P. A. Gale et al.
FULL PAPERS
a method described by Bates et al.[7] N-butyl-7-nitro-1H-indole-2-carbox-
amide (0.25 g, 0.96 mm) and a Pd/C 10% catalyst (0.03 g) were suspended
in ethanol (25 mL). The flask was evacuated and the mixture placed
under a hydrogen atmosphere and stirred vigorously for 3 h. After this
time the palladium catalyst was removed by filtration through celite and
the filtrate taken to dryness and placed under reduced pressure. This
gave a white solid. Assumed yield: 100%. The white solid was dissolved
in a two-phase solution of sat. NaHCO3 (20 mL) and DCM (20 mL). This
solution was stirred vigorously under nitrogen at room temperature and
triphosgene (0.30 g, 1.00 mm) added in two equal aliquots. The solution
was allowed to stir overnight. The two-phase solution was then filtered
and the white solid was sonicated in water (250 mL) for 30 mins. A white
solid was then collected by filtration and washed with DCM (20 mL) and
diethyl ether (20 mL). Yield: 49%; m.p.: 1388C; 1H NMR (300 MHz,
[D6]DMSO): d=0.92 (t, J=7.3 Hz, 3H), 1.36 (dd, J1 =6.93 Hz, J2 =
13.5 Hz, 2H), 1.54 (t, J=7.0 Hz, 2H), 3.33 (m, 2H), 7.01 (t, J=7.7 Hz,
1H), 7.16 (s, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.51 (d, J=7.3 Hz, 2H), 8.51
(s, NH, 1H), 8.88 (s, NH, 1H), 11.37 ppm (s, NH, 1H); 13C{1H} NMR
(75 MHz, [D6]DMSO): d=13.7 (CH3), 19.6 (CH2), 31.3 (CH2), 38.4
(CH2), 102.8 (ArCH), 113.7 (ArCH), 116.0 (ArCH), 120.2 (ArCH), 124.9
(ArC), 128.0 (ArC), 128.6 (ArC), 131.7 (ArC), 153.1 (CO), 160.8 ppm
(CO); IR (film): n˜ =3340, 3270, 1640, 1560 cmÀ1; LRMS (ESÀ): m/z:
487.4 [MÀH]À; HRMS (ES+): m/z: exp: 489.2604 [M+H]+; calcd:
489.2609 [M+H]+.
161.0 ppm (CO); IR (film): n˜ =3290, 1635, 1575 cmÀ1; LRMS (ESÀ): m/z:
555.3 [MÀH]À; HRMS (ES+): m/z: exp: 557.2294 [M+H]+; calcd:
557.2301 [M+H]+
Bis((2-pyridin-2-yl)-7-nitro-1H-indole-2-carboxamine)-urea (4): (2-pyri-
dinyl-2-yl)-7-nitroindole-2-carboxamide (0.179 g, 0.635 mm) was dissolved
in ethanol (50 mL). Palladium on carbon 10% (0.030 g) was added. The
reaction vessel was evacuated and then supplied with hydrogen and
stirred at room temperature for 6 h. The reaction mixture was then fil-
tered through celite and reduced in vacuo to yield a white solid. As-
sumed yield: 100%. The white solid and triphosgene (0.037 g, 0.125 mm)
were dissolved in DCM (50 mL) and saturated sodium bicarbonate solu-
tion (50 mL) and stirred at room temperature for 2 h. The organic phase
was separated and reduced in vacuo. The resulting brown solid was soni-
cated in water (500 mL) for 1 h. The solid was filtered and washed with
water (2ꢄ25 mL) and diethyl ether (2ꢄ25 mL). This yielded a white
solid. Yield: 55%; m.p.: 2198C; 1H NMR (300 MHz, [D6]DMSO): d=
7.06 (t, J=7.7 Hz, 2H), 7.17 (dd, J=6.6 Hz, 4.8 Hz, 2H), 7.38 (d, J=
8.0 Hz, 2H), 7.59 (d, J=7.7 Hz, 2H), 7.70 (s, 2H), 8.25 (d, J=8.4 Hz,
2H), 8.41 (d, J=3.7 Hz, 2H), 8.97 (s, NH, 2H), 10.95 (s, NH, 2H),
11.65 ppm (s , NH, 2H); 13C{1H} NMR (75 MHz, [D6]DMSO): d=105.8
(ArCH), 114.6 (ArCH), 116.6 (ArCH), 119.5 (ArCH), 119.7 (ArCH),
120.5 (ArCH), 125.0 (ArC), 128.6 (ArC), 129.0 (ArC), 130.6 (ArC), 138.2
(ArCH), 148.0 (ArCH), 152.0 (ArC), 153.1 (CO), 160.0 ppm (CO); IR
(film): n˜ =3269, 1644, 1539 cmÀ1; LRMS (ESÀ): m/z: 529.2 [MÀH]À;
HRMS (ES+): m/z: exp: 531.1879 [M+H]+; calcd: 531.1893 [M+H]+.
7,7’-carbonylbis(azanediyl)bis(N-phenyl-1H-indole-2-carboxamide
(2):
The synthesis of 7-nitro-N-phenyl-1H-indole-2-carboxamide is taken
from a method described by Bates et al.[7] 7-Nitro-N-phenyl-1H-indole-2-
carboxamide (0.20 g, 0.71 mm) and a Pd/C 10% catalyst (0.02 g) were
suspended in ethanol (25 mL). The flask was then evacuated and the mix-
ture placed under a hydrogen atmosphere and stirred vigorously for 3 h.
After this time the palladium catalyst was removed by filtration through
celite and the filtrate taken to dryness and placed under reduced pressure
Crystallization
Crystallizations were performed by dissolving ca. 0.05 mmol of receptor 2
in 2 mL of DMSO followed by addition of approximately 0.25 mmol tet-
rabutylammonium dihydrogen phosphate and allowing the solution to
stand.
X-ray Structure Determination
affording
a white solid. 7-Amino-N-phenyl-1H-indole-2 carboxamide
(0.18 g, 0.71 mm) was dissolved in a mixture of DCM (20 mL) and a satu-
rated aqueous solution of NaHCO3 (20 mL). Triphosgene (0.28 g,
0.95 mm) was added in portions to the two-phase solution and the mix-
ture was left stirring under a nitrogen atmosphere overnight. The organic
layer was diluted with DCM (100 mL), washed with water, dried over
MgSO4, filtered, and concentrated in vacuo. The pure product was isolat-
ed by sonication in MeOH (5 mL) for 3 mins and removed by filtration.
The product was isolated as a white solid. Yield: 30%; m.p.: 1748C;
1H NMR (300 MHz, [D6]DMSO): d=7.05–7.15 (m, 4H), 7.36–7.43 (m,
6H), 7.51 (d, J=1.8 Hz, 2H), 7.60 (d, J=7.7 Hz, 2H), 7.84 (d, J=7.7 Hz,
4H), 8.97 (s, urea NH, 2H), 10.30 (s, amide NH, 2H), 11.62 ppm (s,
indole NH, 2H); 13C{1H} NMR (75 MHz, [D6]DMSO): d=104.5 (ArCH),
114.3 (ArCH), 116.3 (ArCH), 120.3 (ArCH), 120.5 (ArCH), 123.7
(ArCH), 125.0 (ArC), 128.6 (ArC), 128.8 (ArCH), 131.3 (ArC), 138.9
Data were collected on a Bruker Nonius KappaCCD with a Mo rotating
anode generator (l=0.71073) employing phi and omega scans; standard
procedures were followed. Lorentz and polarization corrections were ap-
plied during data reduction with DENZO[9] and multi-scan absorption
corrections were applied using SADABS.[10] The structure was solved and
refined using the SHELX suite of programs.[11]
Crystal data for the monohydrogen phosphate complex of compound
2.TBA2HPO4.2H2O: C63H101N8O9P, 0.18ꢄ0.05ꢄ0.02 mm3, Mr =1145.49,
T=120(2) K, Triclinic, space group P-1, a=13.9084(5), b=16.5116(5),
c=16.5971(4) ꢂ, a=65.864(2)8, b=72.349(2)8, g=71.014(2)8, V=
3224.48(17) ꢂ3, 1calc =1.180 MgmÀ3, m=0.102 mmÀ1, Tmin =0.9818 Tmax
=
0.9980, Z=2, reflections collected: 48032, independent reflections: 11275
(Rint =0.0900), 2qmax =25.008, Parameters=768, largest difference peak
and hole=0.748 and À0.753 eꢂÀ3, final R indices [I>2sI]: R1=0.0931,
(ArC), 153.2 (CO), 159.7 ppm (CO); IR (film): n˜ =3289, 1661 cmÀ1
;
wR2=0.1597,
R
indices (all data): R1=0.1586, wR2=0.1914.
