An efficient synthesis of (3-indolyl)acetonitriles by reduction of hydroxamic acids

Article abstract of DOI:10.1007/s10593-016-1881-z

A new,highly efficient method was developed for the synthesis of (3-indolyl)acetonitriles by reduction of readily available (3-indolyl)hydroxamic acids with phosphorus trichloride. The nitriles obtained according to this method are of significant interest

Full text of DOI:10.1007/s10593-016-1881-z

DOI 10.1007/s10593-016-1881-z
Chemistry of Heterocyclic Compounds 2016, 52(5), 299–302
An efficient synthesis of (3-indolyl)acetonitriles
by reduction of hydroxamic acids
1
1
1
1
Alexander V. Aksenov *, Nicolai A. Aksenov , Zarema V. Dzhandigova , Inna V. Aksenova ,
2
1
1,3
Leonid G. Voskressensky , Alexander N. Smirnov , Michael A. Rubin *
1
North-Caucasus Federal University,
1
Pushkina St., Stavropol 355009, Russia; е-mail: alexaks05@rambler.ru
2
3
People’s Friendship University of Russia,
Miklukho-Maklaya St., Moscow 117198, Russia; e-mail: lvoskressensky@sci.pfu.edu.ru
University of Kansas,
251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA; е-mail: mrubin@ku.edu
6
1
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
016, 52(5), 299–302
Submitted April 22, 2016
Accepted May 12, 2016
2
A new, highly efficient method was developed for the synthesis of (3-indolyl)acetonitriles by reduction of readily available (3-indolyl)hydroxamic
acids with phosphorus trichloride. The nitriles obtained according to this method are of significant interest for structure-activity studies
of potential anticancer agents.
Keywords: hydroxamic acids, indoles, nitriles, reduction.
The structural motif of 3-cyanomethylindole, formed as
a result of tryptophan metabolism, is quite frequently found
protocol, using direct reduction of hydroxamic acids 4
(Scheme 1).
1
in the molecules of natural alkaloids that possess a wide
2
range of useful biological properties. It is not surprising
Scheme 1
that the development of synthetic approaches to similar
structures is among the important tasks of contemporary
medicinal chemistry. We have recently reported on unique
3
anticancer activity of (3-indolyl)hydroxamic acids 4.
These acids are formed as stable, isolable intermediates
during the synthesis of 2-quinolones 5 according to an
ANRORC reaction between indoles 1 and nitroolefins 2
4
that we previously investigated (Scheme 1) and showed
high degree of activity by suppressing the growth of
glioma, melanoma, esophageal cancer, and other cancer
cell lines stable against apoptosis and therefore resistant
3
against traditional chemotherapy drugs. Furthermore, we
identified excellent anticancer activity in one structural
analog of hydroxamic acids 4 that contained a nitrile group,
1
2
3
3
compound 6 (R = 2-naphthyl, R = Н, R = Ph). In our
research program devoted to the discovery of new potential
anticancer agents we needed quick access to small libraries
of nitriles similar to compound 6 with readily customized
structures. One possible method for such syntheses, based
5
on reduction of nitroalkanes 3, was reported by us in 2015.
In the current article we propose an alternative synthetic
0
009-3122/16/52(5)-0299©2016 Springer Science+Business Media New York
299

Chemistry of Heterocyclic Compounds 2016, 52(5), 299–302
Scheme 2
The transformation of hydroxycarbamoyl group to a
nitrile is usually achieved employing phosphorus tri-
The likely reaction mechanism is presented in Scheme 3.
We assume that heating the hydroxamic acid 4 in the presence
of phosphorus trichloride first led to phosphorylation of the
hydroxy group, accompanied by cyclocondensation of the
6
7
bromide or thionyl chloride under reflux in nonpolar,
aprotic solvents. However, in our case, the reaction under
these conditions resulted in substantial resinification of the
sensitive indole system. Moreover, partial hydrolysis of the
moisture sensitive reagents led to accumulation of strong
acids in the reaction mixture, catalyzing the rearrangement
intermediate N-[(dichlorophosphanyl)oxy]amide
7
to
Р-chlorodioxoazaphosphole 8. The subsequent elimination of
metaphosphoryl chloride resulted in the formation of nitrile
6 (Scheme 3).
