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1226, 1072, 1005, 948, 793 and 724 cmꢁ1; HRMS (ESIꢁ), calcu- 3 h at room temperature. The resulting mixture was extracted
lated for C15H11N2O2 [M ꢁ H]ꢁ m/z 251.0821, found: 251.0817. with EtOAc three times, washed three times with water, then
with brine, dried over MgSO4 and concentrated under reduced
pressure. The product was puried by column chromatography
on silica gel, eluting with CH2Cl2/EtOAc, 9 : 1 to provide the
pure compound as a white solid (203 mg, 78%). Silica gel TLC Rf
1-(1H-indazol-3-yl)ethanone (19b)
The general procedure was used starting from (262 mg, 2 mmol)
of 3-methyl-indole 19a. Aer addition, the reaction was stirred
1
0.26 (petroleum ether/EtOAc, 3 : 2); mp 181 ꢀC; H NMR (300
ꢀ
48 h at 50 C. The resulting mixture was extracted with EtOAc
MHz, acetone-d6) d 13.06 (brs, 1H), 10.21 (s, 1H), 8.56 (br, 1NH),
8.53 (s, 1H), 7.64 (s, 2H), 1.50 (s, 9H); 13C NMR (75 MHz,
acetone-d6) d 187.5, 153.9, 145.0, 139.0, 137.0, 122.1, 121.6,
111.8, 109.6, 80.1, 28.5; IR (neat) n ¼ 3337, 2989, 1698, 1666,
1534, 1504, 1426, 1324, 1242, 1169, 1050, 908, 852, 813, 797, 723
and 641 cmꢁ1; HRMS (ESIꢁ), calculated for C13H14N3O3 [M ꢁ
H]ꢁ m/z 260.1035, found: 260.1027.
three times, washed three times with water, then with brine,
dried over MgSO4 and concentrated under reduced pressure.
The resulting crude mixture was puried by column chroma-
tography on silica gel, eluting with petroleum ether/EtOAc, 8 : 2
to provide the pure compound as a brown solid (118 mg, 37%).
Silica gel TLC Rf 0.45 (petroleum ether/EtOAc, 3 : 2); mp 172 ꢀC;
1H NMR (300 MHz, acetone-d6) d 12.84 (brs, 1H), 8.29 (dt, J ¼
8.0, 1.0 Hz, 1H), 7.68 (dt, J ¼ 8.5, 1.0 Hz, 1H), 7.44 (ddd, J ¼ 8.5,
7.0, 1.0 Hz, 1H), 7.31 (ddd, J ¼ 8.0, 7.0, 1.0 Hz, 1H), 2.66 (s, 3H);
5-Piperidyl-1H-indazole-3-carboxaldehyde (23b)
13C NMR (75 MHz, acetone-d6) d 195.0, 144.5, 142.5, 127.7, The general procedure was used starting from (200 mg, 1 mmol)
124.0, 122.8, 122.4, 111.4, 26.7; IR (neat) n ¼ 3212, 3191, 1653, of 5-piperidyl-indole 23a. Aer addition, the reaction was stirred
1448, 1342, 1210, 1156, 954, 750 and 610 cmꢁ1; HRMS (ESIꢁ), 3 h at room temperature. The resulting mixture was extracted
calculated for C9H7N2O [M ꢁ H]ꢁ m/z 159.0558, found: with EtOAc three times, washed three times with water, then
159.0556.
with brine, dried over MgSO4 and concentrated under reduced
pressure. The product was puried by column chromatography
on silica gel, eluting with CH2Cl2 to provide the pure compound
as a yellow solid (34 mg, 15%). Silica gel TLC Rf 0.23 (petroleum
ether/EtOAc, 3 : 2); mp 75 ꢀC; 1H NMR (300 MHz, CDCl3) d 11.41
(brs, 1H), 10.27 (s, 1H), 7.66 (d, J ¼ 2.0 Hz, 1H), 7.39 (d, J ¼
9.0 Hz, 1H), 7.26 (dd, J ¼ 9.0, 2.0 Hz, 1H), 3.17 (m, 4H), 1.76 (m,
4H), 1.58 (m, 2H); 13C NMR (75 MHz, CDCl3) d 187.6, 150.4,
144.2, 137.0, 122.8, 122.5, 110.8, 106.1, 52.3, 26.1, 24.3; IR (neat)
n ¼ 2927, 2852, 1666, 1495, 1465, 1451, 1213, 1079, 949, 791 and
708 cmꢁ1; HRMS (ESIꢁ), calculated for C13H14N3O [M ꢁ H]ꢁ m/z
228.1137, found: 228.1129.
7-Methyl-1H-indazole-3-carboxaldehyde (20b)
The general procedure was used starting from (262 mg, 2 mmol)
of 7-methyl-indole 20a. Aer addition, the reaction was stirred
12 h at room temperature. The resulting mixture was extracted
with EtOAc three times, washed three times with water, then
with brine, dried over MgSO4 and concentrated under reduced
pressure. The resulting crude mixture was puried by column
chromatography on silica gel, eluting with petroleum ether/
EtOAc 8 : 2 to provide the pure compound as a yellowish solid
(229 mg, 72%). Silica gel TLC Rf 0.45 (petroleum ether/EtOAc,
1
3 : 2); mp 172 ꢀC; H NMR (300 MHz, CDCl3) d 10.31 (s, 1H),
8.14 (m, 1H), 7.28 (m, 2H), 2.62 (s, 3H); 13C NMR (75 MHz,
1H-indazole-3,5-dicarboxaldehyde (24b)
CDCl3) d 187.7, 145.3, 141.5, 128.2, 124.7, 120.9, 120.2, 119.5, The general procedure was modied. To a solution of NaNO2
16.8; IR (neat) n ¼ 3252, 3077, 1672, 1449, 1326, 1144, 784 and (550 mg, 8 mmol,ꢀ8 equiv.) in 1.6 mL of deionized water and
734 cmꢁ1; HRMS (ESIꢁ), calculated for C9H7N2O [M ꢁ H]ꢁ m/z 3 mL of DMF at 0 C was added slowly HCl (3.5 mL of 2 N aq.,
159.0558, found: 159.0549.
7 mmol, 7 equiv.). Aer 10 min at this temperature, a solution of
indole-5-carbaldehyde 24a (145 mg, 1 mmol, 1 equiv.) in DMF (3
mL) was then added at room temperature over a period of 2
hours using a syringe pump. Aer addition, the reaction was
stirred 2 h at room temperature, then 16 h at 50 ꢀC. The
resulting mixture was extracted with EtOAc three times, washed
three times with water, then with brine, dried over MgSO4 and
concentrated under reduced pressure. The resulting crude
mixture was puried by column chromatography on silica gel,
eluting with petroleum ether/EtOAc, 8 : 2 to provide the pure
compound as a white solid (127 mg, 73%). Silica gel TLC Rf 0.28
(petroleum ether/EtOAc, 3 : 2); mp 242 C; H NMR (300 MHz,
DMSO-d6) d 14.47 (brs, 1H), 10.22 (s, 1H), 10.09 (s, 1H), 8.68 (d, J
¼ 1.5 Hz, 1H), 7.92 (dd, J ¼ 8.5, 1.5 Hz, 1H), 7.80 (d, J ¼ 8.5 Hz,
1H); 13C NMR (75 MHz, DMSO-d6) d 192.6, 187.4, 144.8, 143.4,
132.5, 126.6, 125.6, 120.0, 112.1; IR (neat) n ¼ 3268, 1672, 1616,
1323, 1189, 1151, 1062, 836 and 793 cmꢁ1; HRMS (ESIꢁ),
5-Carboxy-1H-indazole-3-carboxaldehyde (21b)
The general procedure was used starting from (483 mg, 3 mmol)
of 5-carboxy-indole 21a. Aer addition, the reaction was stirred
2 h at 50 ꢀC. The product was puried by centrifugation to
provide (236 mg, 62%) of a white solid. Silica gel TLC Rf 0.21
(EtOAc); mp > 260 ꢀC; 1H NMR (300 MHz, DMSO-d6) d 14.63 (brs,
1H), 13.05 (br, 1H), 10.19 (s, 1H), 8.72 (s, 1H), 8.00 (d, J ¼
9.5, Hz, 1H), 7.76 (d, J ¼ 9.5, 1H); 13C NMR (75 MHz, DMSO-d6)
d 187.5, 167.2, 144.3, 142.9, 127.8, 126.4, 123.3, 120.0, 111.3; IR
(neat) n ¼ 3234, 2787, 1702, 1682, 1416, 1278, 1235, 829, 802,
and 743 cmꢁ1; HRMS (ESIꢁ), calculated for C9H4N2O3 [M ꢁ H]ꢁ
m/z 189.0300, found: 189.0296.
1
ꢀ
5-NHBoc-1H-indazole-3-carbaldehyde (22b)
The general procedure was used starting from (232 mg, 1 mmol) calculated for C9H5N2O2 [M ꢁ H]ꢁ m/z 173.0351, found:
of 5-NHBoc-indole 22a. Aer addition, the reaction was stirred 173.0346.
13126 | RSC Adv., 2018, 8, 13121–13128
This journal is © The Royal Society of Chemistry 2018