Synthesis of 3-(4-fluorophenyl)-3-(4-methoxyphenyl)-1-propanarylamines and their antibacterial activity

Article abstract of DOI:10.1134/S1070363217060275

Condensation of 3-(4-fluorophenyl)-3-(4-methoxyphenyl)-1-propanamine with aromatic aldehydes and ketones followed by the reduction of the obtained azomethines with NaBH₄ afforded secondary propanaryl -amines, whose oxalates and hydrochlorides p

Full text of DOI:10.1134/S1070363217060275

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 6, pp. 1300–1304. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © N.S. Arutyunyan, L.A. Akopyan, R.A. Akopyan, G.M. Stepanyan, G.A. Panosyan, G.A. Gevorgyan, 2017, published in Zhurnal
Obshchei Khimii, 2017, Vol. 87, No. 6, pp. 1028–1032.
LETTERS
TO THE EDITOR
Synthesis
of 3-(4-Fluorophenyl)-3-(4-methoxyphenyl)-1-propanarylamines
and Their Antibacterial Activity
a
a
a
N. S. Arutyunyan , L. A. Akopyan , R. A. Akopyan ,
a
b
a
G. M. Stepanyan , G. A. Panosyan , and G. A. Gevorgyan *
a
Mnjoyan Institute of Fine Organic Chemistry, Scientific and Technological Center of Organic and Pharmaceutical
Chemistry of the National Academy of Sciences of Armenia, Azatutyan pr. 26, Yerevan, 0014 Armenia
b
Molecular Structure Research Center, National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia
*
e-mail: gyulgev@gmail.com
Received January 9, 2017
Abstract—Condensation of 3-(4-fluorophenyl)-3-(4-methoxyphenyl)-1-propanamine with aromatic aldehydes
and ketones followed by the reduction of the obtained azomethines with NaBH afforded secondary propanaryl
amines, whose oxalates and hydrochlorides possess high antibacterial activity.
4
-
Keywords: propanarylamines, azomethines, reduction, oxalates, hydrochlorides, antibacterial activity
DOI: 10.1134/S1070363217060275
One of the main tasks of pharmaceutical chemistry
is the search for new biologically active compounds
with high efficacy and low toxicity. In this regard, the
search for new highly effective drugs does not become
obsolete.
with NaBH afforded secondary amines 5–15. For
4
biological screening, amines 5–15 were converted to
the corresponding oxalates 16–23 and hydrochlorides
24–28 (Scheme 1).
Antibacterial activity of compounds 16–28 with
respect to the gram-positive strain of Staphylococcus
aureus 209 p, 1) and gram-negative strains of Sh.
dysenteriae flexneri 6858 and Escherichia coli 0-55
was studied according to the procedure of [4]. Some of
the compounds obtained were found to exhibit
antibacterial activity. Thus, compounds 17, 18, 25, and
In continuation of our studies in this direction
[1–3], we report here the targeted synthesis of new
biologically active oxalates and hydrochlorides of
substituted propanarilamines, the study and analysis of
their biological activity in comparison with the
reference compounds and their structural analogs in
order to establish the structure–activity relationship,
and also to identify the most promising substances for
further research.
2
7 showed high activity, suppressing the growth of
microorganisms in the zone with a diameter of 22–
8.6 mm. These compounds have a slightly higher
2
activity against gram-positive microorganisms than furazol-
idone (d = 24.3–25 mm). The other substances (d 15–
22 mm) were inferior to furazolidone (d = 24.3–25 mm).
Ethyl (E)-2-cyano-3-(4-methoxyphenyl)-2-propenoate
1
reacted with 4-fluorophenylmagnesium bromide to
give ethyl 2-cyano-3-(4-fluorophenyl)-3-(4-methoxy-
phenyl)propanoate 2. The decarbethoxylation of the
latter led to the formation of the corresponding nitrile
It should be noted that any difference in the anti-
bacterial activity between the hydrochlorides and
oxalates of 3-(4-fluorophenyl)-3-(4-methoxyphenyl)pro-
panamines had not been established.
