M.N. Balfour et al. / European Journal of Medicinal Chemistry 128 (2017) 202e212
209
1
2
1
1
23.8, 106.4, 96.7, 69.3, 31.2 ppm; IR:
931, 2853, 2664, 2248, 2238, 2220, 2211, 2196, 2110, 2082, 2048,
721, 1639, 1607, 1579, 1544, 1510, 1475, 1452, 1421, 1382, 1365,
294, 1264, 1242, 1235, 1203, 1177, 1162, 1112, 1065, 1046, 1020,
n
max 3222, 3138, 3051, 2978,
ppm; 13C NMR (75 MHz, acetone-d6):
d
158.1, 150.8, 149.3, 141.0,
140.1, 132.2, 130.7, 130.2, 125.7, 121.1, 112.4, 106.3, 97.6, 69.1, 55.6,
31.1 ppm; IR: max 3075, 2976, 2935, 2836, 1737, 1667, 1657, 1639,
n
1603, 1579, 1547, 1562, 1510, 1495, 1467, 1423, 1378, 1298, 1276,
ꢃ1
1005, 978, 965, 937, 907, 879, 850, 808, 776, 743, 676 cm ; HRMS
1238, 1181, 1160, 1119, 1102, 1063, 1050, 1024, 976, 942, 873, 845,
O (M þ H)þ 303.1497, found: 303.1370.
827, 810, 795, 760 cm ; HRMS (ESI) m/z: calcd. for C17
ꢃ1
H
19
N
2
O
2
(
ESI) m/z: calcd. for C20
19
H N
2
(
M þ H)þ 283.1447, found: 283.1731.
4
.1.2.8. 2-(4-(2-fluoro-[1,1'-biphenyl]-4-yl)-1H-pyrrolo[3,2-c]pyr-
idin-2-yl)propan-2-ol (19). Light brown solid, 34.0 mg, 83%, m.p.
4.1.2.13. 2-(4-(4-(tert-butyl)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)
ꢁ
1
210e212 C; H NMR (300 MHz, acetone-d6):
d
10.73 (br s,1H), 8.30
propan-2-ol (24). Light brown solid, 30.5 mg, 83%, m.p.
204e206 C; 1H NMR (300 MHz, acetone-d6):
ꢁ
d
10.60 (br s, 1H),
(
7
1
d, J ¼ 5.5 Hz, 1H), 8.05 (d, J ¼ 8.04 Hz, 1H), 8.02e7.90 (m, 1H),
.77e7.62 (m, 3H), 7.57e7.47 (m, 2H), 7.46e7.36 (m, 2H), 6.78 (s,
8.25 (d, J ¼ 5.1 Hz, 1H), 8.02 (d, J ¼ 7.8 Hz, 2H), 7.55 (d, J ¼ 7.7 Hz,
1
3
H) 1.69 (s, 6H) ppm; C NMR (75 MHz, acetone-d6):
d 160.6 (d,
2H), 7.30 (d, J ¼ 5.4 Hz, 1H), 6.68 (s, 1H), 1.66 (s, 6H), 1.38 (s, 9H)
13
J ¼ 243.9 Hz), 150.7, 149.4, 143.5 (d, J ¼ 7.9 Hz), 142.1, 140.9, 136.6,
31.4 (d, J ¼ 3.8 Hz), 129.8 (d, J ¼ 3.0 Hz), 129.4, 128.6, 125.6 (d,
J ¼ 3.1 Hz), 123.6, 116.8, 116.5, 106.9, 96.4, 69.3, 31.2 ppm; IR: [20]
max 3570, 3483, 2976, 2935, 2827, 2110, 2093, 1611, 1581, 1553,
447, 1428, 1402, 1384, 1318, 1296, 1242, 1205, 1171, 1160, 1136, 1104,
ppm; C NMR (75 MHz, acetone-d6): d 151.6, 151.5, 149.9, 141.8,
1
140.9, 139.2, 129.2, 125.9, 106.1, 96.7, 69.3, 35.2, 31.7, 31.1 ppm; IR:
max 3224, 3168, 3067, 2965, 2905, 2868, 1609, 1581, 1562, 1544,
n
n
1512,1501,1460,1423,1400,1380,1365,1317,1296,1262,1236,1177,
1
1158, 1119, 1063, 1020, 979, 962, 948, 871, 845, 739, 717, 698, 678,
ꢃ1
O (M þ H)þ 309.1967,
1
6
3
078, 1061, 1013, 992, 978, 968, 944, 894, 881, 855, 817, 767, 726,
661 cm ; HRMS (ESI) m/z: calcd. for C20
25
H N
2
ꢃ1
O (M þ H)þ
96 cm ; HRMS (ESI) m/z: calcd. for C22
H20FN
2
found: 309.1809.
47.1560, found: 347.1402.
