T. Saito et al. / Bioorg. Med. Chem. 20 (2012) 1122–1138
1135
380.2338. Found: 380.2336; 1H NMR (300 MHz, CDCl3) d7.24–7.37
(m, 1H), 6.73–6.92 (m, 2H), 6.13 (s, 1H), 3.85 (s, 3H), 3.40 (m, 1H),
2.68 (m, 1H), 2.38 (s, 6H), 1.52–1.88 (m, 4H), 0.66–0.97 (m, 8H),
0.43–0.62 (m, 2H); IR (neat) 805, 1041, 1147, 1165, 1217, 1244,
1265, 1284, 1295, 1322, 1351, 1377, 1413, 1455, 1508, 1573,
1504, 1557, 1614, 1632, 1667, 2853, 2873, 2924, 2961, 3193,
3363 cmÀ1; mp 146 °C.
5.1.79. 2-[6-(Difluoromethoxy)-4-methyl-3-pyridinyl]-3,7-
dimethyl-5-(3-pentanyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one
(27)
1608, 1683, 2929, 2960 cmÀ1
.
A white powder. TLC Rf = 0.67 (EtOAc/hexane, 1/3); MS (ESI,
Pos) m/z 391 (M+H)+; FABHRMS calcd for C20H25F2N4O2:
391.1946. Found: 391.1946; 1H NMR (300 MHz, CDCl3) d 8.20
(s, 1H), 7.51 (t, J = 72.73 Hz, 1H), 6.89 (d, J = 0.73 Hz, 1H), 6.20
(s, 1H), 3.40 (m, 1H), 3.18 (s, 3H), 2.37 (dd, J = 8.60, 0.73 Hz,
6H), 1.51–1.85 (m, 4H), 0.86 (t, J = 7.32 Hz, 6H); 13C NMR
(75 MHz, CDCl3) d11.21, 12.28, 19.59, 29.00, 30.87, 39.71,
108.55, 112.25, 113.71, 113.95, 126.09, 129.21, 131.08, 143.92,
146.71, 150.56, 155.19, 159.60; IR (KBr) 451, 458, 574, 628,
674, 685, 700, 755, 805, 813, 880, 967, 1006, 1032, 1072, 1114,
1135, 1172, 1192, 1213, 1245, 1264, 1310, 1340, 1375, 1395,
1405, 1427, 1455, 1468, 1499, 1563, 1615, 1632, 1662, 1733,
2852, 2922, 2961, 3196, 3363 cmÀ1; Anal. Calcd for C20H24F2N4O2;
C, 61.53; H, 6.20; N, 14.35; Found: C, 61.61; H, 6.08; N, 14.33; mp
137 °C.
5.1.75. 2-(2-Chloro-4-methoxyphenyl)-3-cyclopropyl-5-(1-
ethylpropyl)-7-methylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one
(23)
A white powder. TLC Rf = 0.38 (EtOAc/hexane, 1/4); MS (APCI,
Pos) m/z 400 (M+H)+; FABHRMS calcd for C22H27ClN3O2:
400.1792. Found: 400.1790; 1H NMR (300 MHz, CDCl3) d 7.38 (d,
J = 8.6 Hz, 1H), 7.02 (d, J = 2.6 Hz, 1H), 6.93 (dd, J = 8.6, 2.6 Hz,
1H), 6.15 (s, 1H), 3.87 (s, 3H), 3.31–3.50 (m, 1H), 2.76–3.00 (m,
1H), 2.39 (s, 3H), 1.47–1.82 (m, 4H), 0.57–0.98 (m, 9H), 0.43 (m,
1H); IR (KBr) 2957, 2925, 2851, 1686, 1604, 1501, 1462, 1454,
1440, 1415, 1376, 1353, 1330, 1292, 1264, 1213, 1190, 1097,
1052, 1032, 859, 824, 801, 676 cmÀ1; Anal. Calcd for C22H26ClN3O2;
C, 66.07; H, 6.55; N, 10.51; Found: C, 65.92; H, 6.47; N, 10.56; mp
117 °C.
5.1.80. 5-(1-Ethylpropyl)-2-(6-methoxy-2-methyl-3-pyridinyl)-
3,7-dimethylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (28)
5.1.76. 5-(1-Ethylpropyl)-3-isobutyl-2-(4-methoxy-2-
methylphenyl)-7-methylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one
(24)
A white powder. TLC Rf = 0.53 (EtOAc/hexane, 1/3); MS (ESI,
Pos) m/z 355 (M+H)+; FABHRMS calcd for C20H27N4O2:
355.2134. Found: 355.2136; 1H NMR (300 MHz, CDCl3) d 7.55
(m, 1H), 6.70 (dd, J = 8.42, 0.55 Hz, 1H), 6.18 (s, 1H), 3.98 (s,
3H), 3.31–3.48 (m, 1H), 3.18 (s, 3H), 2.45 (s, 3H), 2.39 (s, 3H),
1.49–1.84 (m, 4H), 0.87 (t, J = 7.23 Hz, 6H); 13C NMR (75 MHz,
CDCl3) d 11.11, 12.16, 22.54, 28.92, 30.74, 39.64, 53.70, 108.10,
108.37, 114.09, 120.74, 129.03, 130.76, 139.10, 146.29, 154.98,
155.68, 163.98; IR (KBr) 451, 634, 675, 695, 755, 771, 798, 828,
922, 996, 1004, 1041, 1119, 1166, 1195, 1265, 1276, 1309,
1325, 1347, 1358, 1376, 1408, 1419, 1443, 1457, 1491, 1515,
A colorless viscous oil. TLC Rf = 0.29 (EtOAc/hexane, 1/9); MS
(APCI, Pos) m/z 396 (M+H)+; FABHRMS calcd for C24H34N3O2:
396.2651. Found: 396.2655; 1H NMR (300 MHz, CDCl3) d 7.31 (m,
1H), 6.59–7.18 (m, 2H), 6.16 (s, 1H), 3.69–4.21 (m, 4H), 3.45 (m,
1H), 3.10–3.30 (m, 1H), 2.39 (s, 3H), 2.26 (s, 3H), 1.47–1.99 (m,
5H), 0.80–0.97 (m, 6H), 0.75 (d, J = 6.8 Hz, 3H), 0.69 (d, J = 6.8 Hz,
3H); IR (neat) 675, 737, 758, 806, 848, 1012, 1043, 1066, 1116,
1125, 1163, 1206, 1232, 1243, 1265, 1286, 1296, 1312, 1346,
1377, 1413, 1421, 1436, 1450, 1463, 1507, 1573, 1608, 1633,
1644, 1676, 1684, 2838, 2871, 2960 cmÀ1
.
1573, 1600, 1609, 1666, 2872, 2929, 2962, 3194, 3362 cmÀ1
.
5.1.77. 3-(Cyclopropylmethyl)-5-(1-ethylpropyl)-2-(4-methoxy-
2-methylphenyl)-7-methylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-
one (25)
5.1.81. 2-[6-(Difluoromethoxy)-2-methyl-3-pyridinyl]-3,7-
dimethyl-5-(3-pentanyl)pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one
(29)
A colorless viscous oil. TLC Rf = 0.32 (EtOAc/hexane, 1/9); MS
(APCI, Pos) m/z 394 (M+H)+; FABHRMS calcd for C24H32N3O2:
394.2495. Found: 394.2479; 1H NMR (300 MHz, CDCl3) d 7.35 (m,
1H), 6.73–6.95 (m, 2H), 6.17 (s, 1H), 3.76–4.04 (m, 4H), 3.18–
3.56 (m, 2H), 2.40 (s, 3H), 2.28 (s, 3H), 1.47–1.88 (m, 4H), 0.74–
1.08 (m, 7H), 0.24–0.46 (m, 2H), 0.08–0.22 (m, 2H); 13C NMR
(75 MHz, CDCl3) d 4.14, 4.24, 10.94, 11.16, 12.02, 12.14, 19.96,
28.75, 28.81, 39.49, 47.19, 55.34, 108.08, 111.21, 114.36, 115.71,
125.02, 128.69, 130.54, 130.71, 138.52, 147.14, 155.79, 160.41; IR
(neat) 674, 737, 757, 794, 809, 847, 937, 986, 1021, 1046, 1128,
1164, 1207, 1232, 1244, 1285, 1296, 1313, 1347, 1357, 1377,
A white solid. TLC Rf = 0.50 (EtOAc/hexane, 1/5); MS (ESI, Pos)
m/z 391 (M+H)+; FABHRMS calcd for C20H25F2N4O2: 391.1946.
