Ultrasound Assisted Pictet-Spengler Synthesis of Tetrahydro-β-Carboline Derivatives

Article abstract of DOI:10.1002/jhet.2318

The synthesis of twelve tetrahydro-β-carboline derivatives 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l prepared via the Pictet-Spengler reaction is described. The reaction of tryptamine and a variety of arylaldehydes were carried out under ultrasonic irradiation and trifluoracetic acid catalysis at room temperature. These tetrahydro-β-carbolines have been synthesized in higher yields and shorter reaction times compared to the conventional method. Moreover, the reaction proceeded successfully even employing arylaldehydes with electron-donating or electron-attracting substituents which did not react under conventional method.

Full text of DOI:10.1002/jhet.2318

March 2016
Ultrasound Assisted Pictet–Spengler Synthesis of
Tetrahydro-β-Carboline Derivatives
647
*
Gisela C. Muscia, Leonardo O. De María, Graciela Y. Buldain, and Silvia E. Asís
Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956,
C1113AAB Ciudad Autónoma de Buenos Aires, Argentina
*
E-mail: elizabet@ffyb.uba.ar
Received May 22, 2014
DOI 10.1002/jhet.2318
Published online 29 April 2015 in Wiley Online Library (wileyonlinelibrary.com).
The synthesis of twelve tetrahydro-β-carboline derivatives 3a–3l prepared via the Pictet–Spengler
reaction is described. The reaction of tryptamine and a variety of arylaldehydes were carried out under
ultrasonic irradiation and trifluoracetic acid catalysis at room temperature. These tetrahydro-β-carbolines
have been synthesized in higher yields and shorter reaction times compared to the conventional method.
Moreover, the reaction proceeded successfully even employing arylaldehydes with electron-donating or
electron-attracting substituents which did not react under conventional method.
J. Heterocyclic Chem., 53, 647 (2016).
The β-carboline core is the common nucleus of many
synthetic indole alkaloids as well as those extracted from
natural sources associated with a broad spectrum of
biochemical and pharmacological properties [1–6].
has been reported to show antileishmanial activity
(IC50 34.8 μM) against Leishmania braziliensis (Fig. 1).
Moreover, several synthetically modified β-carboline
derivatives have also been studied against leishmaniasis
[12,13]. The interactions between β-carboline alkaloids and
bovine serum albumin (BSA) were analyzed recently
[14] as well as the wild type B-Raf kinase inhibitory
activity of 1-carboxamide and 6-sulfonamide-substituted
β-carboline derivatives [15] and the antioxidant activity
of 1-aryl-tetrahydro-β-carboline derivatives [16].
The extensive biological activity of this class of molecules
has naturally attracted much attention from the synthetic
community. Traditional methods toward β-carbolines
involve Pictet–Spengler [17] or Bischler–Napieralski con-
densations of tryptamine or tryptophan (Scheme 1), followed
by aromatization. More recent approaches have involved
palladium-catalyzed cross-coupling methodologies [18].
In this regard the use of ultrasound (US) in chemistry
(sonochemistry) offers the synthetic chemist a method of
chemical activation which has broad applications and uses
equipment which is relatively inexpensive. The driving
force for sonochemistry is cavitation, and so a general
requirement is that at least one of the phases of the reaction
mixture should be a liquid. The ever expanding number of
applications of sonochemistry in synthesis has made the
subject attractive to many experimentalists and interest
has spread beyond academic laboratories into industry
and chemical engineering [19].
