Instruments and reagents
All the reactions were carried out in round bottom flasks. All the solvents and chemical materials were purchased from commercial sources. The 1-butyl-1H-indazole-3-carboxamide was prepared according to the reported protocols. 1H and 13C NMR spectra were recorded on Bruker Avance400 spectrometer and are referred to the residual solvent signal CDCl3: (7.26) for 1H and (77.16) for 13C NMR: dimethyl sulfoxide-d6 (2.50) for 1H and (39.50) for 13C NMR: chemical shift (δ) is given in ppm and coupling constant (J) were measured in Hz. The following abbreviations are used: s- singlet, d-doublet, dd-doublet of doublet, t-triplet, td-triplet of doublet, dt- doublet of triplet, q-quartet, qd- quartet of doublet, qn-quintet, br-broad, m-multiplet. HRMS ESI-MS was recorded using Xeo G2 XS OT of (water) and values are given m/z. Colum chromatography was carried out using silica gel (100–200 mesh) packed in a glass column. Analytical TLC was carried out on Macherey-Nagel 60 F245 aluminium-backed silica gel plates.
General Procedure for the Synthesis 8a-8z
A stirred solution of 1-butyl-1H-indazol-3-carboxylic acid (250 mg, 1.146 mmol) was dissolved in DMF (10 mL), HATU (2 equivalents), and DIPEA (3 equivalents) were added to the reaction mixture, then commercial amines (2 equivalents) were added. The reaction mixture was stirred at room temperature for 8-16h. After completion of the reaction, the resultant reaction mixture was poured into water; the solution was extracted with water and ethyl acetate (4 x 20 mL). The organic layer was dried with anhydrous sodium sulfate and the solvent was removed under reduced pressure to afford crude product. The crude was purified by silica gel chromatography to obtain pure products 8a-8z.
Characterization of indazole carboxamide derivatives from 8a-8z.
1-Butyl-1 H -indazol-3-carboxamide (8a). Appearance: Off-white solid (yield = 93.9%, 140 mg). 1H NMR [400 MHz, DMSO-d6]: δ 8.11 (d, J = 8.00 Hz, 1H), 7.69 (d, J = 8.80 Hz, 1H), 7.56 (s, 1H), 7.37 (t, J = 8.00 Hz, 1H), 7.28 (s, 1H), 7.19 (t, J = 7.60 Hz, 1H), 4.40 (t, J = 6.80 Hz, 2H), 1.79 (q, J = 6.80 Hz, 2H), 1.15–1.17 (m, 2H), 0.82 (t, J = 7.60 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 141.04, 137.5, 126.84, 122.68, 122.64, 122.41, 110.71, 48.80, 31.88, 19.87, 13.96. IR STRECHING: (N-H) = 3306 Cm− 1, (C = O) = 1664 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C12H15N3O 217.1215 + found 240.111[M + Na].
1-Butyl-N-phenyl-1 H -indazol-3-carboxamide (8b). Appearance: Pale brown solid (yield = 96.7%, 195 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.19 (s, 1H), 8.24 (d, J = 8.00 Hz, 1H), 7.89 (d, J = 8.00 Hz, 2H), 7.82 (d, J = 8.80 Hz, 1H), 7.49 (t, J = 7.20 Hz, 1H), 7.38–7.36 (m, 3H), 7.10 (q, J = 6.80 Hz, 1H), 4.56 (t, J = 6.80 Hz, 2H), 1.91 (q, J = 6.80 Hz, 2H), 1.34–1.32 (m, 2H), 0.92 (t, J = 7.20 Hz, 3H) .13C NMR [100 MHz, DMSO-d6]: d ppm 161.04, 141.17, 139.21, 137.46, 129.01, 127.17, 123.92, 123.05, 122.25, 120.78, 110.96, 49.08, 32.0, 19.94, 14.02. IR STRECHING: (N-H) = 3306 Cm− 1, (C = O) = 1664 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H19N3O 293.1528 + found 294.1596 [M + H].