3
. The reduction of nitrile 3 with lithium aluminum
hydride afforded 3-(4-fluorophenyl)-3-(4-methoxyphenyl)-
-propanamine 4. Its condensation with various aro-
1
Ethyl (E)-2-cyano-3-(4-methoxyphenyl)-2-propenoate
(1). A mixture of 34 g (0.3 mol) of ethyl cyanoacetate,
40.8 g (0.3 mol) of anisaldehyde and 2 g of ammonium
matic aldehydes and ketones led to the formation of
the corresponding azomethines A, whose reduction
1
300

SYNTHESIS OF 3-(4-FLUOROPHENYL)-3-(4-METHOXYPHENYL)-1-PROPANARYLAMINES
1301
Scheme 1.
O
O
O
4
-FC H MgBr
KOH
CN
O
6
4
CN
O
CN
O
O
F
2
F
3
1
O
R
Ar
Ar
O
NH2
O
N
LiAlH4
R
F
4
F
A
Ar
R
H
O
N
NaBH4
F
C H O
2 4
_
HCl
2
5
15
Ar
R
Ar
R
H
H
O
N
O
N
C H O
2 4
HCl
2
F
F
_
_
1
6 23
24 28
(7, 17, 25), benzo[1,3]dioxol-5-ylmethyl (8), C
6 4
(12, 21); R = CH , Ar = thien-2-yl (13, 28), 4-ClC H
R = H, Ar = 4-FC
6), 4-CH OC
14, 22), C (15, 23).
6
H
4
(5, 16, 24), 2-FC
(10, 19, 27), fur-2-yl (11, 20), 4-i-PrOC
6
H
4
(6), 3,4-(CH
3
O)
2
C
6
6
H
3
6 5
H (9, 18,
2
(
3
6
H
4
H
4
3
6 5
H
acetate in 100 mL of benzene was heated for 4 h with a
Dean–Stark trap until the water was completely
separated. After cooling, the reaction mixture was
washed with water. The solvent was removed, and the
residue was distilled. Yield 84%, bp 178°C (2 mmHg).
–
1
IR spectrum, ν, cm : 2244 (CN), 1715 (C=O), 1600,
1
1580 (C=C ). Н NMR spectrum (DMSO-d –CCl ), δ,
Ar
6
4
ppm (J, Hz): 1.39 t (3H, CH CH , J = 7.1), 3.90 s (3H,
3
2
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1
302
ARUTYUNYAN et al.
OCH ), 4.33 q (2H, OCH , J = 7.1), 7.06 m and 8.03
were successively added. The reaction mixture was
filtered; the inorganic precipitate was washed with
diethyl ether. The organic fractions were combined,
dried, and evaporated. The residue was distilled. Yield
3
2
m (4H, C H ), 8.18 s (1H, CH ). Found, %: С 67.84;
6
4
Ar
Н 6.00; N 6.58. C H NO . Calculated, %: С 67.52; Н
1
3
13
3
5
.67; N 6.06.
–
1
8
3
8%, bp 158–162°C (2 mmHg). IR spectrum, ν, cm :
Ethyl 2-cyano-3-(4-methoxyphenyl)-3-(4-fluoro-
1
300, 3290 (NH ), 1610, 1590 (C=C ). Н NMR
2
Ar
phenyl)propanoate (2). To an ether solution of the
Grignard reagent (obtained from equimolar amounts of
aryl halide and magnesium turnings) was added a
benzene solution of 1 (0.4 mol per 0.48 mol of
Grignard reagent) with gentle boiling and stirring. The
reaction mixture was stirred for 3 h at 42–44°C, then
cooled, acidified with 20% hydrochloric acid, ex-
tracted with diethyl ether, the extract was washed with
water and dried. After removal of the solvents, the
residue was distilled. Yield 83% (two stereoisomers in
a ratio of 1 : 1), bp 205–210°C (2 mmHg). IR spec-
spectrum (DMSO-d –CCl ), δ, ppm (J, Hz): 2.01 m
6
4
(
2H, NH ), 2.07 m (2H, CHCH ), 2.54 t (2H, CH N,
2 2 2
J = 6.9), 3.74 s (3H, OCH ), 4.03 t (1H, ArCH, J =
3
7
.8), 6.78 m and 7.12 m (4H, OC H ), 6.95 m and 7.21
6 4
m (4H, C H F). Found, %: С 74.65; Н 7.23; N 5.85.