β-Carbolines possess planar aromatic tricyclic struc-
tures, and many derivatives are widely distributed in
nature: in plants, marine life, human tissues, and body
fluids. Several β-carboline compounds have antitumor
and anti-cancer properties. Moreover, their multiple physi-
ological effects, such as the inhibition of cyclin-dependent
kinase (CDK), IkappaB kinase (IKK), and topoisomerase I
lead to an increasing interest in this class of structure for
clinical purposes. A series of 3-amino- or 3-benzylamino-
β-carboline derivatives was recently synthesized, and their
antitumor activities for Hela S-3 and Sarcoma 180 cell
lines were evaluated [7]. 3-Benzylamino-β-carboline
derivatives induce apoptosis through G2/M arrest in
human carcinoma cells HeLa S-3 [8]. Mechanistic studies
indicate that β-carboline derivatives inhibit DNA
topoisomerases and interfere with DNA synthesis. They
interact with DNA via both groove binding and
intercalative modes and cause major DNA structural
changes [9]. In this sense, β-carboline derivatives were
tested as novel photosensitizers [10], and their solid-state
photoluminescent properties were also discussed [11].
Many alkaloids have been reported to be active against
leishmaniasis. The β-carboline alkaloid harmaline isolated
from Peganum harmala (Syrian Rue) has exhibited a strong
amastigote specific activity with an IC50 of 1.16 μM. The
metabolite harmine occurring in same plant has also shown
significant activity in vivo. The pyrimidine-β-carboline
alkaloid annomontine, isolated from Annona foetida,
Recently, US has been utilized to accelerate a wide
number of synthetically useful organic reactions. In
addition to the field of organic chemistry, sonochemistry
has also been used in the preparation of micro and
© 2015 HeteroCorporation

648
G. C. Muscia, L. O. De María, G. Y. Buldain, and S. E. Asís
Vol 53
In conclusion, we worked out a novel synthesis of 12
1-aryl-tetrahydro-β-carboline derivatives under ultrasonic
irradiation. We described a mild, convenient, and simple
procedure for the condensation of tryptamine and a
substituted arylaldehyde, and the method can be extended
to aliphatic aldehydes. This series could be obtained in
good yields and short times in a one-pot US-assisted
Pictet–Spengler reaction from affordable starting
materials and under TFA catalysis. These advantages are
noteworthy when the synthesis is focused on designing po-
tential pharmacological compounds such as 1-substituted
tetrahydro-β-carbolines as well as 1-substituted-β-carbolines.
Figure 1. Natural β-carboline alkaloids.
nanomaterials and also has many therapeutic and diagnostic
applications [20].
The Pictet–Spengler synthesis of tetrahydro-β-carbolines
at room temperature, in methylene chloride and trifluoracetic
acid (TFA) as catalyst has been reported by Buthani et al.
[12]. In this work we present the preparation of 1-aryl-
tetrahydro-β-carbolines under US-assisted methodology in
order to remark its advantages [21]. Our interest in this
target heterocycle is stimulated by their close structural
relationship to molecules with antileishmanial and antitu-
bercular activities [22,23].
Table 1
Synthesized tetrahydro-β-carbolines: advantages of sonochemical method
over conventional method.
Conventional
method
Ultrasound
irradiation
Time Yield Time Yield
Herein, the synthesis of 12 tetrahydro-β-carboline deriv-
atives (3a–3l) prepared via the Pictet–Spengler reaction
and a sonochemical method is described (Table 1). The
reaction of tryptamine (1) and a variety of arylaldehydes
(2) was carried out under ultrasonic irradiation in methylene
chloride and TFA catalysis at room temperature in good to
excellent yields (Scheme 2). The reactions proceed to
completion between 1 and 2 h; meanwhile, when they were
performed under conventional method the reaction times ex-
tended to 24–48h, and the yields were lower or similar, and
no reaction took place with some arylaldehydes. Moreover
the US-assisted synthesis succeeded when the conventional
method failed. Arylaldehydes having either electron-
withdrawing or -donating groups underwent Pictet–Spengler
reaction with 1 to furnish 3a–l. This is unlike the traditional
Pictet–Spengler protocol involving aprotic solvents wherein
aldehydes bearing electron-donating substituents failed to
undergo cyclization and furnished imines as the only prod-
uct. This was attributed to the decrease in the reactivity of
the iminium ion intermediate derived from aldehydes bear-
ing the electron-donating group, which in turn prevented
the formation of tetrahydro-β-carbolines [23]. The use of
TFA proved to be more efficient than the hydrochloric acid
catalysis under both experimental conditions and the reac-
Compound
Ar
(h)
(%)
(h) (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
C6H5
24
48
24
48
24
48
12
48
48
24
25
70
50
nr
51
nr
51
nr
nr
2
1
1
1
2
2
2
1
1
1
2
2
66
71
82
87
85
72
64
54
63
43
62
79
2-NO2C6H4
4-NO2C6H4
2-ClC6H4
4-ClC6H4
4-CF3C6H4
3-OCH3-4-OHC6H3
3,4-di-OCH3C6H3
3,5-di-OCH3C6H3
3,4,5-tri-OCH3C6H2
3,5-di-OCH3-4-BrC6H3 24
6-OCH3-2-Naph. 48
3j
3k
3l
33
53
12
nr: no reaction
Scheme 2. Synthesis of 1-aryl- tetrahydro-β-carbolines 3a–l by US-assisted
method.
