3.2.4. General Synthetic Procedure of Compound V
Intermediate IV (1.067 mmol) was dissolved in 80% aqueous sulfuric acid (10 mL) in a 25 mL round-bottom flask. Thereafter, the reaction solution was heated to 100 °C in an oil bath and kept at reflux for 2 h. The reaction mixture was cooled to room temperature and quenched with water. The white solid was collected through filtration and dried to achieve the target compound V (yields 90.1–99.0%).
Compound V-1 4-Amino-3,5-dichloro-6-(3-methyl-5-(p-tolyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.90 (s, 1H), 7.21 (s, 2H), 7.14 (d, J = 8.1 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 6.47 (s, 1H), 2.25 (s, 3H), 2.25 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.94, 150.50, 149.53, 147.69, 147.12, 145.13, 138.41, 129.79, 127.35, 127.13, 113.10, 112.26, 106.17, 21.19, 13.79. HRMS calcd. for C17H14Cl2N4O2 ([M-H]−), 375.0416; found, 375.0413.
Compound V-2 4-Amino-3,5-dichloro-6-(3-(difluoromethyl)-5-(p-tolyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (300 MHz, DMSO-d6) δ 14.03 (s, 1H), 7.35 (s, 2H), 7.19 (d, J = 8.6 Hz, 2H), 7.16 (d, J = 8.6 Hz, 2H), 7.10 (t, J = 54.35 Hz, 1H), 6.99 (s, 1H), 2.27 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.70, 163.80, 161.84, 150.85, 148.00, 147.78, 147.54, 147.30, 146.49, 145.07, 130.24, 130.17, 125.32, 116.60, 116.43, 113.53, 113.01, 112.72, 111.67, 109.82, 104.16. HRMS calcd. for C17H12Cl2F2N4O2 ([M-H]−), 411.0227; found, 411.0239.
Compound V-3 4-Amino-3,5-dichloro-6-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 14.04 (s, 1H), 7.40 (s, 2H), 7.25 (s, 1H), 7.21 (d, J = 8.9 Hz, 2H), 7.18 (d, J = 8.9 Hz, 2H), 2.28 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.73, 150.83, 147.51, 146.63, 146.38, 143.22, 142.92, 142.62, 142.32, 139.77, 130.04, 127.85, 125.32, 124.88, 122.74, 120.60, 118.46, 113.17, 112.73, 104.51, 40.30, 21.22. HRMS calcd. for C17H11Cl2F3N4O2 ([M-H]−), 429.0133; found, 429.0143.
Compound V-4 4-Amino-3,5-dichloro-6-(5-(4-fluorophenyl)-3-methyl-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.83 (s, 1H), 7.25 (s, 2H), 7.24–7.22 (m, 2H), 7.22–7.18 (m, 2H), 6.52 (s, 1H), 2.26 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.88, 163.36, 161.41, 150.61, 149.65, 147.36, 147.15, 144.06, 129.71, 129.64, 126.50, 116.37, 116.19, 112.90, 112.32, 106.68, 13.76. HRMS calcd. for C16H11Cl2FN4O2 ([M-H]−), 379.0165; found, 379.0159.
Compound V-5 4-Amino-3,5-dichloro-6-(3-(difluoromethyl)-5-(4-fluorophenyl)-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.98 (s, 1H), 7.40 (s, 2H), 7.35–7.33 (m, 2H), 7.28–7.24 (m, 2H), 7.13 (t, J = 54.3 Hz, 1H), 7.07 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.70, 163.80, 161.84, 150.85, 148.00, 147.78, 147.54, 147.30, 146.49, 145.07, 130.24, 130.17, 125.32, 116.60, 116.43, 113.53, 113.01, 112.72, 111.67, 109.82, 104.16. HRMS calcd. for C16H9Cl2F3N4O2 ([M-H]−), 414.9976; found, 414.9986.
