N-Propargyl-α-aminophosphonates in 1,3-Dipolar Cycloaddition with Azide-Containing Pharmacophores

Article abstract of DOI:10.1134/S107036321809027X

Some transformations of N-propargyl-α-aminophosphonates synthesized by the Kubachnik–Fields reaction were studied in copper-catalyzed 1,3-dipolar cycloaddition with azide-containing pharmacophores (phenothiazine, tetrahydrocarbazole, carbazole, and 3,5-dimethyl-1-aminoadamantane) leading to the formation of the corresponding 1,4-substituted 1,2,3-triazoles and allowing the introduction of a diethoxyphosphoryl fragment into the molecules of potential neuroprotectors.

Full text of DOI:10.1134/S107036321809027X

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 9, pp. 1922–1926. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © V.B. Sokolov, A.Yu. Aksinenko, 2018, published in Zhurnal Obshchei Khimii, 2018, Vol. 88, No. 9, pp. 1554–1558.
LETTERS
TO THE EDITOR
Dedicated to the 110th anniversary of M.I. Kabachnik’s birth
N-Propargyl-α-aminophosphonates in 1,3-Dipolar Cycloaddition
with Azide-Containing Pharmacophores
a
a
V. B. Sokolov and A. Yu. Aksinenko *
a
Institute of Physiologically Active Substances of the Russian Academy of Sciences,
Severnyi proezd 1, Chernogolovka, 142432 Russia
*
e-mail: alaks@ipac.ac.ru
Received June 28, 2018
Abstract―Some transformations of N-propargyl-α-aminophosphonates synthesized by the Kubachnik–Fields
reaction were studied in copper-catalyzed 1,3-dipolar cycloaddition with azide-containing pharmacophores
(
phenothiazine, tetrahydrocarbazole, carbazole, and 3,5-dimethyl-1-aminoadamantane) leading to the formation
of the corresponding 1,4-substituted 1,2,3-triazoles and allowing the introduction of a diethoxyphosphoryl
fragment into the molecules of potential neuroprotectors.
Keywords: N-propargyl-α-aminophosphonates, phenothiazine, carbazole, 3,5-dimethyl-1-amino-adamantane,
1
,3-dipolar cycloaddition
DOI: 10.1134/S107036321809027X
Aminophosphoryl compounds, which are mainly
synthesized by the three-component Kabachnik–Fields
reaction [1, 2], for many decades attract the attention
of researchers in the field of medical and agro-
chemistry [3, 4]. Among these compounds inhibitors
of enzymes, for example, protein-tyrosine-phosphatase
an alcohol solution of equimolar amounts of diethyl
phosphite 1, carbonyl compound 2a–2c, and propargyl-
amine 3.
The functionalization of phosphonates 4a–4c was
performed by the reaction of alkyne-azide 1,3-dipolar
cycloaddition (Huisgen reaction) [16] in its copper-
catalyzed version [17]. Phosphonates 4a–4c reacted
with N-substituted azidoacetamides 5–8 in the
presence of catalytic amounts of Cu(I) to form the
corresponding 1,4-substituted 1,2,3-triazoles 9–12 in a
[5], urokinase [6], as well as compounds exhibiting
antitumor activity were detected [7, 8].
Apparently one of the most promising trends in the
development of aminophosphonate synthesis is further
development of approaches to the introduction of
reactive functional groups into their molecules that
allow targeted synthesis of substances with useful
properties to be performed. In this regard here we
reported on a method of functionalization of pharmaco-
phore ligands with a diethoxyphosphorylalkyl fragment
based on alkyne-azide copper-catalyzed 1,3-dipolar
cycloaddition of previously unknown N-propargyl-α-
aminophosphonates and azide-containing pharmaco-
phores. The choice of pharmacophore was due to the
data on biological activity of phenothiazine [9, 10],
carbazole [11, 12], tetrahydrocarbazole [13, 14], and
aminoadamantane derivatives [15].