N-Benzyl-1-butyl-1 H -indazol-3-carboxamide (8c). Appearance: Pale yellow solid (yield = 90%, 190 mg). 1H NMR [400 MHz, DMSO-d6]: δ 8.81 (t, J = 6.40 Hz, 1H), 8.11 (d, J = 8.40 Hz, 1H), 7.70 (d, J = 8.80 Hz, 1H), 7.38 (t, J = 0.80 Hz, 1H), 7.19–7.21 (m, 4H), 7.15–7.16 (m, 2H), 4.40–4.41 (m, 4H), 1.79 (q, J = 7.20 Hz, 2H), 1.16–1.16 (m, 2H), 0.82 (t, J = 7.60 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 162.4, 141,140,42,137.36, 128.69, 127.89, 127.15, 126.97, 122.74, 122.63, 122.27, 110.8, 48.88, 42.39, 31.93, 19.91, 14. IR STRECHING: (N-H) = 3381 Cm− 1, (C = O) = 1639 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H21N3O 307.17 + found 308.1760 [M + H].
N-(3-Bromophenyl)-1-butyl-1 H -indazol-3-carboxamide (8d). Appearance: Brown solid (yield = 78.4%, 200 mg). 1H NMR [400 MHz, CDCl3]: δ 8.78 (s, 1H), 8.32 (d, J = 8.40 Hz, 1H), 7.95 (d, J = 1.60 Hz, 1H), 7.60–7.59 (m, 1H), 7.37–7.36 (m, 2H), 7.16 (t, J = 7.20 Hz, 2H), 4.34 (t, J = 7.20 Hz, 2H), 1.87 (q, J = 7.60 Hz, 2H), 1.34–1.32 (m, 2H), 0.89 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, CDCl3]: 160.51, 141.11, 139.38, 136.73, 126.99, 126.83, 123.03, 122.94, 122.73, 122.44, 118.03, 109.48, 49.38, 31.38, 20.07, 13.66. IR STRECHING: (N-H) = 3272 Cm− 1, (C = O) = 1655 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H18BrN3O 371.2660 + found 372.0707[M + H].
2-(1-Butyl-1 H -indazol-3-carboxamido)-5-iodobenzoic acid (8e). Appearance: Yellow solid (yield = 47%, 150 mg). 1H NMR [400 MHz, DMSO-d6]: δ 8.46 (d, J = 8.00 Hz, 1H), 8.38 (s, 1H), 8.24 (d, J = 8.40 Hz, 1H), 7.88 (d, J = 8.40 Hz, 1H), 1887.17 (q, J = 8.40 Hz, 2H), 7.41 (t, J = 7.60 Hz, 1H), 4.58 (t, J = 6.40 Hz, 2H), 1.90 (t, J = 6.80 Hz, 2H), 1.29 (q, J = 6.80 Hz, 2H), 0.91 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 157.97, 153.64, 146.45, 145.49, 141.21, 136.41, 134.02, 129.31, 127.51, 123.75, 122.91, 122.50, 119.65, 111.33, 93.54, 49.40, 31.93, 19.88, 13.98. IR STRECHING: (O-H) = 2947 Cm− 1, (N-H) = 2860 Cm− 1, (C = O) = 1740 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H16IN3O2 445.0287 + found 446.0365[M + H].
1-Butyl-N-(4-(phenylamino)phenyl)-1 H -indazol-3-carboxamide (8f). Appearance: Grey solid (yield = 87%, 230 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.06 (s, 1H), 8.26 (d, J = 8.00 Hz, 1H), 8.08 (s, 1H), 7.78 (t, J = 7.20 Hz, 3H), 7.48 (t, J = 7.20 Hz, 1H), 7.31 (t, J = 7.60 Hz, 1H), 7.22 (t, J = 7.20 Hz, 2H), 7.08 (q, J = 8.40 Hz, 4H), 6.79 (t, J = 7.20 Hz, 1H), 4.53 (t, J = 6.80 Hz, 2H), 1.90 (t, J = 6.80 Hz, 2H), 1.30 (q, J = 7.20 Hz, 2H), 0.90 (t, J = 7.20 Hz, 3H).13C NMR [100 MHz, DMSO-d6]: d ppm 160.64, 144.51, 141.16, 139.64, 137.71, 131.98, 129.62, 127.12, 122.91, 122.88, 122.33, 122.15, 119.55, 118.03, 116.43, 110.89, 49.02, 31.98, 19.93, 14.IR STRECHING: (N-H) = 3342 Cm− 1, (C = O) = 1635 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C24H24N4O 384.4830 + found 384.1970[M + H].