6
4
C H FNO. Calculated, %: С 74.11; Н 7.00; N 5.40.
1
6
18
General procedure for the synthesis of secondary
amines 5–15. A mixture of equimolar amounts of
aromatic aldehyde (or ketone) and amine 4 in benzene
was refluxed for 4 h with a Dean–Stark trap until the
water was completely separated. The benzene was
removed, and the residue was dissolved in methanol
–
1
trum, ν, cm : 2251 (CN), 1748 (C=O), 1600, 1580
1
(
C=C ). Н NMR spectrum (DMSO-d –CCl ), δ, ppm
Ar 6 4
(
60 mL of methanol per 0.01 mol of azomethine A).
(
J, Hz): 1.11 t (3H, CH CH , J = 7.1), 3.75 s and 3.78
3
2
An equimolar amount of NaBH was added in portions
s (3H, OCH ), 4.08 q (2H, OCH , J = 7.1), 4.61 d (1H,
4
3
2
to the solution with stirring and cooling so that the
temperature of the reaction mixture did not exceed 20°C.
The reaction mixture was stirred for 1 h at room
temperature. After removal of methanol, the mixture
was alkalinized with 20% NaOH solution, extracted
with diethyl ether, and dried. After the solvent was
removed the residue was distilled.
CH , J = 9.2), 4.83 d and 4.85 d (1H, CHC=O, J =
Ar
9
.2); 6.77–6.88 m, 7.21 m and 7.31 m (4H, OC H );
6 4
6
.96–7.08 m, 7.33 m and 7.43 m (4H, FC H ). Found,
6 4
%
: С 69.84; Н 5.12; N 4.43. C H FNO . Calculated,
19 18 3
%
: С 69.71; Н 5.54; N 4.28.
-(4-Methoxyphenyl)-2-(4-fluorophenyl)ethyl-
2
cyanide (3). A solution of 37 g (0.66 mol) of KOH in
00 mL of ethylene glycol was added to 110 g
0.33 mol) of compound 2 with stirring. The mixture
General procedure for the synthesis of amine
oxalates 16–23. To a solution of amine 5, 7, 9–12, 14
or 15 (1.5 mmol) in diethyl ether was added dropwise
a solution of oxalic acid (2.0 mmol) in diethyl ether.
The precipitate was filtered off and recrystallized from
ethanol.
2
(
was refluxed for 3 h, and then cooled. Next, 200 mL of
water was added, and the product was extracted with
diethyl ether, washed with water, and dried. After
removal of the solvent, the residue was distilled. Yield
–
1
7
2
3%, bp 186–191°C (2 mmHg). IR spectrum, ν, cm :
General procedure for the synthesis of amine
hydrochlorides 24–28. To a solution of amine 5, 7, 9,
10 or 13 (1.5 mmol) in diethyl ether was added a
saturated solution of hydrogen chloride (2.0 mmol) in
diethyl ether. The precipitate was filtered off and
recrystallized from ethanol.
1
246 (CN), 1610, 1596 (C=C ). Н NMR spectrum
Ar
(
DMSO-d –CCl ), δ, ppm (J, Hz): 3.11 d (2H, CH ,
6
4
2
J = 7.8), 3.76 s (3H, OCH ), 4.34 t (CH, J = 7.8), 6.82
3
m and 7.17 m (4H, OC H ), 7.01 m and 7.28 m (4H,
6
4
FC H ). Found, %: С 75.00; Н 5.13; N 4.55.
6
4
C H FNO. Calculated, %: С 75.28; Н 5.53; N 5.49.
1
6
14
3
-(4-Methoxyphenyl)-3-(4-fluorophenyl)-N-(4-
3
-(4-Methoxyphenyl)-3-(4-fluorophenyl)-1-propan-
fluorobenzyl)-1-propanamine (5). Yield 74%, bp 228–
–
1
1
amine (4). To a pre-cooled solution of 18 g (0.48 mol)
of LiAlH in 200 mL of anhydrous diethyl ether was
230°C (2 mmHg). IR spectrum, ν, cm : 3225 (NH). Н
NMR spectrum (DMSO-d –CCl ), δ, ppm (J, Hz): 1.97
4
6
4
added dropwise an ethereal solution of 60 g (0.24 mol)
of compound 3 maintaining the temperature of the
reaction mixture within the range of 0±2°C. The
mixture was stirred at the same temperature for 1 h,
and then cooled to –10°C. Next, 18 mL of water,
br.s (1H, NH), 2.12 m (2H, CH CHAr), 2.46 t (2H,
2
NCH CH , J = 6.8), 3.64 s (2H, CH Ar), 3.74 s (3H,
2
2
2
OCH ), 4.03 t (1H, CHCH , J = 7.8), 6.76 m and 7.09
3
2
m (4H, OC H ), 6.90–7.00 m and 7.16–7.29 m (4H,
6
4
FC H ). Found, %: С 75.45; Н 6.58; N 3.97.
6
4
1
8 mL of 15% NaOH solution, and 54 mL of water
C H F NO. Calculated, %: С 75.18; Н 6.31; N 3.81.
23 23 2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017

SYNTHESIS OF 3-(4-FLUOROPHENYL)-3-(4-METHOXYPHENYL)-1-PROPANARYLAMINES
1303
Oxalate 16. mp 210–212°C. Hydrochloride 24. mp 79.05; Н 6.92; N 4.01. Oxalate 18. mp 194–195°C.
1
48–149°C.
Hydrochloride 26. mp 118–120°C.
3
-(4-Methoxyphenyl)-3-(4-fluorophenyl)-N-(2-
N-(4-Methoxybenzyl)-3-(4-methoxyphenyl)-3-(4-
fluorophenyl)-1-propanamine (10). Yield 70%,
fluorobenzyl)-1-propanamine (6). Yield 73%, bp 205–
07°C (1 mmHg). IR spectrum, ν, cm : 3230 (NH).
Н NMR spectrum (DMSO-d –CCl ), δ, ppm (J, Hz):
–
1
-1
2
bp 240–245°C (2 mmHg). IR spectrum, ν, cm : 3220
1
1
(NH). Н NMR spectrum (DMSO-d –CCl ), δ, ppm (J,
6
4
6
4
1
.85 br.s (1H, NH), 2.13 m (2H, CH CHAr), 2.48 t
Hz): 1.81 br.s (1H, NH), 2.12 m (2H, CH CHAr), 2.46
2
2
(
(
2H, NCH CH , J = 6.8), 3.72 s (2H, NCH Ar), 3.74 s
t (2H, NCH CH , J = 6.8), 3.59 s (2H, CH Ar), 3.74 s
2
2
2
2
2
2
3H, OCH ), 4.04 t (1H, CHAr, J = 7.7), 6.76 m and
(3H, OCH ), 3.76 s (3H, OCH ), 4.02 t (1H, CHAr,
3
3
3
7
7
.10 m (4H, OC H ), 6.93 m and 7.19 m (4H, C H F);
J = 7.8), 6.73–6.79 m and 7.07–7.17 m (4H, OC H ),
6 4
6
4
6
4
.00 m, 7.08 m, 7.19 m and 7.34 t.d (4Н, C H NH ,
6.93 m and 7.18 m (4H, FC H ). Found, %: С 75.55; Н
6
4
2
6 4
J = 7.6, J = 1.6). Found, %: С 75.50; Н 6.55; N 4.00.
C H F NO. Calculated, %: С 75.18; Н 6.31; N 3.81.
7.25; N 3.88. C H FNO . Calculated, %: С 75.96; Н
24 26 2
6.91; N 3.69. Oxalate 19. mp 215–217°C. Hydro-
chloride 27. mp 178–180°C.
