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Ramakrishna V S Nirogi et al.
(1H, d, J = 7.74 Hz), 7.37 (1H, t, J = 7.49 Hz), 7.27 then refluxed for 4 h and then concentrated to obtain a
(1H, t, J = 7.54 Hz), 2.20 (3H, s). ESI mass: m/e 313.9 crude compound. The crude compound was triturated
(M − H)+.
with ethyl acetate (25 mL) and resultant white solids
were filtered and dried under vacuum to obtain title
compound (1.15 g, 67% yield). H NMR (400 MHz,
DMSO-d6)δ: 7.88 (2H, t, J = 7.44 Hz), 7.81 (2H, d,
J = 7.89 Hz), 7.55–7.67 (15H, m), 7.40 (1H, t, J =
7.87 Hz), 7.18 – 7.29 (4H, m), 5.25 (2H, d, J = 15.78
Hz), 2.18 (3H, s).
1
2.4 General procedure for the preparation
of 3-Methyl-1-(3-hydroxymethyl benzenesulfonyl)-
1H-indole (4m, R1 =3-CH3, R2 = H)
A solution of 3m (1.5 g, 4.76 mmol) in dry THF (25
mL) was added to a stirred suspension of lithium alu-
minium hydride (0.54 g, 14.3 mmol) below 0◦C and
further stirred for 3 h at this temperature. After com-
pletion of the reaction (TLC), ice cold water (5 mL)
was added slowly to the reaction mixture to decompose
excess of LAH. The resultant mixture was filtered and
the residue was washed with ethyl acetate (25 mL × 2).
The filtrate was dried over anhydrous Na2SO4 and con-
centrated under reduced pressure. The resultant crude
compound was chromatographed (SiO2, 25:75 EtOAc-
hexanes as eluent) to afford title compound as syrupy
mass (1.2 g, 84% yield). IR (cm−1): 3199 (ArCH2O-H
stretching vibration), 1371 and 1166 (asymmetric and
symmetric stretching vibrations of –SO2 group respec-
tively). 1H NMR (400 MHz, CDCl3)δ: 7.98 (1H, d, J =
8.27 Hz), 7.86 (1H, bs), 7.77 (1H, d, J = 7.87 Hz), 7.50
(1H, d, J = 7.63 Hz), 7.45 (1H, d, J = 7.57 Hz), 7.39
(1H, t, J = 7.79 Hz), 7.29–7.33 (2H, m), 7.23 (1H, d,
J = 7.16 Hz), 4.68 (2H, d, J = 5.4 Hz), 2.24 (3H, s).
ESI mass: m/e 302.2 (M + H)+.
2.7 General procedure for the preparation of
3-Methyl-1-[3-(1-methylpiperidin-4-ylidene methyl)
benzenesulfonyl]-1H-indole
(8m, R1 =3-CH3, R2 = H)
Sodium hydride (0.096 g, 2.39 mmol, 60% oil sus-
pension) was added to a stirred solution of 6m (1g,
1.59 mmol) at room temperature, then heated to 55◦C
and maintained for 1 h. 1-Methyl-4-piperidone (0.22 g,
1.91 mmol) was added to the above mixture at room
temperature followed by stirring at 60◦C for 3 h. The
reaction mixture was then cooled to room tempera-
ture, poured on to water (50 mL), extracted with ethyl
acetate (50 mL x 4). The organic extracts were com-
bined, washed with brine (50 mL), dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The
resultant crude compound was chromatographed (SiO2,
2:98 ammonical MeOH:EtOAc as eluent) to afford title
compound as syrupy mass (0.41 g, 68% yield). IR
(cm−1): ∼3021 (asymmetric stretching vibrations of -
C=C- functional group), ∼1328 and 1153 (asymmet-
ric and symmetric stretching vibrations of –SO2 group
2.5 General procedure for the preparation of 3-
Methyl-1-(3-bromomethylbenzenesulfonyl)-1H-indole
(5m, R1 =3-CH3, R2 = H)
1
respectively). H NMR (400 MHz, DMSO-d6)δ: 7.99
(1H, d, J = 8.23 Hz), 7.66–7.69 (1H, m), 7.62–7.62
(1H, s), 7.46 (1H, d, J = 7.94 Hz), 7.33–7.37 (2H, m),
7.28–7.31 (2H, m), 7.23–7.24 (1H, m), 6.20 (1H, s),
2.49 (2H, t, J = 5.36 Hz), 2.39 (2H, t, J = 5.60 Hz),
2.31 (3H, s), 2.27–2.30 (4H, m), 2.24 (3H, s). ESI mass:
m/e 381.3 (M + H)+.
Phosphorus tribromide (0.16 mL, 1.66 mmol) was
added to a stirred solution of 4m (1 g, 3.32 mmol)
in DCM (20 mL) at 5–10oC and then stirred below
10◦C for further 0.5 h. After completion of the reac-
tion (TLC), the reaction mixture was poured on to
cold water (25 mL). The organic layer was separated,
washed with saturated NaHCO3 solution (10 mL), brine
solution (10 mL), dried over anhydrous Na2SO4 and
concentrated under reduced pressure to obtain title
compound as oily mass (1.02 g, 85% yield). This was
used as such for further reaction.
2.8 General procedure for the preparation of
3-Methyl-1-[3-(1-methylpiperidin-4-yl methyl)
benzenesulfonyl]-1H-indole (9m, R1 =3-CH3,
R2 = H)
A stirred mixture of 8m (0.4 g, 1.05 mmol) and Pd/C
in methanol was stirred for 4 h under H2 (g) bub-
bling. Then the reaction mixture was filtered and con-
centrated under reduced pressure. The resultant crude
mass was chromatographed (SiO2, 2:98 ammonical
2.6 General procedure for the preparation of
[3-(3-Methyl-1H-indole-1-sulfonyl) benzyl]-triphenyl
phosphonium bromide (6m, R1 =3-CH3, R2 = H)
Triphenyl phosphine (0.72 g, 2.74 mmol) was added to MeOH:EtOAc as eluent) to afford title compound as
a stirred solution of 5m (1 g, 2.74 mmol) in acetonitrile solid mass (0.36 g, 90% yield). IR (cm−1): 2930
(25 mL) at room temperature. The reaction mixture was (due to sp3 C-H stretching vibrations), 1365 and 1171