Ethyl 4-(1-butyl-1 H -indazol-3-carboxamido)benzoate (8g). Appearance: Off white solid (yield = 75.6%, 190 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.58 (s, 1H), 8.24 (d, J = 8.00 Hz, 1H), 8.08 (d, J = 8.80 Hz, 2H), 7.96 (d, J = 8.40 Hz, 2H), 7.84 (d, J = 8.40 Hz, 1H), 7.51 (t, J = 8.00 Hz, 1H), 7.34 (t, J = 7.20 Hz, 2H), 4.57 (t, J = 6.80 Hz, 2H), 4.31 (q, J = 6.80 Hz, 2H), 1.91 (q, J = 7.20 Hz, 2H), 1.26–1.27 (m, 2H), 0.00 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 165.86, 161.38, 143.72, 141.22, 137.08, 130.47, 127.30, 124.86, 123.32, 122.96, 122.12, 120.06, 111.12, 60.90, 49.16, 31.97, 19.92, 14.70, 14.01. IR STRECHING: (N-H) = 3383 Cm− 1, (C = O) = 1712 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C21H23N3O3 365.4330 + found 366.1817[M + H].
1-butyl-N-(4-nitrophenyl)-1 H -indazole-3-carbohydrazide (8h). Appearance: Pale brown solid (yield = 57.8%, 140.5 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.60 (s, 1H), 9.22 (s, 1H), 8.11 (q, J = 9.20 Hz, 3H), 7.83 (d, J = 8.40 Hz, 1H), 7.49 (t, J = 7.60 Hz, 1H), 7.30 (t, J = 7.20 Hz, 1H), 6.83 (d, J = 9.20 Hz, 1H), 4.54 (t, J = 6.80 Hz, 2H), 1.91 (q, J = 7.20 Hz, 2H), 1.27–1.29 (m, 2H), 0.92 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 162.31, 155, 67, 140.87, 138.40, 135.72, 127.21, 126.41, 123.15, 122.96, 121.89, 111.11, 111.02, 49.08, 31.91, 19.92, 14.02. IR STRECHING: (N-H) = 3355 Cm− 1, (C = O) = 1658 Cm− 1, (NO2) = 1595 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H19N5O3 353.3820 + found 354.1569[M + H].
N-(4-Bromophenyl)-1-butyl-1 H -indazol-3-carboxamide (8i). Appearance: Brown solid (yield = 82.5%, 210.6 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.41 (s, 1H), 8.23 (d, J = 8.40 Hz, 1H), 7.90 (d, J = 8.80 Hz, 2H), 7.83 (d, J = 8.40 Hz, 1H), 7.55–7.52 (m, 3H), 7.32 (t, J = 7.60 Hz, 1H), 4.55 (t, J = 7.20 Hz, 2H), 1.90 (q, J = 7.20 Hz, 2H), 1.34–1.32 (m, 2H), 0.91 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 161.16, 141.18, 138.68, 137.23, 131.82, 127.24, 123.18, 122.74, 122.18, 111.04, 55.37, 31.99, 19.92, 14.01. IR STRECHING: (N-H) = 3272 Cm− 1, (C = O) = 1655 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H18BrN3O 371.2660 + found 372.0707[M + H].