2
3
23 2
N-(3,4-Dimethoxybenzyl)-3-(4-methoxyphenyl)-
-(4-fluorophenyl)-1-propanamine (7). Yield 74%,
3
3-(4-Methoxyphenyl)-3-(4-fluorophenyl)-N-(2-
furylmethyl)-1-propanamine (11). Yield 72%, bp
–
1
bp 250–255°C (2 mmHg). IR spectrum, ν, cm : 3233
1
–1
(
NH). Н NMR spectrum (DMSO-d –CCl ), δ, ppm (J,
205–208°C (1 mmHg). IR spectrum, ν, cm : 3320
6
4
1
Hz): 2.12 m (2H, CH CHAr), 2.45 t (2H, NCH CH ,
(NH). Н NMR spectrum (DMSO-d –CCl ), δ, ppm (J,
2
2
2
6
4
J = 6.9), 2.75 m (1H, NH), 3.57 s (2H, NCH Ar); 3.74
Hz): 2.10 m (2H, CH CHAr), 2.15 br.s (1H, NH), 2.46
2
2
s, 3.77 s and 3.78 s (9H, CH O), 4.01 t (1H, CHAr, J =
t (2H, NCH CH , J = 6.8), 3.64 s (2H, CH -furyl),
3
,6
2
2
2
5
2
7
.8), 6.68–6.74 m (2H, H , C H ), 6.83 d (1H, H ,
3.74 s (3H, OCH ), 4.02 t (1H, CHAr, J = 7.8), 6.08 d
6
3
3
C H ), 6.75 m and 7.09 m (4H, OC H ), 6.93 m and
(1H-furyl, J = 3.1), 6.26 d.d (1H-furyl, J = 3.1, 1.9),
6
3
6
4
3
,5
7
3
3
.18 m (4H, C H F). Found, %: С 73.54; Н 7.05; N
7.33 d (1H-furyl, J = 1.9), 6.76 m (2H, H , OC H ),
6
4
6 4
2
,6
.75. C H FNO . Calculated, %: С 73.33; Н 6.89; N
7.10 m (2H, H , OC H ), 6.94 m and 7.19 m (4H,
6 4
2
5
28
3
.42. Oxalate 17. mp 115–117°C. Hydrochloride 25.
C H F). Found, %: С 74.85; Н 6.93; N 4.62. C H FNO .
6 4 21 22 2
mp 130–132°C.
Calculated, %: С 74.31; Н 6.53; N 4.13. Oxalate 20.
mp 202–204°C.
N-(1,3-Benzodioxol-5-ylmethyl)-3-(4-methoxy-
phenyl)-3-(4-fluorophenyl)-1-propanamine (8). Yield
N-(4-Isopropoxybenzyl)-3-(4-methoxyphenyl)-3-
(4-fluorophenyl)-1-propanamine (12). Yield 73%, bp
–
1
6
3
8%, bp 225–230°C (1 mmHg). IR spectrum, ν, cm :
1
–1
228 (NH). Н NMR spectrum (DMSO-d –CCl ), δ,
225–230°C (2 mmHg). IR spectrum, ν, cm : 3325
6
4
1
ppm (J, Hz): 2.05–2.16 m (2H, CH CHAr), 2.44 t (2H,
(NH). Н NMR spectrum (DMSO-d –CCl ), δ, ppm (J,
2
6
4
NCH CH , J = 6.8), 2.24 br.s (1H, NH), 3.57 s (2H,
Hz): 1.31 d (6H, CH CHCH , J = 6.1), 1.95 br.s (1H,
2
2
3 3
NCH Ar), 3.74 s (3H, OCH ), 4.02 t (1H, CHAr, J =
NH), 2.11 m (2H, CH CHAr), 2.46 t (2H, NCH CH ,
2 2 2
2
3
5
7
.7), 5.92 s (2H, OCH ), 6.67 br.s (2H, H , C H ), 6.79
J = 6.8), 3.58 s (2H, CH Ar), 3.74 s (3H, OCH ), 4.03
2
6
3
2
3
6
3,5
br.s (1H, H , C H ), 6.73–6.78 m (2H, H , CH OC H ),
7
t (1H, CHAr, J = 7.8), 4.51 septet (1H, OCH, J = 6.1);
6
3
3
6
4
2
,6
.06–7.12 m (2H, H , CH OC H ), 6.89–6.97 m (2H,
6.71–6.78 m (4H ), 6.93 m (2H ), 7.07–7.14 m
3
6
4
Ar
Ar
3
,5
2,6
H , C H F), 7.15–7.22 m (2H, H , C H F). Found,
(4H ), 7.18 m (2H, H ). Found, %: С 76.85; Н 7.72;
6
4
6
4
Ar Ar
%
: С 73.44; Н 6.52; N 3.85. C H FNO . Calculated,
N 3.82. C H FNO . Calculated, %: С 76.63; Н 7.42;
26 30 2
2
4
24
3
%
: С 73.26; Н 6.15; N 3.56.
