Vol. 26, No. 22 (2014)
Synthesis of Novel N-Aryl-1H-indazolamines from Amino-1H-indazoles and Arylboronic Acids 7541
N-5-(4-Methylphenyl)-1H-5-indazolamine (1e):Yield:
The residue was dissolved in water and acidified with conc.
HCl and product was filtered and washed with water followed
by methanol to give desired compound 8. Yield: 91 %; Light
9
ν
4 %; Light brown color solid; m.p.: 188-193 °C; IR (KBr,
-1
1
max, cm ): 3329, 2992, 2643, 1644, 1512, 1081; H NMR
300 MHz, DMSO-d ): δ 7.94 (s, 1H, Ar-H), 7.44 (d, 1H, J =
.85 Hz, Ar-H), 7.35 (d, 1H, J = 1.50 Hz, Ar-H), 7.15 (dd, 1H,
1
(
8
6
yellow colour solid; m.p.: > 225 °C; H NMR (300 MHz,
CDCl ): δ 8.58 (s, 1H, -NH-), 7.97 (s, 1H, Ar-H), 7.73 (d, 2H,
3
J = 2.01, 6.84 Hz, Ar-H), 7 (dd, 4H, J = 8.37, 13.62 Hz, Ar-
J = 8.70 Hz, Ar-H), 7.50 (dd, 2H, J = 3.60, 1.80 Hz, Ar-H),
7.17 (dd, 1H, J = 1.80, 7.20 Hz, Ar-H), 6.89 (d, 2H, J = 8.70
Hz, Ar-H); ESI-MS: m/z 254 [M + H] .
13
H), 2.18 (s, 3H, -CH
3
); C NMR (75 MHz, DMSO-d ): δ
6
+
1
41.70, 137.26, 136.64, 132.07, 130.00, 129.50, 123.28, 122.45,
+
117.58, 111.64, 106.68, 20.63; ESI-MS: m/z 224 [M + H] .
Typical procedure for amide formation 9a-c: The com-
pound 8 (10 mmol) and amine (11) (20 mmol) were dissolved
in dimethyl sulfoxide at room temperature and followed by
the addition of N,N-diisopropylethylamine (40 mmol) and
TBTU (13.5 mmol) under stirring and reaction mixture was
kept as such for 3 to 6 h at room temperature.After completion
of the reaction as indicated by TLC, water was added. Product
was extracted into ethyl acetate and organic layer was washed
with water, brine and dried over anhydrous sodium sulfate.
Organic layer was concentrated in vacuo to get residue. The
residue was chromatographed on a silica gel column and eluted
with a mixture of ethyl acetate: hexane (1:9) to afford desired
compound 9a-c.
N-5-(4-Methoxyphenyl)-1H-5-indazolamine (1f):Yield:
8
4 %; Light brown colour solid; m.p.: 142-149 °C; IR (KBr,
-1
1
ν
max, cm ): 3394, 2634, 1605, 1509, 1026; H NMR (300 MHz,
): δ 7.95 (s, 1H, Ar-H), 7.44 (d, 1H, J = 8.82 Hz, Ar-
H), 7.32 (s, 1H, Ar-H), 7.15-7.05 (m, 3H, Ar-H), 6.85 (d, 2H, J =
DMSO-d
6
13
8.85 Hz,Ar-H), 3.68 (s, 3H, -CH
3
); C NMR (75 MHz, DMSO-d ):
6
δ 155.97, 137.15, 136.71, 135.28, 132.24, 122.96, 122.30, 121.77,
+
1
15.15, 112.01, 107.75, 55.73; ESI-MS: m/z 240 [M + H] .