1-Butyl-N-(4-hydroxyphenyl)- 1H -indazol-3-carboxamide (8j). Appearance: Off white solid (yield = 72.2%, 153 mg). 1H NMR [400 MHz, DMSO-d6]: δ 9.97 (s, 1H), 9.24 (s, 1H), 8.22 (d, J = 8.00 Hz, 1H), 7.80 (d, J = 8.40 Hz, 1H), 7.64 (dd, J = 1.60, 8.60 Hz, 2H), 7.48 (t, J = 7.60 Hz, 1H), 7.30 (t, J = 8.00 Hz, 1H), 6.75 (d, J = 8.40 Hz, 2H), 4.53 (t, J = 6.80 Hz, 2H), 1.90 (q, J = 6.80 Hz, 2H), 1.28 (q, J = 7.60 Hz, 2H), 0.91 (t, J = 7.20 Hz, 3H).13C NMR [100 MHz, DMSO-d6]: d ppm 160.58, 15.06,141.13, 137.71, 130.75, 127.09, 122.86, 122.61, 122.31, 115.42. 110.88, 48.98, 31.98, 19.92, 14.01. IR STRECHING: (N-H) = 3323 Cm− 1, (C = O) = 1651 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H19N3O2 309.3690 + found 310.1553[M + H].
1-Butyl-N-(2-hydroxy-6methylphenyl)-1 H -indazol-3-carboxamide (8k). Appearance: Pale brown solid (yield = 13.5%, 30 mg). 1H NMR [400 MHz, DMSO-d6]: δ 9.34 (s, 1H), 9.22 (s, 1H), 8.18 (d, J = 8.00 Hz, 1H), 7.81 (d, J = 8.40 Hz, 1H), 7.48 (t, J = 8.00 Hz, 1H), 7.29 (t, J = 7.20 Hz, 1H), 7.02 (t, J = 8.00 Hz, 1H), 6.75 (q, J = 7.20 Hz, 2H), 4.54 (t, J = 7.20 Hz, 2H), 2.20 (s, 3H), 1.91 (q, J = 7.20 Hz, 2H), 1.28–1.30 (m, 2H), 0.94 (t, J = 5.60 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 161.17, 153.47 141.08, 137.35, 137.17, 127.37, 127.05, 124.00, 122.87, 122.79, 122.28, 121.00, 113.95, 110.88, 48.98, 31.42, 22.53, 14.42, 14.01. IR STRECHING: (N-H) = 3355 Cm− 1, (OH) = 3104 Cm− 1, (C = O) = 1643 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H21N3O2 323.3960 + found 324.1711[M + H].
1-Butyl-N-(m-tolyl)-1 H -indazol-3-carboxamide (8l). Appearance: Off white solid (yield = 90.2%, 190 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.07 (s, 1H), 8.23 (d, J = 8.00 Hz, 1H), 7.81 (d, J = 8.40 Hz, 1H), 7.76 (s, 1H), 7.67 (d, J = 8.00 Hz, 1H), 7.49 (t, J = 8.00 Hz, 1H), 7.32 (t, J = 7.60 Hz, 1H), 7.23 (t, J = 8.00 Hz, 1H), 6.92 (d, J = 7.60 Hz, 1H), 4.54 (t, J = 7.20 Hz, 2H), 2.33 (s, 3H), 1.91 (q, J = 7.20 Hz, 2H), 1.30 (q, J = 7.60 Hz, 2H), 0.91 (t, J = 7.20 Hz, 3H).13C NMR [100 MHz, DMSO-d6]: d ppm 160.97,141.18, 139.11, 138.19, 137.47, 128.87, 127.16, 124.64, 123.04, 122.22, 121.26, 117.91, 110.95, 49.05, 31.96, 21.70, 19.93, 14. IR STRECHING: (N-H) = 3316 Cm− 1, (C = O) = 1659 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H21N3O 307.3970 + found 308.1765[M + H].
1-Butyl-N-(o-tolyl)-1 H -indazol-3-carboxamide (8m). Appearance: Off white solid (yield = 90.2%, 190.5 mg). 1H NMR [400 MHz, DMSO-d6]: δ 9.61 (s, 1H), 8.24–8.22 (m, 3H), 7.83 (d, J = 8.40 Hz, 1H), 7.69 (dd, J = 2.40, -8.40 Hz, 1H), 7.50 (td, J = 0.80, -7.00 Hz, 1H), 7.34 (td, J = 0.40, -11.20 Hz, 1H), 4.53 (t, J = 6.80 Hz, 2H), 2.28 (s, 3H), 1.89 (q, J = 7.20 Hz, 2H), 1.28 (q, J = 7.60 Hz, 2H), 0.89 (t, J = 7.60 Hz, 3H).13C NMR [100 MHz, DMSO-d6]: d ppm 160.42, 149.27, 148.46, 141.42, 139.25, 136.37, 129.24, 127.37, 123.49, 122.55, 121.91, 113.34, 111.20, 49.31, 31.77, 19.86, 17.76, 13.93. IR STRECHING: (N-H) = 3391 Cm− 1, (C = O) = 1679 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H21N3O 307.3970 + found 308.1721[M + H].
1-Butyl-N-(5-methylpyridin-2-yl)-1 H -indazol-3-carboxamide (8n). Appearance: Off white solid (yield = 87.5%, 185.5 mg). 1H NMR [400 MHz, DMSO-d6]: δ 9.65 (s, 1H), 8.23 (d, J = 8.00 Hz, 1H), 7.81 (d, J = 8.40 Hz, 1H), 7.69 (d, J = 7.60 Hz, 1H), 7.49 (t, J = 7.20 Hz, 1H), 7.33–7.31 (m, 3H), 7.13 (t, J = 7.60 Hz, 1H), 4.53 (t, J = 6.80 Hz, 2H), 2.31 (s, 3H), 1.90 (q, J = 7.20 Hz, 2H), 1.35–1.34 (m, 2H), 0.91 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 160.80, 141.21, 137.26, 136.54, 132.05, 127.16, 125.62, 125.13, 123.05, 122.76, 122.19, 110.96, 48.98, 31.88, 19.9, 18.16, 13.95. IR STRECHING: (N-H) = 3387 Cm− 1, (C = O) = 1675 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H20N4O 308.3850 + found 309.1719[M + H].
1-Butyl-N-(5-methylpyridin-2-yl)-1 H -indazol-3-carboxamide (8o). Appearance: off white solid (yield = 89.1%, 198 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.11 (s, 1H), 8.24 (d, J = 8.00 Hz, 1H), 7.80 (d, J = 8.80 Hz, 3H), 7.48 (t, J = 7.60 Hz, 1H), 7.30 (t, J = 7.60 Hz, 1H), 6.94 (d, J = 8.80 Hz, 2H), 4.53 (t, J = 7.20 Hz, 2H), 3.76 (s, 3H), 1.90 (q, J = 7.20 Hz, 2H), 1.34–1.30 (m, 2H), 0.90 (t, J = 7.60 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 160.73, 155.9, 141.14, 137.61, 132.31, 127.12, 122.93, 122.86, 122.37, 122.30, 114.17, 110.91, 55.63, 49.02, 31.99, 19.93, 14. IR STRECHING: (N-H) = 3279 Cm− 1, (C = O) = 1651 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H21N3O2 323.3960 + found 324.1711[M + H].
1-Butyl-N-(4-fluorophenyl)-1 H -indazol-3-carboxamide (8p). Appearance: Pale brown solid (yield = 84.3%, 180.5 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.34 (s, 1H), 8.25 (d, J = 8.00 Hz, 1H), 7.96–7.95 (m, 2H), 7.79 (d, J = 8.40 Hz, 1H), 7.48 (t, J = 7.20 Hz, 1H), 7.31 (t, J = 7.60 Hz, 1H), 7.20 (t, J = 9.20 Hz, 2H), 4.53 (t, J = 7.20 Hz, 2H), 1.89 (q, J = 7.20 Hz, 2H), 1.33–1.31 (m, 2H), 0.89 (t, J = 7.60 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 161.04, 159.9, 141.16, 137.36, 127.16, 123.05, 122.93, 122.7, 122.62, 122.24, 115.65, 115.43, 110.93, 49.07, 31.98, 19.91, 13.96. IR STRECHING: (N-H) = 3307 Cm− 1, (C = O) = 1663 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H18FN3O 311.3604 + found 312.1508[M + H].