Compound V-6 4-Amino-3,5-dichloro-6-(5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 14.07 (s, 1H), 7.46 (s, 2H), 7.38–7.36 (m, 2H), 7.35 (s, 1H), 7.31–7.27 (m, 2H). 13C NMR (126 MHz, DMSO-d6) δ 165.61, 164.01, 162.03, 150.97, 147.30, 146.07, 145.56, 143.29, 142.99, 142.69, 142.39, 130.44, 130.37, 124.81, 124.71, 124.68, 124.68, 122.67, 120.53, 118.39, 116.71, 116.54, 113.34, 112.67, 105.06. HRMS calcd. for C16H8Cl2F4N4O2 ([M-H]−), 432.9882; found, 432.9888.
Compound V-7 4-Amino-3,5-dichloro-6-(5-(4-chlorophenyl)-3-methyl-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.50 (s, 1H), 7.43 (d, J = 8.55 Hz, 2H), 7.28 (s, 2H), 7.21 (d, J = 8.55 Hz, 2H), 6.57 (s, 1H), 2.27 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.85, 150.66, 149.78, 147.28, 147.11, 143.85, 133.63, 129.34, 129.16, 128.79, 112.80, 112.39, 106.96, 13.76. HRMS calcd. for C16H10Cl3N4O2 ([M-H]−), 394.9869; found, 395.0023.
Compound V-8 4-Amino-3,5-dichloro-6-(5-(4-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (300 MHz, DMSO-d6) δ 13.95 (s, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.40 (s, 2H),7.30 (d, J = 8.4 Hz, 2H), 7.14 (t, J = 54.3 Hz, 1H), 7.11 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.65, 150.88, 148.08, 147.85, 147.62, 147.31, 146.41, 144.87, 134.49, 129.61, 129.54, 127.61, 113.47, 113.07, 111.62, 109.77, 104.43. HRMS calcd. for C16H8Cl3F2N4O2 ([M-H]−), 430.9681; found, 430.9688.
Compound V-9 4-Amino-3,5-dichloro-6-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 14.06 (s, 1H), 7.51 (d, J = 8.5 Hz, 2H), 7.47 (s, 2H), 7.38 (s, 1H), 7.33 (d, J = 8.5 Hz, 2H). 13C NMR (126 MHz, DMSO-d6) δ 165.61, 151.00, 147.34, 146.00, 145.36, 143.36, 143.06, 142.76, 142.46, 134.90, 129.75, 129.62, 126.99, 124.77, 122.63, 120.49, 118.35, 113.39, 112.58, 105.32. HRMS calcd. for C16H7Cl3F3N4O2 ([M-H]−), 448.9587; found, 448.9592.
Compound V-10 4-Amino-3,5-dichloro-6-(5-(3-chlorophenyl)-3-methyl-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, Chloroform-d) δ 7.29 (s, 1H), 7.28 (d, J = 7.75 Hz, 1H), 7.23 (dd, J = 8.0 Hz, 7.75 Hz, 1H), 6.99 (d, J = 7.75 Hz, 1H), 6.40 (s, 1H), 5.62 (s, 2H), 2.41 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.85, 150.64, 149.79, 147.23, 143.48, 133.82, 131.85, 131.13, 128.77, 127.35, 125.91, 112.85, 112.34, 107.27, 13.77. HRMS calcd. for C16H10Cl3N4O2 ([M-H]−), 394.9869; found, 394.9873.
Compound V-11 4-Amino-3,5-dichloro-6-(5-(3-chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.96 (s, 1H), 7.46–7.45 (m, 1H), 7.45 (s, 1H), 7.43–7.40 (m, 1H), 7.39 (s, 2H), 7.18 (s, 1H), 7.16–7.13 (m, 1H), 7.14 (t, J = 54.2 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.64, 150.87, 148.10, 147.87, 147.64, 147.38, 146.39, 144.50, 134.01, 131.28, 130.68, 129.58, 127.88, 126.30, 113.45, 113.04, 112.71, 111.60, 109.75, 104.81. HRMS calcd. for C16H8Cl3F2N4O2 ([M-H]−), 430.9681; found, 430.9691.
