V. A. Chebanov et al.
FULL PAPER
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 54.73, 55.91, 105.48,
[D6]DMSO): δ = 46.45, 53.12, 55.36, 84.17, 111.00, 120.33, 126.94,
111.20, 118.65, 119.09, 127.29, 127.54, 142.79, 147.71, 149.60, 127.07, 127.30, 128.67, 129.64, 130.21, 134.63, 149.18, 153.57,
149.72, 162.97 ppm. HRMS (EI): calcd. for C13H12N4O4 [M]+
288.0859; found 288.0853.
156.92, 169.14 ppm. HRMS (ESI-APCI): calcd. for C19H18N4O4
[M + H]+ 367.1406; found 367.1396.
7-Hydroxy-5-(3-methoxyphenyl)-6-phenyl-4,5,6,7-tetrahydro-
[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8e): Colourless
solid, m.p. 196–197 °C. 1H NMR (300 MHz, [D6]DMSO): δ =
13.58 (s, 1 H, OH), 7.84 (s, 1 H, NH), 7.47 (s, 1 H, 11.6 CH), 6.99–
7.27 (m, 7 H, Ar), 6.84 (d, J = 6.4 Hz, 2 H, Ar), 6.65 (d, J = 8.5 Hz,
1 H, Ar), 5.01 (d, J = 11.6 Hz, 1 H, CH), 3.74 (d, J = 11.6 Hz, 1 H,
CH), 3.63 (s, 3 H, CH3O) ppm. 13C NMR (75 MHz, [D6]DMSO): δ
= 53.28, 54.92, 55.69, 83.99, 113.19, 113.77, 120.59, 127.07, 127.41,
128.84, 130.58, 134.55, 141.22, 149.24, 153.29, 158.69, 168.98 ppm.
HRMS (ESI-APCI): calcd. for C19H18N4O4 [M + H]+ 367.1406;
found 367.1394.
General Procedure for the Synthesis of 5,6-Diaryl-7-hydroxy-4,5,6,7-
tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acids 8a–
8d, 8f–8i: 3-Amino-1,2,4-triazole (1; 1 mmol) was dissolved in
AcOH (2.5 mL), then the appropriate aldehyde 2a–2d, 2g, 2h
(1 mmol) and the appropriate arylpyruvic acid 7a–7c (1 mmol)
were added. The mixture was put into the ultrasound bath for
60 min. Then the mixture was allowed to stand overnight. After
that, the resulting precipitate was collected by filtration and dried
under vacuum.
General Procedure for the Synthesis of 7-Hydroxy-5-(3-meth-
oxyphenyl)-6-phenyl-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5-a]pyrimid-
ine-7-carboxylic Acid 8e: 3-Amino-1,2,4-triazole (1; 1 mmol) was
dissolved in AcOH (2.5 mL), then 3-methoxybenzaldehyde (2e;
1 mmol) and phenylpyruvic acid (7a; 1 mmol) were added. The
mixture was put into the ultrasound bath for 60 min. Then the
solvent was evaporated, and EtOH (3 mL) was added to the resi-
due. The resulting precipitate was collected by filtration. After that,
it was dissolved in a mixture EtOH/H2O (2:1; 3 mL), and the solu-
tion was stirred under conventional heating (75 °C, 2 h). The mix-
ture was cooled, and the precipitate was collected by filtration and
dried under vacuum.
7-Hydroxy-5-(2-hydroxyphenyl)-6-(4-methoxyphenyl)-4,5,6,7-
tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8f):
Colourless solid, m.p. 187–188 °C. 1H NMR (200 MHz, [D6]-
DMSO): δ = 9.46 (s, 1 H, OH), 7.54 (s, 1 H, NH), 7.40 (s, 1 H,
CH), 7.23 (d, J = 7.4 Hz, 1 H, Ar), 7.11 (d, J = 8.1 Hz, 2 H, Ar),
6.91 (t, J = 7.5 Hz, 1 H, Ar), 6.43–6.75 (m, 4 H, Ar), 5.40 (d, J =
11.8 Hz, 1 H, CH), 3.92 (d, J = 12.0 Hz, 1 H, CH), 3.62 (s, 3 H,
CH3O) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 47.38, 50.88,
54.78, 84.36, 112.70, 115.28, 118.90, 125.37, 126.92, 128.33, 128.98,
131.20, 149.00, 153.52, 155.36, 158.07, 169.43 ppm. MS (FAB): 383
[M + H]+. C19H18N4O5·H2O: calcd. C 57.00, H 5.03, N 13.99;
found C 56.70, H 4.79, N 14.09.
