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One-pot Synthesis of the Indole Derivative
97
EXPERIMENTAL
3
(3) (2.1 g, 0.01 mole) in ethanol (30 cm ) were added at a tem-
perature between –8 °C and –10 °C. After 2 hours of mixing the
precipitated N,N'-dicyclohexylurea was filtered off and the fil-
Elemental analyses were performed on Perkin-Elmer 2400
analyzer in the Regional Laboratory of Jagiellonian University.
Mass spectra were recorded using Finnigan MAT 95 S spectrom-
3
trate was concentrated. To the oil residue 20 cm of methylene
chloride was added. After filtration and drying, crude
Indapamide (1) was obtained with 70% yield. This product was
crystallized from mixture isopropyl alcohol:water = 1:1.5.
According to the described procedure, crystallized Indapamide
(1) was obtained with 55% yield (2.0 g). All spectral data, as well
as physical and chemical properties of the obtained compound 1
are the same as described above for 4-chloro-3-sulfamoyl-N-
(2,3-dihydro-2-methyl-1H-indol-1-yl)benzamide (1) prepared by
using mixed anhydrides.
1
eter. H NMR spectra were recorded in DMSO with a VARIAN
(300 MHz) spectrometer and tetrametylsilane (TMS) as an inter-
nal standard. IR spectra were as KBr pellets on a Perkin-Elmer
type FT-IR PARAGON 1000 spectrometer within the range of
4000 to 400 cm . Chromatographic analyses were performed on
an Alliance 2690 D liquid chromatograph with UV detector
(Waters 2487 Dual λ Absorbance Detector) Waters firm.
-1
Synthesis of 4-Chloro-3-sulfamoyl-N-(2,3-dihydro-2-methyl-
1H-indol-1-yl)benzamide (1) Using Mixed Anhydrides of
Formula 2.
REFERENCES AND NOTES
To a solution of 4-chloro-3-sulfamoylbenzoic acid (4) (2.35 g,
3
0.01mole) in acetone (25 cm ), triethylamine (2.52 g, 0.025
[1] M. Chaffman, R. C. Heel, R. N. Brogden, T. M. Speight and
G. S. Avery, Drugs, 28, 189 (1984)
mole) at a temperature between 0 °C and –4 °C ethyl chlorofor-
mate (1.41 g , 0.013 mole) and after several minutes 1-amino-2-
methylindoline (5) (1.48 g, 0.01 mole) were added. After 1 hour
of mixing, triethylamine hydrochloride was filtered off and the
filtrate was evaporated under reduced pressure. To the residue,
aqueous ammonium hydroxide was added to pH about 9 and the
product was extracted with methylene chloride. The crude prod-
uct, obtained from concentrated solution, was crystallized from a
mixture isopropyl alcohol:water = 1:1.5, resulting in 1.1 mg of 1
(30% yield). A comparable reaction yield of 1 was obtained using
[2] French Patent 2003311 (1969); Chem. Abstr., . 72, 100500t
(1970).
[3] French Patent 2663324 (1990); Chem. Abstr., 116, 86245g
(1992).
[4] French Patent 2663325 (1990); Chem. Abstr., 116, 86246h
(1992).
[5] J. B. Wright and R. E. Willette, J. Med. and Pharm. Chem.,
5, 811 (1962).
[6] Japanese Patent 54030159 (1977); Chem. Abstr., 91,
56813p (1979).
[7] European Patent 54892 (1981); Chem. Abstr., 97, 198194f
(1982).
[8] R. A. Boissonnas, Helv. Chim. Acta, 34, 874 (1951).
[9] T. Wieland, and H. Bernhard, Ann., 572, 190 (1951).
[10] S. L. Schreiber, R. E. Claus, and J. Reagan, Tetrahedron
Lett., 23, 3867 (1982).
[11] Encyclopedia of Reagents for Organic Synthesis, Editor –
in –Chief L. A. Paquette, Vol.1, John Willey & Sons, Chichester, New
York, Brisbane, Toronto, Singapore, 1995, pp. 1751.
1
tetrahydrofurane in place of acetone as solvent. MS and H NMR
-1
data of 1 are presented in a main text; IR: cm 3655 - 3068, 2966
- 2843, 1656, 1599 - 1476, 1539, 1460, 1382, 1342, 1175, 1297,
903, 847, 719.
Anal. Calcd. for C H ClN O S (365.83): C, 52.53; H, 4.41;
16 16
3 3
N, 11.49. Found: C, 52,74; H, 4,55; N, 11,20.
Synthesis of 4-Chloro-3-sulfamoyl-N-(2,3-dihydro-2-methyl-
1H-indol-1-yl)benzamide (1) Using DCC (3).
⁄
⁄
[12] M. Mikolajczyk, and P. Kielbasin´ski; Tetrahedron, 37, 233
(1981).
To a solution of 4-chloro-3-sulfamoylbenzoic acid (4) (2.35 g,
3
0.01 mole) in ethanol (30 cm ), 1-amino-2-methylindoline (5)
(1.48 g, 0.01 mole) followed by N,N'-dicyclohexylcarbodiimide
[13] Polish patent application P-338964.
[14] Polish patent application P-340517.