N-6-Phenyl-1H-6-indazolamine (1g): Yield: 95 %;
-1
Brown colour solid; m.p.: 175-181 °C; IR (KBr, νmax, cm ):
1
3
d
270, 2782, 1643, 1598, 1026; H NMR (300 MHz, DMSO-
): δ 8.15 (s, 1H, Ar-H), 7.63 (d, 1H, J = 8.79 Hz,Ar-H), 7.28
6
(
7
t, 2H, J = 8.37 Hz, Ar-H), 7.16 (t, 2H, J = 7.50 Hz, Ar-H),
N-1-Benzyl-4-(1H-5-indazolylamino)benzamide (9a):
Yield: 76 %; Cream colour solid; m.p.: 160-165 °C; IR (KBr,
13
.06 (d, 1H, J = 0.39 Hz, Ar-H), 6.96-6.89 (m, 2H, Ar-H); C
): δ 143.09, 142.34, 141.77, 131.07,
29.63, 122.80, 121.90, 119.38, 117.06, 115.64, 91.22; ESI-
-1
NMR (75 MHz, DMSO-d
1
MS: m/z 210 [M + H] .
6
ν
max, cm ): 3295, 3063, 2631, 1606, 1557, 1525, 1365, 798;
1
H NMR (300 MHz, CDCl ): δ 8.69 (t, 1H, J = 5, 40 Hz, Ar-
3
+
H), 7.95 (d, 1H, J = 0.90 Hz, Ar-H), 7.43 (d, 2H, J = 8.70 Hz,
N-6-(4-Methylphenyl)-1H-6-indazolamine (1h):Yield:
Ar-H), 7.48 (t, 2H, J = 8.70 Hz, Ar-H), 7.15-7.29 (m, 5H, Ar-H),
-1
13
8
3
8
9 %; White color solid; m.p.: 217-221 °C; IR (KBr, νmax, cm ):
6.91 (d, 2H, J = 9 Hz,Ar-H), 4.43 (d, 2H, J = 6 Hz, -CH
NMR (75 MHz, CDCl
2
-); C
1
292, 2911, 2693, 1640, 805; H NMR (300 MHz, CDCl
3
): δ
3
): δ 166.30, 148.54, 140.54, 137.08,
.22 (dd, 1H, J = 8.7, 1.83 Hz, Ar-H), 7.90 (s, 1H,Ar-H), 7.55
135.53, 132.53, 129.23, 128.53, 127.51, 126.91, 123.91, 123.38,
113.63, 111.61, 109.74, 42.79; ESI-MS: m/z 343 [M + H] .
N-1-(4-Methoxybenzyl)-4-(1H-5-indazolylamino)-
+
(
d, 1H, J = 8.76 Hz, Ar-H), 7.02-7.09 (m, 4H, Ar-H), 6.97 (d,
13
1
H, J = 0.75 Hz, Ar-H), 2.22 (s, 3H, -CH
): δ 145.40, 141.89, 140.12, 132.12, 130.60,
30.06, 122.18, 119.57, 116.25, 115.68, 91.32, 20.72; ESI-MS:
3
); C NMR (75
MHz, DMSO-d
1
6
benzamide (9b):Yield: 84 %; Brown colour solid; m.p.: 148-
-1
153 °C; IR (KBr, νmax, cm ): 3287, 3094, 2925, 1604, 1508,
+
1
m/z 224 [M + H] .
764; H NMR (300 MHz, CDCl ): δ 12.94 (s, 1H, -NH-), 8.61
3
N-6-(4-Methoxyphenyl)-1H-6-indazolamine (1i):Yield:
(t, 1H, J = 5.70 Hz, 6 Hz, Ar-H), 8.39 (s, 1H, Ar-H), 7.95 (s,
1H, Ar-H), 7.70 (d, 2H, J = 8.70 Hz, Ar-H), 7.47 (d, 2H, J =
8.70 Hz, Ar-H), 7.15-7.21 (m, 3H, Ar-H), 6.82-6.93 (m, 3H,
-1
9
3
1 %; brown colour solid; m.p.: > 225 °C; IR (KBr, νmax, cm ):
1
274, 3121, 1641, 1592, 1023; H NMR (300 MHz, DMSO-d ):
6
13
δ 8.04 (s, 1H, Ar-H), 7.55 (d, 1H, J = 9.54 Hz, Ar-H), 7.12
dd, 2H, J = 2.22, 4.47 Hz, Ar-H), 6.91 (dd, 2H, J = 2.22, 4.53
Hz, Ar-H), 6.80 (t, 2H, J = 7.92 Hz, Ar-H), 3.71 (s, 3H, -CH );
): δ 155.57, 148.25, 142.03,
34.57, 130.68, 123.17, 122.96, 116.92, 115.02, 88.86, 55.62;
Ar-H), 4.35 (d, 3.69 (s, 3H, -CH
3
); C NMR (75 MHz, CDCl ):
3
(
δ 166.42, 158.43, 148.74, 134.98, 132.92, 132.28, 129.02,
128.75, 123.77, 123.64, 122.68, 113.72, 113.31, 111.02,
110.44, 55.19, 42.38; IR ESI-MS: m/z 373 [M + H]+.