7-Hydroxy-5-(2-hydroxyphenyl)-6-phenyl-4,5,6,7-tetrahydro-
[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8a): Colourless
solid, m.p. 184–185 °C. 1H NMR (200 MHz, [D6]DMSO): δ = 9.46
(s, 1 H, OH), 6.58–7.48 (m, 9 H, Ar), 7.59 (s, 1 H, NH), 7.44 (s, 1
H, CH), 5.45 (d, J = 11.7 Hz, 1 H, CH), 3.98 (d, J = 11.6 Hz, 1
H, CH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 48.62, 51.66,
84.49, 115.42, 119.01, 125.17, 127.08, 127.38, 128.53, 129.31,
130.33, 135.14, 148.79, 153.45, 155.48, 169.47 ppm. HRMS (ESI-
APCI): calcd. for C18H16N4O4 [M + H]+ 353.1250; found 353.1232.
6-(4-Chlorophenyl)-7-hydroxy-5-(2-hydroxyphenyl)-4,5,6,7-tetra-
hydro-[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8g):
Colourless solid, m.p. 185–186 °C. 1H NMR (200 MHz, [D6]-
DMSO): δ = 9.52 (s, 1 H, OH), 7.62 (s, 1 H, NH), 7.42 (s, 1 H,
CH), 7.20 (pseudopentet, J = 8.8 Hz, 5 H, Ar), 6.92 (td, J = 7.6,
1.6 Hz, 1 H, Ar), 6.64 (pseudotriplet, J = 7.7 Hz, 2 H, Ar), 5.41
(d, J = 11.8 Hz, 1 H, CH), 3.96 (d, J = 11.6 Hz, 1 H, CH) ppm.
13C NMR (150 MHz, [D6]DMSO): δ = 48.00, 51.68, 84.08, 115.26,
118.94, 124.90, 127.22, 128.49, 131.46, 131.72, 131.98, 134.08,
149.09, 153.50, 155.23, 169.15 ppm. MS (FAB): 387 [M + H]+.
C18H15ClN4O4·1.5H2O: calcd. C 52.24, H 4.38, N 13.54; found C
51.95, H 4.32, N 13.6.
7-Hydroxy-5-(3-hydroxyphenyl)-6-phenyl-4,5,6,7-tetrahydro-
[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8b): Colourless
solid, m.p. 191–192 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 9.22
(s, 1 H, OH), 7.81 (s, 1 H, NH), 7.47 (s, 1 H, CH), 7.04–7.23 (m,
6 H, Ar), 6.90 (t, J = 7.8 Hz, 1 H, Ar), 6.68 (t, J = 2.0 Hz, 1 H,
Ar), 6.65 (d, J = 7.7 Hz, 1 H, Ar), 6.47 (ddd, J = 8.1, 2.5, 1.0 Hz,
1 H), 4.92 (d, J = 11.7 Hz, 1 H, CH), 3.67 (d, J = 11.7 Hz, 1 H,
CH) ppm. 13C NMR (150 MHz, [D6]DMSO): δ = 53.35, 56.61,
83.96, 114.55, 114.99, 119.15, 127.06, 127.41, 128.74, 130.49,
134.53, 141.03, 149.21, 153.24, 156.85, 168.98 ppm. HRMS (ESI-
APCI): calcd. for C18H16N4O4 [M + H]+ 353.1250; found 353.1235.
