Reduction of 5-(indol-3-yl)pyrrolidin-2-ones

Article abstract of DOI:10.1007/s10593-016-1832-8

The reduction of activated 5-(indol-3-yl)pyrrolidin-2-ones leading to a mixture of the respective indolyl pyrrolidines and their borane complexes, as well as several other transformations indicate that the electrophilicity of carbonyl group in 5-indolylpy

Full text of DOI:10.1007/s10593-016-1832-8

DOI 10.1007/s10593-016-1832-8
Chemistry of Heterocyclic Compounds 2016, 52(1), 21–24
Reduction of 5-(indol-3-yl)pyrrolidin-2-ones
Andrey V. Sadovoy1, Vita N. Nikitina1, Victor B. Rybakov1,
Konstantin A. Kochetkov2, Lyudmila A. Sviridova1*
1
M. V. Lomonosov Moscow State University,
1, Build. 3 Leninskie Gory , Moscow 119991, Russia; e-mail: svirid42@mail.ru
2
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 Vavilova St., Moscow 119991, Russia; e-mail: const@ineos.ac.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2016, 52(1), 21–24
Submitted December 16, 2015
Accepted January 25, 2016
Method I:
1. BF3·Et2O, Et2O, , 2 h;
2. LiAlH4, , 20 h
Ph
Ph
R2
R2
R2
Ph
R1
N
R1
R1
N
N
N
:
N
N
BH3
O
+
Method II:
1. Et3O+BF4 , CH2Cl2, rt, 18 h;
–
2. LiAlH4, THF, 0°C, 30 min
then , 18 h
The reduction of activated 5-(indol-3-yl)pyrrolidin-2-ones leading to a mixture of the respective indolyl pyrrolidines and their borane
complexes, as well as several other transformations indicate that the electrophilicity of carbonyl group in 5-indolylpyrrolidin-2-ones is
significantly decreased.
Keywords: 1-boryl-2-(indol-3-yl)pyrrolidinium, 2-(indol-3-yl)pyrrolidines, 5-(indol-3-yl)pyrrolidin-2-ones, reduction with complex
metal hydrides.
Pyrrolidine rings are found in a wide range of natural
compounds: α-amino acids (proline, hydroxyproline),
alkaloids (nicotine), and pharmaceuticals (piracetam,
lincomycin).1–3 No less important are indole-containing
compounds, including the α-amino acid tryptophan, indole
alkaloids such as vinblastine and vincristine, and
pharmaceutical substances (indometacin, umifenovir).1–3
We have previously reported a convenient preparative
method for the synthesis of 5-(indol-3-yl)- and 5-(indol-
2-yl)pyrrolidones,4 thus providing an access to these
compounds for synthetic use. Pyrrolidin-2-ones are known
to readily react at the carbonyl group.5 A suppression of
carbonyl group reactivity in 5-substituted pyrrolidones was
observed earlier during the reduction of 1-methyl-
5-phenylpyrrolidin-2-one.6 Our attempts to use indolyl-
pyrrolidones for analogous transformations to those
possible for 5-unsubstituted pyrrolidones5 also showed a
significantly decreased reactivity of carbonyl group in the
case of 5-(indol-3-yl)pyrrolidin-2-ones. We observed this
phenomenon for 5-indolylpyrrolidones and their activated
forms, iminium salts, during many failed attempts of
pyrrolidone ring hydrolysis or hydrazinolysis as well as we
noted the lack of reactivity towards organomagnesium
compounds and other С-nucleophiles, that is, in the same
examples where reactions with pyrrolidones occur quite
readily.5
In all the aforementioned experiments the starting
pyrrolidones were recovered nearly quantitatively, pointing
to the remarkable stability of these compounds. The typical
conditions for the reduction of pyrrolidones to pyrrolidines6–8
by refluxing for 24 h with lithium aluminum hydride in
THF, treating with lithium hydride, etc. (taking into
account the need to preserve the indole ring) did not
produce satisfactory results in the case of (indol-3-yl)-
pyrrolidin-2-ones: the isolated mixtures contained the
expected pyrrolidines along with the starting pyrrolidones,
with the latter as major components. The presence of a labile
indole moiety in the molecule limited the selection of
electrophilic activating agents and prevented the use of protic
acids, metal halides, and some other reagents. On the other
hand, the ability of pyrrolidones to polymerize7 prevented
the use of some phosphorus and sulfur halides and even
triphenylphosphine: the subsequent reduction with sodium
borohydride or lithium aluminum hydride gave not only the
expected pyrrolidines, but also side products: indolyl-
pyrrolidine dimers and polymers, due to incomplete
conversion of the starting pyrrolidones.