4
of indole to 2-quinolone and substantially decreasing the
efficiency of obtaining the desired nitriles. During reaction
optimization, we found that these side reactions can be
suppressed by using phosphorus trichloride instead of
tribromide. Good yields of nitriles were obtained in
reactions carried out in refluxing benzene or ethyl acetate,
the latter of which was found to be more suitable because it
better dissolved the starting hydroxamic acids. Typical
reaction results and the obtained preparative yields of
purified products are shown in Scheme 2. The yields of
nitriles obtained by reducing nitroalkanes 3 according to
Scheme 3
5
the procedure published by us in 2015 are indicated in
parentheses for comparison (Scheme 1). Clearly, the new
synthetic procedure enables preparation of all the studied
compounds in better yields. It is also quite apparent that the
formation of least sterically hindered nitriles 6a,b with a
phenyl substituent at the C-2 atom of the indole ring occurs
most readily when the new synthetic procedure is used.
Nevertheless, the majority of examples were obtained for
indoles with unsubstituted nitrogen atom and 2-naphthyl
substituent at the С-2 atom (compounds 6c–i), because this
type of molecules presents the greatest interest for
investigation of biological activity. Additionally, N-methyl-
substituted indole 6j can be obtained as well, although in a
somewhat lower yield (Scheme 2).
Thus, we have developed a convenient preparative
method for obtaining 2-aryl-2-(indol-3-yl)-substituted
acetonitriles by direct reduction of readily available
hydroxamic acids with phosphorus trichloride. This
3
00

Chemistry of Heterocyclic Compounds 2016, 52(5), 299–302
5
1
method does not rely on heavy metals and is appropriate
for the synthesis of small libraries of compounds for
biomedical studies, such as those performed at our
laboratories for structure optimization of potential
anticancer agents.
(benzene) (mp 146–147°C) . H NMR spectrum (DMSO-d ),
6
δ, ppm (J, Hz): 11.85 (1H, s, NH); 8.11–8.04 (2H, m,
H Ar); 8.02–7.92 (2H, m, H Ar); 7.70 (1H, dd, J = 8.5,
J = 1.8, H Ar); 7.62–7.55 (2H, m, H); 7.47 (2H, d, J = 8.1,
H Ar); 7.42–7.36 (4H, m, H Ar); 7.36–7.28 (1H, m, H Ar);
7
.19 (1H, ddd, J = 8.2, J = 7.1, J = 1.1, H Ar); 7.05 (1H, ddd,
Experimental
J = 8.0, J = .1, J = 0.9, H Ar); 6.08 (1H, s, CH).
