F. Schmidt et al. / Bioorg. Med. Chem. 18 (2010) 5103–5113
5111
+
ꢁ1
1
00). ESI-HRMS Calcd for [M+Na] C28
H
46
N
2
ONa: 449.3508. Found:
127.4, 183.4. IR
m cm : 3394, 3275, 2917, 2849, 2037, 1982, 1669,
4
49.3491.
1629, 1556, 1457, 1375, 1357, 1267, 1224, 1166, 1109, 1057, 1026,
+
1
1
012, 974, 758, 741, 727, 704, 606. MS(ESI) m/z: 423 ([M+Na] ,
00). ESI-HRMS Calcd for [M+Na] C25H N O Na: 423.2987. Found:
40 2 2
+
3
.3.2.6. N-(2-(1H-Indol-3-yl)ethyl)icosadecanamide (1f). Com-
1
423.2978.
pound 1f (563 mg, 50%). H NMR (400 MHz, CDCl
3
) d ppm: 0.88 (t,
J = 6.8 Hz, 3H), 1.25 (m, 30H), 1.57 (m, 2H), 2.09 (t, J = 7.6 Hz, 2H),
2
1
.98 (t, J = 6.8 Hz, 2H), 3.60 (t, J = 6.4 Hz, 1H), 3.62 (t, J = 6.4 Hz,
H), 5.05 (s, 1H), 7.04 (s, 1H), 7.13 (t, J = 8.0 Hz, 1H), 7.21 (t,
3.3.3. General procedure for syntheses of (4a–g, 5, 6)
To a solution of amide 1a (356 mg, 1 mmol, 1 equiv) in tetrahy-
J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 8.10
4
drofuran (10 mL) under nitrogen at 0 °C was added LiAlH (8 mmol,
1
3
(
s, 1H). C NMR (100 MHz, CDCl
3
) d ppm: 14.1, 22.7, 25.4, 25.7,
8 equiv) in small pieces. The mixture was refluxed and stirredfor 2 h,
then quenched by adding water (1 mL) and an aqueous solution of
NaOH (1 M, 1 mL) was added until obtaining of a white precipitate.
2
1
2
1
1
9.3, 29.4, 29.5, 29.7, 31.9, 33.7, 36.9, 39.6, 111.2, 113.1, 118.7,
ꢁ1
19.5, 121.9, 122.2, 136.6, 173.1. IR
m cm : 3394, 3269, 2917,
Ò
850, 1649, 1629, 1552, 1472, 1456, 1424, 1377, 1339, 1299, 1222,
Afiltrationoncelite usingethylacetatewasusedtoremovethepre-
+
095, 1012, 913, 799, 739, 718, 669. MS(ESI) m/z: 477 ([M+Na] ,
4
cipitate. The organic layer was then dried over MgSO , filtered and
00). Anal. Calcd for C30
H
50
N
2
2
Oꢀ2.2H 0: C, 77.84, H, 11.08, N, 6.05.
concentrated in vacuo. A flash chromatography on silica with a mix-
ture of cyclohexane and ethyl acetate (60:40) led to the expected
product.
Found: C, 77.84, H, 11.27, N, 6.31.
3
.3.2.7. N-(2-(1H-Indol-3-yl)ethyl)tricosadecanamide (1g). Com-
1
pound 1g (96 mg, 88%). H NMR (400 MHz, CDCl
3
) d ppm: 0.88 (t,
3.3.3.1. N-(2-(1H-Indol-3-yl)ethyl)tridecan-1-amine (4a). Com-
1
J = 6.6 Hz, 3H), 1.25 (m, 38H), 1.57 (m, 2H), 2.09 (t, J = 7.2 Hz, 2H),
pound 4a (287 mg, 84%). H NMR (300 MHz, CDCl
3
) d ppm: 0.88
2
5
.98 (t, J = 6.4 Hz, 2H), 3.60 (t, J = 6.4 Hz, 1H), 3.62 (t, J = 6.4 Hz, 1H),
.47 (s, 1H), 7.04 (d, J = 2.0 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 7.21 (t,
(t, J = 6.9 Hz, 3H), 1.25 (m, 21H), 1.46 (m, 2H), 2.62 (t, J = 7.2 Hz,
2H), 2.97 (m, 4H), 7.04 (d, J = 2.1 Hz, 1H), 7.12 (td, J = 7.8 Hz,
J = 0.9 Hz, 1H), 7.20 (td, J = 7.2 Hz, J = 1.2 Hz, 1H), 7.36 (d,
J = 7.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 8.02
1
3
13
(
s, 1H). C NMR (100 MHz, CDCl
3
) d ppm: 14.1, 22.7, 25.4, 25.7,
J = 7.8 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 8.10 (s, 1H). C NMR
2
1
2
7
9.3, 29.4, 29.5, 29.7, 31.9, 33.7, 36.9, 39.6, 111.2, 113.1, 118.7,
19.5, 121.9, 122.2, 136.6, 173.1. IR m cm : 3396, 3258, 2959, 2917,
(75 MHz, CDCl
3
) d ppm: 14.1, 22.7, 25.8, 27.4, 29.3, 29.6, 29.7,
ꢁ1
30.1, 32.0, 50.0, 111.1, 114.2, 118.9, 119.2, 121.8, 122.0, 127.5,
ꢁ1
848, 1628, 1564, 1472, 1462, 1377, 1342, 1225, 1093, 983, 800,
136.4. IR
m cm : 3387, 3275, 3139, 3063, 2916, 2849, 1622,
+
38, 719, 612, 580, 560. MS(ESI) m/z: 497 ([M+H] , 100).