1-Butyl-N-(2-methoxyphenyl)-1 H -indazol-3-carboxamide (8q). Appearance: Off white solid (yield = 79.8%, 177.5 mg). 1H NMR [400 MHz, DMSO-d6]: δ 9.44 (s, 1H), 8.40 (dd, J = 7.60, Hz, 1H), 8.26 (d, J = 8.00 Hz, 1H), 7.83 (d, J = 8.80 Hz, 1H), 7.52–7.52 (m, 1H), 7.34 (t, J = 7.60 Hz, 1H), 7.15–7.14 (m, 2H), 4.54 (t, J = 6.80 Hz, 2H), 3.94 (s, 3H), 1.88 (q, J = 7.20 Hz, 2H), 1.34–1.32 (m, 2H), 0.91 (t, J = 7.20 Hz, 3H).13C NMR [100 MHz, DMSO-d6]: d ppm 160.06, 148.68, 141.39, 136.9, 127.55, 127.37, 124.35, 123.41, 122.47, 122.07, 121.13, 119.71, 111.41, 111.17, 56.53, 48.99. 31.8,19.84, 13.88. IR STRECHING: (N-H) = 3307 Cm− 1, (C = O) = 1663 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H21N3O2 323.3960 + found 324.1713[M + H].
1-Butyl-N-(3-hydroxyphenyl)-1 H -indazol-3-carboxamide (8r). Appearance: Pale brown solid (yield = 66%, 140 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.05 (s, 1H), 9.43 (s, 1H), 8.23 (d, J = 8.40 Hz, 1H), 7.80 (d, J = 8.40 Hz, 1H), 7.50–7.50 (m, 2H), 7.31 (t, J = 7.60 Hz, 1H), 7.26 (d, J = 8.40 Hz, 1H), 7.13 (t, J = 8.40 Hz, 1H), 6.52 (dd, J = 1.60, 8.00 Hz, 1H), 4.53 (t, J = 6.80 Hz, 2H), 1.89 (q, J = 2.80 Hz, 2H), 1.33–1.31 (m, 2H), 0.90 (t, J = 7.20 Hz, 3H).13C NMR [100 MHz, DMSO-d6]: d ppm 160.95, 157.99, 141.16, 140.2, 137.53, 129.67, 127.18, 123.04, 122.86, 122.23, 111.56, 111.12, 110.95, 107.88, 49.04, 31.96, 19.91, 13.99. IR STRECHING: (N-H) = 3347 Cm− 1, (OH) = 3200 Cm− 1, (C = O) = 1703 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H19N3O2 309.3690 + found 310.1554[M + H].
1-Butyl-N-(4H-1,2,4-triazol-4yl)-1 H -indazol-3-carboxamide (8s). Appearance: Off white solid (yield = 89%, 174 mg). 1H NMR [400 MHz, DMSO-d6]: δ 12.12 (s, 1H), 8.80 (s, 2H), 8.14 (d, J = 8.00 Hz, 1H), 7.87 (d, J = 8.40 Hz, 1H), 7.52 (t, J = 7.20 Hz, 1H), 7.35 (t, J = 7.60 Hz, 1H), 4.57 (t, J = 7.20 Hz, 2H), 1.91 (q, J = 6.80 Hz, 2H), 1.32–1.31 (m, 2H), 0.91 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 161.53, 144.49, 140.98, 134.46, 127.48, 123.73, 123.01, 121.58, 111.27, 49.26, 31.89, 19.87, 13.99. IR STRECHING: (N-H) = 3112 Cm− 1, Cm− 1 (C = O) = 1695 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C14H16N6O 284.3230 + found 285.1460[M + H].
