Synthesis of N,N-dialkyl-1-(2-alkylthiopyrimidin-4-yl)piperidin- 4-amines as potential heat shock protein inhibitors

Article abstract of DOI:10.1007/s11172-018-2339-5

A new efficient method for synthesizing promising heat shock protein inhibitors, N,N-dialkyl- 1-(2-alkylthiopyrimidin-4-yl)piperidin-4-amines, by the reaction of 2-alkyl-4-chlorothiouracils with 4-(N-alkyl-N-methylamino)piperidines was developed. 2-Alkyl-4-chlorothiouracils were synthesized by alkylation of 2-thiouracil with alkyl iodides and subsequent treatment of the intermediates with POCl₃. 4-(N-Alkyl-N-methylamino)piperidines were prepared by reductive amination of 1-(tert-butoxycarbonyl)-4-piperidinone with methylamine followed by treatment of the intermediate with the appropriate aldehydes.

Full text of DOI:10.1007/s11172-018-2339-5

Russian Chemical Bulletin, International Edition, Vol. 67, No. 11, pp. 2127—2130, November, 2018
2127
Synthesis of N,N-dialkyl-1-(2-alkylthiopyrimidin-4-yl)piperidin-
4
-amines as potential heat shock protein inhibitors
a
b
b
V. N. Aldobaev, M. A. Prezent, and I. V. Zavarzin
aResearch Center for Toxicology and Hygienic Regulation of Biologics —
Branch of the State Scientific Center "Institute of Immunology" of the Federal Medical and Biological Agency of Russia,
02A ul. Lenina, 142253 Bolshevik, Moscow Region, Russian Federation
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
1
b
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
E-mail: zavi@ioc.ac.ru
A new efficient method for synthesizing promising heat shock protein inhibitors, N,N-di-
alkyl-1-(2-alkylthiopyrimidin-4-yl)piperidin-4-amines, by the reaction of 2-alkyl-4-chloro-
thiouracils with 4-(N-alkyl-N-methylamino)piperidines was developed. 2-Alkyl-4-chloro-
thiouracils were synthesized by alkylation of 2-thiouracil with alkyl iodides and subsequent
treatment of the intermediates with POCl . 4-(N-Alkyl-N-methylamino)piperidines were
3
prepared by reductive amination of 1-(tert-butoxycarbonyl)-4-piperidinone with methylamine
followed by treatment of the intermediate with the appropriate aldehydes.
Key words: thiouracil, 1-(tert-butoxycarbonyl)-4-piperidinone, piperidines, reductive
amination, nucleophilic substitution, pyrimidines, heat shock protein inhibitors, antitumor
activity.
A growing number of evidences of drug-resistant
and to evaluate cytotoxicity of the synthesized compounds
against tumor cells and fibroblasts (MSF7, HEP-2, and
L-929) for searching for potential cytostatics and their
further trials.
human tumor cells require development of new drugs with
new target disease-specific mechanisms of cytostatic activ-
ity that can increase the efficiency of cancer therapy. One
of the promising therapeutic approaches in modern cancer
therapy is targeting of heat shock proteins (HSPs) playing
an important role in maintaining cellular homeostasis.
Selective inhibition of at least one of the representatives
of a large family of heat shock proteins promotes cancer
8
Synthetic approach described by Zeng et. al. involves
the successive substitution of the chlorine atoms of 2,4-di-
chloropyrimidine first with tert-butyl N-methyl-N-
(piperidin-4-yl)carbamate and then with sodium meth-
anethiolate, removal of the protecting group, and finally
alkylation with the appropriate benzylic halides. However,
we failed to reproduce substitution of the chlorine atom
at the pyrimidine ring with sodium thiomethoxide. In our
hands, the substitution failed to proceed under conditions
cell apoptosis.1
—5
Several recent publications6
—8
are focused on the
synthesis of different small molecule inhibitors of HSP70.
Structures of these inhibitors were identified by molecular
8
8
docking. Thus, Zeng et. al. have described synthesis of
described by Zeng et. al. and under some other conditions.
6
7 derivatives of 4-aminopiperidine designed as promising
Therefore, it was required to develop new approaches to
8
HSP70 inhibitors. The authors also evaluate in vitro bio-
logical activity of the synthesized compounds, determined
their dissociation constants using surface plasmon reso-
nance studies, and examined the ability of the test com-
pounds to inhibit HSP70 ATPase activity. It should be
emphasized that the results obtained in some steps during the
the most promising piperidines synthesized in work and
their closest homologs.
