Arch. Pharm. Chem. Life Sci. 2007, 340, 154–158
New Niphathesine Analogues
157
2.08 (t, J = 7.4 Hz, 2 H, CH2), 2.41 (t, J = 7.5 Hz, 2 H, CH2), 5.22 (s,
1H, NH), 6.50 (m, 1 H, aromat. CH), 7.22 (m, 2 H, 2 aromat. CH),
7.30 (ddd, J = 0.6 Hz, J = 0.6 Hz, J = 8.3 Hz, 1 H, aromat. CH), 7.72
(m, 1 H, aromat. CH), 8.28 (s, 1 H, NH). 13C-NMR (CDCl3) d (ppm) =
19.47 (CH2), 25.79 (CH2), 28.85 (3 CH3), 28.88 (CH2), 28.94 (CH2),
29.04 (CH2), 29.18 (CH2), 29.27 (CH2), 37.77 (CH2), 51.06 (quart. C),
81.72 (quart. C), 87.49 (quart. C), 102.65 (C-3`), 110.92 (C-7`),
115.21 (quart. C), 124.27 (aromat. CH), 124.99 (aromat. CH),
125.65 (aromat. CH), 127.73 (quart. C), 135.06 (quart. C), 172.58
(CO). MS (CI): m/z (%) = 353 [M++1] (100), 236 (55), 130 (50). HR-MS:
Calcd.: 352.2515, Found: 352.2476.
Undec-10-ynoic acid (1-phenylethyl)amide 5d
The compound was prepared as described for 5a from 500 mg
(2.7 mmol) undec-10-ynoic acid and 653 mg (5.4 mmol) 1-phenyl-
ethyl amine to give 620 mg (80%) of 5d. 1H-NMR (CDCl3) d (ppm) =
1.28 (m, 6 H, 3 CH2), 1.36 (m, 2 H, CH2), 1.48 (d, J = 7.0 Hz, 3 H,
CH3), 1.50 (m, 2 H, CH2), 1.62 (m, 2 H, CH2), 1.92 (t, J = 2.3 Hz, 1 H,
CH), 2.16 (m, 4 H, 2 CH2), 5.14 (q, J = 7.0 Hz, 1 H, CH), 5.69 (s, 1 H,
NH). 13C-NMR (CDCl3) d (ppm) = 18.35 (CH2), 21.67 (CH3), 25.68
(CH2), 28.40 (CH2), 28.63 (CH2), 28.90 (CH2), 29.16 (2 CH2), 36.83
(CH2), 48.56 (CH), 68.08 (quart. C), 84.66 (CH), 126.16 (2 aromat.
CH), 127.33 (aromat. CH), 128.64 (2 aromat. CH), 143.21 (quart.
C), 172.09 (CO). MS (CI): m/z (%) = 286 [M++1] (100). HR-MS: Calcd.:
285.2093, Found: 285.2054.
11-(Pyridin-3-yl)-undec-10-ynoic acid benzylamide 6c
The compound was prepared as described for 6a from 400 mg
(2.0 mmol) 3-iodopyridine and 500 mg (1.95 mmol) 5c to give
476 mg (75%) of 6c. 1H-NMR (CDCl3) d (ppm) = 1.33 (m, 6 H, 3 CH2),
1.44 (m, 2 H, CH2), 1.61 (m, 2 H, CH2), 1.66 (m, 2 H, CH2), 2.22 (t, J =
7.9 Hz, 2 H, CH2), 2.42 (t, J = 7.5 Hz, 2 H, CH2), 4.45 (d, J = 5.9 Hz, 2
H, CH2), 5.83 (s, 1 H, NH), 7.21 (dd, J = 5.0 Hz, J = 7.9 Hz, 1 H, aro-
mat. CH), 7.28 (m, 3 H, 3 aromat. CH), 7.34 (m, 2 H, 2 aromat. CH),
7.67 (ddd, J = 7.7 Hz, J = 1.7 Hz, J = 1.7 Hz, 1 H, aromat. CH), 8.47 (s,
1 H, aromat. CH), 8.63 (s, 1 H, aromat. CH). 13C-NMR (CDCl3) d
(ppm) = 19.41 (CH2), 25.73 (CH2), 28.47 (CH2), 28.79 (CH2), 28.93
(CH2), 29.19 (CH2), 29.25 (CH2), 36.78 (CH2), 43.58 (CH2), 77.42
(quart. C), 94.09 (quart. C), 126.00 (quart. C), 127.48 (aromat. CH),
127.83 (2 aromat. CH), 128.69 (2 aromat. CH), 138.38 (aromat.