N-(2-amino-4-nitrophenyl)-1butyl-1 H -indazol-3-carbohydrazide (8t). Appearance: Brown solid (yield = 84.4%, 205 mg). 1H NMR [400 MHz, DMSO-d6]: δ 9.75 (s, 1H), 8.25 (s, 1H), 8.20 (d, J = 8.40 Hz, 1H), 7.93 (dd, J = 2.80, 9.00 Hz, 1H), 7.83 (d, J = 8.80 Hz, 1H), 7.49 (t, J = 8.00 Hz, 1H), 7.32 (t, J = 7.20 Hz, 1H), 6.85 (t, J = 8.80 Hz, 1H), 6.56 (s, 2H), 4.55 (t, J = 7.20 Hz, 2H), 1.92 (q, J = 7.20 Hz, 2H), 1.28–1.30 (m, 2H), 0.92 (t, J = 7.60 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d 161.70, 150.93, 141.11, 137.06, 136.05, 127.15, 123.77, 123.56, 123.07, 122.94, 121.19, 121.73, 114.58, 110.95, 49.07, 32.00, 19.95, 14.03. IR STRECHING: (N-H) = 3459 Cm− 1, (N-H) = 3327 Cm− 1, (C = O) = 1669 Cm− 1. (NO2) = 1623 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H19N5O3 353.3820 + found 354.1563[M + H].
1-Butyl-N-phenyl-1 H -indazol-3-carbohydrazide (8u). Appearance: Off white solid (yield = 99%, 140 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.14 (d, J = 2.40 Hz, 1H), 8.05 (d, J = 8.00 Hz, 1H), 7.82 (d, J = 2.80 Hz, 1H), 7.73 (d, J = 8.40 Hz, 1H), 7.40 (dt, J = 0.80, 10.80 Hz, 1H), 7.21 (t, J = 7.60 Hz, 1H), 7.08 (t, J = 8.00 Hz, 2H), 6.73 (d, J = 7.60 Hz, 2H), 6.64 (t, J = 7.20 Hz, 1H), 4.46 (t, J = 9.20 Hz, 2H), 1.83 (q, J = 7.20 Hz, 2H), 1.28–1.26 (m, 2H), 0.84 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 162.52, 150.06, 140.81, 136.30, 129.14, 127.07, 122.88, 122.86, 121.97, 118.88, 112.71, 110.89, 48.95, 31.90, 19.92, 14.02. IR STRECHING: (N-H) = 3233Cm− 1, (C = O) = 1645 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H20N4O 308.3850 + found 331.1558[M + Na].
1-Butyl-N-(2,4-dinitrophenyl)-1 H -indazol-3-carbohydrazide (8v). Appearance: Pale brown solid (yield = 18.3%, 50 mg). 1H NMR [400 MHz, DMSO-d6]: δ 11.03 (s, 1H), 10.30 (s, 1H), 8.91 (s, 1H), 8.34 (d, J = 8.40 Hz, 1H), 8.14 (d, J = 7.20 Hz, 1H), 7.86 (d, J = 7.60 Hz, 1H), 7.51 (s, 1H), 7.32 (s, 2H), 4.56 (s, 2H), 1.92 (s, 2H), 1.32 (d, J = 6.00 Hz, 2H), 0.926 (s, 3H). 13C NMR [100 MHz, DMSO-d6]: d 161.89, 149.34, 140.91, 137.14, 135.37, 130.64, 127.31, 123.64, 123.36, 123.02, 121.82, 116.22, 111.10, 49.14, 31.93, 19.91, 14.02. IR STRECHING: (N-H) = 3363 Cm− 1, (N-H) = 3331 Cm− 1, (C = O) = 1691 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H18N6O5 398.3790 + found 399.1414[M + H].
1-Butyl-N-(4-cyanophenyl)-1 H -indazol-3-carbohydrazide (8w). Appearance: Brown solid (yield = 87.3%, 200 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.46 (s, 1H), 8.79 (s, 1H), 8.12 (d, J = 8.00 Hz, 1H), 7.82 (d, J = 8.40 Hz, 1H), 7.56 (d, J = 8.40 Hz, 2H), 7.48 (t, J = 7.60 Hz, 1H), 7.29 (t, J = 7.60 Hz, 1H), 6.83 (d, J = 8.40 Hz, 2H), 4.53 (t, J = 7.20 Hz, 2H), 1.90 (q, J = 7.20 Hz, 2H), 1.26–1.28 (m, 2H), 0.00 (t, J = 7.60 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d 162.39, 153.62, 140.84, 135.87, 133.85, 127.16, 123.07, 122.93, 121.9, 120.58, 112.19, 99.15, 49.04, 31.90, 19.92, 14.01. IR STRECHING: (N-H) = 3343 Cm− 1, (N-H) = 3235 Cm− 1, (CN) = 2220 Cm− 1, (C = O) = 1679 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C19H19N5O 333.3950 + found 334.1668[M + H].