IR spectra were recorded on a Shimadzu IRTracer-100
2-(2-Fluorophenyl)-2-[2-(naphthalen-2-yl)-1H-indol-3-yl]-
1
13
instrument in NaCl. H and С NMR spectra were
acquired on a Bruker Avance III spectrometer (400 and 100
MHz, respectively) with TMS as internal standard. High-
acetonitrile (6d). Yield 289 mg (77%), colorless crystals, mp
5
186–187°C (benzene) (mp 186–187°C) , R
f
0.47 (1:1 hexane–
–1
EtOAc). IR spectrum, ν, cm : 3451, 2357, 2332, 1485,
1
resolution mass spectra were recorded for MeCN/H
solutions on a Bruker maXis Impact quadrupole TOF mass
spectrometer coupled to HPLC, calibration with HCO Na/
HCO H, electrospray ionization. Melting points were deter-
2
O
1454, 1219, 860, 827, 762, 743. H NMR spectrum
(CDCl ), δ, ppm (J, Hz): 8.40 (1H, s, NH); 7.82–7.68 (4H,
3
2
m, H Ar); 7.64 (1H, d, J = 8.0, H Ar); 7.49–7.38 (4H, m,
H Ar); 7.31 (1H, d, J = 8.1, H Ar); 7.22–7.12 (2H, m,
H Ar); 7.06 (1H, t, J = 7.3, H Ar); 7.02–6.90 (2H, m,
2
mined on a Stuart SMP30 apparatus. The reaction progress
and purity of the obtained compounds were controlled by
TLC on Silufol UV-254 plates, with hexane–EtOAc eluent
in the indicated proportions. Synthesis of the starting
hydroxamic acids 4 was described in our previous work.3
Preparation of (2-aryl)-2-(2-aryl-1H-indol-3-yl)aceto-
nitriles 6a–j (General method). Phosphorus trichloride
1
3
H Ar); 5.70 (1H, s, CH). C NMR spectrum (CDCl ), δ, ppm
3
1
(J, Hz): 171.2; 160.2 (d, JCF = 249.3); 136.9; 136.1; 133.3
(d, J = 15.2); 130.3; 130.2; 129.4 (d, J = 8.2); 129.1 (d,
J = 2.7); 128.8; 128.3; 128.0 (d, J = 3.3); 127.1; 127.0;
126.1; 125.8; 124.6 (d, J = 3.7); 123.1; 120.9; 119.7; 118.8;
116.1; 115.9; 111.5; 104.8; 28.2. Found, m/z: 399.1276
+
(
131 μl, 206 mg, 1.50 mmol) was added to a solution of
[M+Na] . C26
H
17FN Na. Calculated, m/z: 399.1268.
2
hydroxamic acid 4 (1.0 mmol) in ethyl acetate and the
obtained mixture was refluxed for 2 h. The mixture was
then cooled and poured into water (50 ml), neutralized with
aqueous ammonia, and extracted with benzene (3×10 ml).
The combined extracts were concentrated under vacuum,
and the dry residue was purified by chromatography on
silica gel.
2-(3-Fluorophenyl)-2-[2-(naphthalen-2-yl)-1H-indol-3-yl]-
acetonitrile (6e). Yield 274 mg (73%), colorless crystals,
R 0.33 (1:1 hexane–EtOAc), mp 92–93°C (benzene) (mp 92–
f
5 –1
93°C) . IR spectrum, ν, cm : 3451, 2357, 2332, 1485, 1454,
1
1219, 860, 827, 762, 743. H NMR spectrum (CDCl ), δ,
3
ppm (J, Hz): 8.43 (1H, s, NH); 8.00–7.94 (2H, m, H Ar);
7.93–7.85 (2H, m, H Ar); 7.62–7.54 (3H, m, H Ar); 7.48
(2H, dd, J = 12.3, J = 8.1, H Ar); 7.42 (1H, d, J = 1.1,
H Ar); 7.38–7.33 (1H, m, H Ar); 7.31–7.26 (3H, m, H Ar);
2
-Phenyl-2-(2-phenyl-1H-indol-3-yl)acetonitrile (6a).5
Yield 258 mg (84%), white amorphous material, R
f
0.46
4:1 hexane–EtOAc). IR spectrum, ν, cm : 3338, 3070,
029, 2376, 2349, 1691, 1659, 1498, 1449, 1207, 1072.