CH), 138.43 (quart. C), 147.86 (aromat. CH), 152.33 (aromat. CH),
172.89 (CO).
1-Morpholin-4-yl-undec-10-yn-1-one 5e
The compound was prepared as described for 5a from 2.15 g
(11.7 mmol) undec-10-ynoic acid and 2.03 g (23.4 mmol) mor-
1
pholine to give 2.94 g (100%) of 5e as a pale yellow oil. H-NMR
(CDCl3) d (ppm) = 1.32 (m, 8 H, 4 CH2), 1.52 (tt, J = 7.0 Hz, J = 7.0 Hz,
2 H, CH2), 1.63 (m, 2 H, CH2), 1.94 (dt, J = 0.7 Hz, J = 2.6 Hz, 1 H,
CH), 2.18 (ddt, J = 0.6 Hz, J = 2.6 Hz, J = 7.0 Hz, 2 H, CH2), 2.31 (t, J =
8.1 Hz, 2 H, CH2), 3.46 (t, J = 5.3 Hz, 2 H, CH2), 3.62 (t, J = 5.1 Hz,
CH2), 3.67 (t, J = 5.3 Hz, 4 H, 2 CH2). 13C-NMR (CDCl3) d (ppm) =
18.38 (CH2), 25.21 (CH2), 28.43 (CH2), 28.67 (CH2), 28.94 (CH2),
29.27 (CH2), 29.40 (CH2), 33.10 (CH2), 41.86 (CH2), 46.04 (CH2),
66.70 (CH2), 66.97 (CH2), 68.11 (CH), 84.73 (quart. C), 171.83 (CO).
MS (CI): m/z (%) = 252 [M++1] (100), 129 (14). HR-MS: Calcd.:
251.1885, Found: 251.1921.
11-(1H-Indol-5-yl)-undec-10-ynoic acid (1-phenyl-
ethyl)amide 6a
11-(Pyridin-3-yl)-undec-10-ynoic acid isopropylamide 6d
The compound was prepared as described for 6a from 1.0 g
(4.9 mmol) 3-iodopyridine and 510 mg (2.3 mmol) of 5a to give
100 mg (0.5 mmol) CuI were dissolved in 50 mL dry EDMA, 1.7 g
(11.0 mmol) of 5d, 160 mg (0.2 mmol) PdCl2(PPh3)2 and 2.05 g
(10.0 mmol) 5-iodoindole were added. The mixture was stirred
for 24 h under N2 atmosphere. The solvent was evaporated and
the residue dissolved in 50 mL of 5% aqueous Na2S2O3 solution,
extracted with diethyl ether (3650 mL) and the combined
organic layers were dried over Na2SO4. The organic solvent was
evaporated and the residue purified by FCC (n-hexane, ethyl acet-
1
460 mg (67%) of 6d as a brown solid. H-NMR (CDCl3) d (ppm) =
1.14 (d, J = 6.8 Hz, 6 H, 2 CH3), 1.34 (m, 6 H, 3 CH2), 1.44 (m, 2 H,
CH2), 1.61 (m, 4 H, 2 CH2), 2.12 (t, J = 7.9 Hz, 2 H, CH2), 2.42 (t, J =
7.2 Hz, 2 H, CH2), 4.08 (h, J = 6.8 Hz, 1 H, CH), 5.29 (s, 1 H, NH),
7.21 (dd, J = 4.8 Hz, J = 7.8 Hz, 1 H, aromat. CH), 7.67 (ddd, J = 1.8
Hz, J = 1.8 Hz, J = 7.8 Hz, 1 H, aromat. CH), 8.48 (d, J = 4.3 Hz, 1 H,
aromat. CH), 8.63 (s, 1 H, aromat. CH). 13C-NMR (CDCl3) d (ppm) =
19.39 (CH2), 22.84 (2 CH3), 25.75 (CH2), 28.23 (CH2), 28.26 (CH2),
28.56 (CH2), 28.97 (CH2), 32.85 (CH2), 36.78 (CH2), 40.92 (CH),
77.00 (quart. C), 94.06 (quart. C), 122.87 (aromat. CH), 128.00
(quart. C), 138.37 (aromat. CH), 147.86 (aromat. CH), 152.32 (aro-
mat. CH), 172.10 (CO). MS (EI): m/z (%) = 300 [M+] (10), 242 (40),
200 (40), 172 (42), 130 (100). HR-MS: Calcd.: 300.2202, Found:
300.2171.