N-Benzyl-3-(4-methoxyphenyl)-3-(4-fluorophenyl)-
-propanamine (9). Yield 75%, bp 225–227°C
N 3.44. Oxalate 21. mp 196–198°C.
3-(4-Methoxyphenyl)-N-[1-(2-thienyl)ethyl]-3-(4-
fluorophenyl)-1-propanamine (13). Yield 65% (two
stereoisomers in a ratio of 1 : 1), bp 213°C (1 mmHg).
1
–
1
1
(
2 mmHg). IR spectrum, ν, cm : 3225 (NH). Н NMR
-
1
1
spectrum (DMSO-d –CCl ), δ, ppm (J, Hz): 2.13 m
IR spectrum, ν, cm : 3328 (NH). Н NMR spectrum
(DMSO-d –CCl ), δ, ppm (J, Hz): 1.36 d (3H, CH CH,
6
4
(
2H, CH CHAr), 2.14 br.s (1H, NH), 2.48 t (2H,
2
6
4
3
NCH CH , J = 6.8), 3.67 s (2H, CH Ar), 3.74 s (3H,
J = 6.6), 1.56 br.s (1H, NH), 2.00–2.17 m (2H,
2
2
2
3
,5
OCH ), 4.04 t (1H, CHAr, J = 7.8), 6.76 m (2H, H ,
CH CH), 2.30–2.58 m (2H, NCH ), 3.73 s and 3.74 s
3
2
2
2
,6
OC H ), 7.10 m (2H, H , OC H ), 6.93 m and 7.18 m
(3H, OCH ), 3.93 q (1H, NCH, J = 6.6), 4.00 q and
6
4
6
4
3
(
4H, FC H ), 7.14–7.27 m (5H, C H ). Found, %: С
4.00 q (1H, CHCH , J = 7.8), 6.71–6.80 m (1H ),
6
4
6
5
2
Ar
7
9.54; Н 7.15; N 3.78. C H FNO. Calculated, %: С
6.88–6.97 m (2H ), 7.04–7.22 m (H ). Found, %: С
2
3
24
Ar Ar
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ARUTYUNYAN et al.
Antibacterial activity of compounds 16–28 was
7
7
1
1.84; Н 6.83; N 4.02. C H FNOS. Calculated, %: С
1.51; Н 6.55; N 3.79. Hydrochloride 28. mp 132–
34°C.
2
2
24
studied according to the procedure [4] with a bacterial
load of 20 million microbial units per 1 mL of
medium. Gram-positive strains of Staphylococcus
aureus 209 p, 1 and gram-negative strains of Sh.
Dysenteriae flexneri 6858 and E. coli 0-55 were used
in the experiments. Solutions of tested compounds and
control compound were prepared in DMSO at a
dilution of 1 : 20. Into Petri dishes with agar medium
with the above-mentioned strains of microorganisms
were added the solutions (0.1 mL). Bacterial growth
was monitored. The statistical treatment was carried
out using the Student–Fisher method. The experiments
were repeated at least 3 times. Furazolidone (Borisov
Plant of Medical Preparations, Belarus) [5] was used
as a positive control.
