10.1002/cmdc.201800707
ChemMedChem
FULL PAPER
6-Methoxy-2-phenethyl-2H-indazole (3i). Yield: 90%; off white solid; 1H
NMR (600 MHz, CDCl3) δ 7.60 (d, J = 9.0 Hz, 1H), 7.55 (s, 1H), 7.26-
7.24 (m, 2H), 7.21 (d, J = 7.3 Hz, 1H) 7.08 (dd, J = 8.3, 1.5 Hz, 2H), 6.97
(dd, J = 9.0, 2.4 Hz, 1H), 6.80 (d, J = 2.4 Hz, 1H), 4.55 (t, J = 7.4 Hz, 2H),
3.79 (s, 3H), 3.27 (t, J = 7.4 Hz, 2H); 13C NMR (150 MHz, CDCl3) δ 154.9,
145.7, 137.9, 128.7, 128.6, 126.7, 122.04, 121.4, 120.5, 118.7, 96.6,
55.3, 54.9, 37.1; MS (GC-MS) 252; HRMS (EI, m/z) calcd for C16H16N2O:
m/z 252.1263; Found 252.1269.
crude compound, which was purified over silica gel column (60–120
mesh) using 5-10% ethyl acetate in hexane as eluent to obtain the
corresponding doubly substituted 2-aryl-2H-indazole 3 as the product.
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2-Phenyl-2H-indazole (3a). Yield: 95%; white solid; H NMR (400 MHz,
CDCl3) δ 8.29 (s, 1H), 7.80 (d, J = 8.6 Hz, 2H), 7.71 (d, J = 8.8 Hz, 1H),
7.60 (d, J = 8.6 Hz, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.29 (t, J = 7.1 Hz, 1H),
7.23 (t, J = 7.5 Hz, 1H) 7.02 (t, J = 7.16 Hz, 1H); 13C NMR (100MHz,
CDCl3) δ 149.8,140.5, 129.6, 128.1, 127.9, 126.8, 122.8, 122.4, 121.0,
120.4, 117.6; MS (GC-MS) 194; HRMS (EI, m/z) calcd for C13H10N3: m/z
194.0844; Found 194.0846.
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6-Methoxy-2-(p-tolyl)-2H-indazole (3j). Yield: 94%; pale white solid; H
2-(4-Methoxyphenyl)-2H-indazole (3b). Yield: 92%; white solid; 1H
NMR (300 MHz, CDCl3) δ 8.33 (d, J = 1.0 Hz, 1H), 7.84-7.79 (m, 3H),
7.71 (dd, J = 8.4, 1.0 Hz, 1H), 7.37-7.34 (m, 1H), 7.15-7.10 (m, 1H), 7.04
(dd, J = 6.9, 2.0 Hz, 2H), 3.86 (s, 3H); 13C NMR (75MHz, CDCl3) δ 159.7,
149.8, 134.5, 126.9, 122.9, 122.8, 122.6, 120.8, 120.7, 118.1, 115.0,
56.0; MS (GC-MS) 224; HRMS (EI, m/z) calcd for C14H12N2O: m/z
224.0950; Found 224.0951.
NMR (600 MHz, CDCl3) δ 8.17 (s,1H), 7.70 (d, J = 8.3 Hz, 2H), 7.66 (dd,
J = 9.0, 0.7 Hz, 1H), 7.25 (dd, J = 8.3, 0.7 Hz, 2H), 7.01 (dt, J =7.3, 2.3
Hz, 1H), 6.84 (d, J = 2.3 Hz, 1H), 3.81 (s, 3H), 2.38 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 155.4,146.5, 138.3, 137.4, 129.9, 122.6, 121.7,
128.4, 119.2, 119.1, 96.3, 55.3, 20.9; MS (GC-MS) 252; HRMS (EI, m/z)
calcd for C15H14N2O: m/z 238.1106; Found 238.1115.
6-Fluoro-2-phenyl-2H-indazole (3c). Yield: 84%; pale brown solid; 1H
NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 7.86 (d, J = 7.6 Hz, 2H), 7.69 (dd,
J = 8.8, 5.2 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.43-7.35 (m, 2H), 6.93 (dt,
J = 9.0, 0.8 Hz, 1H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.2 (d,
JCF = 242 Hz, 1C), 149.5, 140.3, 129.6, 128.0, 122.3, 122.1. 120.8, 120.4,
114.5 (d, JCF = 29 Hz, 1C), 101.1 (d, JCF = 23.7 Hz, 1C); MS (GC-MS)
212; HRMS (EI, m/z) calcd for C13H9FN2: m/z 212.0750; Found 212.0748.
6-Methoxy-2-(4-methoxyphenyl)-2H-indazole (3k). Yield: 94%; pale
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white solid; H NMR (600 MHz, CDCl3) δ 8.12 (s, 1H), 7.72 (dd, J = 6.9,
2.2 Hz, 2H), 7.65 (d, J = 9.2 Hz, 1H), 6.99 (dd, J = 9.2, 2.2 Hz, 1H),
6.85(d, J = 2.2 Hz, 1H), 6.97 (dd, J = 6.9, 2.2 Hz, 2H), 3.82 (s, 3H), 3.81
(s, 3H); 13C NMR (150 MHz, CDCl3) δ 158.9, 155.4, 146.4, 134.2, 122.6,
121.9, 121.5, 119.2, 119.1, 114.5, 96.3, 55.5, 55.3; MS (GC-MS) 254;
HRMS (EI, m/z) calcd for C15H14N2O2: m/z 254.1054; Found 254.1057.
2-(p-Tolyl)-2H-indazole (3d). Yield: 93%; white solid; 1H NMR (400 MHz,
CDCl3) δ 8.36 (s, 1H), 7.78 (t, J = 8.6 Hz, 2H). 7.70 (d, J = 8.5 Hz, 1H),
7.33 (t, J = 8.4Hz, 3H), 7.11 (t, J = 8.0 Hz, 1H), 2.42 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 149.6, 1.8.2, 137.9, 130.0, 126.6, 122.3, 120.9,
120.8, 120.4, 120.3, 117.8, 21.1; MS (GC-MS) 208; HRMS (EI, m/z)
calcd for C14H12N2: m/z 208.1000; Found 208.0996.
6-Methyl-2-(p-tolyl)-2H-indazole (3l). Yield: 95%; pale yellow solid; 1H
NMR (600 MHz, CDCl3) δ 8.26 (s, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.55 (d,
J = 8.3 Hz, 2H), 7.52 (s, 1H), 7.26 (dd, J = 8.0, 0.7 Hz, 2H), 6.93 (d, J =
8.3 Hz, 1H), 2.45 (s, 3H), 2.39 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
150.2, 138.3, 137.5, 136.5, 129.9, 125.2, 121.0, 120.6, 120.0,119.8,
116.1, 22.2, 20.9; MS (GC-MS) 222; HRMS (EI, m/z) calcd for C15H14N2:
m/z 222.1157; Found 222.1154.
6-Fluoro-2-(p-tolyl)-2H-indazole (3e). Yield: 86%; pale brown solid; 1H
NMR (400 MHz, CDCl3) δ 8.34 (d, J = 0.9 Hz, 1H), 7.72 (dd, J = 6.6, 2.0
Hz, 2H), 7.65 (d, J = 0.6 Hz, 1H), 7.30-7.23 (m, 2H), 6.90 (d, J = 2.0 Hz,
1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.8 (d, JCF = 243 Hz,
1C), 149.6, 138.1, 129.9 (t, JCF = 31.3 Hz, 1C), 122.2 (d, JCF = 31.3 Hz,
1C), 120.7, 114.2 9 (t, JCF = 28.5 Hz, 1C), 101.1 (d, JCF = 23.76 Hz, 1C),
21.0; MS (GC-MS) 226; HRMS (EI, m/z) calcd for C14H11FN2: m/z
226.0906; Found 226.0903.
2-(4-Methoxyphenyl)-6-methyl-2H-indazole (3m). Yield: 95%; off white
solid; 1H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 1.0 Hz, 1H), 7.74 (dd, J =
6.9, 2.2 Hz, 2H), 7.54 (d, J = 8.6 Hz, 1H), 7.51(dd, J = 2.2, 0.9Hz, 1H)
6.97(dd, J = 6.9, 2.2Hz, 2H), 6.92 (dd, J = 8.6, 1.0 Hz, 1H), 3.82 (s, 3H),
2.45 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 159.1, 150.2, 136.4, 134.1,
125.1, 122.2, 121.0,120.0, 119.7,116.0, 114.5, 55.5, 22.2; MS (GC-MS)
238; HRMS (EI, m/z) calcd for C15H14N2O: m/z 238.1106; Found
238.1105.
2-Phenethyl-2H-indazole (3f). Yield: 88%; pale white solid; 1H NMR
(400 MHz, CDCl3) δ 7.75 (dd, J = 8.6, 1.2 Hz, 1H), 7.69 (s, 1H), 7.59 (dd,
J = 8.6, 1.0 Hz, 2H), 7.32-7.24 (m, 4H), 7.10 -7.05 (m, 3H), 4.42 (t, J =
7.6 Hz, 2H), 3.32 (t, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 148.9,
137.7, 128.6, 128.5, 126.7, 125.8, 127.9, 121.5, 120.0, 117.3, 55.1, 37.0;
MS (GC-MS) 222; HRMS (EI, m/z) calcd for C15H14N2: m/z 222.1157;
Found 222.1160.
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6-Methoxy-2-phenyl-2H-indazole (3g). Yield: 92%; white solid; H NMR
(600 MHz, CDCl3) δ 8.24 (s, 1H), 7.84 (dd, J = 7.6, 1.0 Hz, 2H) 7.65 (dd,
J = 8.4, 1.0 Hz, 1H) 7.48 (dd, J = 7.4, 1.0 Hz, 1H), 7.36-7.34 (m, 1H),
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2-(4-Isopropylphenyl)-2H-indazole (3n). Yield: 94%; off white solid; H
NMR (600 MHz, CDCl3) δ 8.34 (d, J = 1.0 Hz, 1H), 7.80-7.77 (m, 3H),
7.68 (dd, J = 8.5, 0.9 Hz, 1H), 7.35 (dd, J = 1.7, 2.0 Hz, 2H), 7.31-7.29
(m, 2H), 7.10-7.08 (m, 1H), 2.97 (quart, J = 7.8 Hz, 1H), 1.29 (s, 3H),
7.01 (dd, J = 9.0, 2.1 Hz, 1H), 6.87 (d, J = 2.1 Hz, 1H), 3.83 (s, 3H); 13
C
NMR (150 MHz, CDCl3) δ 155.5, 146.7, 140.6, 129.5,127.5, 122.8, 122.0,
120.6, 119.3, 119.2, 96.3, 55.3; MS (GC-MS) 224; HRMS (EI, m/z) calcd
for C14H12N2O: m/z 224.0950; Found 224.0947.
1.27 (s, 3H); 13C NMR (150 MHz, CDCl3)
δ 149.6,148.8, 138.5,
127.5,126.6,122.7, 122.3, 120.9, 120.3, 120.3, 117.9, 33.7, 23.9; MS
(GC-MS) 236; HRMS (EI, m/z) calcd for C16H16N2: m/z 236.1313; Found
236.1312.
6-Methyl-2-phenyl-2H-indazole (3h). Yield: 95%; white solid; 1H NMR
(600 MHz, CDCl3) δ 8.31 (d, J = 8.8 Hz, 1H), 7.87 (t, J = 1.0 Hz, 1H),
7.85 (dd, J = 1.2, 0.8 Hz, 1H), 7.57 (d, J = 8.6 Hz, 1H), 7.51-7.48 (m, 3H),
7.36 (t, J = 7.3 Hz, 1H), 6.93 (dd, J = 8.6, 1.2 Hz, 1H), 2.45 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 150.4, 140.6, 1368, 129.5, 127.6, 125.5, 121.2,
120.8, 120.2, 119.9, 116.2, 22.3; MS (GC-MS) 208; HRMS (EI, m/z)
calcd for C14H12N2: m/z 208.1000; Found 208.1002.
2-(3,4-dimethoxyphenyl)-2H-indazole (3o). Yield: 93%; white solid; 1H
NMR (600 MHz, CDCl3) δ 8.22 (s, 1H), 7.74 (d, J = 8.8, Hz, 1H), 7.60 (d,
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