Z. Huang, J. Tong, S. Zhou, L. Xiong, H. Wang, and YU. Zhao
Vol 000
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (4-chloro-2-methyl-6-propylcarbamoyl-
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (4-chloro-2-propylcarbamoyl-phenyl)-
phenyl)-amide (18a).
White crystal, yield, 52.2%; mp
amide (18e).
White crystal, yield, 51.6%; mp 185–
1
198–200°C; H NMR (CDCl3, 400MHz) δ: 9.78 (s, 1H,
CONH); 8.24 (d, J=4.6Hz, 1H, pyridyl-H); 7.62 (d,
J=8.0Hz, 1H, pyridyl-H); 7.13 (dd, J1 =4.6Hz,
J2 = 8.0 Hz, 1H, pyridyl-H); 7.02 (d, J=1.8Hz, 1H, Ph-H);
7.00 (d, J=1.8Hz, 1H, Ph-H); 6.39 (s, 1H, pyrazolyl-H);
6.00–6.03 (m, 1H, NHCH2); 4.74 (d, J=2.4Hz, 2H,
OCH2); 3.12–3.15 (m, 2H, CH2NH); 2.48 (t, J=2.4Hz,
1H, CH); 1.98 (s, 3H, PhCH3); 1.36–1.38 (m, 2H, CH2CH3);
0.75 (t, J=7.3Hz, 3H, CH2CH3). The value of HRMS [M
+Na]+ for C23H21Cl2N5O3: 508.0914. Found: 508.0922.
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (2-butylcarbamoyl-4-chloro-6-methyl-
187°C; 1H NMR (CDCl3, 400MHz) δ: 12.06 (s, 1H,
CONH); 8.37–8.42 (m, 2H, pyridyl-H, Ph-H); 7.80 (d,
J = 7.8 Hz, 1H, pyridyl-H); 7.25–7.36 (m, 3H, pyridyl-H,
Ph-H); 6.48 (s, 1H, pyrazolyl-H); 6.19–6.21 (m, 1H,
NH); 4.85 (s, 2H, OCH2); 3.33–3.36 (m, 2H, NHCH2);
2.47 (s, 1H, CH); 1.57–1.59 (m, 2H, CH2CH2); 0.94 (t,
J = 7.3 Hz, 3H, CH2CH3). The value of HRMS [M+ Na]+
for C22H19Cl2N5O3: 494.0757. Found: 494.0764.
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (4-chloro-2-isopropylcarbamoyl-phe-
nyl)-amide (18f).
White crystal, yield, 49.6%; mp 171–
172°C; 1H NMR (CDCl3, 400MHz) δ: 12.18 (s, 1H,
CONH); 8.46–8.51 (m, 2H, pyridyl-H, Ph-H); 7.90 (d,
J=8.0Hz, 1H, pyridyl-H); 7.32–7.42 (m, 3H, pyridyl-H,
Ph-H); 6.57 (s, 1H, pyrazolyl-H); 6.00–6.03 (m, 1H, NH);
4.94 (d, J=2.4Hz, 2H, OCH2); 4.27–4.30 (m, 1H, NHCH);
2.56 (t, J=2.4Hz, 1H, CH); 1.31 (d, J=6.6Hz, 6H, (CH3)2).
Anal. Calcd. for C22H19Cl2N5O3(%): C, 55.94; H, 4.05; N,
14.83. Found: C, 55.72; H, 4.32; N, 14.68.
phenyl)-amide (18b).
White crystal, yield, 54.8%; mp
1
200–202°C; H NMR (CDCl3, 400MHz) δ: 9.87(s, 1H,
CONH); 8.37 (d, J= 4.6 Hz, 1H, pyridyl-H); 7.75 (d,
J =8.0 Hz, 1H, pyridyl-H); 7.26 (dd, J1 = 4.6 Hz,
J2 = 8.0Hz, 1H, pyridyl-H); 7.15 (d, J = 2.0 Hz, 1H, Ph-
H); 7.12 (d, J =2.0 Hz, 1H, Ph-H); 6.50 (s, 1H, pyrazolyl-
H); 6.10–6.13 (m, 1H, NHCH2); 4.87 (d, J= 2.4Hz, 2H,
OCH2); 3.27–3.29 (m, 2H, CH2NH); 2.48 (t, J= 2.4 Hz,
1H, CH); 2.11 (s, 3H, PhCH3); 1.43–1.46 (m, 2H,
CH2CH2); 1.29–1.31 (m, 2H, CH2CH2); 0.86 (t,
J =7.3 Hz, 3H, CH2CH3). The value of HRMS [M + Na]+
for C24H23Cl2N5O3: 522.1070. Found: 522.1065.
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (4-chloro-2-cyclopropylcarbamoyl-phe-
nyl)-amide (18g).