–
1
13
(
7.18–7.12 (1H, m, H Ar); 5.65 (1H, s, CH). C NMR
spectrum (CDCl ), δ, ppm (J, Hz): 160.1 (d, J = 247.3);
3
3
1
H NMR spectrum (CDCl
3
), δ, ppm (J, Hz): 8.28 (1H, s,
137.6; 137.2; 136.3; 135.1; 133.4 (d, J = 10.8); 130.3;
129.5; 128.6; 128.4; 128.3; 128.1; 128.0; 127.5; 127.3;
126.6; 125.7; 125.5; 123.5; 121.1; 119.8; 119.1; 111.5;
NH); 7.42–7.31 (9H, m, H Ar); 7.28–7.20 (3H, m, H Ar);
7
(
.16–7.12 (1H, m, H Ar); 7.03–6.98 (1H, m, H Ar); 5.52
1H, s, CH). 13C NMR spectrum (CDCl
), δ, ppm: 137.0;
105.9; 77.2; 33.3. Found, m/z: 399.1276 [M+Na] .
+
3
1
1
1
36.1; 135.5; 131.6; 129.4 (2C); 129.1 (2C); 128.6 (2C);
28.0; 127.3 (2C); 126.8; 123.2; 120.8; 120.0; 119.7;
C
26
H
17FN Na. Calculated, m/z: 399.1268.
2
2-(2-Bromophenyl)-2-[2-(naphthalen-2-yl)-1H-indol-
3-yl]acetonitrile (6f). Yield 336 mg (77%), colorless
+
11.3; 106.1; 77.2; 33.5. Found, m/z: 331.1207 [M+Na] .
C
22
2
H
16
N
2
Na. Calculated, m/z: 331.1206.
crystals, R 0.27 (1:1 hexane–EtOAc), mp 205–206°C
f
5 –1
-(2-Bromophenyl)-2-(2-phenyl-1H-indol-3-yl)aceto-
nitrile (6b). Yield 314 mg (81%), colorless crystals,
0.30 (1:1 hexane–EtOAc), mp 148–149°C (benzene)
(benzene) (mp 205–206°C) . IR spectrum, ν, cm : 3345,
2361, 1497, 1350, 1026, 957, 897, 814, 756, 736, 708.
1
R
f
H NMR spectrum (CDCl ), δ, ppm (J, Hz): 8.37 (1H, s);
3
5
–1
(
mp 148–149°C) . IR spectrum, ν, cm : 3347, 2363, 2332,
7.86 (1H, d, J = 8.5); 7.84–7.78 (1H, m, H Ar); 7.76–7.72
(2H, m, H Ar); 7.69 (1H, s); 7.63 (1H, dd, J = 7.8, J = 1.5);
7.55 (1H, dd, J = 7.9, J = 1.2); 7.50–7.45 (2H, m, H Ar); 7.43–
7.38 (2H, m, H Ar); 7.25–7.20 (2H, m, H Ar); 7.16–7.11
1
2
(
249, 1458, 1435, 1026, 907, 764, 743. H NMR spectrum
CDCl ), δ, ppm (J, Hz): 8.39 (1H, s, NH); 7.75 (1H, d,
J = 7.9, H Ar); 7.65 (1H, dd, J = 7.8, J = 1.6, H Ar); 7.60
3
13
(
1H, dd, J = 7.9, J = 1.3, H Ar); 7.50–7.40 (4H, m, H Ar);
.37–7.34 (2H, m, H Ar); 7.32–7.25 (2H, m, H Ar); 7.23–
(2H, m, H Ar); 5.76 (1H, s, CH). С NMR spectrum
7
7
(CDCl ), δ, ppm: 137.1; 136.0; 135.1; 133.6; 133.3; 133.1;
3
1
3
.16 (2H, m, H Ar); 5.72 (1H, s, CH). C NMR spectrum
), δ, ppm 137.2; 135.9; 134.9; 133.6; 131.5; 130.0;
29.9; 129.2 (2C); 128.9; 128.3 (2C); 128.0; 127.3; 123.7;
130.1; 130.0; 129.2; 128.7; 128.3; 128.0; 127.9; 127.7;
127.4; 127.0 (2C); 125.3; 123.7; 123.1; 121.0; 119.8;
(
CDCl
3
+
1
118.6; 111.3; 105.1; 34.6. Found, m/z: 459.0469 [M+Na] .