7-Hydroxy-5-(2-hydroxy-3-methoxyphenyl)-6-phenyl-4,5,6,7-tetra-
hydro-[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8h):
Colourless solid, m.p. 192–193 °C. 1H NMR (200 MHz, [D6]-
DMSO): δ = 8.65 (s, 1 H, OH), 7.57 (s, 1 H, NH), 7.43 (s, 1 H,
CH), 7.00–7.29 (m, 6 H, Ar), 6.85 (d, J = 7.2 Hz, 1 H, Ar), 6.54–
6.75 (m, 2 H, Ar), 5.49 (d, J = 11.7 Hz, 1 H, CH), 3.97 (d, J =
12.0 Hz, 1 H, CH), 3.68 (s, 3 H, CH3O) ppm. 13C NMR (150 MHz,
[D6]DMSO): δ = 47.52, 51.60, 55.61, 84.28, 110.47, 118.52, 120.69,
125.43, 126.91, 127.24, 130.15, 135.07, 144.65, 147.05, 149.11,
153.48, 169.29 ppm. MS (FAB): 383 [M + H]+. C19H18N4O5
(382.38): calcd. C 59.68, H 4.74, N 14.65; found C 59.67, H 5.32,
N 14.37.
7-Hydroxy-5-(4-hydroxyphenyl)-6-phenyl-4,5,6,7-tetrahydro-
[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8c): Colourless
solid, m.p. 179–180 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 9.21
(s, 1 H, OH), 7.72 (s, 1 H, NH), 7.45 (s, 1 H, CH), 7.07–7.19 (m,
6 H, Ar), 7.05 (d, J = 8.6 Hz, 2 H, Ar), 6.50 (d, J = 8.5 Hz, 2 H,
Ar), 4.92 (d, J = 11.6 Hz, 1 H, CH), 3.68 (d, J = 11.7 Hz, 1 H,
CH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 53.43, 55.13,
84.01, 114.67, 126.94, 127.40, 129.32, 129.82, 130.56, 134.90,
149.20, 153.39, 156.53, 169.11 ppm. HRMS (ESI-APCI): calcd. for
C18H16N4O4 [M + H]+ 353.1250; found 353.1241.
5-(5-Chloro-2-hydroxyphenyl)-6-(4-chlorophenyl)-7-hydroxy-4,5,6,7-
tetrahydro-[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8i):
Colourless solid, m.p. 189–190 °C. 1H NMR (200 MHz, [D6]-
DMSO): δ = 9.88 (s, 1 H, OH), 7.72 (s, 1 H, NH), 7.46 (s, 1 H,
CH), 7.09–7.29 (m, 4 H, Ar), 6.96 (dd, J = 8.6, 2.5 Hz, 1 H, Ar),
6.63 (d, J = 8.7 Hz, 1 H, Ar), 5.38 (d, J = 11.8 Hz, 1 H, CH) ppm.
13C NMR (150 MHz, [D6]DMSO): δ = 47.56, 51.88, 84.02, 116.88,
7-Hydroxy-5-(2-methoxyphenyl)-6-phenyl-4,5,6,7-tetrahydro-
[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylic Acid (8d): Colourless
solid, m.p. 189–190 °C. 1H NMR (600 MHz, [D6]DMSO): δ = 122.34, 127.32, 128.31, 131.89, 132.00, 133.77, 149.23, 153.43,
13.55 (s, 1 H, OH), 7.68 (s, 1 H, NH), 7.45 (s, 1 H, CH), 7.00–7.19
(m, 7 H, Ar), 6.71–6.86 (m, 2 H, Ar), 5.56 (d, 1 H, CH), 3.78 (d,
1 H, CH), 3.67 (s, 3 H, CH3O) ppm. 13C NMR (150 MHz,
154.14, 159.56, 164.84, 168.99 ppm. MS (FAB): 421 [M + H]+.
C18H14Cl2N4O4·1.5H2O: calcd. C 48.23, H 3.82, N 12.50; found C
48.61, H 4.10, N 12.66.
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Eur. J. Org. Chem. 2015, 4481–4492