3
-(4-Methoxyphenyl)-3-(4-fluorophenyl)-N-[(4-
chlorophenyl)ethyl)]-1-propanamine (14). Yield
7
3
ppm (J, Hz): 1.23 d (3H, CHCH ), 1.48 br.s (1H, NH),
1
3
–
1
2%, bp 225–230°C (1 mmHg). IR spectrum, ν, cm :
323 (NH). Н NMR spectrum (DMSO-d –CCl ), δ,
1
6
4
3
.96–2.15 m (2H, CH CH), 2.19–2.38 m (2H, NCH ),
.61 q (1H, NCH, J = 6.6), 3.73 s (3H, OCH ), 3.97 t
2
2
3
(
(
1H, CHCH , J = 7.8), 6.70–6.76 m and 7.10–7.18 m
4H, OC H ), 6.86–6.96 m and 7.01–7.09 m (4H,
2
6
4
C H F), 7.19 s and 7.20 s (4H, C H Cl). Found, %: С
7
С 72.44; Н 6.33; N 3.52. Oxalate 22. mp 166–168°C.
6
4
6
4
2.65; Н 6.63; N 3.84. C H CIFNO. Calculated, %:
24 25
3
-(4-Methoxyphenyl)-3-(4-fluorophenyl)-N-(1-
phenylethyl)-1-propanamine (15). Yield 68% (two
REFERENCES
stereoisomers in a ratio of 1 : 1), bp 205°C (1 mmHg).
–
1
1
1
. Arutyunyan, N.S., Akopyan, L.A., Nazaryan, R.L.,
Gevorgyan, G.A., Nekotorye uspekhi organicheskoi i
farmatsevticheskoi khimii, Yerevan, 2012.
IR spectrum, ν, cm : 3222 (NH). Н NMR spectrum
DMSO-d –CCl ), δ, ppm (J, Hz): 1.26 d (3H, CHCH ,
(
6
4
3
J = 6.6), 1.58 br.s (1H, NH), 1.98–2.16 m (2H,
CH CH), 2.24–2.40 m (2H, NCH ), 3.62 q (1H, NCH,
2. Arutyunyan, N.S., Akopyan, L.A., Nazaryan, R.L.,
Gevorgyan, G.A., Stepanyan, G.M., Paronikyan, R.V.,
and Panosyan, G.A., Pharm. Chem. J., 2013, vol. 47,
p. 490. doi 10.1007/s11094-013-0987-1
2
2
J = 6.6), 3.73 s and 3.73 s (3H, OCH ), 3.99 t and 3.99
3
t (1H, CHCH , J = 7.7), 6.70–6.77 m and 7.10–7.19 m
2
(
4H, OC H ), 6.86–6.96 m and 7.02–7.10 m (4H,
6 4
3
. Arutyunyan, N.S., Akopyan, L.A., Akopyan, N.Z.,
Gevorgyan, G.A., Stepanyan, G.M., Paronikyan, R.V.,
Malakyan, M.H., Agdzhoyan, R.L., Badzhinyan, S.A.,
and Shakhatuni, A.A., Pharm. Chem. J., 2012, vol. 46,
p. 351. doi 10.1007/s11094-012-0796-y
C H F), 7.21 s and 7.22 s (4H, C H Cl). Found, %: С
6
4
6
4
7
7
9.82; Н 7.00; N 4.12. C H FNO. Calculated, %: С
9.31; Н 7.21; N 3.85. Oxalate 23. mp 115–116°C.
24 26
IR spectra were recorded on a Nicolet Avatar 330
1
FT-IR spectrophotometer. Н NMR spectra were
registered on a Varian Mercury-VX-300 (300 MHz)
spectrometer in DMSO-d –CCl (1 : 3), internal
4. Pershin, G.N., Metody eksperimental’noi khimioterapii
(Methods of Experimental Chemotherapy), Moscow:
Meditsyna, 1971.
6
4
reference TMS. Melting points were measured on a
Boetius apparatus.
5
. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: Meditsyna, 2010.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 6 2017