We developed a procedure that allows one to widen
significantly the scope of combinatorial synthesis of the
target compounds for screening using cell cultures to
identify optimal drug candidates for further development
as cytostatics.
8
work cannot be reproduced. The main aim of the present
work is the development of new simple and efficient synthe-
tic approach towards small molecule inhibitors of HSPs based
on the analysis of both new structures constantly emerging
in scientific literature and the results of SAR modelling.
We intended to synthesize derivatives of 4-amino-
piperidine that exhibited high HSP70 inhibiting activity
Our approach (Scheme 1) takes a simple synthesis of
2-alkylthio-4-chloropyrimidines 3a,b and 4-(N-alkyl-N-
methyl)aminopiperidines 7a—e. The target products 8a—g
were obtained in high yields by substitution of the chlorine
atom of compounds 3a,b with piperidines 7a—e (see
Scheme 1). It is possible to vary the alkyl substituent at
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2127—2130, November, 2018.
066-5285/18/6711-2127 © 2018 Springer Science+Business Media, Inc.
1

2128
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 11, November, 2018
Aldobaev et al.
Scheme 1
2
6
, 3: R1 = Me (a), Et (b)
, 7: R2 = 2,6-Cl C H (a), 4-NCC H (b), 2-ClC H (c), 2-chloro-3-pyridyl (d), 1,5-dimethylpyrazol-4-yl (e)
2
6
3
6
4
6 4
8
R1
R2
8
e
f
R1
Me
Et
R2
a
b
c
d
Me
Me
Me
Me
2,6-Cl C H
1,5-Dimethylpyrazol-4-yl
2,6-Cl C H
2
6 3
4-NCC H
6
4
2 6 3
2-ClC H
g
Et
4-NCC H
6
4
6 4
2-Chloro-3-pyridyl
the sulfur atom, amine used for the modification of the
carbonyl group, and aldehyde.
The synthesis started from the commercially available
thiouracil (1) and 1-(tert-butoxycarbonyl)piperidin-4-
spectra of these compounds reveal the [M + H]+ and
+
[M + Na] peaks.
The developed synthetic approach allows varying the
substituents both at the sulfur atom of the pyrimidine
fragment and at the nitrogen atom of the piperidine
moiety, which is advantageous over method described by
9
one (4). Thiouracil was readily alkylated with alkyl iodides
and subsequent treatment of compounds 2a,b with phos-
1
0
8
phorous oxychloride gives 4-chloropyrimidines 3a,b.
Zeng et. al.
Amination of substituted piperidinone 4 with methyl-
It is of note that the replacement of methylamine (on
the synthesis of piperidine 5) with other amines serves for
synthesizing new 4-dialkylaminopiperidine derivatives that
can be involved in further transformations.
Currently, the synthesized compounds are under in vitro
screening against selected cell lines in the Research Center
for Toxicology and Hygienic Regulation of Biologics —
Branch of the State Scientific Center "Institute of Immun-
ology" of the Federal Medical and Biological Agency
of Russia.
amine1 in the presence of NaBH(OAc) gives compound
1
3
5
. 4-(N-Alkyl-N-methylamino)piperidines 7a—e were
synthesized by the reaction of compound 5 with aldehydes
in the presence of NaBH(OAc) followed by successive
3
treatment first with acid and then with base.
Substitution of the chorine atom of 4-chloropyrimi-
dines 3a,b with amines 7a—e was carried out in refluxing
dioxane in the presence of diisopropylethylamine (DIPEA)
to give the target compounds 8a—g. Products 8a—g are
white solids well soluble in chloroform, benzene, and THF
1
but sparingly soluble in hexane and water. H NMR spec-
Experimental
tra of compounds 8a—g exhibit characteristic signals of
the NCH Ar(Het) group protons at δ 4.00 and the doublets
1
2
H NMR spectra were run on a Bruker WM-300 spectrometer
of the CH= pyrimidine ring protons at δ 6.25 and 8.05.
13
(
a working frequency of 300 MHz) at 303 K. C NMR spectra
IR spectra of compounds 8a—g show vibration bands of
were acquired with a Bruker WM-300 instrument (a working
–
1
the C=N group at 1637—1655 cm . High resolution mass
frequency of 75 MHz). The chemical shifts are given in the δ scale

4
-Amino-1-(alkylthiopyrimidinyl)piperidines
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 11, November, 2018
2129
+
relative to the residual proton signals and the carbon signals of
[M + Na] . Calculated for C H Cl N S: M + H = 397.1015,
18
22
2
4
1
the deuterated solvents (δ 7.27 for CDCl ( H) and δ 39.50 for
M + Na = 419.0834.
3
13
DMSO-d ( C)).
N-(4-Cyanobenzyl)-N-methyl-1-(2-methylthiopyrimidin-4-
yl)piperidin-4-amine (8b). Yield 2.44 g (69%), m.p. 181—183 °C.
6
Melting points were measured with a Boetius apparatus at
a heating rate of 4 °C min– and are given uncorrected. High
resolution electrospray ionization (ESI) mass spectrometry was
performed with a Bruker Daltonics MicrOTOF II instrument.
The mass spectra were acquired over the m/z range of 50—3000 Da
operating in either positive (capillary voltage of 4500 V) or
negative (capillary voltage of 3200 V) ion modes; the probes were
injected as the solutions in MeCN and MeOH via a syringe pump
at a flow rate of 3 μL min– ; interface temperature was 180 °C;
1
–1
1
IR (KBr), ν/cm : 2222 (CN), 1638 (C=N). H NMR (CDCl ),
3
δ: 1.70, 2.10 (both s, 2 H each, C(3)H , C(4)H ); 2.32 (s, 3 H,
2
2
NMe); 2.50 (s, 3 H, SMe); 2.95 (s, 3 H, C(2)H , NCH); 4.00
2
(s, 2 H, CH (benzyl)); 4.55 (s, 2 H, C(1)H ); 6.25 (d, 1 H, =C(5)H,
2
2
J = 2.0 Hz); 7.52, 7.63 (both d, 2 H each, C H , J = 7.0 Hz);
6
4
13
8.05 (d, 1 H, =C(6)H, J = 2.0 Hz). C NMR (DMSO-d ), δ:
6
13.3 (SMe), 27.0 (C(3), C(5)), 37.4 (NMe), 42.9 (C(2), C(6)),
1
56.2 (NCH ), 60.3 (C(4)), 99.0 (C(5´)), 109.4 (C(1´´)), 119.0
2
–
1
nebulizer gas was nitrogen (flow rate of 4.0 L min ). Elemental
analysis was carried out with a Perkin Elmer 2400 Series II
CHNS/O analyzer. Column chromatography was performed
with Acros Organics silica gel 60A (0.060—0.200 mm).
Thiouracil, 1-(tert-butoxycarbonyl)piperidin-4-one, 2-chloro-
pyridine-3-carbaldehyde, 1,5-dimethylpyrazole-4-carbaldehyde,
(CN), 129.1 (C(3´´), C(5´´)), 132.1 (C(2´´), C(6´´)), 146.5
(C(4´´)), 155.5 (C(6´)), 160.2 (C(4´)), 170.0 (C(2´)). HRMS,
+
+
found: m/z 354.1810 [M + H] , 376.1570 [M + Na] . Calculated
for C H N S: M + H = 354.1746, M + Na = 376.1566.
19
23
5
N-(2-Chlorobenzyl)-N-methyl-1-(2-methylthiopyrimidin-4-
yl)piperidin-4-amine hydrochloride (8c•HCl). Yield 2.15 g (54%),
–
1
1
2
-chlorobenzaldehyde, 2,6-dichlorobenzaldehyde, 4-cyanobenz-
m.p. 247—249 °C. IR (KBr), ν/cm : 1637 (C=N). H NMR
aldehyde, NaBH(OAc) , and DIPEA were purchased from
(DMSO-d ), δ: 1.95, 2.40 (both s, 2 H each, C(3)H , C(4)H );
3
6
2
2
Aldrich.