White crystal, yield, 48.3%; mp 230–
232°C; 1H NMR (CDCl3, 400MHz) δ: 12.07 (s, 1H,
CONH); 8.38–8.43 (m, 2H, pyridyl-H, Ph-H); 7.83 (d,
J = 8.0 Hz, 1H, pyridyl-H); 7.27–7.34 (m, 3H, pyridyl-H,
Ph-H); 6.53 (s, 1H, pyrazolyl-H); 6.26–6.29 (m, 1H,
NH); 4.86 (d, J= 2.3 Hz, 2H, OCH2); 2.82–2.85 (m, 1H,
NHCH); 2.47 (t, J =2.3 Hz, 1H, CH); 0.87–0.89(m, 2H,
CH2CH2); 0.78–0.80 (m, 2H, CH2CH2). The value of
HRMS [M + Na]+ for C22H17Cl2N5O3: 492.0601. Found:
492.0610.
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (4-chloro-2-isobutylcarbamoyl-6-methyl-
phenyl)-amide (18c).
White crystal, yield, 48.5%; mp
1
230–231°C; H NMR (CDCl3, 400MHz) δ: 9.84 (s, 1H,
CONH); 8.37 (d, J=4.7Hz, 1H, pyridyl-H); 7.75 (d,
J=8.0Hz, 1H, pyridyl-H); 7.26 (dd, J1 =4.7Hz,
J2 =8.0Hz, 1H, pyridyl-H); 7.18 (m, 1H, Ph-H); 7.14 (m,
1H, Ph-H); 6.46 (s, 1H, pyrazolyl-H); 6.08–6.10 (m, 1H,
NHCH2); 4.87 (d, J=2.4Hz, 2H, OCH2); 3.12–3.14 (m,
2H, CH2NH); 2.48 (t, J=2.4Hz, 1H, CH); 2.12 (s, 3H,
PhCH3); 1.73–1.76 (m, 1H, CHCH2); 0.87 (d, J=6.2Hz,
6H, (CH3)2). Anal. Calcd. for C24H23Cl2N5O3(%): C,
57.61; H, 4.63; N, 14.00. Found: C, 57.42; H, 4.88; N, 13.86.
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (4-chloro-2-cyclohexylcarbamoyl-6-
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (2-butylcarbamoyl-4-chloro-phenyl)-am-
ide (18h): White crystal, yield, 55.1%; mp 142–144°C; H
1
NMR (CDCl3, 400MHz) δ: 12.08 (s, 1H, CONH); 8.37–
8.42 (m, 2H, pyridyl-H, Ph-H); 7.81 (d, J= 8.0Hz, 1H,
pyridyl-H); 7.26–7.36 (m, 3H, pyridyl-H, Ph-H); 6.49 (s,
1H, pyrazolyl-H); 6.16–6.18 (m, 1H, NH); 4.87 (d,
J= 2.4 Hz, 2H, OCH2); 3.37–3.39 (m, 2H, NHCH2); 2.48
(t, J= 2.4Hz, 1H, CH); 1.55–1.57 (m, 2H, CH2CH2); 1.36–
1.38 (m, 2H, CH2CH2); 0.92 (t, J= 7.3 Hz, 3H, CH2CH3).
The value of HRMS [M+Na]+ for C23H21Cl2N5O3:
508.0914. Found: 508.0919.
methyl-phenyl)-amide (18d).
White crystal, yield,
1
57.9%; mp 152–154°C; H NMR (DMSO-d6, 400MHz)
δ: 8.44 (d, J=4.7Hz, 1H, pyridyl-H); 8.10 (d, J=8.0Hz,
1H, pyridyl-H); 7.54 (dd, J1 =4.6Hz, J2 =8.0Hz, 1H,
pyridyl-H); 7.39 (d, J=2.4Hz, 1H, Ph-H); 7.10 (d,
J=2.4Hz, 1H, Ph-H); 6.60 (s, 1H, pyrazolyl-H); 6.25–6.27
(m, 1H, NHCH); 4.82 (d, J=2.3Hz, 2H, OCH2); 3.60 (t,
J=2.3Hz, 1H, CH); 3.48–3.51 (m, 1H, CHNH); 2.05 (s,
3H, PhCH3); 1.95–1.98 (m, 2H, CH2); 1.84–1.86 (m, 2H,
CH2); 1.47–1.49 (m, 2H, CH2); 1.22–1.24 (m, 2H, CH2);
1.01–1.03 (m, 2H, CH2). The value of HRMS [M+Na]+
for C26H25Cl2N5O3: 548.1227. Found: 548.1219.
2-(3-Chloro-pyridin-2-yl)-5-prop-2-ynyloxy-2H-pyrazole-
3-carboxylic acid (4-chloro-2-cyclohexylcarbamoyl-phe-
nyl)-amide (18i).
White crystal, yield, 54.0%; mp
1
163–164°C; H NMR (CDCl3, 400 MHz) δ: 12.07 (s, 1H,
CONH); 8.38–8.48 (m, 2H, pyridyl-H, Ph-H); 7.83 (d,
J = 8.0 Hz, 1H, pyridyl-H); 7.27–7.34 (m, 3H, pyridyl-H,
Ph-H); 6.57 (s, 1H, pyrazolyl-H);5.99–6.01 (m, 1H, NH);
4.94 (d, J =2.4 Hz, 2H, OCH2); 3.89–4.95 (m, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet