194 Gundersen et al.
Arch. Pharm. Pharm. Med. Chem. 2003, 336, 191–195
HRMS: Calcd. for C29H22N2O: 414.1732; found 414.1718. –
Anal: Found: C, 81.16; H, 5.43; N, 6.29. C29H22N2O requires C,
84.03; H, 5.35; N, 6.76%.
ammonium chloride (1 mL) was carefully added to the resulting
mixture before it was evaporated in vacuo. EtOAc (100 mL), di-
ethyl ether (100 mL), and saturated aqueous ammonium chlo-
ride (100 mL) were added to the residue.The phases were sep-
arated and the organic layer washed with water (100 mL), dried
(MgSO4), and evaporated in vacuo.The product was purified by
flash chromatography eluting with EtOAc-hexane (1:29) fol-
lowed by (1:19), (1:9), (1:4), and finally (1:1). Yield 107 mg
(72%), yellow crystals. – Mp. 204–206°C. – Rf = 0.31 (SiO2,
1-[1-Hydroxycyclohexylmethyl]-2,3-diphenyl-7-indolizinecar-
bonitrile (5e)
The compound was prepared as described for compound 5d
and purified by flash chromatography eluting with EtOAc-
hexane (1:39) followed by (1:9). Yield 257 mg (63%), yellow
powdery crystals. – Mp 204–206 °C. – Rf = 0.28 (SiO2, EtOAc-
1
EtOAc-hexane, 1:4). – H-NMR (300 MHz, CDCl3): δ (ppm) =
1
1.7 (br s, 1H, –OH), 4.88 (s, 2H, CH2), 6.55 (dd, J = 7.4 and
1.8 Hz, 1H, H-6), 7.20–7.30 (m, 5H, Ph), 6.95–7.10 (m, 2H,
Ph), 7.30–7.43 (m, 3H, Ph), 8.00 (dd, J = 7.4 and 1.0 Hz, 1H,
H-5), 8.07 (dd, J = 1.8 and 1.0 Hz, 1H, H-8). – 13C-NMR
(75 MHz, CDCl3): δ (ppm) = 55.3, 99.4, 110.6, 116.1, 119.1,
122.5, 124.9, 125.9, 127.2, 128.3, 128.5, 129.1, 129.5, 129.8,
130.3, 130.4, 130.5, 133.2.– MS (EI):324 (M+, 100), 307 (100),
305 (15), 292 (12), 229 (5), 203 (7), 153 (16). – HRMS: Calcd.
for C22H16N2O: 324.1263; found 324.1271.
hexane, 1:4). – H-NMR (500 MHz, CDCl3): δ (ppm) = 0.67–
0.71 (m, 1H, c-hex), 0.96–1.28 (m, 4H, c-hex), 1.56–1.59 (m,
3H, c-hex), 1.72–1.78 (m, 2H, c-hex), 1.96 (d, J = 2.5 Hz, 1H,
OH), 2.04 (m, 1H, c-hex), 4.66 (dd, J = 8.5 and 2.5 Hz, 1H,
CH), 6.52 (dd, J = 7.4 and 1.8 Hz, 1H, H-6), 7.13–7.33 (m,
10H, Ph), 7.99 (dd, J = 7.4 and 0.9 Hz, 1H, H-5), 8.23 (dd, J =
1.8 and 0.9 Hz, 1H, H-8). – 13C-NMR (125 MHz, CDCl3): δ
(ppm) = 25.8, 26.0, 26.2, 29.6, 29.7, 45.6, 73.0, 98.5, 110.2,
119.3, 119.4, 122.4, 125.8, 127.0, 127.1, 127.9, 128.1, 128.2,
128.9, 129.8, 130.2, 130.4, 130.7, 133.9. – MS (EI): 406 (M+,
13), 388 (19), 324 (36), 323 (100), 307 (10), 294 (7), 217 (5). –
HRMS: Calcd. for C28H26N2O: 406.2045; found 406.2055.