2.42 (s, 3 H, NMe); 2.60 (s, 3 H, SMe); 3.25 (s, 2 H, C(2)H );
2
The intermediates (2-alkyl-4-chloropyrimidines 3a,b, 1-(tert-
butoxycarbonyl)-4-(methylamino)piperidine (5), and compounds
3.80 (s, 1 H, NCH); 4.35, 4.60 (both d, 2 H each (benzyl),
J = 5.0 Hz); 4.80 (s, 2 H, C(1)H ); 7.05 (d, 1 H, =C(5)H,
2
7
a—e) were used in the next step without characterization and
purification.
N-Alkyl-N-methyl-1-(2-alkylthiopyrimidin-4-yl)piperidin-4-
amines 8a—g (general procedure). To a solution of piperidine 5
J = 2.0 Hz); 7.40—7.60 (m, 3 H, C H , =C(6)H); 8.05, 8.20
6 4
+
(both d, 1 H each, C H , J = 7.0 Hz); 11.70 (br.s, 1 H, NH ).
6
4
13
C NMR (DMSO-d ), δ: 13.3 (SMe), 25.5 (C(3), C(5)), 38.9
6
(NMe), 43.1 (C(2), C(6)), 52.2 (NCH ), 61.7 (C(4)), 99.40
2
(
(
10 mmol) and the appropriate aldehyde (11 mmol) in CH Cl
(C(5´)), 127.7, 128.1, 129.9, 131.6, 134.1, 134.7 (C H ), 145.2
2
2
6 4
100 mL), NaBH(OAc) (20 mmol) was added. After 20 h stir-
(C(6´)), 159.2 (C(4´)), 164.90 (C(2´)). HRMS, found: m/z
3
+
+
ring, 10% aqueous NaOH (50 mL) was added and stirring was
continued for 1 h. The organic layer was separated, dried with
363.1411 [M + H] , 385.1230 [M + Na] . Calculated for
C H ClN S: M + H = 363.1405, M + Na = 385.1224.
18
23
4
MgSO , and concentrated in vacuo. The oily residue was treated
N-[(2-Chloro-3-pyridyl)methyl]-N-methyl-1-(2-methylthio-
pyrimidin-4-yl)piperidin-4-amine hydrochloride (8d•HCl). Yield
4
with 20% HCl (10 mL), the mixture was stirred for 6 h, basified
with concentrated aqueous NaOH to pH 10, and extracted with
ethyl acetate (2×30 mL). After drying, the combined organic
extracts were transferred into a weighted flask and concentrated
in vacuo. To the obtained oily amine 7a—e, dioxane (20 mL),
DIPEA (2 equiv.), and 4-chloropyrimidine 3a,b (1.2 equiv.) were
added, the mixture was refluxed for 6 h, cooled down, and con-
centrated in vacuo. The residue was extracted with dichlorometh-
ane, the extracts were washed with water, dried, and concen-
trated in vacuo. Purification of the residue by silica gel column
chromatography (elution first with petroleum ether—ethyl acetate
–
1
2.04 g (51%), m.p. 268—270 °C. IR (KBr), ν/cm : 1655 (C=N).
2.00, 2.42 (both s, 2 H each, C(3)H , C(4)H ); 2.42 (s, 3 H,
2
2
NMe); 2.55 (s, 3 H, SMe); 3.25 (s, 2 H, C(2)H ); 3.80 (s, 1 H,
2
NCH); 4.35, 4.60 (both d, 2 H, CH (benzyl), J = 5.0 Hz); 4.80
2
(s, 2 H, C(1)H ); 7.00 (d, 1 H, =C(5)H (pyrimidine), J = 2.0 Hz);
2
7.50 (t, 1 H, =CH (pyridine), J = 2.0 Hz); 8.10 (d, 1 H, =C(6)H
(pyrimidine), J = 2.0 Hz); 8.50 (d, 1 H, =CH (pyridine),
J = 2.0 Hz); 8.75 (d, 1 H, =CH (pyridine), J = 2.0 Hz); 12.50
+
13
(br.s, 1 H, NH ). C NMR (DMSO-d ), δ: 13.3 (SMe), 25.2,
25.6 (C(3), C(5)), 37.9 (NMe), 43.1 (C(2), C(6)), 52.2 (NCH ),
6
2
(
1 : 5) then with ethanol—dichloromethane (1 : 20), removal of
61.6 (C(4)), 99.4 (C(5´)), 123.60 (C(4´´)), 129.7 (C(5´´)), 143.2
(C(3´´)), 145.7 (C(6´)), 156.9 (C(6´´)), 151.5 (C(2´´)), 159.0
the solvents in vacuo, and trituration of the residue with hexane
gives the title products. Compounds 8a,b,e,f were obtained as
bases; compounds 8c,d,g were converted into hydrochlorides by
dissolving in MeOH saturated with HCl (10 mL) followed by
removal of the solvent.
+
(C(4´)), 165.0 (C(2´)). HRMS, found: m/z 364.1364 [M + H] ,
+
387.1185 [M + Na] . Calculated for C H ClN S: M + H =
17
22
5
= 364.1357, M + Na = 387.1177.
N-[(1,5-Dimethylpyrazol-4-yl)methyl]-N-methyl-1-(2-me-
thylthiopyrimidin-4-yl)piperidin-4-amine (8e). Yield 1.95 g (51%),
N-(2,6-Dichlorobenzyl)-N-methyl-1-(2-methylthiopyrimidin-
-yl)piperidin-4-amine (8a). Yield 2.46 g (62%), m.p. 146—147 °C.
–
1
1
4
m.p. 121—123 °C. IR (KBr), ν/cm : 1637 (C=N). H NMR
(DMSO-d ), δ: 1.70, 1.90 (both s, 2 H each, C(3)H , C(4)H );
–
1
1
IR (KBr), ν/cm : 1637 (C=N). H NMR (CDCl ), δ: 1.70, 2.10
3
6
2
2
(
(
(
both s, 2 H each, C(3)H , C(4)H ); 2.32 (s, 3 H, NMe); 2.50
2.15 (s, 3 H, Me); 2.32 (s, 3 H, NMe); 2.40 (s, 3 H, NMe); 2.55
2
2
s, 3 H, SMe); 2.95 (s, 3 H, C(2)H , NCH); 4.00 (s, 2 H, CH
(s, 3 H, SMe); 2.95 (s, 3 H, C(2)H , NCH); 3.80 (s, 2 H, CH2
2
2
2
benzyl)); 4.55 (s, 2 H, C(1)H ); 6.25 (d, 1 H, =C(5)H, J = 2.0 Hz);
(benzyl)); 4.50 (s, 2 H, C(1)H ); 6.30 (d, 1 H, =C(5)H,
2
2
7
.15—7.40 (m, 3 H, C H ); 8.05 (d, 1 H, =C(6)H, J = 2.0 Hz).
J = 2.0 Hz); 7.10 (s, 1 H, CH (pyrazole)); 7.95 (d, 1 H, =C(6)H,
6
3
1
3
13
C NMR (DMSO-d ), δ: 13.4 (SMe), 26.0 (C(3), C(5)), 38.9
J = 2.0 Hz). C NMR (DMSO-d ), δ: 9.4 (Me), 13.4 (SMe),
6
6
(
(
1
(
NMe), 43.1 (C(2), C(6)), 52.2 (NCH ), 60.9 (C(4)), 99.0
25.0, 26.0 (C(3), C(5)), 36.7, 38.9 (2 NMe), 43.1, 44.3 (C(2),
2
C(5´)), 128.6 (C(4´´), C(6´´)), 129.7 (C(5´´)), 134.70 (C(2´´)),
C(6)), 46.2 (NCH ), 59.9 (C(4)), 99.00 (C(5´)), 128.6 (C(4´´),
2
36.1 (C(1´´), C(3´´)), 155.5 (C(6´)), 160.2 (C(4´)), 170.0
C(6´´)), 129.7 (C(5´´)), 134.7 (C(2´´)), 136.1 (C(1´´), C(3´´)),
155.5 (C(6´), 160.2 (C(4´)), 170.0 (C(2´)). HRMS, found:
+
C(2´)). HRMS, found: m/z 397.1023 [M + H] , 419.0840

2130
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 11, November, 2018
Aldobaev et al.
+
+
m/z 347.2020 [M + H] , 369.1838 [M + Na] . Calculated for
C H Cl N S: M + H = 347.2012, M + Na = 369.1831.
References
17
26
2
6
N-(2,6-Dichlorobenzyl)-1-(2-ethylthiopyrimidin-4-yl)-N-
methylpiperidin-4-amine (8f). Yield 2.54 g (62%), m.p. 123—124 °C.
1
. M. Daugaard, M. Rohde, M. Jaattela, FEBS Lett., 2007,
5
81, 3702.