Compound V-12 4-Amino-3,5-dichloro-6-(5-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 14.01 (s, 1H), 7.52–7.39 (m, 6H), 7.15 (d, J = 7.7 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.58, 151.00, 147.29, 145.97, 144.98, 143.37, 143.07, 142.77, 142.47, 134.10, 131.36, 130.01, 129.95, 128.09, 126.36, 125.69, 124.74, 124.60, 122.60, 120.46, 118.33, 113.36, 112.67, 105.70. HRMS calcd. for C16H7Cl3F3N4O2 ([M-H]−), 448.9587; found, 448.9592.
Compound V-13 4-Amino-6-(5-(4-bromophenyl)-3-methyl-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.85 (s, 1H), 7.56 (d, J = 8.2 Hz, 2H), 7.23 (s, 2H), 7.14 (d, J = 8.3 Hz, 2H), 6.57 (s, 1H), 2.27 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.90, 150.62, 149.77, 147.25, 143.89, 132.26, 129.41, 129.15, 122.28, 112.67, 112.30, 106.93, 13.76. HRMS calcd. for C16H10BrCl2N4O2 ([M-H]−), 440.9344; found, 440.9348.
Compound V-14 4-Amino-6-(5-(4-bromophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.92 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.38 (s, 2H), 7.23 (d, J = 8.5 Hz, 1H), 7.13 (t, J = 54.2 Hz, 1H), 7.11 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.61, 150.89, 148.10, 147.88, 147.65, 147.26, 146.41, 144.93, 132.45, 129.83, 127.97, 123.21, 113.47, 113.10, 112.64, 111.61, 109.76, 104.43. HRMS calcd. for C16H8BrCl2F2N4O2 ([M-H]−), 476.9155; found, 476.9159.
Compound V-15 4-Amino-6-(5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.92 (s, 1H), 7.57 (d, J = 8.5 Hz, 2H), 7.39 (s, 2H), 7.31 (s, 1H), 7.18 (d, J = 8.5 Hz, 2H). 13C NMR (126 MHz, DMSO-d6) δ 165.58, 151.01, 147.27, 145.99, 145.42, 143.38, 143.08, 142.77, 142.48, 132.54, 129.95, 127.33, 124.76, 123.64, 122.62, 120.48, 118.34, 113.42, 112.58, 105.32. HRMS calcd. for C16H7BrCl2F3N4O2 ([M-H]−), 494.9061; found, 494.9066.
Compound V-16 4-Amino-6-(5-(2-bromophenyl)-3-methyl-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.71 (s, 1H), 7.66 (dd, J = 7.9, 1.1 Hz, 1H), 7.31 (td, J = 7.5, 1.2 Hz, 1H), 7.26 (td, J = 7.7, 1.8 Hz, 1H), 7.16 (s, 2H), 7.15 (dd, J = 7.7, 1.8 Hz, 1H), 6.48 (s, 1H), 2.30 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.79, 150.43, 149.03, 146.67, 146.64, 143.25, 133.51, 132.02, 131.26, 130.98, 127.84, 123.02, 112.09, 111.70, 109.10, 13.83. HRMS calcd. for C16H10BrCl2N4O2 ([M-H]−), 440.9344; found, 440.9351.
Compound V-17 4-Amino-6-(5-(2-bromophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.82 (s, 1H), 7.71 (dd, J = 7.7, 1.1 Hz, 1H), 7.38–7.27 (m, 4H), 7.22 (dd, J = 7.3, 2.0 Hz, 1H), 7.17 (t, J = 54.2 Hz, 1H), 6.98 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.61, 150.66, 147.38, 147.15, 146.92, 146.85, 145.86, 144.28, 133.60, 132.27, 131.73, 129.98, 128.01, 123.25, 113.51, 112.45, 112.13, 111.66, 109.81, 106.57, 40.30. HRMS calcd. for C16H8BrCl2F2N4O2 ([M-H]−), 476.9155; found, 476.9158.