1
23.0; 120.9; 119.7; 118.7; 111.4; 104.6; 34.5. Found, m/z:
C
26
H
17BrN Na. Calculated, m/z: 459.0467.
2
+
4
09.0319 [M+Na] .
09.0311.
-[2-(Naphth-2-yl)-1H-indol-3-yl]-2-phenylacetonitrile
6с). Yield 304 mg (75%), colorless crystals, mp 146–147°C
C
22
H
15BrN
2
Na. Calculated, m/z:
2-[2-(Naphthalen-2-yl)-1Н-indol-3-yl]-2-(4-nitrophenyl)-
acetonitrile (6g). Yield 286 mg (71%), light-brown
4
5
2
crystals, mp 98–99°С (benzene) (mp 98–99°С) , R
f
0.26
–
1
(
(1:1 hexane–EtOAc). IR spectrum, ν, cm : 3383, 2920,
3
01

Chemistry of Heterocyclic Compounds 2016, 52(5), 299–302
2
8
853, 1599, 1518, 1454, 1342, 1242, 1109, 1015, 905, 854,
H Ar); 7.45–7.39 (2Н, m, H Ar); 7.32 (1Н, dd, J = 11.2,
J = 4.1, H Ar); 7.25 (1Н, ddd, J = 8.7, J = 7.5, J = 1.7,
H Ar); 7.19 (1Н, dd, J = 11.1, J = 4.0, H Ar); 7.09 (1Н, dt,
J = 7.6, J = 0.8, H Ar); 6.97 (1Н, dd, J = 9.8, J = 8.8,
1
22, 743, 727, 708. Н NMR spectrum (CDCl
3
), δ, ppm (J,
Hz): 8.43 (1H, s, NH); 8.07–8.02 (2H, m, H Ar); 7.89–7.83
(
2H, m, H Ar); 7.83–7.74 (2H, m, H Ar); 7.50–7.44 (5H,
13
m, H Ar); 7.37 (1H, d, J = 8.2, H Ar); 7.30 (1H, d, J = 8.0,
H Ar); 5.53 (1Н, s, СH), 3.64 (3Н, s, СH
3
). C NMR
H Ar); 7.20 (1H, s); 7.03 (1H, t, J = 7.5, H Ar); 5.63 (1H, s,
spectrum (CDCl ), δ, ppm (J, Hz): 160.1 (d, J = 249.4);
3
13
CH). C NMR spectrum (100 MHz, CDCl
3
), δ, ppm:
139.6; 137.4; 133.3 (d, J = 21.0); 130.4; 130.1; 129.4;
128.7; 128.4; 128.0; 127.8; 127.7; 127.3; 125.9; 124.4 (d,
J = 3.6); 123.5; 123.4; 122.6; 120.6; 119.5; 119.0; 116.1;
1
(
47.7; 142.7; 137.5; 136.3; 133.4; 133.4; 129.6; 128.3
3С); 128.1 (2С); 127.4 (2С); 126.3; 125.6; 124.3 (2С);
23.7; 121.3; 119.4; 118.6; 111.7; 105.3; 33.6; 29.8. Found,
1
115.8; 110.0; 105.5; 31.2; 29.9. Found, m/z: 391.1612
+
+
m/z: 426.1211 [M+Na] . C26
H
17
N
3
NaO
2
. Calculated, m/z:
[M+Н] . C27
H
20FN . Calculated, m/z: 391.1605.
2
4
26.1213.
2
-(4-Ethoxyphenyl)-2-[2-(naphthalen-2-yl)-1Н-indol-
-yl]acetonitrile (6h). Yield 297 mg (74%), light-gray
0.28 (1:1 hexane–
This study was performed with financial support from
the Russian Science Foundation (grant No. 14-13-01108).