8
1–89% yield.
The composition and the structure of compounds 4,
–12 were confirmed by elemental analysis and NMR
9
spectroscopy data. The signals of the phosphorus atom
of these compounds are registered in the 24–32 ppm
region characteristic of the 1-aminophosphonic acids
1
derivatives. In the H NMR spectra the proton signals
with characteristic spin-spin coupling constants are
observed. Thus, the signal of the methyl group at the
position 1 relative to the phosphorus atom appears as a
3
doublet with J = 16 Hz. The α-proton signal is also
PH
2
recorded as a doublet with JPH = 19 Hz. For
N-Propargylaminophosphonates 4a–4c were syn-
compounds 9–12 (Scheme 1), the singlet signal of the
thesized by Kubachnik–Fields reaction by heating (60°C)
1,2,3-triazole ring at 7.6–7.8 ppm is characteristic.
1
922

N-PROPARGYL-α-AMINOPHOSPHONATES IN 1,3-DIPOLAR CYCLOADDITION
1923
Scheme 1.
(
C H O) P(O)H
2
5
2
1
N
N
N
N
O
O
R1
R2
O
O R1
N
N
(
C H O) P
NH
N
(C H O) P
NH
N
2
5
2
2
5
2
R2
S
O
R1
R2
а_9c
_
_
9
2а 2c
10а 10c
F
O
3
O
N
3
N
N3
N
S
F
5
6
O
R1
(
C H O) P
NH
2
5
2
2
R
_
O
4
а 4c
O
N3
N3
NH
N
7
8
N
N
N
O
N
O
O
R1
O
R1
N
N
(
C H O) P
NH
N
(C H O) P
NH
NH
2
5
2
2
5
2
R2
R2
_
_
11а 11c
1
2а 12c
1
2
1
2
1
2
R = R = СН
3
(а); R = СН
3
, R = С
2
Н
5
(b); R = H, R = С
6
Н
5
(c).
In summary, an algorithm for the functionalization
compounds 2a–3c, and propargylamine 3 (Aldrich)
of biologically active substances (phenothiazine,
carbazole, tetrahydrocarbazole and 3,5-dimethyl-1-
aminoadamantane) with a diethoxyphosphorylalkyl
group using two standard Kabachnik–Fields and Huisgen
reactions was developed. It allows the preparation of a
wide range of potential biologically active substances.
were used without preliminary purification.
Diethyl 2-(prop-2-yn-1-ylamino)propane-2-phos-
phonate (4a). A mixture of 10 mmol of diethyl
phosphite 1, 10.5 mmol of acetone 2a, 10.5 mmol of
propargylamine, and 50 mL of ethanol was stirred at
6
0°C for 8 h. After removal of the solvent the residue
Azides 5–8 were prepared by azidation of the
corresponding chloroacetyl derivatives according to
the procedure [18]. Diethyl phosphite 1, carbonyl
was chromatographed on silica gel (60 mesh, methanol–
chloroform, 1 : 20). Yield 1.9 g (81%), oil. Н NMR
1
spectrum (CDCl ), δ, ppm (J, Hz): 1.31 d (6H, CH CP,
3
3
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

1
924
SOKOLOV, AKSINENKO
3
3
JPH = 15.5), 1.32 t (6H, CH CH O, J = 7.6), 1.73
31.8 ppm. Found, %: С 55.68; Н 5.70; N 13.40.
3
2
HH
4
br. s (1H, PCNH), 2.21 t (1H, HC≡C, J = 2.5), 3.57
d (1H, CH N, J = 2.5), 3.58 d (1H, CH N, J =
2
(
C H N O PS. Calculated, %: C 55.91; H 5.87; N
HH
24 30
5
4
4
4
2
HH
2
HH
13.58.
3
1
.5), 4.05–4.24 m (4H, CH CH O). Р NMR spectrum
3 2
CDCl ): δ 31.2 ppm. Found, %: С 51.68; Н 8.42; N
.82. C H NO P. Calculated, %: C 51.49; H 8.64; N 6.01.
10 20 3
Diethyl 2-[({1-[2-oxo-2-(10H-phenothiazin-10-yl)-
ethyl]-1H-1,2,3-triazol-4-yl}methyl)amino]butane-
3 Р
5
2
-phosphonate (9b) was prepared similarly. Yield
1
Diethyl 2-(prop-2-yn-1-ylamino)butane-2-phos-
phonate (4b) was prepared similarly. Yield 1.9 g
(
Hz): 0.97 t (3H, CH CH C, J = 7.6), 1.26 d (3H,
CH CP, J = 15.6), 1.34 t (6H, CH CH O, J
0.22 g (83%), mp 223–225°C. Н NMR spectrum
(CDCl ), δ, ppm (J, Hz): 0.96 t (3H, CH CH C, J =
7.3), 1.26 d (3H, CH CP, J = 15.6), 1.32 t (6H,
3 PH
CH CH O, J = 7.6), 1.57–1.97 m (2H, CH CH C),
3
3
3
2
HH
1
3
77%), oil. Н NMR spectrum (CDCl ), δ, ppm (J,
3
3
3
3
2
HH
3 2 HH 3 2
3
3
=
2.20 br. s (1H, PCNH), 3.98 (1H, CH N, АВ-system,
3
PH
3
2
HH
2
2
2
7
.6), 1.53–1.92 m (3H, CH CH C + PCNH), 2.23 t
1H, HC≡C, J = 2.4), 3.51 (1H, CH N, АВ-system,
JAB = 16.0, J = J = 2.4), 3.62 (1H, CH N, АВ-
JAB = 13.4), 4.07 (1H, CH N, АВ-system, J
=
3
2
2
AB
4
(
13.4), 4.07–4.27 m (4H, CH CH O), 5.30 br. s [2H,
HH
2
3 2
2
3
4
CH C(O)], 7.22–7.42 m (4H, CH ), 7.48 d (2H, CH ,
2 Ar Ar
HH
HH
2
2
3
4
3
3
system, J = 16.0, J = 2.1, J = 2.4), 4.06–4.25
m (4H, CH CH O). Р NMR spectrum (CDCl ): δР
JHH = 7.6), 7.60 d (2H, CH , J = 7.6), 7.67 s (1H,
AB
HH
HH
Ar HH
3
1
31
=CHNN). Р NMR spectrum (CDCl ): δ 31.9 ppm.
3 P
3
2
3
3
1.3 ppm. Found, %: С 53.68; Н 8.72; N 5.82.
Found, %: С 56.58; Н 5.90; N 13.40. C H N O PS.
25 32 5 4
C H NO P. Calculated, %: C 53.43; H 8.97; N 5.66.
Calculated, %: C 56.70; H 6.09; N 13.22.
1
1
22
3
Diethyl phenyl(prop-2-yn-1-ylamino)methane-
phosphonate (4c) was prepared similarly. Yield 2.3 g
Diethyl {[({1-[2-oxo-2-(10H-phenothiazin-10-yl)-
ethyl]-1H-1,2,3-triazol-4-yl}methyl)amino](phenyl)-
methyl}phosphonate (9c) was obtained similarly.