Found: 391.1946; 1H NMR (300 MHz, CDCl3)
d 7.69 (d,
J = 8.23 Hz, 1H), 7.62 (t, J = 72.64 Hz, 1H), 6.87 (d, J = 8.23 Hz,
1H), 6.19 (s, 1H), 6.19 (s, 1H), 3.31–3.48 (m, 1H), 3.18 (s, 3H),
2.47 (s, 3H), 2.38 (s, 3H), 1.50–1.84 (m, 4H), 0.86 (t, J = 7.32 Hz,
6H); 13C NMR (75 MHz, CDCl3) d 11.06, 12.16, 22.42, 28.91,
30.74, 39.66, 108.58, 108.73, 110.33, 113.71, 114.03, 117.10,
124.33, 129.27, 131.15, 140.69, 145.23, 155.40, 155.63, 158.81;
IR (KBr) 444, 460, 480, 557, 632, 666, 678, 696, 755, 770, 804,
813, 838, 855, 920, 1003, 1024, 1036, 1070, 1097, 1121, 1145,
1171, 1194, 1261, 1276, 1289, 1328, 1356, 1375, 1406, 1427,
1445, 1482, 1513, 1562, 1585, 1594, 1610, 1661, 2874, 2930,
2963, 3048, 3163, 3411 cmÀ1; mp 175 °C.
1413, 1428, 1461, 1507, 1573, 1607, 1676, 2871, 2960, 3082 cmÀ1
.
5.1.78. 5-(1-Ethylpropyl)-2-(6-methoxy-4-methyl-3-pyridinyl)-
3,7-dimethylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (26)
5.1.82. 2-(2-Chloro-4-methoxyphenyl)-5-isopropyl-3,7-
dimethylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (31)
A white powder. TLC Rf = 0.60 (EtOAc/hexane, 1/3); MS (ESI, Pos)
m/z 355(M+H)+; FABHRMS calcd for C20H27N4O2: 355.2134. Found:
355.2133; 1H NMR (300 MHz, CDCl3) d 8.16 (s, 1H), 6.68–6.74 (m,
1H), 6.19 (s, 1H), 3.98 (s, 3H), 3.30–3.48 (m, 1H), 3.18 (s, 3H), 2.39
(d, J = 0.73 Hz, 3H), 2.28 (d, J = 0.55 Hz, 3H), 1.50–1.84 (m, 4H),
0.87 (t, J = 7.41 Hz, 6H); 13C NMR (75 MHz, CDCl3) d 11.11, 12.16,
19.30, 28.90, 30.82, 39.65, 53.73, 108.42, 111.72, 114.09, 123.04,
129.10, 130.84, 145.06, 146.83, 148.43, 155.60, 164.97; IR (KBr)
453, 677, 701, 761, 799, 861, 945, 1004, 1023, 1051, 1151, 1174,
1196, 1245, 1282, 1312, 1328, 1348, 1357, 1370, 1408, 1431, 1450,
A white powder. TLC Rf = 0.57 (EtOAc/hexane, 1/2); MS (ESI,
Pos) m/z 346 (M+H)+; FABHRMS calcd for C18H21ClN3O2:
346.1322. Found: 346.1317; 1H NMR (300 MHz, CDCl3) d 7.36
(d, J = 8.4 Hz, 1H), 7.04 (d, J = 2.6 Hz, 1H), 6.94 (dd, J = 8.4,
2.6 Hz, 1H), 6.25 (s, 1H), 3.87 (s, 3H), 3.76 (m, 1H), 3.21 (s, 3H),
2.37–2.41 (m, 3H), 1.26–1.40 (m, 6H); IR (KBr) 811, 1036, 1239,
1271, 1292, 1351, 1411, 1428, 1466, 1503, 1605, 1633, 1680,
2852, 2922, 2960, 3362 cmÀ1; mp 157 °C.