COMPUTER MODELING AND SYNTHESIS OF POTENTIAL INHIBITORS
197
13
zotriazole (BtOH) (50 mg, 0.38 mmol), DMAP
(46 mg, 0.38 mmol), and a solution of amine (13)
(91 mg, 0.38 mmol) in CH2Cl2 (5 mL) were succes-
sively added to a solution of acid (12) (105 mg,
0.34 mmol) in CH2Cl2–DMF (10 mL, 1 : 1). Then,
DCC (79 mg, 0.38 mmol) was poured, and the mix-
ture was stirred for 16 h. The precipitate was filtered
and washed on a filter. The solvent was evaporated to
a volume of 5 mL under low pressure, and the residue
was poured into water (50 mL) under stirring. The
resulting sediment was filtered and washed on a filter
with 2 mL of 96% EtOH. After recrystallization of
crystals from isopropanol, product (I) was obtained as
white powder. Yield 132 mg (73%); Rf 0.29 (MeOH–
(br s, 1 H). С NMR (DMSO-d6): 106.55, 107.98,
109.73, 115.28, 122.01, 124.55, 132.91, 135.645,
136.63, 147.32, 150.58, 157.53, 159.47, 160.12, 175.44.
5-((4-(Pyridin-3-yl)pyrimidine-2-yl)carbamoyl)-
1H-pyrrol-2-carboxylic acid (12). A suspension of
potassium permanganate (135 mg, 0.85 mmol) in 8
mL of an acetone–water mixture (1 : 1) was added for
1 h to 2 mL of a solution of carboxamide (11) (132 mg,
0.42 mmol) in acetone. The solution was additionally
stirred for 1 h at 40°С and then for 1 h at room tem-
perature. Sodium thiosulfate was added in portions
until the solution was bleached. Acetone was removed
under low pressure, and the aqueous layer was acidi-
fied to a pH value of 3–4 with a 5% HCl solution. The
resulting precipitate was washed with water on a filter.
The white sediment was dried under low pressure.
Product (12) was used at the next stage without addi-
tional purification. Yield 130 mg (96%); Rf 0.19
1
CHCl3 1 : 4); mp 228.6°С. H NMR (DMSO-d6):
3.34 (s, 3H), 4.68 (s, 2H), 6.06 (m, 1Н), 6.28 (m, 1H),
7.30 (d, J 5.0, 1H), 7.41 (d, J 4.0, 1H), 7.53 (d, J 8.1,
1H),7.65 (m, 1H), 7.78 (m, 1H), 7.90 (t, J 7.8, 1H),
8.04 (d, J8.1, 1H), 8.45 (m, 2H), 8.69 (d, J 5.0, 1H),
9.29 (s, 1H), 12.35 (br s, 2Н). 13С NMR (DMSO-d6):
13.62, 37.15, 88.03, 108.33, 109.88 110.03, 110.20,
110.38, 112.84, 114.18, 115.36, 122.6, 125.45, 127.55,
128.80, 135.06, 135.96, 137.66, 140.39, 145.55, 149.47,
150.32, 153.77, 157.21, 160.50, 161.68.
1
(MeOH–CHCl3 1 : 8); mp 197.3°С. H NMR
(DMSO-d6): 7.04–7.05 (m, 1 H), 7.06–7.08 (m, 1 H),
7.14 (d, J 5.2, 1H), 7.57 (dd, J 4.7, 8.0, 1H), 8.16 (d, J
8.0, 1H), 8.65 (d, J 5.2, 1H), 8.75 (d, J 4.7, 1H), 9.02
(s, 1H), 10.71 (s, 1 H), 11.65 (br s, 1 H), 12.06 (br s,
13
1 H). С NMR (DMSO-d6): 107.55, 110.98, 111.73,
N-(3-(4-Methyl-1H-imidazol-1-yl)-5-(trifluoro-
methyl)phenyl)-5-(((4-(pyridin-3-yl)pyrimidin-2-yl)-
amino)metyl)-1H-pyrrol-2-carboxamide (2). Com-
pound (2) was obtained from acid (14) by the same
method as compound (1) as a pale yellow powder.