1-Butyl-N-(4-hydroxyphenyl)-1 H -indazol-3-carbohydrazide (8x). Appearance: Pale brown solid (yield = 60.5%, 135 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.19 (d, J = 9.60 Hz, 2H), 10.09 (s, 1H), 8.14 (d, J = 8.40 Hz, 3H), 7.82 (d, J = 8.40 Hz, 1H), 7.47 (t, J = 0.40 Hz, 1H), 7.30 (t, J = 7.20 Hz, 1H), 6.86 (d, J = 8.40 Hz, 2H), 4.52 (t, J = 7.20 Hz, 2H), 1.90 (q, J = 6.80 Hz, 2H), 1.26–1.26 (m, 2H), 0.91 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d 165.93, 161.90, 161.07, 140.84, 136.07, 129.98, 1247.09, 123.78, 122.99, 122.93, 121.96, 115.44, 110.93, 48.96, 31.89, 19.90, 14.00. IR STRECHING: (N-H) = 3359 Cm− 1, (OH) = 3204 Cm− 1, (C = O) = 1679 Cm− 1.HRMS (ESI) m/z: [M + H] calculated C19H20N4O3 352.3940 + found 353.1595[M + H].
N-(4-Bromophenyl)-1butyl-1 H -indazol-3-carbohydrazide (8y). Appearance: Brown solid (yield = 75.3%, 200 mg). 1H NMR [400 MHz, DMSO-d6]: 10.28 (s, 1H), 8.12 (s, 2H), 7.81 (d, J = 8.40 Hz, 1H), 7.47 (t, J = 8.00 Hz, 1H), 7.29 (t, J = 11.60 Hz, 3H), 6.74 (d, J = 8.40 Hz, 2H), 4.52 (t, J = 6.80 Hz, 2H), 1.90 (q, J = 6.80 Hz, 2H), 1.24–1.26 (m, 2H), 0.91 (t, J = 7.20 Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d 162.48, 149.45, 140.81, 136.12, 131.77, 127.10, 122.95, 121.93, 114.69, 110.91, 109.60, 48.98, 31.89, 19.91, 14.01. IR STRECHING: : (N-H) = 3343, 3231 Cm− 1, (C = O) = 1658 Cm− 1 HRMS (ESI) m/z: [M + H] calculated C18H19BrN4O2 386.2810 + found 409.0665[M + Na].
1-Butyl-N-(4-nitrophenyl)-1 H -indazol-3-carboxamide (8z). Appearance: Yellow solid (yield = 25.7%, 40 mg). 1H NMR [400 MHz, DMSO-d6]: δ 10.88 (s, 1H), 8.26 (q, J = 9.20 Hz, 5H), 7.86 (d, J = 8.40 Hz, 1H), 7.52 (t, J = 7.60 Hz, 1H), 7.36 (t, J = 7.20 Hz, 1H), 4.58 (t, J = 6.80 Hz, 2H), 1.92 (q, J = 7.60 Hz, 2H), 1.27–1.28 (m, 2H), 0.92 (t, J = 7.20 Hz, 3H), (t, J = Hz, 3H). 13C NMR [100 MHz, DMSO-d6]: d ppm 161.60, 145.67, 142.80, 141.25, 136.80, 127.39, 125.17, 123.04, 122.06, 120.39, 111.21, 49.25, 31.99, 19.92, 14.01. IR STRECHING: (N-H) = 3383 Cm− 1, (C = O) = 1712 Cm− 1. HRMS (ESI) m/z: [M + H] calculated C18H18N4O3 338.14 + found 361.1274[M + Na].