1
tions did not take place without catalysis [23–25]. The H
NMR, 13C NMR spectra, and HSQC data unequivocally
proved the 1-aryl-tetrahydro-β-carboline structures.
Scheme 1. Pictet–Spengler synthesis of tetrahydro-β-carbolines.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2016
Ultrasound Assisted Synthesis β-Carboline Derivatives
649
1H-NMR: δ 2.93–3.10 (2H, m, 4-CH2), 3.27–3.47 (2H, m,
3-CH2), 6.09 (1H, s, CH), 7.02–7.14 (3H, m, Ph-H), 7.28 (1H, d,
J = 7.8 Hz, Het-H), 7.37 (1H, t, J = 7.3 Hz, Het-H), 7.47–7.55
(2H, m, Het-H y Ph-H), 7.66 (1H, d, J = 7.8 Hz, Het-H),
9.35 (1H, s, NH), 10.91 (1H, s, NH). 13C-NMR: δ 19.4,
52.9, 108.6, 111.9, 118.6, 119.5, 122.4, 126.2, 127.7, 128.1,
129.1, 130.4, 131.6, 131.8, 134.1, 134.5, 136.9. Anal. Calcd.
for C17H15ClN2: C, 72.21; H, 5.35; N, 9.91. Found: C,
71.80; H, 5.54; N, 10.11.
EXPERIMENTAL
Melting points were determined in a capillary Electrothermal
9100 SERIES-Digital apparatus and are uncorrected. 1H and
13C-NMR spectra were recorded at room temperature using a
Bruker 300-MHz spectrometer and DMSO-d6 as solvent. The
operating frequencies for protons and carbons were 300.13 and
75.46 MHz, respectively. The chemical shifts (δ) were given in
ppm. IR spectra were recorded on an FT Perkin Elmer Spectrum
One from KBr discs. Mass spectra were measured on MS/DSQ II.
Elemental analysis (C, H, and N) were performed on an Exeter
CE 440, and the results were within 0.4% of the calculated
values. Analytical TLCs were performed on DC-Alufolien
Kieselgel 60F254 Merck. The ultrasonic irradiation was performed
by using an Arcano ultrasonic cleaner bath, with digital timer and
heater switch, 70 W, 2.0 L, and 40 KHz.
( ) 1-(4-Chlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]-
indole 3e. The product was triturated with CH2Cl2 at rt, yellow
powder, mp 220–222°C.
1H-NMR: δ 3.00–3.16 (2H, m, 4-CH2), 3.44–3.50 (2H, m,
3-CH2), 6.00 (1H, s, CH), 7.07 (1H, t, J = 7.8 Hz, Het-H), 7.14
(1H, t, J = 7.8 Hz, Het-H), 7.31 (1H, d, J = 8.0 Hz, Het-H), 7.40
(2H, d, J = 8.7 Hz, Ph-H), 7.56 (1H, d, J = 7.8 Hz, Het-H), 7.59
(2H, d, J = 8.5 Hz, Ph-H), 9.20 (1H, s, NH), 10.90 (1H, s, NH).
13C-NMR: δ 18.6, 55.3, 197.9, 112.0, 118.7, 119.6, 122.6, 126.1,
128.5, 129.4, 132.3, 134.0, 135.1, 137.0. Anal. Calcd. for
C17H15ClN2: C, 72.21; H, 5.35; N, 9.91. Found: C, 72.50; H,
5.21; N, 9.76.
General procedure for the synthesis of compounds 3a–3l. A
mixture of 1.00mmol (0.16g) of tryptamine, 1.5 mmol of a variety
of arylaldehydes, 0.15mL TFA, and 10mL of CH2Cl2 was
subjected to ultrasonic irradiation or conventional method, at
room temperature. The reaction was monitored by TLC (CH2Cl2:
CH3OH, 4:1).
( ) 2,3,4,9-Tetrahydro-1-phenyl-1H-pyrido[3,4-b]-indole 3a.
The product was triturated with benzene at rt, white powder, mp
160–162°C according to lit 160–161°C [26].
1H-NMR: δ 3.05–3.10 (2H, m, 4-CH2), 3.46–3.51 (2H, m,
3-CH2), 6.07 (1H, s, CH), 7.11 (1H, t, Het-H, J = 7.6 Hz), 7.15
(1H, t, Het-H, J = 7.8 Hz), 7.27–7.44 (7H, m, Ph-H and H-Het),
9.70 (1H, s, NH), 10.8 (1H, s, NH). 13C-NMR: δ 22.6, 58.1,
107.2, 111.0, 118.4, 119.5, 121.7, 127.4, 128.3, 128.7, 129.2,
134.7, 136.5, 142.3. IR (cmÀ1): υ 3401, 2930, 2857, 1597, 770.
Anal. Calcd. for C17H16N2: C, 82.22; H, 6.49; N, 11.28. Found:
C, 81.92; H, 6.17; N, 11.16.
( ) 1-(4-(Trifluorometyl)phenyl)-2,3,4,9-tetrahydro-1H-pyrido
[3,4-b]-indole 3f. The product was triturated with hot CH2Cl2,
white powder, mp 243–245°C.
1H-NMR: δ 3.04–3.08 (2H, m, 4-CH2), 3.36–3.51 (2H, m,
3-CH2), 6.10 (1H, s, CH), 7.06 (1H, t, J = 7.0 Hz, Het-H),
7.14 (1H, t, J = 6.9 Hz, Het-H), 7.30 (1H, d, J = 8.0 Hz, Het-H),
7.56 (1H, d, J = 7.6 Hz, Het-H), 7.62 (2H, d, J = 8.0 Hz, Ph-H),
8.00 (2H, d, J = 7.9 Hz, Ph-H), 9.70 (1H, s, NH), 10.90 (1H, s,
NH). 13C-NMR: δ 18.6, 55.4, 108.1, 112.0, 118.8, 119.7, 122.7,
126.1, 126.3, 128.2, 130.4, 130.8, 131.4, 137.0, 139.6. Anal. Calcd.
for C18H15F3N2: C, 68.35; H, 4.78; N, 8.86. Found: C, 68.13; H,
4.89; N, 8.97.
( ) 2,3,4,9-Tetrahydro-1-(2-nitrophenyl)-1H-pyrido[3,4-b]-
indole 3b. The product was crystallized from benzene, yellow
powder, mp 212–215°C.
( )1-(4-Hydroxy-2-methoxyphenyl)-2,3,4,9-tetrahydro-1H-
pyrido[3,4-b]-indole 3g. The product was triturated with hot
CH2Cl2, white powder, mp 217–219°C.
1H-NMR: δ 3.02–3.08 (2H, m, 4-CH2), 3.13–3.19 (1H, m,
3-H), 3.56–3.60 (1H, m, 3′-H), 6.45 (1H, s, CH), 7.05–7.17 (2H,
m, Ph-H), 7.23–7.26 (1H, m, Het-H), 7.34 (1H, d, J = 7.9 Hz, Het-
H), 7.58 (1H, d, J = 7.6 Hz, Het-H), 7.77- 7.80 (2H, m, Ph-H),
8.32- 8.35 (1H, m, Het-H), 9.44 (1H, s, NH), 10.20 (1H, s, NH).
