Molecules 2005, 10
490
The temperature of the reactions at the point when TREN is added seems to have a significant
impact on the success of the reactions. Several attempts to add TREN at room temperature resulted in
dark-colored gums, while additions in an ice bath gave relatively clean products. The rapidity of the
addition of TREN is also critical, as the acyl chloride derivatives initially prepared are moisture
sensitive.
Conclusions
We have developed a facile method for the synthesis of two novel tris-indolyl amines. These
tripodal compounds are important intermediates in the development of new drugs with potential iron-
chelating abilities. As efforts to improve the water-solubility of these compounds are underway, the
success in their preparation should provide a general route to a new class of compounds.
Experimental
General
1
Melting points are uncorrected. H-NMR spectra were obtained using a Bruker 250 MHz multi-
nuclear spectrometer. MS were measured using a Shimadzu QP 5050A instrument.
Tris(2-[indole-3-glyoxylamido]ethyl)amine (4). To indole (10.07 g, 86.1 mmol) in ether (200 mL) was
added dropwise oxalyl choride (14.6 g, 114.6 mmol) over 15 mins. After stirring for 30 min, the
solution was filtered to yield 3 as a yellow solid, which was rapidly dissolved in THF (50 mL). To 3
in THF at 0°C was added a solution of TREN (6.14 g, 42.0 mmol) and TEA (42.3 mmol) in THF (10
mL). After stirring at 0°C for 1 h, the solution was filtered and the filtrate was evaporated to yield 4 as
a beige solid which crystallized from MeOH. Yield 5.93 g (31.4%); mp > 250°C. 1H-NMR (250 MHz,
DMSO-d6) 8.75 (s, 3H, H2), 8.65 (t, J=5.29 Hz, 3H, H1), 8.14 (d, J=6.9 Hz, 3H, H4), 7.47 (d, J=7.1
Hz, 3H, H7), 7.22 (t, J=7.0 Hz, 3H, H5 or H6), 7.16 (t, J=7.0 Hz, 3H, H6 or H5), 3.31 (m, 6H, Ha), 2.71
(bt, 6H, Hb); MS (M+1)+ = 660 for C36H33N7O6
Tris(2-[indole-3-amido]ethyl)amine (5). Indole-3-carboxylic acid (0.56 g, 3.4 mmol) dissolved in
SOCl2 (6 mL) was stirred at 0°C. After 1.5 h, the solution was rotary evaporated, and to the resulting
oil was added TREN (0.62 g, 4.2 mmol) and TEA (0.46 g, 4.6 mmol) in THF (25 mL). After stirring
at 0°C for 30 min, the solution was vacuum filtered to yield 5 as a beige solid which was recrystallized
1
from MeOH. Yield 0.28 g (43.0%); mp > 250°C. H-NMR (250 MHz, DMSO-d6) 7.98 (s, 3H, H2),
7.44 (m, 3H, H1), 7.17 (m, 3H, H4), 7.15 (d, 3H, H7), 7.14 (m, 3H, H5 or H6), 7.12 (m, 3H, H6 or H5),
3.40 (m, 12H, Ha and Hb); MS (M+1)+ = 576 for C33H33N7O3.
References
1. Shrader, W. D.; Celebuski, J.; Kline, S. J.; Johnson, D. Tetrahedron Lett. 1988, 29, 1351.
2. Baret, P.; Béguin, C. G.; Boukhalfa, H.; Caris, C.; Laulhére, J.-P.; Pierre, J.-L.; Serratrice, G.
J. Am. Chem. Soc. 1995, 117, 9760.