 150–152 °C.
IR (KBr): 3745, 3315, 3031, 2920, 2216, 1909, 1709, 1611, 1490,
1370, 1352, 1195, 1132, 1093, 993, 821, 754, 692, 662, 490, 481
cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C17H11Br2NO2Na: 441.9054;
found: 441.9050.
1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.25 (s, 3 H), 3.58
(br s, 1 H), 6.88 (d, J = 7.7 Hz, 1 H), 7.10 (d, J = 7.2 Hz, 2 H), 7.17
(t, J = 7.5 Hz, 1 H), 7.33–7.41 (m, 3 H), 7.62 (d, J = 7.1 Hz, 1 H).
1-Benzyl-3-hydroxy-3-(4-tolylethynyl)-1,3-dihydro-2H-indol-2-
one (3ac)
White solid; yield: 0.36 g (96%); mp 202–203 °C.
13C NMR (100 MHz, CDCl3): δ = 21.5, 26.6, 69.5, 84.8, 86.6, 108.8,
118.5, 123.7, 124.7, 128.9, 129.0, 130.5, 132.0, 139.3, 143.1, 173.9.
HRMS (ESI): m/z [M + Na]+ calcd for C18H15NO2Na: 300.1000;
IR (KBr): 3317, 2937, 2221, 1708, 1612, 1492, 1457, 1267, 1170,
1082, 874, 762, 694, 615, 480 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.78 (br s, 1 H), 4.92
(s, 2 H), 6.71 (d, J = 7.8 Hz, 1 H), 7.08–7.13 (m, 3 H), 7.22–7.35
(m, 8 H), 7.61 (dd, J = 0.9, 7.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 21.5, 44.1, 69.6, 84.8, 86.8, 109.9,
118.5, 123.7, 124.8, 127.2, 127.8, 128.9, 129.0, 129.0, 130.3, 132.0,
135.0, 139.3, 142.1, 174.2.
found: 300.1009.
5-Fluoro-3-hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-
2H-indol-2-one (3fc)
White solid; yield: 0.39 g (95%); mp 134–136 °C.
IR (KBr): 3736, 3315, 2217, 1708, 1611, 1469, 1370, 1255, 1196,
1093, 993, 937, 821, 754, 693, 582, 532, 482 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C24H19NO2Na: 376.1313;
found: 376.1311.
Synthesis 2014, 46, 195–202
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Assembly of 3-(Arylethynyl)-3-hydroxyindolin-2-ones Using CuI/DBU
201
1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.23 (s, 3 H), 3.80
(br s, 1 H), 6.78–6.80 (m, 1 H), 7.09 (d, J = 7.6 Hz, 3 H), 7.19–7.36
(m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 21.5, 26.8, 69.6, 84.2, 87.0, 109.4,
112.8, 113.0, 116.6, 118.2, 129.0, 130.3, 132.0, 139.5, 158.5, 160.9,
173.7.
HRMS (ESI): m/z [M + Na]+ calcd for C18H15NO3Na: 316.0950;
found: 316.0956.
1-Benzyl-3-hydroxy-3-[(2-(trifluoromethyl)phenyl)ethynyl]-
1,3-dihydro-2H-indol-2-one (3ae)
White solid; yield: 0.41 g (96%); mp 155–157 °C.
IR (KBr): 3128, 2953, 2822, 1909, 1682, 1598, 1361, 1222, 1137,
1012, 997, 961, 918, 829, 740, 614, 544, 498, 465 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.88 (br s, 1 H), 4.86 (d, J = 15.8
Hz, 1 H), 5.00 (d, J = 15.8 Hz, 1 H), 6.72 (d, J = 7.8 Hz, 1 H), 7.10–
7.14 (m, 1 H), 7.23–7.34 (m, 6 H), 7.40–7.48 (m, 2 H), 7.60–7.64
(m, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C18H14FNO2Na: 318.0906;
found: 318.0908.
5-Chloro-3-hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-
2H-indol-2-one (3gc)
White solid; yield: 0.38 g (96%); mp 199–200 °C.
IR (KBr): 3377, 3055, 2936, 2233, 1699, 1610, 1491, 1349, 1262,
1106, 1049, 883, 824, 816, 731, 684, 545, 477 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.23 (s, 3 H), 3.62
(br s, 1 H), 6.78 (d, J = 8.3 Hz, 1 H), 7.09 (d, J = 7.9 Hz, 2 H), 7.32–
7.36 (m, 3 H), 7.58 (d, J = 2.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 44.1, 69.6, 82.3, 90.9, 109.9,
123.8, 124.9, 125.8, 125.9, 127.1, 127.8, 128.3, 128.9, 128.9, 130.5,
131.4, 132.3, 134.3, 134.9, 142.1, 173.7.
HRMS (ESI): m/z [M + Na]+ calcd for C24H16F3NO2Na: 430.1031;
found: 430.1035.
13C NMR (100 MHz, CDCl3): δ = 21.5, 26.8, 69.4, 84.0, 87.2, 109.8,
118.1, 125.3, 129.0, 129.1, 130.3, 130.4, 132.0, 139.5, 141.6, 173.5.
HRMS (ESI): m/z [M + Na]+ calcd for C18H14ClNO2Na: 334.0611;
3-Hydroxy-1-methyl-3-[(2-(trifluoromethyl)phenyl)ethynyl]-
1,3-dihydro-2H-indol-2-one (3ee)
White solid; yield: 0.48 g (93%); mp 175–177 °C.
found: 334.0610.
IR (KBr): 3292, 2227, 1706, 1611, 1291, 1473, 1376, 1318, 1207,
1166, 1106, 1030, 997, 936, 753, 605, 492 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.80 (br s, 1 H), 6.86
(d, J = 7.8 Hz, 1 H), 7.15–7.19 (m, 1 H), 7.37–7.47 (m, 3 H), 7.58–
7.63 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 26.7, 69.5, 82.1, 90.9, 108.9,
123.8, 124.9, 125.8, 125.9, 128.3, 128.9, 130.7, 131.4, 132.4, 134.3,
139.1, 143.1, 173.4.
5-Bromo-3-hydroxy-1-methyl-3-(4-tolylethynyl)-1,3-dihydro-
2H-indol-2-one (3hc)
White solid; yield: 0.35 g (95%); mp 216–218 °C.
IR (KBr): 3315, 3053, 2922, 2230, 1705, 1607, 1493, 1350, 1261,
1178, 1105, 1050, 815, 785, 683, 605, 531, 473 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.22 (s, 3 H), 3.72
(br s, 1 H), 6.73 (d, J = 8.2 Hz, 1 H), 7.09 (d, J = 7.6 Hz, 2 H), 7.33
(d, J = 7.4 Hz, 2 H), 7.50 (d, J = 8.2 Hz, 1 H), 7.71 (s, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C18H12F3NO2Na: 354.0718;
found: 354.0718.
13C NMR (100 MHz, CDCl3): δ = 21.5, 26.7, 69.3, 84.1, 87.2, 110.3,
116.3, 118.2, 128.0, 129.0, 130.7, 132.0, 133.2, 139.5, 142.1, 173.5.
HRMS (ESI): m/z [M + Na]+ calcd for C18H14BrNO2Na: 378.0106;
found: 378.0101.
1-Benzyl-3-hydroxy-3-(pyridin-2-ylethynyl)-1,3-dihydro-2H-
indol-2-one (3af)
White solid; yield: 0.34 g (95%); mp 166–168 °C.
IR (KBr): 3736, 2230, 1707, 1608, 1491, 1351, 1216, 1178, 1142,
1105, 1050, 995, 872, 815, 785, 684, 605, 531, 474 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.93 (s, 2 H), 6.02 (br s, 1 H), 6.70
(d, J = 7.8 Hz, 1 H), 7.08–7.32 (m, 8 H), 7.42 (d, J = 7.8 Hz, 1 H),
7.61 (t, J = 7.7 Hz, 1 H), 7.73 (d, J = 7.4 Hz, 1 H), 8.58 (d, J = 4.2
Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 44.2, 69.5, 85.0, 86.2, 109.8,
123.5, 123.9, 125.2, 127.2, 127.6, 127.7, 127.8, 128.9, 130.4, 135.1,
136.4, 141.9, 142.2, 149.8, 174.0.
1-Benzyl-3-hydroxy-3-[(2-methoxyphenyl)ethynyl]-1,3-di-
hydro-2H-indol-2-one (3ad)
White solid; yield: 0.37 g (95%); mp 184–187 °C.
IR (KBr): 3737, 3293, 3060, 2223, 1707, 1616, 1492, 1466, 1348,
1271, 1171, 1018, 976, 813, 760, 748, 701, 651, 547, 494 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.81 (br s, 1 H), 3.85 (s, 3 H), 4.93
(s, 2 H), 6.70 (d, J = 7.8 Hz, 1 H), 6.84–6.89 (m, 2 H), 7.09–7.27
(m, 2 H), 7.28–7.41 (m, 7 H), 7.62–7.64 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 44.1, 55.8, 69.8, 83.2, 89.4, 109.8,
110.7, 110.8, 120.3, 123.7, 124.9, 127.2, 127.8, 128.8, 128.9, 130.3,
130.6, 133.9, 135.1, 142.2, 160.6, 174.2.
HRMS (ESI): m/z [M + Na]+ calcd for C22H16N2O2Na: 363.1109;
found: 363.1122.
HRMS (ESI): m/z [M + Na]+ calcd for C24H19NO3Na: 392.1263;
found: 392.1268.
3-Hydroxy-1-methyl-3-(pyridin-2-ylethynyl)-1,3-dihydro-2H-
indol-2-one (3ef)
White solid; yield: 0.40 g (96%); mp 175–177 °C.
3-Hydroxy-3-[(2-methoxyphenyl)ethynyl]-1-methyl-1,3-di-
hydro-2H-indol-2-one (3ed)
IR (KBr): 3303, 2225, 1705, 1614, 1462, 1373, 1271, 1201, 1089,
1000, 939, 858, 782, 747, 696, 628, 609, 538, 494, 484 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 5.19 (br s, 1 H), 6.84
(d, J = 7.8 Hz, 1 H), 7.12–7.16 (m, 1 H), 7.22–7.26 (m, 1 H), 7.34–
7.38 (m, 1 H), 7.43 (d, J = 7.8 Hz, 1 H), 7.60–7.64 (m, 1 H), 7.69
(d, J = 7.4 Hz, 1 H), 8.55 (d, J = 4.7 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 26.7, 69.4, 84.9, 85.9, 108.8,
123.5, 123.8, 125.0, 127.5, 128.6, 130.6, 136.3, 141.9, 143.1, 149.9,
173.6.
White solid; yield: 0.42 g (93%); mp 214–216 °C.
IR (KBr): 3377, 2233, 1701, 1610, 1491, 1349, 1136, 1106, 1049,
883, 816, 684, 545, 530, 477 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.24 (s, 3 H), 3.76 (br s, 1 H), 3.85
(s, 3 H), 6.83–6.88 (m, 3 H), 7.13–7.18 (m, 1 H), 7.29–7.39 (m, 3
H), 7.61–7.63 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 26.6, 55.8, 69.7, 83.0, 89.4, 108.8,
110.7, 110.8, 120.3, 123.7, 124.8, 128.9, 130.5, 130.6, 133.9, 143.2,
160.5, 173.9.
HRMS (ESI): m/z [M + Na]+ calcd for C16H12N2O2Na: 287.0796;
found: 287.0796.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 195–202

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M. Chouhan et al.
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Acknowledgment
Research funding from the National Institute of Pharmaceutical
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Supporting Information for this article is available online at
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Synthesis 2014, 46, 195–202
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