13C-NMR: δ 11.8, 50.8, 108.8, 112.2, 118.9, 119.7, 122.8, 125.9,
126.0, 127.6, 129.9, 131.8, 132.9, 135.0, 136.9, 149.2. MS (m/z):
293 (M+, 100), 247 ([M+ À NO2], 22), 171 ([M+ À C6H4NO2],
60), 69 (C4H7N, 81). Anal. Calcd. for C17H15N3O2: C, 69.60; H,
5.15; N, 14.30. Found: C, 70.20; H, 5.47; N, 13.8.
1H-NMR: δ 2.97–3.13 (2H, m, 4-CH2), 3.46–3.48 (2H, m,
3-CH2), 3.74 (3H, s, OCH3), 5.84 (1H, s, CH), 6.70 (1H, d,
J = 8.1 Hz, Ph-H), 6.85 (1H, d, J = 8.3 Hz, Ph-H), 7.01–7.14 (3H,
m, 2 Het-H y Ph-H), 7.30 (1H, d, J = 8.0 Hz, Het-H), 7.52 (1H, d,
J = 7.6 Hz, Het-H), 9.48 (1H, s, NH), 9.77 (1H, s, OH), 9.82 (1H,
s, NH). 13C-NMR: δ 18.6, 56.1, 56.2, 107.6, 112.0, 114.2,
115.9, 118.6, 119.5, 122.4, 123.1, 125.5, 126.1, 129.2, 136.9,
148.2, 148.5. MS (m/z): 293 (M+, 28), 294 ([M++1], 40), 171
([M++1- C7H7O2], 13), 69 (C4H7N, 100). Anal. Calcd. for
C
18H18N2O2: C, 70.45; H, 6.17; N, 9.50. Found: C, 70.40; H,
( ) 2,3,4,9-Tetrahydro-1-(4-nitrophenyl)-1H-pyrido[3,4-b]-
indole 3c. The product was triturated with hot CH2Cl2, yellow
powder, mp 194–196°C.
6.36; N, 9.02.
( ) 2,3,4,9-Tetrahydro-1-(3,4-dimethoxyphenyl)-1H-pyrido
[3,4-b]-indole 3h. The product was triturated with hot CH2Cl2,
white powder, mp 238–239°C.
1H-NMR: δ 3.06–3.10 (2H, m, 4-CH2), 3.45–3.49 (2H, m,
3-CH2), 6.14 (1H, s, CH), 7.06 (1H, t, J = 7.3 Hz, Het-H), 7.13
(1H, t, J = 7.3Hz, Het-H), 7.29 (1H, d, J= 8.1 Hz, Het-H), 7.55
(1H, d, J = 8.1Hz, Het-H), 7.67 (2H, d, J = 8.8Hz, Ph-H), 8.34
(2H, d, J = 8.8 Hz, Ph-H), 9.79 (1H, s, NH), 10.95 (1H, s, NH).
13C-NMR: δ 18.1, 54.6, 107.7, 111.6, 118.3, 119.2, 122.2, 123.8,
125.6, 127.5, 131.6, 136.6, 141.5, 148.3. IR (cmÀ1): υ 3394,
2495, 1666, 1514, 1353, 1178, 842. Anal. Calcd. for C17H15N3O2:
C, 69.60; H, 5.15; N, 14.30. Found: C, 69.30; H, 5.35; N, 14.10.
( ) 1-(2-Chlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]-
indole 3d. The product was crystallized from cyclohexane,
white powder mp 206–209°C.
1H-NMR: δ 3.03–3.10 (2H, m, 4-CH2), 3.10–3.45 (2H, m,
3-CH2), 3.74 (3H, s, OCH3), 3.78 (3H, s, OCH3), 5.89 (1H,
s, CH), 6.82 (1H, d, J = 8.3 Hz, Ph-H), 7.03–7.15 (4H, m,
Ph-H y Het-H), 7.30 (1H, d, J = 7.9 Hz, Het-H), 7.53 (1H,
d, J = 7.7 Hz, Het-H), 9.21 (1H, s, NH), 9.83 (1H, s, NH).
13C-NMR: δ 18.6, 56.1, 99.1, 107.6, 112.0, 112.2, 113.7,
118.7, 119.5, 122.5, 122.9, 126.1, 127.0, 129.1, 136.9,
149.3, 150.4. MS (m/z): 308 (M+, 100), 248 ([M+- 2(CH3)],
46), 171 ([M+- C8H9O2], 38), 69 (C4H7N, 55). Anal. Calcd.
for C19H20N2O2: C, 74.20; H, 6.51; N, 9.08. Found: C,
73.81; H, 6.04; N, 8.94.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

650
G. C. Muscia, L. O. De María, G. Y. Buldain, and S. E. Asís
Vol 53
( ) 2,3,4,9-Tetrahydro-1-(3,5-dimethoxyphenyl)- 1H-pyrido
[3,4-b]-indole 3i. The product was triturated with hot CH2Cl2,
white powder, mp 208–209°C.
Acknowledgments. Financial help was received from Consejo
Nacional de Investigaciones Científicas y Técnicas (CONICET)
to G. Y. Buldain (PIP 441) and from Universidad de Buenos
Aires (UBACyT B-109).
1H-NMR: δ 2.97–3.15 (2H, m, 4-CH2), 3.38–3.53 (2H, m,
3-CH2), 3.75 (6H, s, OCH3), 5.88 (1H, s, CH), 6.56 (2H, s,
Ph-H), 6.65 (1H, s, Ph-H), 7.05 (1H, t, J = 6.9 Hz, Het-H),
7.13 (1H, t, J = 6.0 Hz, Het-H), 7.31 (1H, d, J = 8.0 Hz, Het-H),
7.53 (1H, d, J = 7.7 Hz, Het-H), 9.31 (1H, s, NH), 9.92 (1H, s,
NH). 13C-NMR: δ 19.3, 46.2, 55.9, 56.2, 101.5, 107.6, 108.3,
112.0, 118.7, 119.5, 122.5, 126.1, 128.7, 136.9, 137.1, 159.2,
161.2. Anal. Calcd. for C19H20N2O2: C, 74.00; H, 6.54; N, 9.08.
Found: C, 73.65; H, 6.69; N, 9.28.
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1H-NMR: δ 2.98–3.04 (1H, m, 4-H), 3.11–3.17 (1H, m, 4′-H),
3.44–3.46 (1H, m, 3-H), 3.58–3.60 (1H, m, 3′-H), 3.70 (3H, s,
OCH3), 3.74 (6H, s, OCH3), 5.89 (1H, s, CH), 6.75 (2H, s,
Ph-H), 7.06 (1H, t, J = 7.7 Hz, Het-H), 7.11 (1H, t, J = 7.1 Hz,
Het-H), 7.32 (1H, d, J = 8.0 Hz, Ph-H), 7.54 (1H, d, J = 7.6 Hz,
Het-H), 9.46 (1H, s, NH), 9.87 (1H, s, NH). 13C-NMR: δ 18.7,
23.4, 56.5, 56.7, 60.5, 107.6, 107.7, 112.1, 118.7, 119.5, 122.5,
126.2, 128.9, 130.4, 137.0, 139.0, 153.5. Anal. Calcd. for
C20H22N2O3: C, 70.99; H, 6.55; N, 14.18. Found: C, 71.30; H,
6.41; N, 13.97.
( ) 1-(4-Bromo-3,5-dimethoxyphenyl)-2,3,4,9-tetrahydro-1H-
pyrido[3,4-b]-indole 3k. The product was triturated with hot
CH2Cl2, yellow powder, mp 166–169°C.