3
crystals, mp 149–150°С (benzene), R
f
–
1
References
EtOAc). IR spectrum, ν, cm : 3335, 2922, 2237, 1740,
1
. (a) Yang, L.; Wang, G.; Wang, M.; Jiang, H.; Chen, L.; Zhao, F.;
Qiu, F. Fitoterapia 2014, 95, 175. (b) Zhang, J.; Wang, J.-D.;
Liu, C.-X.; Yuan, J.-H.; Wang, X.-J.; Xiang, W.-S. Nat. Prod.
Res. 2014, 28, 431. (с) Pedras, M. S. C.; Yaya, E. E. Chem.
Biodiversity 2014, 11, 910. (d) Chen, M.; Gan, L.; Lin, S.;
Wang, X.; Li, L.; Li, Y.; Zhu, C.; Wang, Y.; Jiang, B.; Jiang, J.;
Yang, Y.; Shi, J. J. Nat. Prod. 2012, 75, 1167. (e) Wu, Q.;
Bang, M.-H.; Lee, D.-Y.; Cho, J.-G.; Jeong, R.-H.; Shrestha, S.;
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Comp. 2012, 48, 281. [Khim. Prirod. Soedin. 2012, 251.]
1
1
607, 1508, 1445, 1389, 1346, 1302, 1254, 1236, 1177,
1
113, 1043, 957, 903, 816, 758, 739, 704. Н NMR
spectrum (CDCl
3
), δ, ppm (J, Hz): 8.43 (1H, s, NH); 7.98–
7
.80 (4H, m, H Ar); 7.62–7.51 (4H, m, H Ar); 7.44 (1H, d,
J = 8.1, H Ar); 7.35 (2H, t, J = 8.9, H Ar); 7.30–7.21 (1H,
m, H Ar); 7.13 (1H, t, J = 7.5, H Ar); 6.85 (2H, d, J = 8.7,
H Ar); 5.63 (1H, s, CH); 4.00 (2H, d, J = 7.0, CH
3H, t, J = 7.0, CH
2
); 1.40
1
3
(
3
). C NMR spectrum (CDCl
3
), δ, ppm:
1
1
1
3
58.7; 136.8; 136.3; 133.4; 133.2; 129.3; 128.9; 128.5;
2
. (a) Cho, E.-J.; Shin, J.-S.; Chung, K.-S.; Lee, Y. S.; Cho, Y.-W.;
Baek, N.-I.; Chung, H.-G.; Lee, K.-T. J. Agric. Food Chem.
2012, 60,7398. (b) Wu, Y.; Zhang, Z.-X.; Hu, H.; Li, D.; Qiu, G.;
Hu, X.; He, X. Fitoterapia 2011, 82, 288.
28.3 (2С); 128.0; 127.9; 127.4; 127.1 (2C); 126.9; 125.8;
23.2; 120.9; 120.1; 120.0; 115.0 (2С); 111.3; 106.9; 63.6;
+
2.9; 14.9. Found, m/z: 425.1631 [M+Na] . C28
H
22
2
N NaO.
Calculated, m/z: 425.1624.
-(4-Methoxyphenyl)-2-[2-(naphthalen-2-yl)-1Н-indol-
-yl]-acetonitrile (6i). Yield 298 mg (77%), light-brown
crystals, mp 198–199°С (benzene), R 0.24 (1:1 hexane–
EtOAc). IR spectrum, ν, cm : 3345, 2363, 1508, 1439,
3
. Aksenov, A. V.; Smirnov, A. N.; Magedov, I. V.; Reisenauer, M. R.;
Aksenov, N. A.; Aksenova, I. V.; Pendleton, A. L.; Nguyen, G.;
Johnston, R. K.; Rubin, M.; De Carvalho, A.; Kiss, R.;
Mathieu, V.; Lefranc, F.; Correa, J.; Cavazos, D. A.; Brenner,. J.;
Bryan, B. A.; Rogelj, S.; Kornienko, A.; Frolova, L. V. J. Med.
Chem. 2015, 58, 2206.