1553, 1504, 1467, 1453, 1376, 1358, 1341, 1309, 1221, 1104,
1
078, 1010, 914, 886, 842, 804, 739, 722, 611, 592, 565. MS(ESI)
+
+
m/z: 343 ([M+H] , 100). ESI-HRMS Calcd for [M+H]
343.3113. Found: 343.3120. Anal. Calcd for C23
7
23 38 2
C H N :
3
.3.2.8. N-(2-(1H-Indol-3-yl)ethyl)-octadeca-9Z,12Z-dienamide
1
H
38
N
2
2
ꢀ1.4H 0: C,
(
2). Compound 2 (372 mg, 81%). H NMR (400 MHz, CDCl
3
) d ppm:
7.72, H, 11.18, N, 7.88. Found: C, 77.86, H, 11.11, N, 7.82.
0
4
2
.90 (t, J = 6.8 Hz, 3H), 1.25 (m, 14H), 1.59 (t, J = 6.8 Hz, 2H), 2.06 (m,
H), 2.10 (t, J = 7.2 Hz, 2H), 2.79 (t, J = 6.4 Hz, 2H), 2.98 (t, J = 6.4 Hz,
H), 3.59 (t, J = 6.4 Hz, 1H), 3.62 (t, J = 6.4 Hz, 1H), 5.37 (m, 4H), 5.63
3
.3.3.2. N-(2-(1H-Indol-3-yl)ethyl)pentadecan-1-amine (4b). Com-
1
3
pound 4b (118 mg, 83%). H NMR (300 MHz, CDCl ) d ppm: 0.89 (t,
J = 6.9 Hz, 3H), 1.26 (m, 24H), 1.46 (m, 2H), 2.62 (t, J = 7.2 Hz, 2H),
2.97 (m, 4H), 7.04 (d, J = 1.8 Hz, 1H), 7.12 (td, J = 7.8 Hz, J = 1.2 Hz,
(s, 1H), 7.00 (d, J = 1.6 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.21 (t,
J = 7.6 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 7.6 Hz, 1H), 8.47
1
3
(
2
1
s, 1H). C NMR (100 MHz, CDCl
3
) d ppm: 14.0, 22.5, 25.3, 25.6,
5.7, 27.1, 29.1, 29.2, 29.3, 29.4, 29.6, 31.5, 36.8, 39.7, 111.3, 112.8,
18.6, 119.3, 122.0, 127.3, 127.8, 128.0, 130.0, 130.2, 136.4, 173.2.
1H), 7.20 (td, J = 8.1 Hz, J = 1.2 Hz, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.64 (d,
13
J = 7.5 Hz, 1H), 8.18 (s, 1H). C NMR (75 MHz, CDCl
22.7, 25.8, 27.4, 27.5, 29.4, 29.6, 29.7, 30.1, 31.9, 50.0, 111.1, 114.1,
3
) d ppm: 14.1,
ꢁ1
IR
m cm : 3386, 3264, 3010, 2920, 2851, 1650, 1629, 1555, 1456,
ꢁ1
118.9, 119.2, 121.8, 122.0, 128.4, 133.4. IR
m cm : 3387, 2916, 2649,
1
8
425, 1377, 1340, 1299, 1269, 1225, 1126, 1094, 1069, 1011, 931,
01, 739, 719, 608, 580, 560. MS(ESI) m/z: 445 ([M+Na] , 100). Anal.
+
1630, 1454, 1341, 1222, 1104, 1011, 914, 874, 805, 739, 721, 611, 592.