N-1-(4-Fluorobenzyl)-4-(1H-5-indazolylamino)-
benzamide (9c): Yield: 68 %; White powder; m.p.: 208-215
3
13
C NMR (75 MHz, DMSO-d
6
1
+
ESI-MS: m/z 240 [M + H] .
-1
Ethyl-4-(1H-5-indazolylamino)benzoate (7): Yield:
°C; IR (KBr, νmax, cm ): 3297, 3064, 2633, 1607, 1528, 1366,
1
9
0 %; Light brown colour solid; 111-115 °C; IR (KBr, νmax
,
799; H NMR (300 MHz, CDCl ): δ 8.77 (br, 3H, -NH-), 8 (d,
3
-1
1
cm ): 3349, 3070, 2926, 2559, 1678, 1596, 1284, 773; H
NMR (300 MHz, DMSO-d ): δ 7.97 (d, 1H, J = 0.93 Hz),
.73 (dd, 2H, J = 1.89, 5.07 Hz), 7.49-7.52 (m, 2H), 7.17 (dd,
H, J = 1.86, 7.02 Hz), 6.93 (dd, 2H, J = 1.89, 5.04 Hz), 4.21
1H, J = 0.60 Hz, Ar-H), 7.75 (d, 2H, J = 8.70 Hz, Ar-H), 7.49
(dd, 2H, J = 8.70, 0.60 Hz, Ar-H), 7.29-7.33 (m, 2H, Ar-H),
7.20 (dd, 1H, J = 2.10, 6.90 Hz, Ar-H), 7.07-7.13 (m, 2H, Ar-
6
7
1
(
H), 6.95 (d, 2H, J = 8.70 Hz, Ar-H), 4.39 (d, 2H, J = 4,20 Hz,
13
13
q, 2H, J = 7.08 Hz), 1.25 (t, 3H, J = 7.11 Hz); C NMR (75
MHz, DMSO-d ): δ 14.69, 60.10, 111.39, 111.49, 113.24,
18.71, 123.29, 123.58, 131.38, 133.06, 134.40, 137.46,
-CH
2
-); C NMR (75 MHz, CDCl
3
): δ 166.31, 163, 159.80,
6
148.29, 136.91, 136.72, 136.68, 135.93, 132.01, 129.54,
129.43, 129.25, 123.98, 123.13, 115.34, 115.06, 113.84,
1
1
+
+
50.51, 165.99; ESI-MS: m/z 282 [M + H] .
111.81, 109.31, 42.13; ESI-MS: m/z 361 [M + H] .
Typical procedure for ester hydrolysis (8): The com-
pound 7 (2.6 mmol) and lithium hydroxide monohydrate (3.9
RESULTS AND DISCUSSION
mmol) in THF (10 mL) and water (0.5 mL) was refluxed for
Here in we report the synthesis, starting from 1H-indazole
of several indazole derivatives substituted at the 4 , 5 and 6
positions with substituted phenyl groups. Nitroindazole
th
th
th
2
h. After completion of the reaction, as indicated by TLC,
the reaction mixture was concentrated in vacuo to get residue.