T. Tremmel, F. Bracher / Tetrahedron 71 (2015) 4640e4646
4645
0
0
0
2
CH
.7 Hz, 1H, 5-H), 8.01 (dd, J¼5.1 Hz, 0.7 Hz, 1H, 4-H), 7.64e7.58 (m,
(100 MHz, CDCl
3
):
d
¼190.4 (C-1 ), 163.9 (C-3 ), 141.1 (C-8a), 138.4
0
H, 7-H, 8-H), 7.38e7.30 (m, 1H, 6-H), 6.94 (s, 1H, 4 -H), 2.46 (s, 3H,
(C-1), 137.9 (C-3), 136.0 (C-9a), 131.2 (C-4a), 128.9 (C-7), 121.9 (C-5),
121.0 (C-4b), 120.2 (C-6), 117.4 (C-4), 111.9 (C-8), 92.2 (C-2 ), 23.2 (C-
) ppm. 13C NMR (125 MHz, CDCl
):
d
¼170.0 (C-5 ), 160.7 (C-3 ),
0
0
0
3
3
0
140.6 (C-8a), 139.2 (C-3), 132.8 (C-9a), 130.9 (C-4a), 130.0 (C-1),
4 ) ppm. IR: ~v ¼3422, 3302, 3129, 2361, 2344, 1633, 1610, 1587, 1530,
129.2 (C-7), 121.8 (C-5), 120.9 (C-4b), 120.6 (C-6), 115.9 (C-4), 111.8
1488, 1428, 1318, 1281, 1256, 1217, 1145, 1067, 806, 746, 638, 569,
0
ꢂ1
þ
ꢃ
(
C-8), 102.8 (C-4 ), 11.6 (CH
3
) ppm. IR: ~v ¼3316, 3100, 3057, 2927,
537 cm . MS (EI, 70 eV): m/z (%)¼251 (100) [M ], 222 (60), 182
þ
2
361, 2342, 1717, 1629, 1612, 1560, 1496, 1448, 1426, 1374, 1319,
(75). HRMS (EI): calcd for C15
251.1060.
H
13
N
3
O: 251.1059 [M] ; found
1300, 1285, 1260, 1226, 1126, 1067, 972, 881, 803, 797, 743, 624, 595,
ꢂ1
þ
ꢃ
5
61, 477 cm . MS (EI, 70 eV): m/z (%)¼249 (100) [M ], 180 (20).
þ
ꢃ
HRMS (EI): calcd for C15
11
H N
3
O: 249.0902 [M ]; found 249.0906.
4.15. (Z)-3-Amino-1-(9H-pyrido[3,4-b]indol-1-yl)pent-2-en-1-
one (10b)
4
.12. 3-Ethyl-5-(9H-pyrido[3,4-b]indol-1-yl)isoxazole (9b)
Prepared from the isoxazole 9b (145 mg, 0.55 mmol) in the same
manner as described in chapter 4.14 to give 130 mg of 10b
Prepared from N-chlorosuccinimide (139 mg, 1.04 mmol), pyri-
dine (12 L, 0.16 mmol), propionaldehyde oxime (80 L,1.04 mmol),
(200 mg, 1.04 mmol), and triethylamine (0.16 mL, 1.15 mmol) in
the same manner as described in chapter 4.11 to give 172 mg of 9b
ꢀ
1
m
m
(0.49 mmol, 89% yield) as a yellow solid. Mp 139 C, H NMR
(500 MHz, CDCl ): ), 8.49 (d,
8
3
d
¼10.73 (s, 1H, NH), 10.33 (s, 1H, NH
2
J¼5.0 Hz, 1H, 3-H), 8.13 (d, J¼7.8 Hz, 1H, 5-H), 8.04 (d, J¼5.0 Hz, 1H,
ꢀ
1
(
(
0.65 mmol, 63% yield) as a pale yellow solid. Mp 153 C, H NMR
500 MHz, CDCl ):
¼9.53 (s, 1H, NH), 8.52 (d, J¼5.1 Hz, 1H, 3-H),
4-H), 7.58e7.51 (m, 2H, 7-H, 8-H), 7.28 (ddd, J¼8.0 Hz, 5.6 Hz,
0
3
d
2.5 Hz, 1H, 6-H), 6.74 (s, 1H, 2 -H), 5.39 (s, 1H, NH
2
), 2.41 (q,
0
0
13
8
2
1
.15 (d, J¼7.9 Hz, 1H, 5-H), 8.00 (d, J¼5.1 Hz, 1H, 4-H), 7.64e7.54 (m,
J¼7.6 Hz, 2H, 4 -H), 1.29 (t, J¼7.7 Hz, 3H, 5 -H) ppm. C NMR
0
0
H, 7-H, 8-H), 7.33 (ddd, J¼8.0 Hz, 6.3 Hz, 1.7 Hz, 1H, 6-H), 6.99 (s,
(125 MHz, CDCl
3
):
d
¼190.5 (C-1 ), 169.2 (C-3 ), 140.9 (C-8a), 138.3
0
H, 4 -H), 2.84 (q, J¼7.6 Hz, 2H, CH
2
),1.38 (t, J¼7.6 Hz, 3H, CH
3
) ppm.
(C-1), 137.7 (C-3), 135.8 (C-9a), 131.0 (C-4a), 128.7 (C-7), 121.7 (C-5),
120.8 (C-4b), 120.0 (C-6), 117.2 (C-4), 111.8 (C-8), 90.7 (C-2 ), 30.1 (C-
1
3
0
0
0
C NMR (125 MHz, CDCl
a), 139.3 (C-3), 132.9 (C-9a), 131.1 (C-4a), 130.2 (C-1), 129.3 (C-7),
3
):
d
¼170.0 (C-5 ), 166.2 (C-3 ), 140.8 (C-
0
0
8
4 ), 12.3 (C-5 ) ppm. IR: ~v ¼3423, 3057, 2973, 1718, 1609, 1528, 1491,
1
21.9 (C-5), 121.1 (C-4b), 120.7 (C-6), 116.0 (C-4), 112.0 (C-8), 101.6
1454, 1426, 1341, 1317, 1282, 1250, 1216, 1142, 1065, 811, 754,
0
ꢂ1
þ
ꢃ
(
C-4 ), 19.7 (CH
2
), 12.9 (CH
3
) ppm. IR: ~v ¼3422, 3321, 3060, 2969,
636 cm . MS (EI, 70 eV): m/z (%)¼265 (100) [M ], 250 (70), 236
2
937,1891,1629,1609,1558,1492,1426,1411,1321,1299,1285,1261,
(80), 222 (28), 168 (44). HRMS (EI): calcd for C16 O: 265.1215
15 3
H N
ꢂ1
þ
ꢃ
1229, 1125, 1068, 975, 963, 833, 813, 742, 625, 598, 561 cm . MS
[M ]; found 265.1223.
þ
ꢃ
(
C
EI, 70 eV): m/z (%)¼263 (100) [M ], 248 (55). HRMS (EI): calcd for
þ
ꢃ
H
16 13
N
3
O: 263.1059 [M ]; found 263.1063.
4.16. (Z)-3-Amino-3-phenyl-1-(9H-pyrido[3,4-b]indol-1-yl)
prop-2-en-1-one (10c)
4
.13. 3-Phenyl-5-(9H-pyrido[3,4-b]indol-1-yl)isoxazole (9c)
Prepared from N-chlorosuccinimide (139 mg, 1.04 mmol), pyri-
Prepared from the isoxazole 9c (111 mg, 0.36 mmol) in the same
manner as described in chapter 4.14 to give 84 mg of 10c
ꢀ
1
dine (12
.04 mmol), 8 (200 mg, 1.04 mmol), and triethylamine (0.16 mL,
.15 mmol) in the same manner as described in chapter 4.11 to give
31 mg of 9c (0.42 mmol, 40% yield) as a pale yellow solid. Mp
m
L, 0.16 mmol), (E)-benzaldehyde oxime (126 mg,
(0.27 mmol, 75% yield) as a yellow solid. Mp 221 C, H NMR
(500 MHz, CDCl ): ), 8.51 (d,
¼10.74 (s, 1H, NH), 10.48 (s, 1H, NH
J¼5.0 Hz, 1H, 3-H), 8.15 (d, J¼7.8 Hz, 1H, 5-H), 8.07 (d, J¼5.0 Hz, 1H,
1
1
1
3
d
2
0
0
00
4-H), 7.75 (dd, J¼7.8 Hz,1.8 Hz, 2H, 2 -H, 6 -H), 7.60e7.53 (m, 2H, 7-
ꢀ
1
00 00 00
1
66 C, H NMR (500 MHz, CD
2
Cl
2
):
d
¼9.64 (s, 1H, NH), 8.54 (d,
H, 8-H), 7.53e7.42 (m, 3H, 3 -H, 4 -H, 5 -H), 7.32e7.28 (m, 1H, 6-
0
13
J¼5.1 Hz, 1H, 3-H), 8.19 (d, J¼7.9 Hz, 1H, 5-H), 8.06 (d, J¼5.0 Hz, 1H,
H), 7.20 (s, 1H, 2 -H), 5.60 (s, 1H, NH
2
) ppm. C NMR (125 MHz,
00
00
00
0
0
4
-H), 7.99e7.91 (m, 2H, 2 -H, 6 -H), 7.68e7.59 (m, 2H, 7-H, 8-H),
CDCl
3
): d
¼191.0 (C-1 ), 163.2 (C-3 ), 140.9 (C-8a), 138.3 (C-1), 137.8
0
0
00
0
00
00
7.56e7.48 (m, 3H, 3 -H, 4 -H, 5 -H), 7.44 (s, 1H, 4 -H), 7.34 (ddd,
(C-3), 137.3 (C-1 ), 135.9 (C-9a), 131.1 (C-4a), 130.80 (C-4 ), 129.0 (C-
13
00
00
00
00
J¼8.0 Hz, 6.4 Hz, 1.7 Hz, 1H, 6-H) ppm. C NMR (125 MHz, CD
2
Cl
2
):
3 , C-5 ), 128.7 (C-7), 126.5 (C-2 , C-6 ), 121.7 (C-5), 120.8 (C-4b),
0
0
0
d
¼171.3 (C-5 ), 163.4 (C-3 ), 141.2 (C-8a), 139.7 (C-3), 133.2 (C-9a),
