10.1002/ejoc.202100827
European Journal of Organic Chemistry
FULL PAPER
1H), 3.48 (dq, J = 10.8, 7.1 Hz, 1H), 2.59 (s, 3H), 1.79 (h, J = 7.5 Hz, 2H),
1.00 (dt, J = 13.7, 7.3 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 165.83,
152.00, 148.51, 148.16, 144.21, 140.72, 134.02, 131.54, 124.80, 122.45,
115.01, 112.00, 111.06, 105.34, 59.92, 45.14, 23.22, 14.23, 12.14, 11.55.
HRMS (ESI+): m/z calculated for C20H21ClN2O3 [M+H]+: 373.1313, found
373.1310. IR: 3323, 2958, 2935, 2872, 1644, 1586, 1574, 1556, 1518,
1477, 1454, 1422, 1396, 1374, 1356, 1332, 1300, 1290, 1271, 1244, 1228,
1206, 1183, 1163, 1147, 1121, 1082, 1050, 1036, 1009, 966, 928, 903,
890, 862, 814, 790, 759, 752, 731, 701 cm-1.
General procedures for the synthesis of cyclized adduct (14 and 15):
To a solution of 13a (189 mg, 0.57 mmol) in anhydrous DMF (2 ml) was
added potassium carbonate (192 mg, 1.71 mmol) and the mixture was
refluxed at 130 ºC for 2 h. After completion of the reaction, the reaction
mixture was extracted with ethyl acetate. The combined organic extracts
were dried over anhydrous MgSO4, then filtered and concentrated under
reduced pressure to give crude product. Finally, the crude product was
purified by column chromatography to give the desired product.
Ethyl
2-methyl-1H-pyrido[3',2':4,5]furo[2,3-f]indole-3-carboxylate
Ethyl
1-benzyl-6-(2-chloropyridin-3-yl)-5-hydroxy-2-methyl-1H-
(14a): Yellow solid (140 mg, 83%). Mp 260 – 262 °C; 1H NMR (400 MHz,
DMSO) δ 12.14 (s, 1H), 8.61 (dd, J = 7.5, 1.8 Hz, 1H), 8.36 (dd, J = 4.9,
1.7 Hz, 1H), 8.11 (d, J = 0.8 Hz, 1H), 8.10 (s, 1H), 7.43 (dd, J = 7.6, 4.9
indole-3-carboxylate (13c): Yellow solid (50 mg, 11%). Mp 185 – 187 °C;
1H NMR (400 MHz, CDCl3) δ 8.38 (dd, J = 4.8, 2.0 Hz, 1H), 7.81 (s, 1H),
7.72 (dd, J = 7.5, 2.0 Hz, 1H), 7.31 – 7.25 (m, 4H), 7.07 (s, 1H), 6.98 (d, J
= 7.8 Hz, 2H), 5.32 (s, 2H), 4.40 (q, J = 7.1 Hz, 2H), 2.72 (s, 3H), 1.43 (t,
J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 166.24, 151.38, 148.84,
148.67, 146.65, 141.20, 136.21, 134.18, 131.50, 129.14, 128.44, 127.90,
126.03, 122.38, 120.72, 111.61, 107.55, 104.30, 59.85, 46.92, 14.79,
12.34. HRMS (ESI+): m/z calculated for C24H21ClN2O3 [M+H]+: 421.1313,
found 421.1307. IR: 3246, 2969, 2920, 2849, 1735, 1694, 1627, 1581,
1562, 1527, 1495, 1449, 1395, 1377, 1357, 1322, 1298, 1221, 1201, 1176,
1124, 1092, 1077, 1051, 1017, 1009, 989, 924, 894, 881, 868, 856, 802,
795, 777, 750, 730, 716, 695 cm-1.
Hz, 1H), 4.32 (q, J = 7.1 Hz, 2H), 2.72 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H). 13
C
NMR (101 MHz, DMSO) δ 164.85, 163.02, 150.11, 147.35, 145.27, 132.04,
129.95, 127.90, 119.16, 117.32, 117.27, 103.78, 102.98, 101.54, 58.97,
14.48, 14.08. HRMS (ESI+): m/z calculated for C17H14N2O3 [M+H]+:
295.1077, found 295.1074. IR: 3200, 3066, 2976, 2924, 2851, 1680, 1645,
1599, 1583, 1544, 1511, 1480, 1468, 1455, 1433, 1403, 1384, 1324, 1298,
1255, 1235, 1207, 1186, 1159, 1130, 1116, 1109, 1082, 1036, 999, 980,
922, 882, 856, 834, 811, 794, 783, 772, 755, 741, 698, 663, 622, 583 cm-
1
.
Ethyl
2-methyl-3H-pyrido[3',2':4,5]furo[3,2-e]indole-1-carboxylate
Ethyl
1-benzyl-4-(2-chloropyridin-3-yl)-5-hydroxy-2-methyl-1H-
(15a): White solid (39.5 mg, 89%). Mp 233 – 235 °C; 1H NMR (400 MHz,
DMSO) δ 12.24 (s, 1H), 8.92 (dd, J = 7.8, 1.8 Hz, 1H), 8.38 (dd, J = 4.8,
1.7 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.46 (dd, J
= 2, 4.8 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 2.69 (s, 3H), 1.36 (t, J = 7.1 Hz,
3H). 13C NMR (101 MHz, DMSO) δ 165.25, 161.99, 150.53, 144.50,
144.05, 134.76, 131.76, 120.24, 118.96, 117.30, 112.66, 112.62, 106.31,
104.98, 59.67, 14.62, 14.42. HRMS (ESI+): m/z calculated for C17H14N2O3
[M+H]+: 295.1077, found 295.1075. IR: 2822, 1693, 1618, 1587, 1543,
1486, 1462, 1441, 1425, 1404, 1393, 1371, 1338, 1320, 1285, 1264, 1231,
1191, 1154, 1115, 1096, 1076, 1060, 1050, 1019, 998, 942, 932, 903, 876,
865, 854, 797, 773, 754, 662, 642, 628, 580, 547 cm-1.
indole-3-carboxylate (13'c): Yellow solid (323 mg, 73%). Mp 83 – 85 °C;
1H NMR (400 MHz, CDCl3) δ 8.41 (dd, J = 4.8, 2.0 Hz, 1H), 7.67 (dd, J =
7.5, 2.0 Hz, 1H), 7.34 – 7.27 (m, 4H), 7.19 (d, J = 8.8 Hz, 1H), 7.05 – 7.02
(m, 2H), 6.88 (d, J = 8.8 Hz, 1H), 5.33 (s, 2H), 3.88 (dq, J = 10.8, 7.1 Hz,
1H), 3.57 (dq, J = 10.8, 7.2 Hz, 1H), 2.58 (s, 3H), 1.05 (t, J = 7.1 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 165.67, 152.08, 148.60, 148.42, 144.53,
140.76, 136.37, 133.70, 132.00, 129.13, 127.88, 126.15, 124.92, 122.50,
115.10, 112.33, 111.34, 106.11, 60.06, 46.96, 14.26, 12.24. HRMS (ESI+):
m/z calculated for C24H21ClN2O3 [M+H]+: 421.1313, found 421.1301. IR:
1681, 1605, 1573, 1562, 1523, 1496, 1463, 1434, 1421, 1393, 1371, 1332,
1299, 1270, 1226, 1205, 1180, 1153, 1122, 1084, 1054, 1028, 1016, 1003,
939, 902, 865, 797, 757, 727, 703, 647, 623, 601, 562, 523 cm-1.
Ethyl
2-methyl-1-propyl-1H-pyrido[3',2':4,5]furo[2,3-f]indole-3-
carboxylate (14b): White solid (58.7 mg, 81%). Mp 138 – 140 °C; 1H NMR
(400 MHz, DMSO) δ 8.53 (dd, J = 7.5, 1.7 Hz, 1H), 8.37 (dd, J = 4.9, 1.7
Hz, 1H), 8.32 (d, J = 0.8 Hz, 1H), 8.11 (d, J = 0.7 Hz, 1H), 7.43 (dd, J =
7.5, 5 Hz, 1H), 4.33 (q, J = 7.1 Hz, 2H), 4.24 (t, J = 7.4 Hz, 2H), 2.77 (s,
3H), 1.78 (h, J = 7.4 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.4 Hz,
3H). 13C NMR (101 MHz, DMSO) δ 164.70, 163.05, 150.20, 147.36,
145.31, 133.00, 129.68, 126.97, 119.16, 117.38, 117.22, 102.93, 101.72,
59.01, 22.33, 14.39, 11.88, 10.98. HRMS (ESI+): m/z calculated for
C20H20N2O3 [M+H]+: 337.1547, found 337.1542. IR: 3021, 2978, 2930,
2905, 2879, 1690, 1638, 1592, 1531, 1499, 1478, 1467, 1452, 1442, 1402,
1377, 1367, 1345, 1315, 1285, 1250, 1231, 1208, 1177, 1156, 1136, 1124,
1098, 1058, 1018, 998, 947, 914, 890, 870, 857, 834, 814, 799, 773, 742,
729, 700, 684, 661 cm-1.
Ethyl
6-(2-chloropyridin-3-yl)-5-hydroxy-2-methyl-1-phenyl-1H-
indole-3-carboxylate (13d): White solid (23 mg, 2%). Mp 252 – 254 °C;
1H NMR (400 MHz, DMSO) δ 9.40 (s, 1H), 8.36 (dd, J = 4.8, 2 Hz, 1H),
7.77 (dd, J = 7.5, 2.0 Hz, 1H), 7.66 (s, 1H), 7.66 – 7.61 (m, 2H), 7.59 –
7.54 (m, 1H), 7.51 – 7.48 (m, 2H), 7.40 (dd, J = 7.5, 4.8 Hz, 1H), 6.70 (s,
1H), 4.34 (q, J = 7.1 Hz, 2H), 2.52 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H). 13C
NMR (150 MHz, DMSO) δ 164.98, 150.47, 150.13, 148.07, 145.72, 141.05,
135.73, 134.61, 131.07, 129.95, 128.91, 127.95, 127.31, 122.73, 121.00,
111.62, 105.84, 103.52, 59.07, 14.53, 12.94. HRMS (ESI+): m/z calculated
for C23H19ClN2O3 [M+H]+: 407.1157, found 407.1159. IR: 3276, 3053, 3002,
2920, 2846, 1736, 1648, 1595, 1555, 1521, 1493, 1469, 1458, 1443, 1416,
1392, 1375, 1308, 1276, 1231, 1197, 1174, 1160, 1124, 1083, 1058, 1024,
1001, 991, 972, 947, 921, 892, 871, 863, 852, 809, 783, 763, 752, 720,
699, 677, 664, 651, 618, 555, 544 cm-1.
Ethyl
2-methyl-3-propyl-3H-pyrido[3',2':4,5]furo[3,2-e]indole-1-
°
carboxylate (15b): Yellow solid (38.5 mg, 85%). Mp 104 – 106 C; 1H
NMR (400 MHz, DMSO) δ 8.66 (dd, J = 7.9, 1.7 Hz, 1H), 8.38 (dd, J = 4.9,
1.7 Hz, 1H), 7.81 (d, J = 8.9 Hz, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.46 (dd, J
= 7.8, 4.8 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 4.26 (t, J = 7.5 Hz, 2H), 2.70
(s, 3H), 1.72 (h, J = 7.4 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H), 0.90 (t, J = 7.4
Hz, 3H). 13C NMR (101 MHz, DMSO) δ 165.35, 162.07, 150.66, 144.60,
143.60, 134.55, 132.54, 119.57, 118.96, 117.11, 112.58, 111.66, 106.24,
105.19, 59.94, 44.61, 22.67, 14.36, 12.14, 10.98. HRMS (ESI+): m/z
calculated for C20H20N2O3 [M+H]+: 337.1547, found 337.1544. IR: 2951,
2924, 2872, 2851, 1683, 1605, 1580, 1511, 1464, 1431, 1401, 1386, 1378,
1342, 1295, 1261, 1235, 1192, 1171, 1150, 1119, 1091, 1066, 1052, 1036,
1016, 969, 913, 898, 878, 859, 806, 796, 776, 749, 731, 659 cm-1.
Ethyl
4-(2-chloropyridin-3-yl)-5-hydroxy-2-methyl-1-phenyl-1H-
indole-3-carboxylate (13'd): Yellow solid (95 mg, 8%). Mp 187 – 189 °C;
1H NMR (400 MHz, CDCl3) δ 8.44 (dd, J = 4.8, 2.0 Hz, 1H), 7.68 (dd, J =
7.5, 2.0 Hz, 1H), 7.60 – 7.50 (m, 3H), 7.39 – 7.29 (m, 3H), 6.96 (d, J = 8.8
Hz, 1H), 6.85 (d, J = 8.8 Hz, 1H), 3.96 – 3.88 (m, 1H), 3.60 – 3.52 (m, 1H),
2.43 (s, 3H), 1.07 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 165.65,
152.19, 148.80, 148.57, 144.84, 140.70, 136.66, 133.60, 133.40, 129.95,
129.07, 128.46, 124.63, 122.58, 114.71, 112.40, 112.33, 106.50, 60.12,
29.84,
14.29,
13.25.
HRMS
(ESI+):
m/z
calculated
for
C23H19ClN2O3[M+H]+: 407.1157, found 407.1153. IR: 3053, 2956, 2918,
2848, 1687, 1668, 1595, 1572, 1531, 1495, 1474, 1455, 1433, 1397, 1385,
1370, 1322, 1306, 1275, 1248, 1202, 1171, 1131, 1085, 1075, 1068, 1059,
1051, 1012, 999, 963, 942, 924, 890, 871, 851, 798, 782, 769, 757, 749,
719, 707, 693, 664, 652, 631, 602, 566 cm1-.
Ethyl
1-benzyl-2-methyl-1H-pyrido[3',2':4,5]furo[2,3-f]indole-3-
carboxylate (14c): Yellow solid (26 mg, 57%). Mp 178 – 180 °C; 1H NMR
(400 MHz, DMSO) δ 8.50 (dd, J = 7.5, 1.7 Hz, 1H), 8.37 (d, J = 5 Hz, 2H),
9
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