Compound V-18 4-Amino-6-(5-(2-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.91 (s, 1H), 7.73 (dd, J = 7.6, 1.5 Hz, 1H), 7.37 (m, 4H), 7.26(dd, J = 7.3, 2.0 Hz, 1H), 7.25 (s, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.53, 150.77, 146.84, 145.45, 144.81, 142.67, 142.37, 142.07, 141.77, 133.62, 132.37, 132.08, 129.32, 128.07, 124.80, 123.36, 122.66, 120.52, 118.38, 112.78, 112.16, 107.41. HRMS calcd. for C16H7BrCl2F3N4O2 ([M-H]−), 494.9061; found, 494.9064.
Compound V-19 4-Amino-3,5-dichloro-6-(5-(4-isopropylphenyl)-3-methyl-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.78 (s, 1H), 7.23 (s, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 6.48 (s, 1H), 2.84 (hept, J = 6.9 Hz, 1H), 2.25 (s, 3H), 1.16 (d, J = 6.9 Hz, 6H). 13C NMR (126 MHz, DMSO-d6) δ 165.92, 150.52, 149.50, 149.12, 147.78, 147.12, 145.03, 127.36, 127.19, 113.23, 112.31, 106.24, 33.52, 24.05, 13.78. HRMS calcd. for C19H17Cl2N4O2 ([M-H]−), 403.0729; found, 403.0734.
Compound V-20 4-Amino-3,5-dichloro-6-(3-(difluoromethyl)-5-(4-isopropylphenyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.95 (s, 1H), 7.36 (s, 2H), 7.27 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 8.3 Hz, 2H), 7.11 (t, J = 54.3 Hz, 1H), 7.01 (s, 1H), 2.86 (hept, J = 6.9 Hz, 1H), 1.17 (d, J = 6.9 Hz, 6H). 13C NMR (126 MHz, DMSO-d6) δ 166.42, 150.45, 149.91, 147.80, 147.57, 147.34, 146.81, 145.97, 127.74, 127.38, 126.33, 113.63, 112.33, 112.16, 111.78, 109.93, 103.57, 33.56, 24.01. HRMS calcd. for C19H15Cl2F2N4O2 ([M-H]−), 439.0540; found, 439.0550.
Compound V-21 4-Amino-3,5-dichloro-6-(5-(4-isopropylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 13.98 (s, 1H), 7.43 (s, 2H), 7.34–7.21 (m, 5H), 2.87 (hept, J = 6.9 Hz, 1H), 1.17 (d, J = 6.9 Hz, 5H). 13C NMR (126 MHz, DMSO-d6) δ 165.68, 150.89, 150.40, 147.31, 146.54, 146.48, 143.24, 142.94, 142.64, 142.34, 127.88, 127.47, 125.64, 124.88, 122.74, 120.60, 118.46, 113.28, 112.90, 104.60, 33.59, 23.97. HRMS calcd. for C19H14Cl2F3N4O2 ([M-H]−), 457.0446; found, 457.0461.
Compound V-22 4-Amino-3,5-dichloro-6-(5-(3,4-dichlorophenyl)-3-methyl-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.89 (s, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 2.0 Hz, 1H), 7.27 (s, 2H), 7.05 (dd, J = 8.4, 2.1 Hz, 1H), 6.68 (s, 1H), 2.27 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.86, 150.71, 149.88, 147.37, 147.00, 142.49, 131.98, 131.58, 131.50, 130.40, 129.41, 127.30, 112.65, 112.39, 107.61, 13.75. HRMS calcd. for C16H9Cl4N4O2 ([M-H]−), 430.9450; found, 430.9460.