–
1
1
IR (KBr), ν/cm : 1637 (C=N). H NMR (DMSO-d ), δ: 1.40
6
2
3
. M. Powers, P. Workman, FEBS Lett., 2007, 581, 3758.
(
t, 3 H, Me, J = 5.0 Hz); 1.70, 2.10 (both s, 2 H each, C(3)H2,
. S. Patury, Y. Miyata, J. Gestwicki, Curr. Top. Med. Chem.,
C(4)H ); 2.22 (s, 3 H, NMe); 2.70—2.95 (m, 3 H, C(2)H ,
2
2
2
009, 9, 1337.
. J. Brodsky, G. Chiosis, Curr. Top. Med. Chem., 2006,
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. M. Powers, P. Clarke, P. Workman, Cancer Cell., 2008,
4, 250.
NCH); 3.00 (q, 2 H, CH N, J = 5.0 Hz); 3.80 (s, 2 H, CH
2
2
4
5
6
(
benzyl)); 4.55 (m, 2 H, C(1)H ); 6.25 (d, 1 H, =C(5)H, J = 2.0 Hz);
2
6
7
.15—7.40 (m, 3 H, C H ); 8.05 (d, 1 H, =C(6)H, J = 2.0 Hz).
6 3
1
3
C NMR (DMSO-d ), δ: 14.8 (Me), 24.2 (SCH ), 26.9 (C(3),
6
2
1
C(5)), 36.0 (NMe), 43.1 (C(2), C(6)), 52.2 (NCH ), 60.9 (C(4)),
2
. T. Taldone, Y. Kang, H. Patel, M. Patel, P. Patel, J. Med.
Chem., 2014, 57, 1208.
9
9.0 (C(5´)), 128.6 (C(4´´), C(6´´)), 129.7 (C(5´´)), 134.7
(
C(2´´)), 136.1 (C(1´´), C(3´´)), 155.5 (C(6´)), 160.2 (C(4´)),
7
8
9
. Y. Kang, T. Taldone, H. Patel, P. Patel, J. Med. Chem., 2014,
+
1
70.0 (C(2´)). HRMS, found: m/z 411.1182 [M + H] , 433.0998
5
7, 1188.
+
[
M + Na] . Calculated for C H Cl N S: M + H = 411.1171,
19 24 2 4
. Y. Zeng, R. Cao, T. Zhang, S. Li, W. Zhong, Eur. J. Med.
M + Na = 433.0991.
Chem., 2015, 97, 19.
N-(4-Cyanobenzyl)-1-(2-ethylthiopyrimidin-4-yl)-N-methyl-
piperidin-4-amine hydrochloride (8g•HCl). Yield 2.78 g (69%),
. T. Francesco, S. Marco, P. Giovanni, Tetrahedron, 2010,
6
6, 1280.
–
1
m.p. 154—156 °C. IR (KBr), ν/cm : 2245 (CN), 1637 (C=N).
1
0. M. Arnaiz, D. Eagen, K. Erickson, J. Med. Chem., 2007,
0, 1146.
1. Pat. US 2001044435; https://worldwide.espacenet.com.
1
H NMR (DMSO-d ), δ: 1.40 (t, 3 H, Me, J = 5.0 Hz); 2.00,
6
5
2
3
.40 (both s, 2 H each, C(3)H , C(4)H ); 2.52 (s, 3 H, NMe);
2 2
1
.30 (s, 4 H, CH N, C(2)H ); 3.80 (s, 1 H, NCH); 4.35, 4.60
2
2
(
both d, 2 H, CH (benzyl), J = 5.0 Hz); 4.80 (s, 2 H, C(1)H );
2
2
7
8
3
.10 (d, 1 H, =C(5)H, J = 2.0 Hz); 7.52 (s, 3 H, C H , =C(6)H);
6 4
+
.20 (s, 2 H, C H ); 12.20 (br.s, 1 H, NH ). HRMS, found: m/z
68.1909 [M + H] , 390.1730 [M + Na] . Calculated for
6
4
+
+
C20H25N S: M + H = 368.1903, M + Na = 390.1722.
5
Received July 2, 2018;
in revised form September 27, 2018;
accepted October 3, 2018
This work was financially supported by the Russian
Science Foundation (Project No. 14-50-00126).