1-(1-Hydroxyetyl)-2,3-diphenyl-7-indolizinecarbonitrile (5b)
Methyllithium (0.309 mL of a 1.6 M solution in hexane,
0.495 mmol) was added dropwise to a stirred solution of com-
pound 4a (145 mg, 0.45 mmol) in dry THF (20 mL) at –78°C
under N2.The reaction mixture was stirred at –78°C for 4 h be-
fore saturated aqueous ammonium chloride (1 mL) was added
dropwise.The reaction mixture was heated to ambient temper-
ature and EtOAc (100 mL), diethyl ether (100 mL), and saturat-
ed aqueous ammonium chloride (100 mL) were added. The
phases were seperated and the organic layer washed with wa-
ter (100 mL), dried (MgSO4), and evaporated in vacuo. The
product was purified by flash chromatography eluting with
EtOAc-hexane (1:29) followed by (1:19), (1:9), and finally (1:4).
Yield 148 mg (97%), yellow crystals. – Mp 197–198°C. – Rf =
0.35 (SiO2, EtOAc-hexane, 1:4). – 1H-NMR (200 MHz, CDCl3):
δ (ppm) = 1.68 (d, J = 13.0 Hz, 3H, CH3), 2.12 (br d, J = 2.2 Hz,
1H, OH), 5.27 (dq, J = 13.0 and 2.2 Hz, 1H, CH), 6.58 (dd, J =
7.4 and 1.8 Hz, 1H, H-6), 7.15–7.45 (m, 10H, Ph), 8.05 (dd, J =
7.4 and 1.0 Hz, 1H, H-5), 8.39 (dd, J = 1.8 and 1.0 Hz, 1H, H-8).
– MS (EI): 338 (M+, 42), 323 (100), 320 (78), 319 (82), 293 (7),
242 (9), 215 (10), 152 (8). – HRMS: Calcd. for C23H18N2O:
338.1419; found 338.1429.
1-[1-Hydroxy(4-chlorophenyl)methyl]-2,3-diphenyl-7-indol-
izinecarbonitrile (5f)
The compound was prepared as described for compound 5d
above and purified by flash chromatography, eluting with
EtOAc-hexane (1:29) followed by (1:9). Yield 183 mg (84%),
yellow crystals. – Mp 186–188 °C. – Rf = 0.25 (SiO2, EtOAc-
hexane, 1:4). – 1H-NMR (500 MHz, CDCl3): δ (ppm) = 2.26 (d,
J = 3.4 Hz, 1H, OH), 6.12 (d, J = 3.4 Hz, 1H, CH), 6.54 (dd, J =
7.4 and 1.7 Hz, 1H, H-6), 7.10–7.39 (m, 14H, Ph), 7.92 (br s,
1H, H-8), 8.01 (br d, J = 7.4 Hz, 1H, H-5). – 13C-NMR
(125 MHz, CDCl3): δ (ppm) = 69.3, 99.9, 111.1, 119.3, 119.5,
123.1, 126.3, 126.9, 127.8, 128.2, 128.8, 128.9, 129.0, 129.5,
129.9, 130.6, 130.7, 131.0, 133.6, 133.7, 142.4.– MS (EI):436/
434 (M+, 35/100), 418 (25), 417 (43), 323 (50), 293 (19), 292
(20), 139 (12), 195 (17), 77 (11). – HRMS: Calcd. for
C28H19ClN2O: 434.1186; found 434.1311. – Anal: Found: C,
77.00;H, 4.73;N, 6.05.C28H19ClN2O requires C, 77.33;H, 4.40;
N, 6.44%.