MS(ESI) m/z: 371 ([M+H] , 100). ESI-HRMS Calcd for [M+H]
+
+
Calcd for C28
42
H N
2 2
Oꢀ1.0H 0: C, 79.20, H, 10.44, N, 6.60. Found: C,
C
25
42 2
H N : 371.3426. Found: 371.3419.
7
9.33, H, 10.37, N, 6.46.
3
.3.3.3. N-(2-(1H-Indol-3-yl)ethyl)hexadecan-1-amine (4c). Com-
3
.3.2.9. N-(2-(1H-Indol-3-yl)ethyl)-15-hydroxypentadecanamide
1
pound 4c (121 mg, 70%). H NMR (300 MHz, CDCl
J = 6.9 Hz, 3H), 1.25 (m, 26H), 1.47 (m, 2H), 2.61 (t, J = 7.2 Hz, 2H),
3
) d ppm: 0.88 (t,
(
3). To a solution of tryptamine (320 mg, 2 mmol, 1 equiv) and
hydroxypentadecanoic acid (518 mg, 2 mmol, 1 equiv) in dichloro-
methane (40 mL) under nitrogen at room temperature was added
triethylamine (6 mmol, 3 equiv), EDC (768 mg, 4 mmol, 2 equiv)
and HOBt (405 mg, 3 mmol, 1.5 equiv). The mixture was stirred
overnight at room temperature then quenched by adding water
2
1
.97 (m, 4H), 7.04 (d, J = 1.8 Hz, 1H), 7.11 (td, J = 8.1 Hz, J = 1.2 Hz,
H), 7.19 (td, J = 8.1 Hz, J = 1.2 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.62
13
(d, J = 7.8 Hz, 1H), 8.21 (s, 1H). C NMR (75 MHz, CDCl
3
) d ppm: 14.1,
2
1
2
6
2.7, 25.6, 27.3, 29.3, 29.5, 29.6, 29.7, 29.8, 30.0, 31.9, 50.0, 111.1,
13.8, 118.8, 119.2, 122.0, 127.4, 136.4. IR
849, 1621, 1454, 1341, 1222, 1105, 1011, 910, 886, 803, 739, 721,
11, 592. MS(ESI) m/z: 385 ([M+H] , 100). ESI-HRMS Calcd for
ꢁ1
m cm : 3139, 3053, 2916,
(
(
20 mL) and extracted three times with dichloromethane
3 ꢂ 60 mL). The combined organic layers were washed three times
+
dichloromethane (3 ꢂ 30 mL). Combined organic layers were
+
[M+H] C26
44 2
H N : 385.3583. Found: 385.3569.
washed with a saturated NH
MgSO , filtered and concentrated in vacuo. A flash chromatography
on silica gel with a mixture of cyclohexane and ethyl acetate (95:5)
4
Cl aqueous solution then dried over
4
3.3.3.4. N-(2-(1H-Indol-3-yl)ethyl)heptadecan-1-amine (4d). Com-
pound 4d (122 mg, 90%). H NMR (300 MHz, CDCl ) d ppm: 0.88 (t,
3
1
1
led to a clear beige powder (182 mg, 60%). H NMR (400 MHz, CDCl
3
)
d ppm: 1.25 (m, 22H), 1.57 (m, 4H), 2.09 (t, J = 7.2 Hz, 2H), 2.98 (t,
J = 6.8 Hz, 2H), 3.59-3.65 (m, 4H), 5.48 (s, 1H), 7.04 (d, J = 1.6 Hz,
J = 6.9 Hz, 3H), 1.25 (m, 28H), 1.46 (m, 2H), 2.61 (t, J = 7.2 Hz, 2H), 2.97
(m, 4H), 7.05 (d, J = 2.1 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.20 (t, J = 7.5 Hz,
1H), 7.37 (d, J = 8.1 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 8.05 (s, 1H). 13C NMR
1
H), 7.13 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.38 (d,
1
3
J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 8.06 (s, 1H). C NMR
100 MHz, CDCl ) d ppm: 24.8, 25.4, 25.7, 26.3, 29.3, 29.4, 29.5,
0.4, 39.6, 63.1, 105.1, 111.2, 118.5, 118.8, 119.5, 121.9, 122.3,
(75 MHz, CDCl
50.0, 111.1, 114.2, 118.9, 119.2, 121.8, 122.0, 127.5, 136.4. IR
3141, 3064, 2916, 2849, 1622, 1505, 1454, 1358, 1342, 1223, 1105,
3
) d ppm: 14.1, 22.7, 25.9, 27.4, 29.3, 29.6, 29.7, 30.2, 31.9,
ꢁ
1
(
3
m cm :
3