Compound V-23 4-Amino-3,5-dichloro-6-(5-(3,4-dichlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 14.03 (s, 1H), 7.69 (d, J = 2.1 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.42 (s, 2H), 7.23 (s, 1H), 7.14 (t, J = 54.2 Hz, 1H), 7.12 (dd, J = 8.4, 2.1 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.66, 150.96, 148.15, 147.92, 147.69, 147.41, 146.16, 143.52, 132.49, 132.21, 131.65, 130.02, 129.20, 127.62, 113.40, 113.12, 112.55, 111.54, 109.69, 105.15, 40.30. HRMS calcd. for C16H7Cl4F2N4O2 ([M-H]−), 466.9262; found, 466.9273.
Compound V-24 4-Amino-3,5-dichloro-6-(5-(3,4-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 14.11 (s, 1H), 7.74 (d, J = 2.1 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.48 (s, 1H), 7.45 (s, 2H), 7.14 (dd, J = 8.4, 2.1 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 165.69, 151.02, 147.80, 145.74, 144.00, 143.38, 143.08, 142.78, 142.48, 132.90, 132.30, 131.73, 130.24, 128.55, 127.70, 124.69, 122.55, 120.41, 118.27, 113.33, 112.39, 105.99. HRMS calcd. for C16H6Cl4F3N4O2 ([M-H]−), 484.9176; found, 484.9181.
Compound V-25 4-Amino-3,5-dichloro-6-(5-(4-ethylphenyl)-3-methyl-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.22 (s, 1H),7.21 (s, 2H), 7.17 (d, J = 8.2 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 6.48 (s, 1H), 2.56 (q, J = 7.6 Hz, 2H), 1.14 (t, J = 7.6 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.94, 150.51, 149.52, 147.72, 147.12, 145.09, 144.55, 128.60, 127.39, 127.34, 113.15, 112.27, 106.21, 28.22, 15.58, 13.78. HRMS calcd. for C18H15Cl2N4O2 ([M-H]−), 389.0572; found, 389.0584.
Compound V-26 4-Amino-3,5-dichloro-6-(3-(difluoromethyl)-5-(4-ethylphenyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 14.05 (s, 1H), 7.37 (s, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.11 (t, J = 54.2 Hz, 1H), 7.00 (s, 1H), 2.59 (q, J = 7.6 Hz, 2H), 1.15 (t, J = 7.6 Hz, 3H). 13C NMR (126 MHz, DMSO) δ 166.37, 150.46, 147.82, 147.59, 147.36, 146.76, 146.06, 145.36, 128.76, 127.77, 126.23, 113.63, 112.37, 112.18, 111.78, 109.93, 103.54, 40.28, 28.24, 15.51. HRMS calcd. for C18H13Cl2F2N4O2 ([M-H]−), 425.0384; found, 425.0394.
Compound V-27 4-Amino-3,5-dichloro-6-(5-(4-ethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.95 (s, 1H), 7.41 (s, 2H), 7.26 (s, 1H), 7.24 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 8.3 Hz, 2H), 2.59 (q, J = 7.6 Hz, 2H), 1.15 (t, J = 7.6 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.67, 150.86, 147.27, 146.61, 146.40, 145.88, 143.23, 142.94, 142.64, 142.34, 128.86, 127.89, 125.50, 124.86, 122.72, 120.58, 118.44, 113.25, 112.85, 104.55, 28.23, 15.48. HRMS calcd. for C18H12Cl2F3N4O2 ([M-H]−), 443.0289; found, 443.0306.
Compound V-28 4-Amino-3,5-dichloro-6-(3-methyl-5-(4-propylphenyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 14.14 (s, 1H), 7.21 (s, 2H), 7.15 (d, J = 8.3 Hz, 2H), 7.11 (d, J = 8.3 Hz, 2H), 6.48 (s, 1H), 2.51 (t, J = 7.6 Hz, 2H), 2.26 (s, 3H), 1.61–1.49 (m, 2H), 0.85 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.94, 150.51, 149.52, 147.71, 147.12, 145.10, 142.99, 129.15, 127.37, 127.31, 113.11, 112.24, 106.20, 37.29, 24.17, 14.11, 13.79. HRMS calcd. for C19H17Cl2N4O2 ([M-H]−), 403.0729; found, 403.0742.