1-[1-Hydroxy(4-methylphenyl)methyl]-2,3-diphenyl-7-indol-
izinecarbonitrile (5g)
1-[1-Hydroxy-1-phenylethyl]-2,3-diphenyl-7-indolizinecarboni-
The compound was prepared as described for compound 5d
above and purified by flash chromatography, eluting with
EtOAc-hexane (1:29) followed by (1:9). Yield 115 mg (55%),
yellow crystals. – Mp 158–160°C. – Rf = 0.23 (SiO2, EtOAc-
hexane, 1:4). – 1H-NMR (500 MHz, CDCl3): δ (ppm) = 2.34 (s,
4H, OH and CH3), 6.11 (s, 1H, CH), 6.51 (dd, J = 7.3 and
1.3 Hz, 1H, H-6), 7.12–7.37 (m, 14H, Ph), 7.97 (br s, 1H, H-8),
8.06 (br d, J = 7.3 Hz, 1H, H-5). – 13C-NMR (125 MHz, CDCl3):
δ (ppm) = 21.1, 69.3, 98.9, 110.4, 119.5, 112.4, 125.3, 125.6,
125.8, 126.9, 127.1, 127.8, 128.1, 128.3, 128.9, 129.1, 129.7,
130.1, 130.2, 130.6, 133.4, 137.1, 140.6. – MS (EI): 414 (M+,
100), 413 (10), 398 (24), 397 (48), 323 (39), 321 (10), 295 (15),
91 (7), 91 (6). – HRMS: Calcd. for C29H22N2O: 414.1732; found
414.1725.
trile (5d)
n-Butyllithium (0.42 mL of a 1.32 M solution in hexane,
0.56 mmol) was added dropwise to a stirred solution of com-
pound 2a (187 mg, 0.50 mmol) in dry THF (10 mL) at –78°C
under N2. After 30 min, acetophenone (0.177 mL, 1.50 mmol)
was added and the resulting mixture was stirred for additional
1.5 h. EtOAc (50 mL), diethyl ether (50 mL), and saturated
aqueous ammonium chloride (30 mL) were added to the cold
reaction mixture. The phases were separated and the organic
layer was washed with water (3 × 30 mL), dried (MgSO4), and
evaporated in vacuo.The product was purified by flash chroma-
tography eluting with EtOAc-hexane (1:29) followed by (1:9).
Yield 47 mg (22%), yellow powdery crystals. – Mp 170–171°C,
1
– Rf = 0.33 (SiO2, EtOAc-hexane, 1:4). – H-NMR (500 MHz,
1-[1-Hydroxy(4-methoxyphenyl)methyl]-2,3-diphenyl-7-indol-
izinecarbonitrile (5h)
CDCl3):δ (ppm) = 1.77 (s, 3H, CH3), 2.31 (s, 1H, OH), 6.49 (dd,
J = 7.3 and 1.4 Hz, 1H, H-6), 6.86 (m, 2H, Ph), 7.04–7.18 (m,
5H, Ph), 7.2–7.4 (m, 8H, Ph), 7.91 (br d, 1H, J = 7.3 Hz, H-5),
8.31 (br s, 1H, H-8). – 13C-NMR (125 MHz, CDCl3): δ (ppm) =
32.6, 76.4, 99.3, 110.4, 120.0, 122.9, 124.1, 126.1, 127.4,
127.5, 127.6, 127.9, 128.0, 128.6, 128.6, 129.1, 129.8, 130.1,
130.7, 131.5, 135.3, 148.8, one signal was hidden. – MS (EI):
414 (M+, 4), 397 (27), 396 (100), 319 (18), 291 (8), 159 (6). –
The compound was prepared as described for compound 5d
above and purified by flash chromatography, eluting with
EtOAc-hexane (1:29) followed by (1:9). Yield 162 mg (75%),
yellow crystals. – Mp 111–112°C. – Rf = 0.25 (SiO2, EtOAc-
hexane, 1:4). – 1H-NMR (300 MHz, CDCl3): δ (ppm) = 2.42 (s,
1H, OH), 3.79 (s, 3H, OCH3), 6.11 (s, 1H, CH), 6.51 (dd, J = 7.2