The activation of carbonyl group in compounds 1a–e by
complex formation with boron trifluoride allowed to
prepare the target pyrrolidines 2a–e only by treatment with
lithium aluminum hydride (and not with sodium
borohydride) (Scheme 1). In the case of compounds 1b–e,
0009-3122/16/52(1)-0021©2016 Springer Science+Business Media New York
21

Chemistry of Heterocyclic Compounds 2016, 52(1), 18–21
Scheme 1
pounds 2a–e and 5a,b were in agreement with the proposed
structures. All signals in the spectra of compounds 3b–e
were significantly shifted towards the downfield region.
Mass spectra of compounds 2b–e and the respective
complexes 3b–e were practically identical, except for
additional weak signals (Irel 3–5%) that were observed as
expected in the spectra of borane amines 3b–e, with m/z
values higher by 14 units compared to the respective pyr-
rolidines 2b–e. The structure of complex 3b was estab-
lished conclusively by X-ray structural analysis (Fig. 1).
the isolated mixtures contained pyrrolidines 2b–e and their
borane complexes (compounds 3b–e), formed from boron
trifluoride and an excess of lithium aluminum hydride. The
obtained mixtures of pyrrolidines 2b–e and complexes 3b–e
were separated by column chromatography. It was not
possible to determine the initial obtained product ratio,
since the treatment of reaction mixture led to a partial
decomposition of complexes 3 (according to 1H NMR data,
the typical ratio of complex 3 : amine 2 : pyrrolidone 1
after the work-up of reaction mixture was approximately
2 : 1 : 0.6).
The same mixture of indolylpyrrolidines 2b–e and their
borane complexes 3b–e was obtained by activation of
pyrrolidones 1b–e with triethyloxonium tetrafluoroborate,
followed by reduction with lithium aluminum hydride (no
reduction with sodium borohydride occurred also with this
method of indolylpyrrolidone activation). An exception
was observed when reducing 1-benzyl-5-(indol-3-yl)-
pyrrolidin-2-one (1a) under the same conditions, where
borane complex was not formed and the reduction gave
1-benzyl-2-(indol-3-yl)pyrrolidine (2a) in a good yield
(63%) (Scheme 1). The reduction of 1-benzyl-5-(3-methyl-
indol-2-yl)pyrrolidin-2-one (4a) isomeric to compound 1с
under the same conditions (method II) also led to the
formation of the respective pyrrolidine 5a only (Scheme 2).
We additionally found that 1-benzyl-5-[3-(4-methyl-
phenyl)indol-2-yl]pyrrolidin-2-one (4b) was rapidly reduced
with lithium aluminum hydride without prior activation of
carbonyl group with boron trifluoride or triethyloxonium
tetrafluoroborate, giving a high yield of pyrrolidine 5b
(Scheme 2).
Figure 1. The structure of 1-benzyl-1-boryl-2-[2-(4-methyl-
phenyl)-1H-indol-3-yl]pyrrolidinium (3b) with atoms represented
by thermal vibration ellipsoids of 50% probability.
Thus, the reduction of activated 5-(indol-3-yl)pyrrolidin-
2-ones to obtain a mixture of the respective indolyl
pyrrolidines and their borane complexes as well as a range
of other transformations provide an evidence that the
electrophilicity of carbonyl group in 5-indolylpyrrolidin-
2-ones is significantly suppressed. Our developed reduction
methods generally were not preparative, but in some cases
allowed to obtain indolylpyrrolidines in sufficiently high
yields.
Experimental
IR spectra were recorded for Nujol mulls on a UR-20
1
instrument. H and 13C NMR spectra were acquired for
СDCl3 solutions on Bruker Avance-400 (400 МHz) and
Аgilent 400-MR (100 МHz) spectrometers, respectively,
the internal standard was TMS. Mass spectra were recorded
on a Bruker Autoflex II instrument, EI ionization (70 eV).
Elemental analysis was performed on a Carlo Erba ER-20
CHN-analyzer. Melting points were determined on an
Electrothermal IA9100 apparatus.
Scheme 2
The reaction mixtures were separated by flash
chromatography on a column with dry L grade (5/40) silica
gel, the eluent was benzene. The reaction progress, column
chromatography fractions, and the purity of compounds
were controlled by TLC on Silufol UV-254 plates, eluent
10:1 benzene–EtOAc, visualization with iodine vapor.
The starting pyrrolidones 1a–e, 4a,b were synthesized
according to a published procedure.4
IR spectra of the obtained compounds lacked absorption
1
bands due to carbonyl groups. Н NMR spectra of com-
22

Chemistry of Heterocyclic Compounds 2016, 52(1), 18–21
Reduction of 5-indolylpyrrolidones 1a–e (General
159 (24), 91 (100), 265 (15). Found, %: C 70.44; H 6.43;
N 5.86. C26H26N2·0.5H2B4O7. Calculated, %: C 70.16;
H 6.11; N 6.29.
method). Method I. 5-Indolylpyrrolidone 1a–e (0.25 mmol)
was added to a refluxing solution of BF3·Et2O (0.07 ml,
0.53 mmol) in anhydrous Et2O (15 ml). The mixture was
refluxed for 2 h, then cooled and treated by portionwise
addition of LiAlH4 (47 mg, 1.25 mmol), followed by
refluxing of the mixture for 20 h. The reaction mixture was
treated with saturated aqueous KF solution (0.8 ml), stirred
for 30 min until the formation of a white precipitate of
decomposition products. The ether layer was then decanted
and the residue was extracted with ether. The ether extracts
were combined, washed several times with water, and dried
over anhydrous Na2SO4. Ether was removed by
evaporation, the product mixture was separated by flash
chromatography.
3-(1-Benzylpyrrolidin-2-yl)-1-methyl-1H-indole (2c).
1
Yield 19% (method I), 25% (method II), oil. H NMR
spectrum, δ, ppm (J, Hz): 1.78–1.81 (1H, m) and 1.93–1.95
(1H, m, 4-СН2); 2.03–2.05 (1H, m, 3-СНА); 2.17–2.21 (2H,
m, 3-СНВ, 5-СНА); 3.05 (1H, d, J = 13.1) and 4.03 (1H, d,
J = 13.2, CH2Ph); 3.11–3.13 (1H, m, 5-СНВ); 3.67 (1H, dd,
J = 7.8, J = 8.1, 2-СН); 3.72 (3H, s, NCH3); 7.06–7.08 (1H,
m, H Ar); 7.12–7.38 (8H, m, H Ar); 7.90 (1H, d, J = 8.2,
H Ar). Mass spectrum, m/z (Irel, %): 290 [M]+ (45), 247
(31), 199 (14), 171 (66), 157 (33), 144 (57), 91 (100), 65
(20). Found, %: C 83.09; H 7.89; N 9.17. C20H22N2.
Calculated, %: C 82.72; H 7.64; N 9.65.
Method II. 5-Indolylpyrrolidone 1a–e (1.0 mmol) was
3-(1-Benzylpyrrolidin-2-yl)-1,2-dimethyl-1H-indole (2d).
–
1
added to a solution of Et3O+BF4 (247 mg, 1.3 mmol) in
Yield 18% (method I), 20% (method II), oil. H NMR
anhydrous CH2Cl2 (15 ml); the mixture was stirred for 3 h
and left overnight at room temperature. On the next day,
the reaction mixture was evaporated, the residue was dis-
solved in anhydrous THF (15 ml), cooled to 0°С, and treated
by portionwise addition of LiAlH4 (190 mg, 5.0 mmol),
while maintaining the temperature at approximately 0°С.
The mixture was stirred and cooled for another 30 min,
then refluxed for 18 h, and worked up in the same way as
in method I. The obtained product mixture was separated by
flash chromatography, boranamines 3b–e were purified by
suspending in a 1:1 hexane–EtOAc mixture. Filtration of the
suspension gave white crystals that were stable in air and
burned with a flash when ignited.
spectrum, δ, ppm (J, Hz): 1.82–1.84 (1H, m) and 1.98–2.02
(1H, m, 4-СН2); 2.10–2.13 (3H, m, 3-СН2, 5-СНА); 2.51
(3H, s, 2-CH3); 2.96 (1H, d, J = 12.9) and 3.92 (1H, d,
J = 13.1, CH2Ph); 3.12–3.15 (1H, m, 5-СНВ); 3.67 (1H, dd,
J = 7.9, J = 10.2, 2-СН); 3.69 (3H, s, 1-CH3); 7.12–7.30
(8H, m, H Ar); 8.00 (1H, d, J = 7.9, H Ar). 13C NMR spectrum,
δ, ppm: 10.5; 22.2; 29.4; 31.7; 53.4; 58.2; 62.3; 99.8;
108.4; 118.5; 120.4; 126.3; 127.9 (3C); 128.7 (2C); 132.8;
136.1. Mass spectrum, m/z (Irel, %): 304 [M]+ (26), 225
(11), 211 (21), 185 (22), 171 (12), 160 (42), 159 (41), 120
(22), 91 (100), 65 (16). Found, %: C 82.97; H 8.14; N 9.28.
C21H24N2. Calculated, %: C 82.85; H 7.95; N 9.20.
3-(1-Benzylpyrrolidin-2-yl)-1-methyl-2-(4-methyl-
phenyl)-1H-indole (2e). Yield 28% (method I), 31%
3-(1-Benzylpyrrolidin-2-yl)-1H-indole (2a). Yield 63%
(method I), 60% (method II), oil. IR spectrum, ν, cm–1: 3400
(method II), oil. H NMR spectrum, δ, ppm (J, Hz): 1.75–
1
1
(N–H). H NMR spectrum, δ, ppm (J, Hz): 1.80–1.82 (1H,
1.77 (1H, m, 4-СНА); 1.97–2.02 (3H, m, 3-СН2, 4-СНВ);
2.25–2.27 (1H, m) and 3.05–3.07 (1H, m, 5-СН2); 2.50
(3H, s, ArCH3); 2.83 (1H, d, J = 13.1) and 3.94 (1H, d,
J = 13.1, CH2Ph); 3.45 (1H, dd, J = 7.9, J = 9.8, 2-СН);
3.59 (3H, s, NCH3); 7.16–7.38 (12H, m, H Ar); 8.26 (1H,
d, J = 8.1, H Ar). Mass spectrum, m/z (Irel, %): 380 [M]+
(71), 337 (45), 289 (76), 261 (69), 234 (36), 218 (23), 159
(53), 91 (100), 65 (19). Found, %: C 84.77; H 6.94; N 6.98.
C27H28N2. Calculated, %: C 85.22; H 7.42; N 7.36.
m) and 1.94–1.96 (1H, m, 4-СН2); 2.04–2.06 (1H, m,
3-СНА); 2.19–2.21 (2H, m, 3-СНВ, 5-СНА); 3.07 (1H, d,
J = 13.2) and 4.03 (1H, d, J = 13.1, CH2Ph); 3.12–3.13
(1H, m, 5-СНВ); 3.70 (1H, dd, J = 8.1, J = 8.9, 2-СН); 7.13–
7.48 (9H, m, H Ar); 7.92 (1H, d, J = 7.8, H Ar); 8.03 (1H,
br. s, NH). Mass spectrum, m/z (Irel, %): 276 [M]+ (31), 233
(14), 185 (12), 157 (38), 143 (17), 130 (25), 120 (19), 117
(35), 91 (100), 65 (20). Found, %: С 82.17; H 7.47; N 9.95.
C19H20N2. Calculated, %: C 82.57; H 7.29; N 10.14.
1-Benzyl-1-boryl-2-[2-(4-methylphenyl)-1H-indol-3-yl]-
pyrrolidinium (3b). Yield 32% (method II), mp 166–168°С
(decomp.). IR spectrum: 2300–2400 cm–1 (B–H), 3400 (N–H).
1H NMR spectrum, δ, ppm (J, Hz): 1.33–1.93 (3H, m,
BH3); 2.23–2.25 (1H, m) and 2.44–2.46 (1H, m, 4-СН2);
2.47 (3H, s, ArCH3); 2.69–2.72 (2H, m, 3-СН2); 3.00–3.02
(1H, m) and 3.28–3.30 (1H, m, 5-СН2); 3.54 (1H, d,
J = 12.1) and 3.81 (1H, d, J = 12.2, CH2Ph); 5.25 (1H, dd,
J = 8.1, J = 10.2, 2-СН); 7.26–7.56 (12H, m, H Ar); 7.71
(1H, d, H Ar); 8.30 (1H, br. s, NH). Mass spectrum, m/z
(Irel, %): 380 [M]+ (6), 366 (11), 275 (72), 247 (56), 230
(33), 220 (100), 207 (42), 159 (41), 91 (97), 65 (26).
1-Benzyl-1-boryl-2-(1-methyl-1H-indol-3-yl)pyrroli-
dinium (3c). Yield 28% (method II), mp 198–200°С. IR
spectrum, ν, cm–1: 2300–2400 (B–H), 3400 (N–H).
1H NMR spectrum, δ, ppm (J, Hz): 1.32–2.07 (3H, m,
BH3); 2.22–2.24 (2H, m, 4-СН2); 2.64–2.66 (2H, m,
3-СН2); 3.00–3.02 (1H, m) and 3.20–3.22 (1H, m, 5-СН2);
3-(1-Benzylpyrrolidin-2-yl)-2-(4-methylphenyl)-1H-indole
(2b). Yield 15% (method I), 17% (method II), oil. IR
spectrum, ν, cm–1: 3400 (N–H). 1H NMR spectrum, δ, ppm (J,
Hz): 1.83–1.86 (1H, m, 4-СНА); 2.04–2.08 (2H, m, 4-СНВ,
3-СНА); 2.14–2.16 (1H, m) and 2.28–2.30 (1H, m, 3-СНВ,
5-СНА); 2.47 (3H, s, ArCH3); 2.90 (1H, d, J = 13.6) and
3.90 (1H, d, J = 13.3, CH2Ph); 3.11–3.13 (1H, m, 5-СНВ);
3.75 (1H, dd, J = 7.8, J = 10.1, 2-СН); 7.18–7.40 (10H, m,
H Ar); 7.50 (2H, d, J = 7.9, H Ar); 8.02 (1H, br. s, NH);
8.26 (1H, d, J = 7.9, H Ar). 13C NMR spectrum, δ, ppm:
21.3; 31.2; 44.1; 53.3; 58.2; 61.9; 110.6; 119.2; 120.4;
122.0; 127.9 (2C); 128.4 (2C); 128.7 (4C); 129.3 (2C); 136.3;
136.6. Mass spectrum, m/z (Irel, %): 366 [M(base)*]+ (33),
323 (34), 275 (93), 265 (15); 247 (55), 220 (28), 207 (17),
* Here and below М(base) – the molar mass of the base.