1
ate, EDMA; 20:3:1) to give 3.5 g (87%) of 6a. H-NMR (CDCl3) d
(ppm) = 1.32 (m, 8 H, 4 CH2), 1.47 (d, J = 7.7 Hz, 3 H, CH3), 1.61 (m,
2 H, CH2), 2.16 (t, J = 7.7 Hz, 2 H, CH2), 2.41 (t, J = 7.1 Hz, 2 H, CH2),
5.14 (m, 1 H, CH), 5.65 (s, 1 H, NH), 6.49 (m, 1 H, aromat. CH), 7.18
(dd, J = 2.5 Hz, J = 2.5 Hz, 1 H, aromat. CH), 7.22 (dd, J = 1.5 Hz, J =
8.6 Hz, 1 H, aromat. CH), 7.30 (m, 6 H, 6 aromat. CH), 7.71 (s, 1 H,
aromat. CH), 8.37 (s, 1 H, NH). 13C-NMR (CDCl3) d (ppm) = 19.42
(CH2), 21.68 (CH3), 25.71 (CH2), 28.79 (CH2), 28.89 (CH2), 28.96
(CH2), 29.17 (CH2), 48.54 (CH), 81.75 (quart. C), 87.44 (quart. C),
102.58 (aromat. CH), 110.92 (aromat. CH), 115.16 (quart. C),
124.23 (aromat. CH), 124.85 (aromat. CH), 125.60 (aromat. CH),
126.15 (2 aromat. CH), 127.31 (aromat. CH), 127.71 (quart. C),
128.64 (aromat. CH), 135.06 (quart. C), 143.27 (quart. C), 172.16
(CO). MS (CI): m/z (%) = 401 [M++1] (80), 284 (50), 169 (100). HR-MS:
Calcd.: 400.2515, Found: 400.2533.
1-Morpholin-4-yl-11-(pyridin-3-yl)-undec-10-yn-1-one 6e
The compound was prepared as described for 6a from 3.27 g
(16 mmol) 3 iodopyridine and 2.45 g (9.8 mmol) of 5a to give
2.38 g (74%) of 6d as a brown oil. 1H-NMR (CDCl3) d (ppm) = 1.35
(m, 6 H, 3 CH2), 1.44 (m, 2 H, CH2), 1.62 (m, 4 H, 2 CH2), 2.31 (t, J =
7.8 Hz, 2 H, CH2), 2.42 (t, J = 6.8 Hz, 2 H, CH2), 3.46 (t, J = 3.9 Hz, 2
H, CH2), 3.61 (t, J = 4.5 Hz, 2 H, CH2), 3.66 (t, J = 3.9 Hz, 2 H, CH2),
3.68 (t, J = 4.5 Hz, 2 H, CH2), 7.21 (dd, J = 5.0 Hz, J = 7.9 Hz, 1 H,
aromat. CH), 7.67 (ddd, J = 7.9 Hz, J = 1.6 Hz, J = 1.6 Hz, 1 H, aro-
mat. CH), 8.48 (dd, J = 1.6 Hz, J = 5.0 Hz, 1 H, aromat. CH), 8.63 (d, J
= 1.2 Hz, 1 H, aromat. CH). 13C-NMR (CDCl3) d (ppm) = 19.40 (CH2),
25.17 (CH2), 28.48 (CH2), 28.76 (CH2), 28.82 (CH2), 29.20 (CH2),
29.27 (CH2), 33.06 (CH2), 41.85 (CH2), 46.02 (CH2), 66.69 (CH2),
66.95 (CH2), 77.00 (quart. C), 94.04 (quart. C), 121.16 (quart. C),
11-(1H-Indol-5-yl)-undec-10-ynoic acid tert. butylamide
6b
The compound was prepared as described for 6a from 500 mg
(2.1 mmol) 5b and 510 mg (2.1 mmol) 5-iodoindole to give
1
590 mg (80%) of 6b. H-NMR (CDCl3) d (ppm) = 1.27 (m, 8 H, 4
CH2), 1.34 (s, 9 H, 3 CH3), 1.46 (m, 2 H, CH2), 1.61 (m, 2 H, CH2),
i 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim