Synthetic Procedures and Physical Characterization Data in Details for the
Synthesis of the Compounds (2-11c)
Methyl 2-(3-methoxybenzylidene)-3-oxobutanoate (2, scheme 1): A solution of manisaldehyde (1.36 g, 10 mmol), methylacetoacetate (1.39 g, 12 mmol) and piperidinium acetate
(catalytic amount) in toluene (40 mL) was refluxed in a Dean-Stark trap for 7 h and then
concentrated. Chromatography of the residue eluting with ethyl acetate/hexane (1:4) gave (10) as
yellow viscous mass (1.17 g, 50%) as a mixture of geometric isomers (0.9:1.0). FTIR (CHCl3, ν,
cm-1): 3020 ( C-H stretch, Ar), 2982 and 2919 (C-H stretch of –CH3, antisymmetric and
symmetric), 1734 (C=O stretch, ester), 1625 (C=O stretch, ketone), 1255 (C-O stretch, ester),
1215 (C-O stretch, aralkyl ether) 756 (C-C out of plane bending, phenyl ring 1,3-disubstituted);
l
H NMR (CDCl3, δ, ppm): 2.34 and 2.42 (two singlets, 3H each, -COCH3), 3.79 and 3.80 (two
singlets, 3H each, -OCH3), 3.83 and 3.84 (two singlets, 3H each, -COOCH3), 6.91-6.98 (m, 2H,
Ar), 7.01-7.03 (m, 1H, Ar), 7.26-7.32 (m, 1H, Ar), 7.66 and 7.54 (two singlets, 1H each,
benzylidene) respectively for the minor and the major geometrical isomers; 13C NMR (CDCl3, δ,
ppm): 194.71 (C=O of COCH3), 168.25 (C=O of COOCH3), 159.80, 141.51, 134.11, 129.98,
122.01, 116.86, 114.25, 113.13, 52.57 (COOCH3), 26.47 (-COCH3); GCMS m/z (%): 234 [M]+,
219, 203; Anal. % Calcd. for C13H14O4: C, 66.66; H, 6.02. Found: C, 66.91; H, 6.35.
Methyl-2-(3-hydroxybenzylidene)-3-oxobutanoate (3, scheme1): To a solution of 2 (3 g,
0.0128 mol) in DCM at 0°C was added BBr3 in DCM (13 ml, 1M solution) dropwise while
stirring and stirring continued of 2 h at 0°C and then at room temperature for 16 h. The contents
treated with ice cold water and the organic layers separated, washed with brine, dried over
sodium sulphate, filtered and solvent evaporated and the residue purified by column
chromatography EtOAc/Hexane (1:4) to yield 3a as pale yellow solid (1.04gm, 37%). mp: 135138 °C. FTIR (KBr, ν, cm-1): 3350 (O-H stretch, H-bonded), 3059 (C-H stretch, aromatic), 2940
and 2890 (C-H stretch of –CH3, antisymmetric and symmetric), 1732 (C=O stretch, ester), 1646
(C=O stretch, ketone), 1598 (C=C stretch, Ar), 1573 (C=C stretch, Ar), 1510 (C=C stretch, Ar),
1483 (C-H bending, Methyl), 679 (C-C out of plane bending, phenyl ring 1,3-disubstituted); 1H
NMR (CDCl3) δ, ppm: 2.42 (s, 3H, -COCH3), 3.83 (s, 3H, -COOCH3), 5.56 (s, 1H, -OH), 6.90
(m, 2H, Ar), 6.99 (m, 1H, Ar), 7.27 (m, 1H, Ar), 7.51 (s, 1H, benzylidene); 13C NMR (CDCl3, δ,
ppm):208.45 and 198.38 (C=O of COCH3), 169.13 and 165.18 (C=O of COOCH3), 158.91,
158.54, 141.17, 141.04, 131.97, 131.89, 131.36, 130.69, 125.09, 124.90, 116.13, 116.11, 62.03
and 61.59 (COOCH3), 37.08 and 31.78 (-COCH3); GCMS (m/z): 220 (M.+), 205, 189, 160; Anal.
% Calcd. for C12H12O4: C, 65.45; H, 5.49; Found: C, 65.27; H, 5.33.
Ethyl 1-methyl-1H-indole-2-carboxylate (5, scheme 2): To a stirred solution of sodium
hydride (1.100g, 27.5mmol, 60% w/w) in dry DMF (100ml) was added (4) (4.160g, 22mmol) at
2-5°C, and the mixture was stirred for 30 min at room temperature. A solution of iodomethane
(3.750g, 26.4mmol) in dry DMF (5ml) was added dropwise over 15 min at 2-5°C, and stirred for
28h at room temperature. The reaction mixture was quenched with water, and extracted with
EtOAc (3×25ml). The combined organic extracts were washed with brine and water, dried, and
concentrated. The product (5) was isolated by column chromatography (EtOAc/ hexane, 1:20) as
a white solid (3.35g, 75%). mp: 68-70 °C. FTIR (KBr), ν, cm-1: 3048 (C-H stretch, Ar), 2982 and
2850 (C-H stretch N-CH3, antisymmetric and symmetric), 1703 (C=O stretch, ester), 1515 and
1469 (C=C stretch, Ar), 1465 (bending antisymmetric, CH2CH3), 1400 (bending symmetric,
CH2CH3), 1378 (C-N stretch, Ar), 1251 (C-O stretch ester), 1087 (C-N stretch N-Me), 747 (C-C
out of plane bending, phenyl ring 1,3-disubstituted); 1H NMR, (CDCl3), δ, ppm: 1.41 (t, 3H, OCH2CH3), 4.08 (s, 3H, N-CH3), 4.37 (q, 2H, -OCH2CH3), 7.16-7.12 (m, 1H, Ar), 7.30 (s, 1H,
Ar), 7.36-7.31 (m, 1H, Ar), 7.42-7.37 (m, 1H, Ar), 7.67 (d, 1H, Ar); 13C NMR (CDCl3, δ, ppm):
162.30 (C=O of ester), 139.66, 128.04, 125.04, 125.91, 124.93, 122.63, 120.59, 110.12, 60.56
(COOCH2CH3), 31.62 (N-CH3), 14.42 (COOCH2CH3); Anal. % Calcd. for C12H13NO2: C,
70.92; H, 6.45; N, 6.89. Found: C, 71.08; H, 6.57; N, 6.60.
(1-methyl-1H-indol-2-yl)methanol (6, scheme 2): To a stirred suspension of lithium aluminium
hydride (7.600g, 200mmol) in THF (100ml) was added (5) (4.060g, 20mmol) in THF (5ml), and
the mixture was stirred at room temperature (ca. 30°C) for 36h. The reaction mixture was
quenched with ice water, acidified with 2N- HCl, and extracted with ethyl acetate (3×20ml). The
combined organic extracts were dried over sodium sulfate and concentrated to a white solid
which upon recrystallization from ethyl acetate gave (6) (3.06g, 95%) as a white solid. mp: 108110 °C. FTIR (KBr), ν, cm-1: 3600-3400 (O-H stretch, alcohol), 3049 (C-H stretch, Ar), 2962 (CH stretch N-CH3, antisymmetric and symmetric), 2929 and 2850 (C-H stretch CH2-OH,
antisymmetric and symmetric), 1612 (C=C stretch, Ar), 1515 (C=C stretch, Ar), 1468 (C=C
stretch, Ar); 1H NMR (CDCl3), δ, ppm: 3.80 (s, 3H, N-CH3), 4.80 (s, 2H, -CH2OH), 6.45 (s, 1H,
Ar), 7.08-7.11 (m, 1H, Ar), 7.21-7.25 (m, 1H, Ar), 7.30-7.33 (m, 1H, Ar), 7.59-7.57 (m, 1H, Ar);
13
C NMR (CDCl3, δ, ppm): 138.71, 138.12, 127.21, 122.00, 120.85, 119.61, 109.29, 101.29,
57.31 (-CH2O-), 29.73(N-CH3); Anal. % Calcd. for C10H11NO: C, 74.51; H, 6.88; N, 8.69.
Found: C, 74.38; H, 6.59; N, 8.52.
3-[(1-methyl-1H-indol-2-yl)methoxy]benzaldehyde (7, scheme 2): A solution of diethyl
azodicarboxylate (1.6 g, 9 mmol) and triphenylphosphine (2.33 g, 9 mmol) in THF (40 ml) at 0
°C was added dropwise to a stirred mixture of (6) (0.805 gm, 5 mmol) and 3hydroxybenzaldehyde (0.700 gm, 6 mmol) taken in THF (10 ml) at 0 °C. The reaction mixture
was stirred at 0 °C for an hour and then at room temperature for 16 h and solvent removed under
reduced pressure. The residue was taken up in 30 ml of EtOAc/ water (2:1). The organic layer
was separated, dried over anhydrous sodium sulphate, filtered and solvent evaporated in vaccuo
and the residue upon preparative chromatography using EtOAc: n-hexane (15:85) gave the
desired title compound (7) (0.600 g, 45.5%). mp: 102-105 °C. FTIR (CHCl3, ν, cm-1): 3065 (C-H
stretch, Ar), 2963 and 2923 (C-H stretch N-CH3, antisymmetric and symmetric), 2850 and 2729
(C-H stretch, aldehyde), 1697 (C=O stretch, aldehyde), 1594 (C=C stretch, Ar), 1484 (C=C
stretch, Ar), 1469 (C=C stretch, Ar), 755 (C-C out of plane bending, phenyl ring 1,3disubstituted); 1H NMR (CDCl3, δ, ppm): 3.80 (s, 3H, N-CH3), 5.26 (s, 2H, -CH2O-), 7.10-7.13
(m, 1H, Ar), 7.25 (m, 2H, Ar), 7.35 (m, 1H, Ar), 7.46 (m, 2H, Ar), 7.55 (m, 1H, Ar), 7.61 (m,
1H, Ar), 9.99 (s, 1H, -CHO); 13C NMR (CDCl3, δ, ppm): 193.55 , 157.07, 138.32, 130.35,
127.26, 123.09, 119.70, 114.93, 109.43, 101.60, 57.13, 29.64; LCMS (m/z): 266 [M+1]+; Anal.
% Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C, 76.58; H, 5.55; N, 5.60.
5-{3-[(1-methyl-1H-indol-2-yl)methoxy]benzylidene}-1,3-thiazolidine-2,4-dione (7a, scheme
2): A mixture of (7) (0.265 gm; 1 mmol), thiazolidine-2,4-dione (0.117 gm; 1 mmol), and
piperidinium acetate (0.1ml) in toluene (25 ml) was refluxed for 7 h with continuous removal of
water using a Dean-Stark trap. The reaction mixture was cooled to room temperature and
evaporated to dryness under reduced pressure. The crude product was purified by column
chromatography using a mixture of ethyl acetate/hexane (1:4) as eluent to obtain the title
compound (7a) (0.26 g, 72%) as yellow solid. mp: 168-172 oC. FTIR (CHCl3, ν, cm-1): 3361 (NH stretch), 2923 and 2852 (C-H stretch N-CH3, antisymmetric and symmetric), 1728 (C=O
stretch), 1706 (C=O stretch), 1614 (C=C stretch, Ar), 1500 (C=C stretch, Ar), 1452 (C=C stretch,
Ar), 1445 (C=C stretch, Ar), 760 (C-C out of plane bending, phenyl ring 1,3-disubstituted); lH
NMR (CDCl3, δ, ppm): 3.81 (s, 3H, N-CH3), 5.22 (s, 2H, -CH2O-), 6.59 (s, 1H, Ar), 6.94 (m,
2H, Ar), 7.11 (m, 1H, Ar), 7.30 (m, 3H, Ar), 7.49 (m, 1H, Ar), 7.60 (m, 1H, Ar), 7.86 (s, 1H,
benzylidene); 13C NMR (CDCl3, δ, ppm): 138.66, 136.36, 127.49, 122.33, 120.84, 120.80,
119.59, 119.38, 119.24, 118.95, 117.29, 109.26, 108.96, 108.82, 107.03, 101.39, 57.48 (-CH2O), 29.76 (N-CH3); LCMS (m/z): 364 [M+1]+; Anal. % calcd. for C20H16N2O3S: C, 65.92; H, 4.43;
N, 7.69; S, 8.80. Found: C, 66.11; H, 4.28; N, 7.35, S, 8.88.
Diethyl 2-{3-[(1-methyl-1H-indol-2-yl)methoxy]benzylidene}propanedioate (7b, scheme 2):
A mixture of (7) (0.265 gm, 1 mmol), diethylmalonate (0.160 gm, 1 mmol), and piperidinium
acetate (0.1ml) in toluene (25 ml) was refluxed for 14 h with continuous removal of water using
a Dean-Stark trap. After cooling to room temperature, the solution was concentrated to crude
reaction mixture, which was purified by column chromatography using a mixture of ethyl
acetate/hexane (1:4) as eluent to obtain the title compound (7b) (0.205 g, 50%) as white solid.
mp: 156-159 oC. FTIR (CHCl3, ν, cm-1): 3057 (C-H stretch, Ar), 2924 and 2851 (C-H stretch NCH3, antisymmetric and symmetric), 1728 (C=O stretch, ester), 1700 (C=O stretch, ester), 1629
(C=C stretch, Ar), 1597 (C=C stretch, Ar), 1578 (C=C stretch, Ar), 1469 (C=C stretch, Ar),
1447, 1225 (C-O-C asymmetric stretch, aralkyl), 1094, 1064, 786, 751; lH NMR (CDCl3, δ,
ppm): 1.27 (t, 3H, -OCH2CH3), 1.33 (t, 3H, -OCH2CH3), 3.79 (s, 3H, N-CH3), 4.31 (two
overlapping quartets, 2H each, -OCH2CH3), 5.18 (s, 2H, -CH2O-), 6.60 (s, 1H, Ar), 7.18 (m, 4H,
Ar), 7.30 (m, 3H, Ar), 7.61 (d, 1H, Ar), 7.70 (s, 1H, benzylidene); 13C NMR (CDCl3, δ, ppm):
169.14 (2 C=O of ester), 139.22, 138.55, 138.13, 136.33, 136.03, 129.73, 127.16, 122.34,
120.87, 119.99, 119.38, 117.30, 115.85, 114.01, 109.50, 101.45, 61.70 (-CH2O), 57.40
(COOCH2CH3), 34.54 (N-CH3), 14.02 (COOCH2CH3); LCMS (m/z): 408 [M+1]+; Anal. %
calcd. for C24H25NO5: C, 70.74; H, 6.18; N, 3.44; Found: C, 70.33; H, 5.99; N, 3.55.
Methyl 2-{3-[(1-methyl-1H-indol-2-yl)methoxy]benzylidene}-3-oxobutanoate (8, scheme 2):
A solution of diethyl azodicarboxylate (0.157 g, 0.9 mmol) and triphenylphosphine (0.236 g,
0.9 mmol) in THF (5 ml) at 0 °C was added dropwise to a stirred mixture of (6) (0.97 g, 0.6
mmol) and (3) (0.159 g, 0.72 mmol) in THF (10 ml) at 0 °C. The reaction mixture was stirred at
0 °C for an hour and then at room temperature for 16 h and solvent removed under reduced
pressure. The residue was taken up in 30 ml of EtOAc/water (2:1). The organic layer was
separated, dried over anhydrous sodium sulphate, filtered and solvent evaporated under vacuum
and the residue upon preparative chromatographyusinf EtOAc:n-hexane (15:85) gave the
coupled targeted compound (8) (0.055 g, 15.3%). mp: 153-156 °C. FTIR (CHCl3, ν, cm-1): 3020
(C-H stretch, Ar), 2924 and 2874 (C-H stretch N-CH3, antisymmetric and symmetric), 1720
(C=O stretch, ester), 1699 (C=O stretch, ketone), 1520 (C=C stretch, Ar), 1450 (C=C stretch,
Ar), 1113, 1056, 752 (C-C out of plane bending, phenyl ring 1,3-disubstituted); 1H NMR
(CDCl3), mixture of E and Z isomers, δ, ppm: 2.32 (s, 3H, -COCH3), 2.42 (s, 3H, -COCH3), 3.79
(s, 3H, -OCH3), 3.80 (s, 3H, -OCH3), 3.83 (s, 3H, -NCH3), 3.84 (s, 3H, -NCH3), 5.16 (s, 2H, CH2O-), 5.19 (s, 2H, -CH2O-), 6.58 (s, 1H, Ar), 6.61 (s, 1H, Ar), 6.94 (m, 1H, Ar), 6.99 (m, 4H,
Ar), 7.09 (m, 2H, Ar), 7.23 (m, 2H, Ar), 7.28 (m, 2H, Ar), 7.33 (m, 3H, Ar), 7.54 (s, 1H,
benzylidene), 7.61 (two overlapping doublets, J = 7.8 Hz, 1H each, Ar), 7.65 (s, 1H,
benzylidene); 13C NMR (CDCl3, mixture of E and Z isomers, δ, ppm): 208.16 and 198.13 (C=O
of COCH3), 169.05 and165.16 (C=O of COOCH3), 158.96 and 158.61, 141.03 and 140.83,
138.49 and 138.12, 136.32 and 136.03, 131.98 and 131.90, 131.34 and 130.74, 127.48 and
127.15, 125.06 and 124.87, 122.36 and 122.04, 120.84 and 120.79, 119.98 and 119.60, 119.39
and 119.25, 118.94 and 117.29, 116.07 and110.30, 109.27 and 108.97, 108.84 and 107.02, 61.95
and 61.54 (-CH2O-), 57.43 and 54.39 (-COOCH3), 29.82 and 29.74 (N-CH3), 22.47 and 20.47 (COCH3); LCMS (m/z): 386 (M.++23), 363 (M.+); Anal. % Calcd for C22H21NO4: C, 72.71; H,
5.82; N, 3.85. Found: C, 72.63; H, 5.57; N, 3.68.
Ethyl 3-bromo-1H-indole-2-carboxylate (9, scheme 3): To a solution of (4) (0.378 gm, 2
mmol) in dry DMF (10 ml) was added NBS (0.355 gm, 2 mmol). The resulting mixture was
stirred at room temperature under nitrogen for 12 h. Crushed ice was then added into the reaction
mixture and the white precipitate thus separated was filtered, washed with cold water
recrystallized from EtOAc to get the title compound (9) (0.42 g, 78 %). mp: 146-148 oC. FTIR
(KBr, ν, cm-1): 3378 (N-H stretch), 3297 (C-H stretch, Ar), 2953 and 2899 (C-H stretch N-CH3,
antisymmetric and symmetric), 1688 (C=O stretch, ester), 1574 (C=C stretch, Ar), 1516 (C=C
stretch, Ar), 1473 (C=C stretch, Ar), 742 (C-C out of plane bending, phenyl ring), 643 (C-Br
stretch); 13C NMR (CDCl3, δ, ppm): 160.15 (C=O of ester), 135.76, 126.84, 125.59, 123.85,
120.81, 120.01, 112.88, 95.94, 60.58 (COOCH2CH3), 14.12 (COOCH2CH3); GCMS (m/z): 270
[M+2]+, 269 [M+1]+, 268 [M]+, 267 [M-1]+; Anal. % calcd. for C11H10BrNO2: C, 49.28; H, 3.76;
N, 5.22. Found: C, 49.71; H, 3.98; N, 5.31.
Ethyl 3-bromo-1-methyl-1H-indole-2-carboxylate (10, scheme 3): To a solution of (9) (0.268
gm, 1 mmol) and potassium carbonate (0.414 gm, 3mmol) in dry DMF (10 ml) was added CH3I
(0.169 gm, 1.2 mmol). The resulting mixture was stirred at room temperature under nitrogen for
24 h. Crushed ice was then added and the white precipitate thus separated was filtered, washed
with cold water, and dried to get the title compound (10) (0.24 g, 85%) as white solid. mp: 128130 oC. FTIR (KBr, ν, cm-1): 3052 (C-H stretch, Ar), 2981 and 2923 (C-H stretch N-CH3,
antisymmetric and symmetric), 1704 (C=O stretch, ester), 1500, 1465, 1398, 1380, 771 (C-C out
of plane bending, phenyl ring), 600 (C-Br stretch); lH NMR (CDCl3, δ, ppm): 1.47 (t, 3H, OCH2CH3), 4.03 (s, 3H, N-CH3), 4.45 (q, 2H, -OCH2CH3), 7.22 (m, 1H, Ar), 7.38 (m, 2H, Ar),
7.67 (m, 1H, Ar); 13C NMR (CDCl3, δ, ppm): 161.46 (C=O of ester), 138.11, 126.68, 126.08,
125.56, 121.47, 121.24, 110.32, 98.60, 61.21 (COOCH2CH3), 32.65 (N-CH3), 14.32
(COOCH2CH3); GCMS (m/z): 284 [M+2]+, 283 [M+1]+, 282 [M]+, 281 [M-1]+; Anal. % calcd.
for C12H12BrNO2: C, 51.09; H, 4.29; N, 4.96. Found: C, 51.66; H, 3.85; N, 4.38.
Ethyl 3-(3-formylphenyl)-1-methyl-1H-indole-2-carboxylate (11, scheme 3): To a solution of
(10) (0.282 g, 1 mmol) and 3-boronobenzaldehyde (0.209 g, 1.4 mmol) in 25 ml of
Dioxane:Water (4:1) was added potassium carbonate (0.414 g, 3 mmol). The resulting mixture
was degassed, stirred at ambient temperature for 20 minutes and catalytic amount (0.005 mmol)
of Pd(PPh3)4 was added. The mixture was degassed again and then refluxed under nitrogen for 8
h and then allowed to cool, filtered through celite and extracted using EtOAc (3×20 ml). The
organic layer dried over anhydrous sodium sulphate, filtered and upon concentration under
reduced pressure gave an oil which was subjected to column chromatography using acetone/nhexane (2:8) to afford the title compound (11) (0.25 g, 82%) as white solid. mp: 89-92 °C. FTIR
(KBr, ν, cm-1): 3060 (C-H stretch, Ar), 2975 and 2928 (C-H stretch N-CH3, antisymmetric and
symmetric), 2825 and 2782 (C-H stretch, aldehyde), 1783 (C=O stretch, ester), 1693 (C=O
stretch, aldehyde), 1605 (C=C stretch, Ar), 1575 (C=C stretch, Ar), 1532 (C=C stretch, Ar), 1465
(C=C stretch, Ar), 748 (C-C out of plane bending, phenyl ring 1,3-disubstituted), 701, 686; lH
NMR(CDCl3, δ, ppm): 1.02 (t, 3H, -OCH2CH3), 4.11 (s, 3H, N-CH3), 4.17 (q, 2H, -OCH2CH3),
7.16 (m, 1H, Ar), 7.42 (m, 2H, Ar), 7.50 (m, 1H, Ar), 7.60 (t, J = 7.60 Hz, 1H, Ar), 7.71 (m,
1H, Ar), 7.90 (m, 1H, Ar), 7.96 (m, 1H, Ar), 10.09 (s, 1H, -CHO); 13C NMR (CDCl3, δ, ppm):
192.59 (C=O of ester), 161.62 (C=O of aldehyde), 156.70, 138.14, 137.77, 130.36, 126.67,
126.15, 125.50, 123.29, 122.15, 121.48, 121.27, 114.84, 110.35, 98.78, 61.33 (COOCH2CH3),
32.68 (N-CH3), 14.30 (COOCH2CH3); GCMS m/z: 307 [M]+; Anal. % calcd. for C19H17NO3: C,
74.25; H, 5.58; N, 4.56. Found: C, 73.91; H, 5.27; N, 4.71.
Ethyl
3-{3-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl}-1-methyl-1H-indole-2carboxylate (11a, scheme 3): A mixture of (11) (0.307 gm; 1 mmol), thiazolidine-2,4-dione
(0.117 gm; 1 mmol), and piperidinium acetate (0.15ml) in toluene (25 ml) was refluxed for 7 h
with continuous removal of water using a Dean-Stark trap. The crude reaction mixture was
cooled to room temperature and concentrated to a viscous residue, which was purified by column
chromatography using EtOAc/hexane (3:7) as eluent to afford the desired compound (11a)
(0.195 g, 77%) as yellow viscous mass. FTIR (CHCl3, ν, cm-1): 3271 (N-H stretch), 3051 (C-H
stretch, Ar), 2935and 2851, 1756 (C=O stretch, ester), 1701, 1614 (C=C stretch, Ar), 1532 (C=C
stretch, Ar), 1465 (C=C stretch, Ar), 745 (C-C out of plane bending, phenyl ring 1,3disubstituted), 706; lH NMR (CDCl3, δ, ppm): 1.01 (t, 3H, -OCH2CH3), 4.08 (s, 3H, N-CH3),
4.17 (q, 2H, -OCH2CH3), 7.05 (s, 1H, Ar), 7.33 (m, 3H, Ar), 7.42 (m, 3H, Ar), 7.57 (d, J =8.08
Hz, 1H, Ar), 7.79 (s, 1H, benzylidene); 13C NMR (CDCl3, δ, ppm): 170.76 (C=O of
thiazolidinedione ring), 168.08 (C=O of thiazolidinedione ring), 162.67 (C=O of ester), 144.41,
138.37, 134.65, 131.89, 130.79, 129.77, 128.58, 127.41, 126.65, 125.31, 125.03, 124.13, 121.59,
120.75, 110.09, 105.12, 60.61 (COOCH2CH3), 31.97 (N-CH3), 13.69 (COOCH2CH3); LCMS
(m/z): 407 [M+1]+; Anal. % calcd. for C22H18N2O4S: C, 65.01; H, 4.46; N, 6.89; S, 7.89. Found:
C, 64.71; H, 4.07; N, 6.37; S, 7.49.
Diethyl 2-{3-[(2-ethoxycarbonyl)-1-methyl-1H-indol-3-yl]benzylidene}propanedioate (11b,
scheme 3): A mixture of (11) (0.307, 1 mmol), diethylmalonate (0.160, 1 mmol), and
piperidinium acetate (0.15ml) in toluene (25ml) was refluxed for 14 h with continuous removal
of water using a Dean-Stark trap. After cooling to room temperature, the solution was
concentrated to crude reaction mixture, which was purified by column chromatography using
EtOAc/hexane (3:7) as eluent to afford the desired compound (11b) (0.38 g, 85%) as reddish
brown viscous mass. FTIR (CHCl3, ν, cm-1): 2982 (C-H stretch, Ar), 2936 and 2903 (C-H stretch
N-CH3, antisymmetric and symmetric), 1725 (C=O stretch, ester), 1706 (C=O stretch, ester),
1629, 1532 (C=C stretch, Ar), 1465 (C=C stretch, Ar), 744 (C-C out of plane bending, phenyl
ring 1,3-disubstituted); lH NMR (CDCl3), δ, ppm: 1.02 (t, 3H, -OCH2CH3), 1.23 (t, J = 7.2 Hz,
3H, -OCH2CH3), 1.33 (t, 3H, -OCH2CH3), 4.09 (s, 3H, N-CH3), 4.16 (q, J = 7.08 Hz, 2H, OCH2CH3), 4.29 (two overlapping quartets, 7.12 Hz, 2H each, -OCH2CH3), 7.16 (m, 1H, Ar),
7.46 (m, 7H, Ar), 7.77 (s, 1H, benzylidene); 13C NMR (CDCl3, δ, ppm): 166.76 (C=O of ester),
164.24 (C=O of ester), 162.42 (C=O of ester), 142.08, 138.45, 136.71, 132.95, 132.39, 131.68,
128.26, 127.99, 126.43, 126.36, 126.15, 123.29, 121.26, 121.08, 110.31, 110.20, 61.75
(COOCH2CH3), 61.68 (COOCH2CH3), 60.66 (COOCH2CH3), 32.11 (N-CH3), 14.17
(COOCH2CH3), 14.09 (COOCH2CH3); LCMS (m/z): 449 [M]+; Anal. % calcd. for C26H27NO6:
C, 69.47; H, 6.05; N, 3.12. Found: C, 69.14; H, 5.83; N, 2.86.
Methyl 2-{3-[(2-ethoxycarbonyl)-1-methyl-1H-indol-3-yl]benzylidene}-3-oxobutanoate (11c,
scheme 3): A mixture of (11) (0.307, 1 mmol), methyl acetoacetate (0.160, 1 mmol), and
piperidinium acetate (0.15ml) in toluene (25ml) was refluxed for 14 h with continuous removal
of water using a Dean-Stark trap. After cooling to room temperature, the solution was
concentrated to crude reaction mixture, which was purified by column chromatography using
EtOAc/hexane (3:7) as eluent to afford the desired compound (11c) (0.205 g, 50%) as pale
brown viscous mass. FTIR (CHCl3, ν, cm-1): 2951 (C-H stretch, Ar), 2865 and 2844 (C-H stretch
N-CH3, antisymmetric and symmetric), 1738 (C=O stretch, ester), 1641 (C=O stretch, ketone),
1528 (C=C stretch, Ar), 1454 (C=C stretch, Ar), 744 (C-C out of plane bending, phenyl ring 1,3disubstituted); lH NMR (CDCl3), mixture of geometric isomers, δ, ppm: 1.02 (t, 3H, OCH2CH3), 1.03 (t, 3H, -OCH2CH3), 2.38 (s, 3H, -COCH3), 2.43 (s, 3H, -COCH3), 3.78 (s, 3H,
-OCH3), 3.84 (s, 3H, -OCH3), 4.09 (two overlapping s, 3H each, N-CH3), 4.17 (two overlapping
quartets, 2H each, -OCH2CH3), 7.16 [m, 2H (1H each, Ar)], 7.44 [m, 14H (7H each, Ar)], 7.62
(s, 1H, benzylidene), 7.74 (s, 1H, benzylidene); 13C NMR (CDCl3, mixture of E and Z isomers,
δ, ppm): 208.13 and 198.12 (C=O of COCH3), 169.04 and165.18 (C=O of COOCH3), 159.02
and 158.66 (C=O of ester), 140.82 and 140.68, 138.51 and 138.12, 137.69 and137.15, 136.33
and 136.04, 132.00 and 131.91, 127.16 and 127.09, 125.03 and 124.84, 122.36 and 122.04,
120.89 and 120.84, 120.80 and 120.58, 119.98 and119.60, 119.27 and 118.96, 117.30 and
116.06, 109.54 and109.33, 108.98 and 108.86, 101.46 and 99.89, 61.94 and 61.54
(COOCH2CH3), 57.41 and 54.37 (-COOCH3), 37.05 and 31.79 (N-CH3), 29.80 and 29.74 (COCH3), 14.22 and 13.97 (COOCH2CH3); LCMS (m/z): 405 [M]+; Anal. % calcd. for
C24H23NO5: C, 71.10; H, 5.72; N, 3.45. Found: C, 70.94; H, 5.43; N, 2.96.