2
3
f
–
1
1
1
248, 1179, 1024, 826, 741. Н NMR spectrum (CDCl
ppm (J, Hz): 8.41 (1H, s, NH); 7.96 (2H, d, J = 8.9, H Ar);
.93–7.82 (2H, m, H Ar); 7.60 (1H, dd, J = 8.4, J = 1.8,
3
), δ,
4
. (a) Aksenov, A. V.; Smirnov, A. N.; Aksenov, N. A.;
Aksenova, I. V.; Frolova, L. V.; Kornienko, A.; Magedov, I. V.;
Rubin, M. Chem. Commun. 2013, 49, 9305. (b) Aksenov, A. V.;
Smirnov, A. N.; Aksenov, N. A.; Aksenova, I. V.; Bijieva, A. S.;
Rubin, M. Org. Biomol. Chem. 2014, 12, 9786. (c) Aksenov, A. V.;
Smirnov, A. N.; Aksenov, N. A.; Aksenova, I. V.; Matheny, J. P.;
Rubin, M. RSC Adv. 2015, 5, 8647.
7
H Ar); 7.58–7.51 (3H, m, H Ar); 7.45 (1H, d, J = 8.1,
H Ar); 7.35 (2H, d, J = 8.6, H Ar); 7.29–7.23 (1H, m,
H Ar); 7.16–7.10 (1H, m, H Ar); 6.90–6.83 (2H, m, H Ar);
1
3
5
.63 (1H, s, CH); 3.79 (3H, s, CH ). C NMR spectrum
3
(
CDCl
3
), δ, ppm: 159.3; 136.8; 136.3; 133.5; 133.3; 129.3;
5. Aksenov, A. V.; Aksenov, N. A.; Dzhandigova, Z. V.;
Aksenov, D. A.; Rubin, M. RSC Adv. 2015, 5, 106492.
1
1
28.9; 128.5 (2С); 128.3; 128.0; 127.9; 127.6; 127.2;
27.1; 126.9; 125.8; 123.3; 120.9; 120.1; 120.0; 114.5
6. (a) Liguori, A.; Sindona, G.; Romeo, G.; Uccella, N. Synthesis
1
987, 168. (b) Ashworth, I. W.; Bowden, M. C.; Dembofsky, B.;
(
[
2С); 111.3; 106.9; 55.5; 32.9. Found, m/z: 411.1476
+
Levin, D.; Moss, W.; Robinson, E.; Szczur, N.; Virica, J. Org.
Proc. Res. Dev. 2003, 7, 74.
M+Na] . C27
-(2-Fluorophenyl)-2-[1-methyl-2-(naphthalen-2-yl)-
Н-indol-3-yl]acetonitrile (6j). Yield 265 mg (68%),
0.47
benzene). IR spectrum, ν, cm : 2920, 2851, 1742, 1478,
H
20
N
2
NaO. Calculated, m/z: 411.1468.
2
7
. (a) Middleton, W. J. J. Org. Chem. 1983, 48, 3845.
1
(b Thompson, H. W.; Rashid, S. Y. J. Org. Chem. 2002, 67,
colorless crystals, mp 65–66°С (benzene), R
f
2
813. (c) Reiner, J. E.; Siev, D. V.; Araldi, G.-L.; Cui, J. J.;
–
1
(
Ho, J. Z.; Reddy, K. M.; Mamedova, L.; Vu, P. H.; Lee, K.-S. S.;
Minami, N. K.; Gibson, T. S.; Anderson, S. M.; Bradbury, A. E.;
Nolan, T. G.; Semple, J. E. Bioorg. Med. Chem. Lett. 2002, 12,
1203.
1
1
456, 1364, 1231, 907, 862, 824, 814, 739. H NMR
spectrum (CDCl ), δ, ppm (J, Hz): 7.92–7.79 (4H, m,
H Ar); 7.71 (1Н, d, J = 8.0, H Ar); 7.62–7.54 (3Н, m,
3
3
02