Yield 124 mg (71%); mp 204.2°С; Rf 0.35(MeOH–
115.08, 121.01, 124.55, 138.91, 139.58, 140.33, 149.47,
154.59, 155.88, 157.43, 160.12, 160.34.
5-(4-(Pyridin-3-ylpyrimidine-2-yl)aminometyl-
1H-pyrrol-2-carboxylic acid (14). Anhydrous AcOH
(14 mL, 244 mmol) was added for 1 h at 0–5°С to a
suspension of NaBH4 (2.00 g, 53 mmol) in CHCl3 (22
mL). The mixture was additionally stirred at 0–5°С
for 1.5 h. Aldehyde acid (7) (3.480 g, 25 mmol) and a
solution of amine (10) (4.472 g, 26 mmol) in CHCl3
(12 mL) were added to the resulting suspension, and
the mixture was stirred for 1 h at 0–5°С and then for
12 h at room temperature. To the mixture, H2O
(15 mL) and Na2CO3 were added to a pH value of 9–10.
The aqueous phase was washed with CHCl3 (3 × 10 mL).
Then, the pH of the solution was brought to 4 with a
1 M HCl solution. The precipitate was filtered and
washed with H2O on a filter. The resulting yellow crys-
tals were dried in a vacuum at room temperature. Yield
50% (3.688 g); Rf 0.23 (MeOH–CHCl3 1 : 8); mp
CHCl3 1 : 4). 1H NMR (DMSO-d6): 3.32 (s, 3H), 6.08
(m, 1Н), 6.20 (m, 1H), 7.26 (d, J 4.9 , 1H), 7.39 (d, J
4.0, 1H), 7.33 (d, J 8.0, 1H), 7.64 (m, 1H), 7.78 (m,
1H), 7.90 (t, J 8.0, 1H), 8.06 (d, J 8.0, 1H), 8.43 (m,
2H), 8.54 (d, J 5.0, 1H), 9.31 (s, 1H), 11.98 (br s, 2Н).
13С NMR (DMSO-d6): 13.62, 107.06, 108.36, 109.88,
110.04, 110.06, 112.23, 114.18, 114.63, 115.38, 122.06,
122.60, 125.71, 128.80, 129.73, 138.34, 140.33, 144.41,
149.47, 150.72, 154.59, 155.88, 156.90, 157.31, 157.40
158.28.
COMPLIANCE WITH ETHICAL STANDARDS
The paper does not contain any studies involving animals
or human participants performed by any of the authors.
1
186.23°С. H NMR (DMSO-d6): 2.48 (s, 2Н), 4.52
(m, 1Н), 6.01 (m, 1Н), 6.60 (m, 1Н), 7.23 (d, J 5.16,
1Н), 7.55 (br s, 1Н), 7.58 (dd, J 4.94, 8.03, 1Н), 8.39
(d, J 5.00, 1Н), 8.50 (m, 1Н), 8.68 (d, J 5.00, 1Н),
9.25 (m, 1Н), 11.48 (br s, 1Н). 13С NMR (DMSO-d6,
δ): 37.70, 106.56, 107.99, 109.71, 115.27, 122.02,
124.56, 132.90, 135.65, 136.64, 147.33, 150.59, 159.47,
162.01, 164.45. IR (in KBr, ν, cm–1): 3436, 1668.
N2-(3-(4-Methyl-1H- imidazol-1-yl)-5-(trifluoro-
methyl)phenyl-N5-(4-(pyridin-3-yl)pyrimidin-2-yl)-
aminometyl-1H-pyrrol-2.5-dicarboxamide (1). Ben-
Conflict of Interests
The authors declare that there is no conflict of interest.
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Ther., 2008, vol. 8, no. 9, pp. 1387–1398.
2. Lin, Y., Meng, Y., and Huang, L., J. Am. Chem. Soc.,
2014, vol. 136, pp. 14753–14762.
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 2 2020