Compound V-29 4-Amino-3,5-dichloro-6-(3-(difluoromethyl)-5-(4-propylphenyl)-1H-pyrazol-1-yl)picolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 14.18 (s, 1H), 7.25 (s, 2H), 7.19 (t, J = 1.7 Hz, 4H), 7.10 (t, J = 54.2 Hz, 1H), 6.99 (s, 1H), 2.51 (t, J = 7.6 Hz, 2H), 1.60–1.50 (m, 2H), 0.85 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.75, 150.74, 147.93, 147.71, 147.47, 147.31, 146.83, 146.11, 143.88, 129.34, 127.69, 126.20, 113.59, 112.88, 111.74, 109.89, 103.65, 37.28, 24.12, 14.10. HRMS calcd. for C19H15Cl2F2N4O2 ([M-H]−), 439.0540; found, 439.0554.
Compound V-30 4-Amino-3,5-dichloro-6-(5-(4-propylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)picolinic acid. Yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 14.13 (s, 1H), 7.42 (s, 2H), 7.26 (s, 1H), 7.22 (s, 4H), 2.57–2.50 (m, 2H), 1.56 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz, DMSO-d6) δ 165.66, 150.87, 147.28, 146.62, 146.41, 144.31, 143.23, 142.93, 142.64, 142.33, 129.41, 127.82, 125.56, 124.87, 122.74, 120.60, 118.46, 113.22, 112.83, 104.55, 37.28, 24.09, 14.07. HRMS calcd. for C19H14Cl2F3N4O2 ([M-H]−), 457.0446; found, 457.0459.
Compound V-31 4-Amino-6-(5-(4-(tert-butyl)phenyl)-3-methyl-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.89 (s, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.24 (s, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.49 (s, 1H), 2.25 (s, 3H), 1.24 (s, 9H). 13C NMR (126 MHz, DMSO) δ 165.94, 151.39, 150.54, 149.50, 147.82, 147.13, 144.88, 127.04, 126.08, 113.27, 112.35, 106.27, 40.14, 34.86, 31.39, 13.78. HRMS calcd. for C20H19Cl2N4O2 ([M-H]−), 417.0885; found, 417.0903.
Compound V-32 4-Amino-6-(5-(4-(tert-butyl)phenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.92 (s, 1H), 7.77 (s, 2H), 7.42 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 7.11 (t, J = 54.2 Hz, 1H), 7.05 (s, 1H), 1.25 (s, 9H). 13C NMR (126 MHz, DMSO-d6) δ 166.91, 152.13, 150.16, 147.67, 147.44, 147.21, 146.77, 145.76, 127.43, 126.25, 126.04, 113.66, 111.81, 111.78, 111.45, 109.97, 34.93, 31.35. HRMS calcd. for C20H17Cl2F2N4O2 ([M-H]−), 453.0697; found, 453.0713.
Compound V-33 4-Amino-6-(5-(4-(tert-butyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-3,5-dichloropicolinic acid. White solid. 1H NMR (500 MHz, DMSO-d6) δ 13.99 (s, 1H), 7.43 (d, J = 8.5 Hz, 2H), 7.32 (s, 2H), 7.27 (d, J = 8.6 Hz, 3H), 1.25 (s, 9H). 13C NMR (126 MHz, DMSO-d6) δ 166.52, 152.57, 150.42, 146.40, 146.30, 143.03, 142.73, 142.43, 142.13, 127.57, 126.35, 125.51, 125.37, 124.93, 122.79, 120.65, 118.52, 112.35, 111.71, 104.46, 34.97, 31.32. HRMS calcd. for C20H16Cl2F3N4O2 ([M-H]−), 471.0602; found, 471.0620.