4
.1.2.14. 2-(4-(4-fluorophenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)
ꢁ
4
.1.2.9. 2-(4-(4-methylphenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)
propan-2-ol (25). White solid, 26.1 mg, 81%, m.p. 191e193 C; IR:
max 3224, 3212, 3159, 2980, 2568, 1739, 1609, 1579, 1562, 1547,
propan-2-ol (20). Light brown solid, 22.2 mg, 70%, m.p.
n
ꢁ
2
8
6
20e220 C; 1H NMR (300 MHz, acetone-d6):
.24 (d, J ¼ 5.6 Hz, 1H), 7.97 (d, J ¼ 7.4 Hz, 2H), 7.35e7.25 (m, 3H),
d
10.61 (br s, 1H),
1514, 1460, 1441, 1423, 1400, 1371, 1315, 1298, 1264, 1238, 1223,
1192, 1171, 1158, 1192, 1097, 1091, 1061, 1046, 1018, 979, 961, 944,
871, 842, 775, 724, 696, 661 cm ; H NMR (300 MHz, acetone-d6):
1
3
ꢃ1 1
.66 (s, 1H), 2.40 (s, 3H), 1.65 (s, 6H) ppm; C NMR (75 MHz,
151.6, 149.8, 141.8, 140.8, 139.2, 138.4, 129.7, 129.4,
23.4, 106.1, 96.7, 69.2, 31.1, 21.3 ppm; IR: max 2974, 2929, 1609,
581, 1546, 1516, 1460, 1423, 1402, 1380, 1365, 1331, 1315, 1298,
acetone-d6):
d
d
10.67 (br s, 1H), 8.25 (d, J ¼ 5.6 Hz, 1H), 8.18e8.06 (m, 2H), 7.33 (d,
13
1
1
1
7
n
J ¼ 5.6 Hz, 1H), 7.30e7.20 (m, 2H), 6.67 (s, 1H), 1.66 (s, 6H) ppm;
C
NMR (75 MHz, acetone-d6):
d
163.6 (d, J ¼ 243.6 Hz), 150.3, 150.2,
266, 1171, 1154, 1112,1063, 1022, 1004, 978, 944, 871, 834, 815, 775,
72, 694, 670, 663 cm ; HRMS (ESI) m/z: calcd. for C17
M þ H) 267.1497, found: 267.1362.
141.9, 140.9, 138.3 (d, J ¼ 3.0 Hz), 131.3 (d, J ¼ 8.2 Hz), 123.4, 115.8 (d,
ꢃ1
H
19
N
2
O
J ¼ 21.4 Hz), 106.4, 96.4, 69.3, 31.1 ppm; [22] HRMS (ESI) m/z: calcd.
þ
O (M þ H)þ 271.1247, found: 271.1120.
(
for C16H16FN
2
4.1.2.10. 2-(4-(3,5-bis(trifluoromethyl)phenyl)-1H-pyrrolo[3,2-c]pyr-
4.1.2.15. 2-(4-(2-(hydroxymethyl)phenyl)-1H-pyrrolo[3,2-c]pyridin-
idin-2-yl)propan-2-ol (21). Light brown solid, 22.7 mg, 49%, m.p.
2-yl)propan-2-ol (26). Light brown solid, 22.0 mg, 66%, m.p.
ꢁ
1
ꢁ
1
2
8
1
d
30e232 C; H NMR (300 MHz, acetone-d6):
d
10.87 (br s, 1H),
179e181 C; H NMR (300 MHz, CDCl ): d 8.93 (br s, 1H), 8.30 (d,
3
.67 (s, 2H), 8.36 (d, J ¼ 5.6 Hz, 1H), 8.09 (s, 1H), 7.47 (d, J ¼ 5.6 Hz,
J ¼ 5.8 Hz, 1H), 7.81e7.73 (m, 1H), 7.57e7.50 (m, 1H), 7.50e7.38 (m,
2H), 7.32e7.24 (m, 1H), 6.44 (s, 1H), 4.43 (s, 2H), 1.69 (s, 6H) ppm;
13
H), 6.71 (s, 1H), 1.68 (s, 6H) ppm; C NMR (75 MHz, acetone-d6):
13
151.7, 147.4, 144.3, 142.3, 141.2, 132.2 (q, J ¼ 32.9 Hz), 129.4, 124.6
C NMR (75 MHz, acetone-d6):
139.4, 131.3, 131.2, 129.2, 128.0, 124.8, 106.8, 96.9, 69.2, 64.8,
31.1 ppm; IR: max 3378, 3229, 3205, 3175, 3060, 3030, 2969, 2983,
d 152.7, 150.6, 142.5, 141.8, 140.7,
(
d, J ¼ 270.3 Hz), 123.7, 122.2 (apparent quintet, J ¼ 3.6 Hz), 107.7,
ꢃ1
9
5.5, 69.3, 31.1 ppm; [21] IR (cm ); 3475, 3168, 2978, 2816, 1613,
n
1
1
581, 1546, 1480, 1460, 1421, 1382, 1369, 1354, 1326, 1305, 1279,
238, 1169, 1127, 1067, 1005, 992, 953, 935, 905, 881, 849, 832, 823,
2942, 2862, 1737, 1721, 1613, 1585, 1572, 1549, 1493, 1458, 1434,
1421,1398,1376,1367,1350,1317,1305,1292,1281,1266,1240,1201,
8
04, 775, 719, 707, 678; HRMS (ESI) m/z: calcd. for C18
H
15
F
6
N
2
O
1190, 1177, 1145, 1121, 1104, 1065, 1048, 1002, 964, 946, 883, 871,
þ
ꢃ1
(
M þ H) 389.1089, found: 389.0941.
851, 806, 780, 754 cm ; HRMS (ESI) m/z: calcd. for C17
(
H
19
N
2
O
2
M þ H)þ 283.1447, found: 283.1642.
4
.1.2.11. 2-(4-(4-(ethylthio)phenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)
ꢁ
propan-2-ol (22). Light brown solid, 27.3 mg, 73%, m.p. 177e179 C;
4.1.2.16. 2-(4-(cyanophenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)propan-
1
ꢁ
1
H NMR (300 MHz, acetone-d6):
J ¼ 5.6 Hz, 1H), 8.04 (d, J ¼ 8.1 Hz, 2H), 7.45 (d, J ¼ 8.2 Hz, 2H), 7.31
d, J ¼ 5.6 Hz, 1H), 6.68 (s, 1H), 3.05 (q, J ¼ 7.3 Hz, 2H), 1.66 (s, 6H),
d
10.64 (br s, 1H), 8.25 (d,
2-ol (27). White solid, 16.1 mg, 49%, m.p. 168e170 C; H NMR
(300 MHz, acetone-d6): 10.79 (br s, 1H), 8.40e8.25 (m, 3H),
7.95e7.85 (m, 2H), 7.42 (d, J ¼ 5.7 Hz, 1H), 6.73 (s, 1H), 1.67 (s, 1H)
d
(
13
13
1
1
3
2
.33 (t, J ¼ 7.3 Hz, 3H) ppm; C NMR (75 MHz, acetone-d6):
50.1, 141.9, 140.9, 139.4, 137.8, 129.9, 128.9, 123.4, 106.3, 96.6, 69.3,
1.1, 27.5, 14.7 ppm; IR: max 3077, 2974, 2926, 2857, 2766, 2572,
121, 2099, 1885, 1737, 1609, 1600, 1581, 1562, 1544, 1536, 1510,
499, 1460, 1445, 1423, 1397, 1382, 1369, 1317, 1298, 1261, 1236,
d
150.8,
ppm; C NMR (75 MHz, acetone-d6):
141.0, 133.0, 130.1, 123.9, 119.5, 112.1, 107.3, 96.2, 69.3, 31.1 ppm; IR:
max 3226, 3172, 2972, 2929, 2874, 2549, 2227, 1739, 1721, 1678,
d 151.1, 149.0, 146.2, 142.1,
n
n
1657, 1609, 1579, 1562, 1544, 1510, 1454, 1439, 1423, 1400, 1380,
1371, 1315, 1298, 1262, 1238, 1181, 1158, 1141, 1112, 1065, 1045, 1018,
1
ꢃ1
1186, 1164, 1145, 1112, 1093, 1059, 1018, 979, 961, 940, 869, 842, 825,
981, 963, 871, 853, 815, 776, 663 cm ; HRMS (ESI) m/z: calcd. for
ꢃ1
OS (M þ H)þ
O (M þ H)þ 278.1293, found: 278.1153.
8
08, 780 cm ; HRMS (ESI) m/z: calcd. for C18
H
21
N
2
17 16 3
C H N
313.1375, found: 313.1215.
4
.1.2.17. 1-(4-(2-(2-hydroxypropan-2-yl)-1H-pyrrolo[3,2-c]pyridin-
4
.1.2.12. 2-(4-(2-methoxyphenyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)
4-yl)phenyl)ethanone (28). Yellow solid, 30.1 mg, 86%, m.p.
ꢁ
ꢁ
1
propan-2-ol (23). Light brown solid, 24.7 mg, 74%, m.p. 108e110 C;
185e187 C; H NMR (300 MHz, acetone-d6):
d 10.73 (br s,1H), 8.31
1
H NMR (300 MHz, acetone-d6):
d
8.22 (d, J ¼ 5.6 Hz, 1H), 7.55e7.27
(d, J ¼ 5.6 Hz, 1H), 8.22 (d, J ¼ 8.3 Hz, 2H), 8.12 (d, J ¼ 8.6 Hz, 2H),
13
(
m, 3H), 7.23e6.97 (m, 2H), 6.15 (s, 1H), 3.75 (s, 3H), 1.60 (s, 6H)
7.39 (d, J ¼ 5.6 Hz,1H), 6.72 (s,1H), 2.64 (s, 3H),1.67 (s, 6H) ppm;
C