1
(
82%), oil. Н NMR spectrum (CDCl ), δ, ppm (J,
3
3
1
Hz): 1.20 t (3H, CH CH O, J = 7.6), 1.27 t (3H,
CH CH O, J = 7.6), 2.24 t (1H, HC≡C, J = 2.4),
Yield 0.25 g (89%), mp 90–91°C. Н NMR spectrum
3
2
HH
3
4
3
(CDCl ), δ, ppm (J, Hz): 1.17 t (3H, CH CH O, J
=
3
2
HH
HH
3
3
2
HH
3
2
.35 br. s (1H, PCNH), 3.17 (1H, CH N, АВ-system,
7.0), 1.26 t (3H, CH CH O, J = 7.0), 2.51 br. s (1H,
PCNH), 3.76 (1H, CH N, АВ-system, J = 14.0),
2 AB
3.93 (1H, CH N, АВ-system, J = 14.0), 3.87–4.14
m (4H, CH CH O), 4.12 d (1H, CHP, J = 19.0),
3 2 PH
2
3 2 HH
2
4
2
JAB = 17.0, J = 2.4), 3.62 (1H, CH N, АВ-system,
JAB = 17.0, J = 2.1, J = 2.4), 3.82–4.25 m (4H,
HH
2
2
3
4
2
HH
HH
2 AB
2
2
CH CH O), 4.38 d (1H, CHP, J = 18.0), 7.26–7.42
m (3H, CH ), 7.42–7.55 m (2H, CH ). Р NMR
3
2
PH
3
1
5.30 br. s [2H, CH C(O)], 7.23–7.62 m (13H, CH ),
Ar
Ar
2 Ar
3
1
spectrum (CDCl ): δ 24.5 ppm. Found, %: С 53.68; Н
7.64 s (1H, =CHNN). Р NMR spectrum (CDCl ): δ
3 P
3
Р
8
7
.72; N 5.82. C H NO P. Calculated, %: C 59.78; H
24.3 ppm. Found, %: С 59.48; Н 5.58; N 12.60.
C H N O PS. Calculated, %: C 59.67; H 5.37; N
28 30 5 4
1
4
20
3
.17; N 4.98.
Diethyl 2-[({1-[2-oxo-2-(10H-phenothiazin-10-yl)-
ethyl]-1H-1,2,3-triazol-4-yl}methyl)amino]propane-
-phosphonate (9a). To a solution of 0.5 mmol of
1
2.43.
Diethyl 2-({[1-(2-(6-fluoro-3-methyl-3,4-dihydro-
1H-carbazol-9(2H)-yl-2-oxoethyl)-1H-1,2,3-triazol-
2
phosphonate 4a in 20 mL of methylene chloride were
4-yl]methyl}amino)propane-2-phosphonate (10a)
added 0.5 mmol of azide 5, 0.1 mmol of CuSO in
was obtained similarly. Yield 0.22 g (85%), mp 79–
4
1
1
1
mL of H O, and 0.1 mmol of sodium ascorbate in
80°C. Н NMR spectrum (CDCl ), δ, ppm (J, Hz):
2
3
3
mL of H O. The reaction mixture was stirred for 6 h
1.16 d (3H, CH Cring, JHH = 6.4), 1.36 t (6H,
2
3
3
3
at 40°C, then washed with 10 mL of a 1% aqueous
ammonia solution. The organic layer was separated,
the methylene chloride was evaporated, the residue
was chromatographed on silica gel (60 mesh, methanol–
CH CH O, J = 7.0), 1.41 d (6H, CH CP, J
=
3
2
HH
3
PH
16.0), 1.35–1.72 m (1H, CH), 1.86–2.30 m (4H, PCNH +
2
3
CH ), 2.74 d. d (1H, CH , J = 16.4, J = 4.0),
2
2
HH
HH
2.93–3.16 m (2H, CH ), 4.05–4.357 m (6H, CH N +
2
2
chloroform, 1 : 10). Yield 0.22 g (85%), mp 223–225°C.
CH CH O), 5.67 and 5.78 [2H, CH C(O), АВ-system,
3 2 2
1
2
Н NMR spectrum (CDCl ), δ, ppm (J, Hz): 1.14–1.64
JAB = 17.5), 6.89–7.09 m (2H, CH ), 7.77 s (1H,
Ar
3
3
19
m (12H, CH CP + CH CH O), 2.23 br. s (1H, PCNH),
=CHNN), 8.08 d. d (1H, CH , J = 9.0). F NMR
3
3
2
Ar HH
3
4
.06 s (2H, CH N), 4.07–4.34 m (4H, CH CH O), 5.30
spectrum (CDCl ), δ , ppm: –42.6 t. d (1F, J = 8.0,
3 F HF
JHF = 4.6). Р NMR spectrum (CDCl ): δ 31.5 ppm.
2
3
2
4
31
br. s [2H, CH C(O)], 7.13–7.45 m (4H, CH ), 7.48 d
2
Ar
3 P
3
3
(
7
2H, CH , J = 7.3), 7.59 d (2H, CH , J = 7.3),
Found, %: С 57.58; Н 6.95; N 13.60. C H FN O P.
25 35 5 4
Calculated, %: C 57.79; H 6.79; N 13.48.
Ar
HH
Ar
HH
3
1
.67 s (1H, =CHNN). Р NMR spectrum (CDCl ): δ
3
P
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

N-PROPARGYL-α-AMINOPHOSPHONATES IN 1,3-DIPOLAR CYCLOADDITION
1925
Diethyl 2-({[1-(2-(6-fluoro-3-methyl-3,4-dihydro-
H-carbazol-9(2H)-yl-2-oxoethyl)-1H-1,2,3-triazol-
phonate (11b) was obtained similarly. Yield 0.21 g
1
1
4
(84%), oil. Н NMR spectrum (CDCl ), δ, ppm (J,
3
3
-yl]methyl}amino)butane-2-phosphonate (10b) was
Hz): 0.99 t (3H, CH CH C, J = 7.6), 1.31 d (3H,
3
2
HH
1
3
3
obtained similarly. Yield 0.23 g (86%), oil. Н NMR
CH CP, J = 16.2), 1.34 t (6H, CH CH O, J
=
3
PH
3
2
HH
spectrum (CDCl ), δ, ppm (J, Hz): 1.01 t (3H,
7.6), 1.60–1.99 m (2H, CH CH C), 2.30 br. s (1H,
PCNH), 3.97–4.27 m (6H, CH N + CH CH O), 5.88 s
2 3 2
3
3 2
3
3
CH CH C, J = 7.3), 1.17 d (3H, CH C , J
=
3
2
HH
3
ring
PH
3
6
.4), 1.33 d (3H, CH CP, J = 15.6), 1.37 t (6H,
[2H, CH C(O)], 7.32–7.51 m (4H, CH ), 7.78 s (1H,
3
PH
2 Ar
3
3
4
CH CH O, J = 7.6), 1.51–2.40 m (7H, PCNH +
CH CH C + CH ), 2.76 d. d (1H, CH C , J
=CHNN), 7.91 d. d (2H, CH , J = 7.0, J = 1.8),
3
2
HH
Ar
HH
31
HH
2
3
=
8.04 d (2H, CH , J = 7.6). Р NMR spectrum
3
2
2ring
2
ring
HH
Ar
HH
3
1
5.6, J = 4.0), 3.05 br. s (2H, CH Cring), 4.04–4.30
(CDCl ): δ 31.8 ppm. Found, %: С 60.52; Н 6.29; N
HH
2
3 P
m (6H, CH N + CH CH O), 5.67 (1H, CH N, АВ-
14.30. C H N O P. Calculated, %: C 60.35; H 6.48;
25 32 5 4
N 14.08.
2
3
2
2
2
system, J = 17.0), 5.80 (1H, АВ-system, CH N,
AB
2
2
JAB = 17.0), 6.89–7.11 m (2H, CH ), 7.77 s (1H,
CHNN), 8.10 d. d (1H, CH , J = 8.8, J = 4.4).
Ar
Diethyl {[({1-[2-(9H-carbazol-9-yl)-2-oxoethyl]-
H-1,2,3-triazol-4-yl}methyl)amino](phenyl)methyl}-
3
4
=
Ar HH HF
1
1
3
9
F NMR spectrum (CDCl ), δ , ppm: –42.9 t. d (1F,
3
F
phosphonate (11c) was obtained similarly. Yield
4
31
JHF = 8.0, J = 4.6). Р NMR spectrum (CDCl ): δ
1
HF
3
Р
0
.22 g (83%), 105–107°C. Н NMR spectrum (CDCl ),
3
3
1.7 ppm. Found, %: С 58.38; Н 6.75; N 13.31.
3
δ, ppm (J, Hz): 1.19 t (3H, CH CH O, J = 7.0), 1.30
t (3H, CH CH O, J = 7.0), 2.62 br. s (1H, PCNH),
3
2
HH
C H FN O P. Calculated, %: C 58.53; H 6.99; N 13.13.
3
26
37
5
4
3
2
HH
Diethyl {[({1-[2-(6-fluoro-3-methyl-1,2,3,4-tetra-
hydro-9H-carbazol-9-yl)-2-oxoethyl]-1H-1,2,3-triazol-
-yl}methyl)amino](phenyl)methyl}phosphonate (10c)
3.77–4.20 m (6H, CH
2
N + CH
CHP, JPH = 19.0), 6.00 s [2H, CH
(9H, CHAr), 7.77 s (1H, =CHNN), 8.03 d (2H, CHAr
3
CH
2
O), 4.20 d (1H,
2
C(O)], 7.32–7.64 m
2
4
,
3
3
31
was obtained similarly. Yield 0.23 g (81%), mp 67–68°
JHH = 7.0), 8.16 d (2H, CH , J = 7.9). Р NMR
Ar HH
1
C. Н NMR spectrum (CDCl ), δ, ppm (J, Hz): 1.09–1.38
spectrum (CDCl ): δ 24.3 ppm. Found, %: С 63.32; Н
3 P
3
m (6H, CH C
+ CH CH O), 1.50–1.72 m (1H,
5.90; N 13.40. C H N O P. Calculated, %: C 63.27;
3
ring
3
2
28 30 5 4
CHring), 1.87–2.35 m (2H, PCNH + CH2ring), 2.79 d. d
H 5.69; N 13.18.
2
3
(
1H, CH C , J = 16.0, J = 4.0), 3.07 br. s (2H,
2 ring HH HH
Diethyl 2-{[(1-(2-{[(3,5-dimethyladamantan-1-yl)-
amino]-2-oxoethyl}-1H-1,2,3-triazol-4-yl)methyl]-
amino}propane-2-phosphonate (12a) was obtained
CH C ), 3.73–4.20 m (6H, CH N + CH CH O), 4.16
2
ring
2
3
2
2
d (1H, CHP, J = 19.2), 5.70 (1H, CH N, АВ-
PH
2
2
system, J = 17.0), 5.81 (1H, CH N, АВ-system,
JAB = 17.0), 6.94–7.14 m (4H, CH ), 7.24–7.58 m
1
AB
2
similarly. Yield 0.21 g (85%), 113–115°C. Н NMR
2
Ar
spectrum (CDCl ), δ, ppm (J, Hz): 0.85 s (6H, CH3Ad),
3
(
8H, CH ), 7.71 s (1H, =CHNN), 8.14 d. d (1H, CH ,
Ar
Ar
1
.15 br. s (2H, CH2Ad), 1.36 t (10H, CH
+
=
3
4
19
2Ad
JHH = 8.8, J = 4.4). F NMR spectrum (CDCl ), δ ,
ppm: –42.4 t. d (1F, J = 8.8, J = 4.4). Р NMR
3
3
HF
3
F
CH CH O, J = 7.0), 1.40 d (6H, CH CP, J
3
4
31
3
2
HH
3
PH
HF
HF
1
5.6), 1.53–1.69 m (4H, CH2Ad), 1.76–1.86 m (2H,
spectrum (CDCl ): δ 24.4 ppm. Found, %: С 61.58; Н
3
Р
CH2Ad), 2.09–2.20 m (1H, CH ), 2.28 br. s (1H,
Ad
6
.45; N 12.11. C H FN O P. Calculated, %: C 61.37;
29 35 5 4
PCNH), 4.11 s (2H, CH N), 4.12–4.31 m (4H,
2
H 6.22; N 12.34.
CH CH O), 4.95 s [2H, CH C(O)], 6.18 br. s (1H, NH),
3
2
2
3
1
Diethyl 2-[({1-[2-(9H-carbazol-9-yl)-2-oxoethyl]-
H-1,2,3-triazol-4-yl}methyl)amino]propane-2-phos-
7.65 s (1H, =CHNN). Р NMR spectrum (CDCl ): δ
3 Р
1
31.5 ppm. Found, %: С 58.37; Н 8.71; N 14.38.
phonate (11a) was obtained similarly. Yield 0.21 g
C H N O P. Calculated, %: C 58.16; H 8.54; N 14.13.
24
42
5
4
1
(
87%), oil. Н NMR spectrum (CDCl ), δ, ppm (J, Hz):
3
Diethyl 2-{[(1-(2-{[(3,5-dimethyladamantan-1-yl)-
1
.20–1.57 m (12H, CH CP + CH CH O), 2.30 br. s
3 3 2
amino]-2-oxoethyl}-1H-1,2,3-triazol-4-yl)methyl]-
amino}but-2-yl)phosphonate (12b) was obtained
(
1H, PCNH), 4.02–4.30 m (6H, CH N + CH CH O),
2 3 2
5
.87 s [2H, CH C(O)], 7.29–7.50 m (4H, CH ), 7.77 s
1
2
Ar
similarly. Yield 0.21 g (82%), 107–109°C. Н NMR
3
(
1H, =CHNN), 7.89 d (2H, CH , J = 7.0), 8.03 d
Ar HH
spectrum (CDCl ), δ, ppm (J, Hz): 0.83 s (6H, CH3Ad),
3
31
3
(
2H, CH , J = 7.9). Р NMR spectrum (CDCl ): δ
P
3
Ar
HH
3
0
.99 t (3H, CH CH C, J = 7.3), 1.20 d (3H, CH CP,
3
2
HH
3
3
1.6 ppm. Found, %: С 59.41; Н 6.44; N 14.31.
3
JPH = 15.6), 1.21–1.48 m (12H, CH2Ad + CH CH O),
3
2
C H N O P. Calculated, %: C 59.62; H 6.25; N 14.48.
24
30
5
4
1
.50–1.97 m (8H, CH2Ad + CH CH C), 2.04–2.21 m
3 2
Diethyl 2-[({1-[2-(9H-carbazol-9-yl)-2-oxoethyl]-
H-1,2,3-triazol-4-yl}methyl)amino]butane-2-phos-
(1H, CHAd), 2.28 br. s (1H, PCNH), 3.90–4.36 m (6H,
CH N + CH CH O), 4.95 br. s [2H, CH C(O)], 6.38 s
1
2
3
2
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

1
926
SOKOLOV, AKSINENKO
3
1
(
(
1
1H, NH), 7.67 s (1H, =CHNN). Р NMR spectrum
6. Joossens, J., Van der Veken, P., Surpateanu, G.,
Lambeir, A.-M., El-Sayed, I., Ali O.M., Augustyns, K.,
and Haemers, A., J. Med. Chem., 2006, vol. 49, no. 19,
p. 5785. doi 10.1021/jm060622g
CDCl ): δ 31.6 ppm. Found, %: С 59.11; Н 8.92; N
3.58. C H N O P. Calculated, %: C 58.92; H 8.70;
25 44 5 4
3
P
N 13.74.
7
. Bhattacharya, A.K., Raut, D.S., Rana, K.C., Polanki, I.K.,
Khan, M.S., and Iram, S., Eur. J. Med. Chem., 2013,
vol. 66, no. 8, p. 146. doi 10.1016/j.ejmech.2013.05.036
Diethyl [{[(1-{2-[(3,5-dimethyladamantan-1-yl)-
amino]-2-oxoethyl}-1H-1,2,3-triazol-4-yl)methyl]-
amino}(phenyl)methyl]phosphonate (12c) was
obtained similarly. Yield 0.22 g (81%), oil. Н NMR
spectrum (CDCl ), δ, ppm (J, Hz): 0.80 s (6H, CH3Ad),
8
. Rezaei, Z., Firouzabadi, H., Iranpoor, N., Ghaderi, A.,
Jafari, M.R., Jafari, A.A., and Zare, H.R., Eur. J. Med.
Chem., 2009, vol. 44, no. 11, p. 4266. doi 10.1016/
j.ejmech.2009.07.009
1
3
1
.00–1.44 (12H, CH2Ad + CH CH O), 1.47–1.71 m
3 2
(
(
4H, CH2Ad), 1.70–1.92 m (2H, CH2Ad), 2.03–2.20 m
9. Bachurin, S.O., Sokolov, V.B., Aksinenko, A.Yu.,
Epishina, T.A., Goreva, T.V., Gabrel’yan, A.V., and
Grigor’ev, V.V., Russ. Chem. Bull., 2015, vol. 64, no. 6,
p. 1354. doi 10.1007/s11172-015-1017-0
10. Bandgar, B.P., Adsul, L.K., Chavan, H.V., Jalde, S.S.,
Shringare, S.N., Shaikh, R., Meshram, R.J., Nacche, G.R.,
and Masand, V., Bioorg. Med. Chem. Lett., 2012,
vol. 22, no. 18, p. 5839. doi 10.1016/j.bmcl.2012.07.080
1H, C H), 2.60 br. s (1H, PCNH), 3.67–4.20 m (6H,
Ad
2
CH N + CH CH O), 4.14 d (1H, CHP, J = 19.4),
4
(
2
3
2
PH
.94 s [2H, CH C(O)], 6.28 s (1H, NH), 7.21–7.54 m
2
3
1
5H, CH ), 7.61 s (1H, =CHNN). Р NMR spectrum
Ar
(CDCl ): δ 24.3 ppm. Found, %: С 61.65; Н 7.96; N
3
P
1
2.66. C H N O P. Calculated, %: C 61.86; H 7.79;
28 42 5 4
N 12.88.
1
1. Zhu, D., Chen, M., Li, M., Luo, B., Zhao, Y., Huang, P.,
Xue, F., Rapposelli, S., Pi, R., and Wen, S., Eur. J. Med.
Chem., 2013, vol. 68, no. 10, p. 81. doi 10.1016/
j.ejmech.2013.07.029
1
19
31
H, F, and P NMR spectra were recorded on a
Bruker DPX 200 spectrometer at 200.13, 188.0 and
1.0 MHz, respectively. Melting points were deter-
mined in a glass capillary.
8
1
2. MacMillan, K.S., Naidoo, J., Liang, J., Melito, L.,
Williams, N.S., Morlock, L., Huntington, P.J., Estill, S.J.,
Longgood, J., Becker, G.L., McKnight, S.L., Pieper, A.A.,
De Brabander, J.K., and Ready, J.M., J. Am. Chem.
Soc., 2011, vol. 133, no. 5, p. 1428. doi 10.1021/
ja108211m
ACKNOWLEDGMENTS
This work was supported by the Ministry of
Education and Science of Russia in the framework of
the governmental task for 2018 (no. 0090-2017-0023).
1
3. Sokolov, V.B., Aksinenko, A.Yu., Goreva, T.V.,
Epishina, T.A., Grigor’ev, V.V., Gabrel’yan, A.V.,
Vinogradova, D.V., Dubova, L.G., Schevtsov, P.N.,
Schevtsova, E.F., and Bachurin, S.O., Russ. Chem.
Bull., 2016, vol. 65, no. 5, p. 1346. doi 10.1007/s11172-
CONFLICT OF INTERESTS
No conflict of interests was declared by the authors.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018