120.1 (C-6), 117.4 (C-4), 111.8 (C-8), 91.6 (C-2 ) ppm. IR: ~v ¼3448,
00
00
00
1
31.3 (C-4a),130.7 (C-4 ),130.3 (C-1),129.6 (C-7),129.4 (C-3 , C-5 ),
3406, 3055, 2924, 1602, 1590, 1561, 1527, 1486, 1423, 1337, 1313,
0
0
00
00
ꢂ1
129.2 (C-1 ), 127.3 (C-2 , C-6 ), 122.2 (C-5), 121.3 (C-4b), 121.0 (C-6),
1283, 1264, 1235, 1214, 1136, 1061, 812, 740 cm . MS (EI, 70 eV): m/
z (%)¼313 (100) [M ], 284 (95), 146 (39). HRMS (EI): calcd for
0
þ
ꢃ
1
16.4 (C-4), 112.3 (C-8), 100.3 (C-4 ) ppm. IR: ~v ¼3424, 3230, 3058,
þ
ꢃ
1653, 1630, 1611, 1557, 1493, 1441, 1399, 1323, 1286, 1229, 757, 739,
C
20
H
15
N
3
O: 313.1215 [M ]; found 313.1225.
ꢂ1
þ
ꢃ
6
84, 566 cm . MS (EI, 70 eV): m/z (%)¼311 (100) [M ], 283 (15).
þ
ꢃ
13 3
HRMS (EI): calcd for C20H N O: 311.1059 [M ]; found 311.1063.
4.17. 4-(9H-Pyrido[3,4-b]indol-1-yl)but-3-yn-1-ol (11)
4
.14. (Z)-3-Amino-1-(9H-pyrido[3,4-b]indol-1-yl)but-2-en-1-
To a mixture of 7 (400 mg, 1.62 mmol), Pd(dppf)
0.08 mmol) and CuI (62 mg, 0.32 mmol) in deoxygenated THF
4.5 mL) and triethylamine (5 mL) was added a solution of 3-butyn-
2 2
Cl (59 mg,
one (10a)
(
The isoxazole 9a (150 mg, 0.60 mmol) was dissolved in ethanol
12 mL), and KOH (452 mg, 8.05 mmol) and palladium (10 wt. %) on
1-ol (0.15 mL, 1.94 mmol) in deoxygenated THF (0.5 mL) under
a nitrogen atmosphere. The mixture was heated to reflux for
30 min. Then saturated NaCl solution (50 mL) was added and the
mixture was extracted with ethyl acetate (3ꢁ30 mL). The combined
(
activated carbon catalyst (25 mg) were added. The resulting mix-
ture was hydrogenated at atmospheric pressure and rt for 3 h. The
catalyst and salts were removed by washing the mixture through
silica gel with 19:1 methylene chlorideemethanol, evaporation of
the eluate gave 151 mg of 10a (0.60 mmol, 99% yield) as a yellow
2 4
organic layers were dried over Na SO and the solvents were
concentrated under reduced pressure. Purification was accom-
plished by FCC using ethyl acetate to give 272 mg of 11 (1.15 mmol,
ꢀ
1
ꢀ
1
solid. Mp 195 C, H NMR (400 MHz, CDCl
3
):
), 8.49 (d, J¼5.0 Hz, 1H, 3-H), 8.14 (dd, J¼7.9 Hz,
.9 Hz, 1H, 5-H), 8.05 (dd, J¼5.1 Hz, 0.7 Hz, 1H, 4-H), 7.60e7.53 (m,
H, 7-H, 8-H), 7.29 (ddd, J¼8.0 Hz, 5.5 Hz, 2.6 Hz, 1H, 6-H), 6.71 (d,
d
¼10.69 (s, 1H, NH),
71% yield) as a pale yellow solid. Mp 189 C, H NMR (500 MHz,
DMSO-d ):
1
0
2
0.24 (s, 1H, NH
2
6
d
¼11.59 (s, 1H, NH), 8.45e8.26 (m, 1H, 3-H), 8.23 (d,
J¼7.8 Hz, 1H, 5-H), 8.09 (d, J¼4.6 Hz, 1H, 4-H), 7.64 (d, J¼8.2 Hz, 1H,
8-H), 7.57 (ddd, J¼8.1 Hz, 7.0 Hz, 0.9 Hz, 1H, 7-H), 7.26 (ddd,
J¼8.2 Hz, 7.1 Hz, 1.0 Hz, 1H, 6-H), 5.01 (t, J¼5.7 Hz, 1H, OH), 3.74 (dt,
0
0
13
J¼1.5 Hz,1H, 2 -H), 5.31 (s,1H, NH
2
), 2.16 (s, 3H, 4 -H) ppm. C NMR