LRMS (ESÀ): m/z: 527.5 [MÀH]À; HRMS (ES+): m/z: exp: 551.1794
CCDC 734479 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
[M+Na]+; calcd: 551.1802 [M+Na]+
Bis(benzyl-7-nitro-1H-indole-2-carboxamine)-urea (3): N-benzyl-7-nitro-
indole-2-carboxamide (0.243 g, 0.824 mm) was dissolved in ethanol
(20 mL). Palladium on carbon 10% (0.025 g) was added. The reaction
vessel was evacuated and placed under a hydrogen atmosphere and
stirred at room temperature for 6 h. The reaction mixture was then fil-
tered through celite and reduced in vacuo to yield a white solid. As-
sumed yield: 100%. The white solid and triphosgene (0.051 g, 0.171 mm)
were dissolved in a two-phase solution of DCM (50 mL) and saturated
sodium bicarbonate solution (50 mL) and stirred at room temperature
for 2 h. The two-phase solution was then filtered. The resulting grey solid
was sonicated in water (500 mL) for 1 hr. A white solid was collected by
filtration and washed with water (2ꢄ25 mL), DCM (10 mL), and diethyl
ether (2ꢄ25 mL). Yield: 56%; m.p.: 1628C; 1H NMR (300 MHz,
[D6]DMSO): d=4.53 (d, J=5.85 Hz, 4H), 7.02 (t, J=7.9 Hz, 2H), 7.20–
7.38 (m, J=7.7 Hz, 14H), 7.52 (d, J=7.7 Hz, 2H), 8.89 (s, NH, 2H), 9.13
(t, J=5.9 Hz, NH, 2H), 11.46 ppm (s, NH, 2H); 13C{1H} NMR (75 MHz,
[D6]DMSO): d=42.2 (CH2), 103.4 (ArCH), 113.3 (ArCH), 115.9
(ArCH), 120.3 (ArCH), 125.2 (ArCH), 126.8 (ArC), 127.3 (ArCH), 128.1
Acknowledgements
P.A.G. thanks the EPSRC for funding and for access to the crystallo-
graphic facilities at the University of Southampton. C.C. would like to
thank Italian Ministero dell’Istruzione, dell’Universitꢀ e della Ricerca
Scientifica (MIUR) for financial support (Project PRIN-2007C8RW53).
[1] a) S. Camiolo, P. A. Gale, M. B. Hursthouse, M. E. Light, A. J. Shi,
11228–11229; c) S. Camiolo, P. A. Gale, M. B. Hursthouse, M. E.
Gale, K. Navakhun and M. Maynard-Smith, Acta Crystallogr. 2005,
(ArC), 128.3 (ArCH), 128.5 (ArC), 131.4ACTHUNRGTNE(NUG ArC), 139.6 (ArC), 153.2 (CO),
560
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 555 – 561