1H-RMN: δ 3.05–3.18 (2H, m, 4-CH2), 3.61–3.65 (2H, m,
3-CH2), 3.80 (6H, s, OCH3), 5.95 (1H, s, CH), 6.83 (2H, s,
Ph-H), 7.05 (1H, t, J = 6.9 Hz, Het-H), 7.13 (1H, t,
J = 7.0 Hz, Het-H), 7.30 (1H, d, J = 7.9 Hz, Het-H), 7.53
(1H, d, J = 7.7 Hz, Het-H), 9.51 (1H, s, NH), 10.11 (1H, s,
NH). 13C-RMN: δ 18.6, 41.6, 57.0, 101.7, 106.8, 107.7, 112.1,
118.8, 119.6, 122.6, 126.1, 128.6, 135.8, 137.1, 157.2. Anal. Calcd.
for C19H19BrN2O2: C, 58.93; H, 4.95; N, 7.23. Found: C, 59.19; H,
4.80; N, 7.16.
[15] Xin, B.; Tang, W.; Wang, Y.; Lin, G.; Liu, H.; Jiao, Y.; Zhu, Y.;
Yuan, H.; Chen, Y.; Lu, T. Bioorg Med Chem Lett 2012, 22, 4783.
[16] Hadjaz, F.; Besret, S.; Martin-Nizard, F.; Yous, S.; Dilly, S.;
Lebegue, N.; Chavatte, P.; Duriez, P.; Berthelot, P.; Carato, P. Eur J
Med Chem 2011, 46, 2575.
( ) 2,3,4,9-Tetrahydro-1-(2-methoxynaphthalen-6-yl)-1H-pyrido
[3,4-b]-indole 3l. The product was triturated with hot CH2Cl2,
white powder, mp 234–236°C.
[17] Zeng, L.; Zhang, J. Bioorg Med Chem Lett 2012, 22, 3718.
[18] Mulcahy, S. P.; Varelas, J. G. Tetrahedron Lett 2013, 54, 6599.
[19] Mason, T. J Chem Soc Rev 1997, 26, 443.
1H-RMN: δ 3.02–3.16 (2H, m, 4-CH2), 3.51–3.52 (2H, m,
3-CH2), 3.90 (3H, s, OCH3), 6.09 (1H, s, CH), 7.07–7.13
(2H, m, Het-H), 7.23 (1H, dd, J = 2.5 y 8.9 Hz, Naft-H),
7.28 (1H, d, J = 7.8 Hz, Het-H), 7.40 (1H, d, J = 2.1 Hz,
Naft-H), 7.45 (1H, d, J = 8.5 Hz, Naft-H), 7.56 (1H, d,
J = 7.5 Hz, Het-H), 7.88–7.95 (3H, m, Naft-H), 9.36 (1H, s,
NH), 9.98 (1H, s, NH). 13C-RMN: δ 55.8, 56.4, 106.3,
107.9, 112.1, 118.7, 119.6, 119.9, 122.5, 126.2, 127.6,
127.9, 128.4, 129.0, 129.9, 130.0, 135.4, 137.1, 158.6. Anal.
Calcd. for C22H20N2O: C, 80.46; H, 6.14; N, 8.53. Found:
C, 80.83; H, 5.93; N, 8.29.
[20] Cella, R.; Stefani, H. A. Tetrahedron 2009, 65, 2619.
[21] Pacheco, D. J.; Prent, L.; Trilleras, J.; Quiroga, J. Ultrason
Sonochem 2013, 20, 1033.
[22] Becher, P.; Beuchat, J.; Gademann, K.; Jüttner, F. J Nat Prod
2005, 68, 1793.
[23] Muscia, G. C.; Buldain, G. Y.; Asís, S. E. Eur J Med Chem
2014, 73, 243.
[24] Jiang, W.; Suia, Z.; Chen, X. Tetrahedron Lett 2002, 43, 8941.
[25] Muscia, G. C.; Hautmann, S.; Buldain, G. Y.; Asís, S. E.;
Gütschow, M. Bioorg Med Chem Lett 2014, 24, 1545.
[26] Saha, B.; Sharma, S.; Sawant, D.; Kundu, B. Tetrahedron Lett
2007, 48, 1379.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet