326
W. Löwe, S. Witzel, S. Tappmeyer and R. Albuschat
Vol. 41
mixture was poured onto ice and extracted with ethyl acetate. The
combined organic layers were washed with water, dried (sodium sul-
fate) and evaporated. The resulting raw product was purified by col-
umn chromatography (silica gel, dichloromethane/methanol 9:1, v/v).
The collected fractions (Rf-ethyl acetate 0.88-0.90) were evaporated
and the resulting residue was redissolved in a mixture of ethyl acetate
and n-hexane (1:1, v/v) and the resulting solid was collected to obtain
33 as pale beige powder, yield 0.2 g (26%), mp 193 ºC, ir (potassium
hexene were added and the mixture was heated to reflux for 4
hours. Then it was filtered hot and the filtrate was evaporated.
The raw product was purified by flash chromatography (silica
gel, dichloromethane/methanol 9:1, v/v). Compound 36 was
obtained as green powder, yield 19 mg (9.5%), mp 184 ºC; ir
(potassium bromide): OH 3404, 3191, CH 2930, arOCH
-1
3
2855, CO 1621 cm ; H nmr (dimethyl sulfoxide-d ): δ 12.64
1
6
(s, 1H, OH), 10.36 (s, 1H, OH), 8.08 (s, 1H, indole), 8.00 (d,
1H, J = 8.7 Hz, phenyl), 7.80 (d, 1H, J = 8.7 Hz, indole), 7.15
(d, 1H, J = 2.1 Hz, indole), 6.87 (dd, J = 2.1, 8.9 Hz, indole),
6.42 (dd, 1H, J = 2.3, 8.8 Hz, phenyl), 6.30 (d, 1H, J = 2.3 Hz,
phenyl), 4.28 (q, 2H, J = 7.1 Hz, CH ), 3.84 (s, 3H, OCH ),
-1 1
bromide): OH, NH 3425, CO 1624 cm ; H nmr (dimethyl sulfox-
2
ide-d ): δ 10.78 (s, br, 1H, OH), 8.15 (s, 1H, chromone), 7.94 (d, 1H,
6
J = 8.7 Hz, chromone), 6.93 (dd, 1H, J = 2.1, 8.7 Hz, phenyl), 6.92 (d,
1H, J = 8.1 Hz, phenyl), 6.87 (d, 1H, J = 2.0 Hz, phenyl), 6.74 (d, 1H,
J = 1.9 Hz, chromone), 6.57 (dd, 1H, J = 1.9, 8.0 Hz, chromone), 5.17
2
3
1.40 ppm (t, 3H, J = 7.11 Hz, CH ); ms (electron impact, 70
3
+
eV): m/z 311 (M , 49%).
Anal. Calcd for C H NO : C, 69.44; H, 5.50; N, 4.50.
18 17 4
Found: C, 69.38; H, 5.70; N, 4.44.
ppm (s, 2H, NH , deuterium oxide-exchangeable); ms (electron
+
2
impact, 70 eV): m/z 287 (M , 31%, Cl).
Anal. Calcd. for C H ClNO •0.5H O: C, 60.72; H, 3.74; N,
35
15 10
4.72. Found: C, 61.39; H, 3.66; N, 4.50.
3
2
8-Methoxy-3-(2-piperidin-1-yl-ethoxy)-benzopyrano[2, 3-b]-
indol-11-one (37).
(6-Chloro-1H-indol-3-yl)-(2,4-dihydroxy-phenyl)-methanone
(34).
Compound 28 (400 mg, 0.9 mmole) and 0.8 g zinc dust were
heated at reflux in 25 mL acetic acid (50%) for 2 hours at 100 ºC.
After cooling the mixture was poured onto 100 mL ice and stan-
dardized on pH 8 with 10 N solution of sodium carbonate. The
solution was first extracted with dichloromethane, afterwards with
ethyl acetate. The combined organic layers were dried (sodium sul-
fate) and the solvent was evaporated. The raw product was purified
by flash chromatography (silica gel, dichloromethane/methanol
9:1, v/v) to obtain compound 39 as white powder, yield 11 mg
(2.9%), mp 263 ºC; ir (potassium bromide): NH 3433, CH 2933,
Compound 34 was obtained similarly to compound 3 3, but the
ethyl acetate/n-hexane (1:1, v/v) filtrate - resulting after compound
33 was removed by filtration - was evaporated and the residue was
dried in vacuum to obtain 210 mg (28%) of 34 as yellow powder,
-1
mp 178 ºC; ir (potassium bromide): OH, NH 3395, CO 1627 cm ;
1
H nmr (dimethyl sulfoxide-d ): δ 12.51 (s, 1H, OH, deuterium
6
oxide-exchangeable), 12.19 (s, 1H, NH, deuterium oxide-
exchangeable), 10.41 (s, 1H, OH, deuterium oxide-exchangeable),
8.13 (s, 1H, indole), 8.09 (d, 1H, J = 8.6 Hz, indole), 7.79 (d, 1H, J
= 8.7 Hz, phenyl), 7.56 (d, 1H, J = 1.9 Hz, indole), 7.23 (dd, 1H, J
-1
1
ArOCH 2853, CO 1630 cm ; H nmr (dimethyl sulfoxide-d ): δ
3
6
12.64 (s, 1H, NH), 8.10 (d, 1H, J = 8.8 Hz, phenyl), 7.93 (d, 1H, J
= 8.6 Hz, phenyl), 7.25 (d, 1H, J = 2.2 Hz, phenyl), 7.09 (dd, 1H, J
= 2.2, 8.8 Hz, phenyl), 6.98 (d, 1H, J = 2.2 Hz, phenyl), 6.88 (dd,
= 1.9, 8.6 Hz, indole), 6.41 (dd, 1H, J = 2.4, 8.8 Hz, phenyl), 6.33
13
ppm (d, 1H, J = 2.4 Hz, phenyl); C nmr (dimethyl sulfoxide-d ,
6
400 MHz): δ 191.6, 163.5, 163.4, 136.8, 134.9, 133.5, 127.4,
1H, J = 2.2, 8.5 Hz, phenyl), 4.23 (t, 2H, J = 5.8 Hz, CH ), 3.81 (s,
2
3H, OCH ), 2.72 (t, 2H, J = 5.8 Hz, CH ), 2.39,2.48 (m, 4H, piperi-
125.1, 122.6, 121.8, 114.2, 113.8, 111.8, 107.6, 102.7 ppm; ms
+
35
(electron impact, 70 eV): m/z 287 (M , 3%, Cl).
Anal. Calcd. for C H ClNO •0.5H O: C, 60.72; H, 3.74; N,
4.72. Found: C, 61.20; H, 3.88; N, 4.49.
3
dine), 1.44,1.58 (m, 4H, piperidine), 1.32,1.44 ppm (m, 2H, piperi-
2
15 10
3
2
13
dine); C nmr (dimethyl sulfoxide-d , 400 MHz): δ 171.0, 161.8,
6
156.6, 155.3, 154.9, 132.8, 126.5, 120.9, 116.9, 115.4, 113.4,
110.2, 101.6, 98.2, 96.1, 66.3, 57.0, 55.3, 54.2, 25.4, 23.7 ppm; ms
3-(2-Amino-4-methoxy-phenyl)-7-hydroxy-chromen-4-one (35).
+
(electron impact, 70 eV): m/z 392 (M , 8%).
Anal. Calcd. For C H N O •H O: C, 67.30; H, 6.38; N,
Compound 27 (1.0 g, 3.2 mmoles) was dissolved in 120 mL
ethanol. Palladium on carbon (10%, 1.0 g) and 6 mL cyclohexene
were added and the mixture was heated to reflux for 2 hours.
Then it was filtered hot and the filtrate was evaporated. The raw
product was resuspended in dichloromethane/methanol (9:1, v/v)
and 410 mg (45%) of 35 as pale yellow crystals could collected
23 24
2
4
6.82. Found: C, 67.81; H, 6.25; N, 6.60
2
REFERENCES AND NOTES
by filtratoin, mp 205 ºC; ir (potassium bromide): OH, NH 3321
-1
,
3262, ArOCH 2837, CO 1623 cm ; H nmr (dimethyl sulfox-
[*] Corresponding Author: Werner Löwe, Institute of Pharmacy,
Free University of Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin,
Germany; Telephone number: 0049-30-83858250; Fax number: 0049-30-
83853854; e-mail: wloewe@zedat.fu-berlin.de
1
3
ide-d ): δ 10.73 (s, 1H, OH), 8.08 (s, 1H, chromone), 7.94 (d, 1H,
6
J = 8.7 Hz, chromone), 6.93 (dd, 1H, J = 2.2, 8.7 Hz, chromone),
6.87 (d, 1H, J = 2.3 Hz, chromone), 6.85 (d, 1H, J = 8.4 Hz,
phenyl), 6.31 (d, 1H, J = 2.5 Hz, chromone), 6.19 (dd, 1H, J =
[1] A. Brzezinski, A. Debi, Eur. J. Obstetrics Gyn Reprod. Biol.,
85, 47 (1999)
2.5, 8.3 Hz, phenyl), 4.81 (s, 2H, NH ), 3.70 ppm (s, 3H, OCH );
2
3
[2] M. Makosza, M. Wenäll, M. Golinski, A. Kinowski, Bull. Soc.
Sci. Chim. Polon., 33, 427 (1985)
+
ms (electron impact, 70 eV): m/z 283 (M , 10%).
Anal. Calcd. for C NO : C, 67.84; H, 4.63; N, 4.94.
Found: C, 67.77; H, 4.40; N, 4.80.
H
16 13
4
[3] I. Vlattas, Eur. Pat. Appl., Europäisches Patentamt, 56 pp., EP
81461 A2 19830615, (1983), Chem. Abstr., 99,158476 (1983).
[4] W. Löwe, R. Gust, S. Witzel, C. Dietrich, German Offen.,
12pp., DE 19947863 A1 20010405, (2001), Chem. Abstr., 134, 280704
(2000).
(2, 4-Dihydroxy-phenyl)-(1-ethyl-5-methoxy-1H-indol-3-yl)-
methanone (36).
Compound 27 (0.2 g, 0.6 mmole) was dissolved in 50 mL
ethanol. Palladium on carbon (10%, 0.2 g) and 3 mL cyclo-
[5] I. D. Entwistle, R. A. W. Johnstone, T. J. Povall, J. Chem.
Soc., Perkin Trans. I, 1300 (1975).