23

Chemistry of Heterocyclic Compounds 2016, 52(1), 18–21
3.54 (1H, d, J = 12.1) and 3.80 (1H, d, J = 12.1, CH2Ph);
J = 8.1, H Ar); 8.84 (1H, br. s, NH). 13C NMR spectrum,
δ, ppm: 21.2; 29.6; 35.9; 52.9; 58.9; 60.4; 110.9; 119.1; 119.7;
121.9; 128.1 (2C); 129.2 (3C); 129.5 (4C); 131.9; 133.4; 134.6.
Mass spectrum, m/z: 366 [M]+. Found,%: C 79.63; H 6.45;
N 7.48. C26H26N2·0.5H2CO3. Calculated, %: C 80.07; H 6.85;
N 7.05.
3.86 (3H, s, NCH3); 5.00 (1H, dd, J = 8.9, J = 10.1, 2-CH);
7.23–7.39 (9H, m, H Ar); 7.95 (1H, d, J = 8.1, H Ar). Mass
spectrum, m/z (Irel, %): 304 [M]+ (4), 290 (19), 171 (38),
157 (24), 144 (100), 115 (17), 91 (77), 65 (18).
1-Benzyl-1-boryl-2-(1,2-dimethyl-1H-indol-3-yl)pyrro-
lidinium (3d). Yield 20% (method II), mp 181–182°С. IR
X-ray structural analysis of compound 3b. Crystals of
compound 3b suitable for X-ray structural analysis were
obtained by suspension in 1:1 hexane–EtOAc mixture.
White crystals were filtered off and dried. The X-ray
structural studies were performed at 295(2) K on a STOE &
Cie StadiVari automated X-ray diffractometer (CuKα
irradiation, λ 1.54186 Å), equipped with a DECTRIS
Pilatus-100K position-sensitive detector controlled by the
X-AREA software.9 Accounting for aborption was
performed with DIFABS software.10 The structure was
solved by direct methods using the SHELXS97 program.11
The structures were refined by F2 using the SHELXL97
program.11 Graphical representation of molecular structure
was obtained with the ORTEP-3 program.12 The
crystallographic information was deposited at the
Cambridge Crystallographic Data Center (deposit CCDC
912382).
1
spectrum, ν, cm–1: 2300–2400 (B–H). H NMR spectrum,
δ, ppm (J, Hz): 1.30–1.87 (3H, m, BH3); 2.31–2.34 (2H, m,
4-СН2); 2.52–2.54 (1H, m) and 2.87–2.90 (1H, m, 3-СН2);
2.63 (3H, s, ArCH3); 3.03–3.05 (1H, m) and 3.29–3.31
(1H, m, 5-СН2); 3.67 (1H, d, J = 12.1) and 3.72 (1H, d,
J = 12.2, CH2Ph); 3.75 (3H, s, NCH3); 4.97–5.00 (1H, m,
2-СН); 7.24–7.40 (8H, m, H Ar); 7.59 (1H, d, J = 8.2,
H Ar). Found, %: C 78.72; H 8.53; N 8.21. C21H27BN2.
Calculated, %: C 79.25; H 8.55; N 8.80.
1-Benzyl-1-boryl-2-[1-methyl-2-(4-methylphenyl)-
1H-indol-3-yl]pyrrolidinium (3e). Yield 13% (method II),
mp 163–165°С. IR spectrum, ν, cm–1: 2300–2400 (B–H).
1H NMR spectrum, δ, ppm (J, Hz): 1.32–1.79 (3H, m,
BH3); 2.18–2.21 (1H, m) and 2.37–2.39 (1H, m, 4-СН2);
2.51 (3H, s, ArCH3); 2.66–2.69 (2H, m, 3-СН2); 2.92–2.94
(1H, m) and 3.22–3.24 (1H, m, 5-СН2); 3.55 (1H, d,
J = 12.1) and 3.80 (1H, d, J = 12.1, CH2Ph); 3.59 (3H, s,
NCH3); 4.99–5.01 (1H, m, 2-СН); 7.26–7.47 (12H, m,
H Ar); 7.76–7.79 (1H, m, H Ar). Mass spectrum, m/z (Irel,
%): 394 [M]+ (9), 380 (17), 337 (21), 289 (35), 261 (40),
234 (64), 159 (28), 91 (100), 65 (20).
Supplementary information files containing X-ray
structural analysis data for compound 3b are available
online at http://link.springer.com/journal/10593.
This work was financially supported by the Russian
Foundation for Basic Research (project 15-29-05785 ofi_m
and 15-54-45051 ind_a).
2-(1-Benzylpyrrolidin-2-yl)-3-methyl-1H-indole (5a)
was obtained according to method II from 1-benzyl-5-(3-
methylindol-2-yl)pyrrolidin-2-one (4a). Yield 59%, oil. IR
1
spectrum, ν, cm–1: 3400 (N–H). H NMR spectrum, δ, ppm
NMR spectroscopy and X-ray structural analysis were
partly performed on equipment paid for by the development
program MGU.u67or (Agilent 400-MR spectrometer and
STOE StadiVari Pilatus-100K diffractometer).
(J, Hz): 1.86–1.90 (3H, m, 3-СНА, 4-СН2); 2.19–2.21 (1H,
m, 3-СНВ); 2.29–2.31 (1H, m) and 3.14–3.16 (1H, m, 5-
СН2); 2.36 (3H, s, CH3); 3.20 (1H, d, J = 13.1) and 3.91
(1H, d, J = 13.2, CH2Ph); 3.80 (1H, dd, J = 7.8, J = 9.3, 2-
СН); 7.06–7.08 (1H, m, H Ar); 7.17–7.36 (7H, m, H Ar);
7.57 (1H, d, J = 8.1, H Ar); 8.51 (1H, br. s, NH). Mass
spectrum, m/z (Irel, %): 290 [M(base)]+ (27), 260 (13), 247
(83), 246 (35), 232 (27), 231 (25), 171 (27), 157 (26), 120
(49), 101 (17), 91 (100), 40 (31). Found, %: C 75.03;
H 7.07; N 8.64. C20H22N2·0.5H3ВO3. Calculated, %:
C 74.76; H 7.37; N 8.72.
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2. Granik, V. G. Fundamentals of Medicinal Chemistry [in
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3. Kovalenko, L. V. Biochemical Foundations of the Chemistry
of Biologically Active Compounds [in Russian]; BINOM:
Moscow, 2010, p. 73, 77.
2-(1-Benzylpyrrolidin-2-yl)-3-(4-methylphenyl)-1H-indole
(5b). A solution of 1-benzyl-5-[3-(4-methyl-phenyl)indol-
2-yl]pyrrolidin-2-one (4b) (0.10 g, 0.26 mmol) in anhydrous
THF (10 ml) was cooled with ice and treated by addition of
LiAlH4 (0.05 g, 1.30 mmol), while maintaining the
temperature at approximately 0°С. The mixture was stirred
and cooled for an additional 30 min, then refluxed for 4 h.
The reaction mixture was worked up in the same way as in
methods I and II, pyrrolidine 5b was purified by
chromatography. Yield 0.06 g (62%), oil. IR spectrum, ν,
cm–1: 3320 (N–H). 1H NMR spectrum, δ, ppm (J, Hz): 1.83
–1.85 (1H, m, 4-СНА); 2.00–2.04 (2H, m, 4-СНВ, 3-СНА);
2.25–2.29 (2H, m, 3-СНВ, 5-СНА); 2.47 (3H, s, ArCH3);
3.11–3.17 (2H, m, 5-СНВ, CHАPh); 3.75–3.90 (2H, m,
2_СН, CHВPh); 7.14–7.45 (12H, m, H Ar); 7.70 (1H, d,
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