Less Lipophilic Derivatives of PMS1062
FULL PAPER
room temperature for 12 h. The solvent was then removed, and the
product was taken up in AcOEt, washed with water, dried with
MgSO4, and filtered, and the solvents were evaporated. The residue
was purified on a silica gel column with 30% dichloromethane in
petroleum ether to yield 2a (1.1 g, 91%) as a pale yellow oil: 1H
NMR (200 MHz, CDCl3): δ = 2.17 (m, 2 H, CH2), 3.54 (s, 2 H,
yield the amidoxime 3b (2.4 g, 85%) as a viscous yellow product.
1H NMR (200 MHz, CDCl3): δ = 1.43 (t, 2 H, CH2), 1.71 (m, J =
7.1 Hz, 4 H, CH2), 3.31 (s, 2 H, CH2–C=N), 3.81 (t, J = 6.28 Hz,
2 H, CH2O), 4.00 (t, J = 6.9 Hz, 2 H, CH2N), 4.39 (s, 2 H, NH2),
6.39 (d, J = 3.12 Hz, 1 H, Hind), 6.74 (d, J = 8.60, 2 H, Ph-H),
6.98–7.16 (m, 3 H, Hind), 7.07 (d, J = 8.60 Hz, 2 H, Ph-H), 7.28
CH2CN), 3.74 (t, J = 5.74 Hz, 2 H, CH2O), 4.26 (t, J = 6.56 Hz, (d, J = 7.44 Hz, 1 H, Hind), 7.55 (d, J = 7.13 Hz, 1 H, Hind) ppm.
2 H, CH2N), 6.40 (d, J = 3.10 Hz, 1 H, Hind), 6.76 (d, J = 8.40 Hz,
2 H, Ph-H), 6.96–7.06 (m, 3 H, Hind), 7.11 (d, J = 8.40, 2 H, Ph-
H), 7.27 (d, J = 8.02 Hz, 1 H, Hind), 7.55 (d, J = 7.68 Hz, 1 H,
Hind) ppm. 13C NMR (50 MHz, CDCl3): δ = 22.67, 29.63, 42.55,
64.26, 101.22, 109.20, 114.96, 118.12, 119.28, 120.92, 121.46,
13C NMR (50 MHz, CDCl3): δ = 23.55, 28.83, 29.95, 36.71, 46.20,
67.55, 100.92, 109.27, 114.72, 119.16, 120.91, 121.31, 127.67,
127.73, 128.52, 129.87, 135.85, 153.28, 158.09 ppm. IR (neat): ν =
˜
3496, 3391 (NH2), 3180 (OH), 1663 (C=N) cm–1.
N-Hydroxy-2-{4-[3-(indol-1-yl)propoxy]phenyl}acetamidine
(3a):
121.97, 127.99, 128.54, 129.05, 135.80, 158.31 ppm. IR (neat): ν =
˜
1
64% (yellow oil). H NMR (200 MHz, CDCl3): δ = 2.17 (quintt, J
= 6.30 Hz, 2 H, CH2), 3.32 (s, 2 H, CH2CN), 3.75 (t, J = 5.70 Hz,
2 H, CH2O), 4.27 (t, J = 6.58 Hz, 2 H, CH2N), 4.41 (s, 2 H, NH2),
2249 (CN), 1611 (C=C) cm–1.
{4-[5-(Indol-1-yl)pentoxy]phenyl}acetonitrile (2b): 75% (green oil):
1H NMR (200 MHz, CDCl3): δ = 1.37 (m, 2 H, CH2), 2.17 (m, 4 6.40–7.56 (m, 10 H, Har) ppm. 13C NMR (50 MHz, CDCl3): δ =
H, CH2), 3.52 (s, 2 H, CH2CN), 3.79 (t, J = 6.35 Hz, 2 H, CH2O), 29.71, 36.71, 42.65, 64.24, 101.20, 109.25, 114.75, 119.29, 120.93,
4.26 (t, J = 6.94 Hz, 2 H, CH2N), 6.40–7.57 (m, 10 H, Har) ppm. 121.46, 128.01, 128.08, 128.58, 129.94, 135.83, 153.22, 157.80 ppm.
13C NMR (50 MHz, CDCl3): δ = 22.61, 23.44, 28.70, 29.86, 46.10, IR (neat): ν = 3493, 3435 (NH ), 3207 (OH), 1661 (C=N) cm–1.
˜
2
67.58, 100.87, 109.25, 114.93, 115.86, 118.18, 119.12, 120.86,
N-Hydroxy-2-{4-[6-(indol-1-yl)hexoxy]phenyl}acetamidine (3c): 80%
121.26, 121.57, 127.71, 128.48, 128.95, 129.06, 135.80, 158.58 ppm.
(yellow oil). 1H NMR (200 MHz, CDCl3): δ = 1.34 (m, 4 H, CH2),
IR (neat): ν = 2249 (CN), 1612 (C=C) cm–1.
˜
1.71 (m, 4 H, CH2), 3.31 (s, 2 H, CH2CN), 3.80 (t, J = 6.26 Hz, 2
{4-[6-(Indol-1-yl)hexoxy]phenyl}acetonitrile (2c): 85% (yellow oil):
H, CH2O), 4.04 (t, J = 7.00 Hz, 2 H, CH2N), 4.41 (s, 2 H, NH2),
1H NMR (200 MHz, CDCl3): δ = 1.35 (m, 4 H, CH2), 1.65 (m, 4 6.40–7.56 (m, 10 H, Har) ppm. 13C NMR (50 MHz, CDCl3): δ =
H, CH2), 3.53 (s, 2 H, CH2CN), 3.80 (t, J = 6.30 Hz, 2 H, CH2O), 25.66, 26.66, 29.02, 30.10, 36.65, 46.18, 67.64, 100.84, 109.27,
4.02 (t, J = 7.01 Hz, 2 H, CH2N), 6.40–7.57 (m, 10 H, Har) ppm. 114.71, 119.14, 120.885, 121.26, 127.50, 127.70, 128.49, 129.85,
13C NMR (50 MHz, CDCl3): δ = 22.77, 25.71, 26.71, 29.02, 30.16, 135.85, 153.25, 158.16 ppm. IR (neat): ν = 3493, 3381 (NH ), 3223
˜
2
46.25, 67.80, 100.92, 109.35, 115.04, 118.27, 119.19, 120.96, 121.34, (OH), 1661 (C=N) cm–1.
121.63, 127.78, 128.58, 129.05, 135.93, 158.77 ppm. IR (neat): ν =
˜
N-Hydroxy-2-{4-[7-(indol-1-yl)heptoxy]phenyl}acetamidine
84% (yellow oil). H NMR (200 MHz, CDCl3): δ = 1.31 (m, 6 H,
CH2), 1.70 (m, 4 H, CH2), 3.32 (s, 2 H, CH2CN), 3.80 (t, J =
(3d):
2249 (CN), 1612 (C=C) cm–1.
1
{4-[7-(Indol-1-yl)heptoxy]phenyl}acetonitrile (2d): 61% (orange oil).
1H NMR (200 MHz, CDCl3): δ = 1.30 (m, 6 H, CH2), 1.69 (m, 4 6.39 Hz, 2 H, CH2O), 4.04 (t, J = 7.04 Hz, 2 H, CH2N), 4.39 (s, 2
H, CH2), 3.55 (s, 2 H, CH2CN), 3.80 (t, J = 6.38 Hz, 2 H, CH2O), H, NH2), 6.40–7.56 (m, 10 H, Har) ppm. 13C NMR (50 MHz,
4.02 (t, J = 7.02 Hz, 2 H, CH2N), 6.40–7.57 (m, 10 H, Har) ppm. CDCl3): δ = 25.90, 26.90, 28.95, 29.10, 30.14, 36.72, 46.33, 67.82,
13C NMR (50 MHz, CDCl3): δ = 22.69, 25.81, 26.84, 28.90, 28.98, 100.83, 109.31, 114.77, 119.13, 120.91, 121.27, 127.45, 127.73,
30.08, 46.26, 67.84, 100.79, 109.27, 114.96, 118.18, 119.08, 120.85, 128.52, 129.87, 135.89, 153.36, 158.28 ppm. IR (neat): ν = 3495,
˜
121.22, 121.50, 127.69, 128.46, 128.96, 135.85, 158.74 ppm. IR 3386 (NH2), 3199 (OH), 1663 (C=N) cm–1.
(neat): ν = 2248 (CN), 1612 (C=C) cm–1.
˜
N-Hydroxy-2-{4-[8-(indol-1-yl)butoxy]phenyl}acetamidine
(3e):
1
{4-[8-(Indol-1-yl)octoxy]phenyl}acetonitrile (2e): 70% (yellow oil):
62%, (yellow oil). H NMR (200 MHz, CDCl3): δ = 1.26 (m, 8 H,
1H NMR (200 MHz, CDCl3): δ = 1.25 (m, 8 H, CH2), 1.69 (m, 4 CH2al), 1.65 (m, 4 H, CH2al), 3.31 (s, 2 H, CH2CN), 3.82 (t, J =
H, CH2), 3.54 (s, 2 H, CH2CN), 3.81 (t, J = 6.41 Hz, 2 H, CH2O), 6.33 Hz, 2 H, CH2O), 4.02 (t, J = 7.01 Hz, 2 H, CH2N), 4.39 (s, 2
4.01 (t, J = 7.03 Hz, 2 H, CH2N), 6.40–7.57 (m, 10 H, Har) ppm. H, NH2), 6.40–7.56 (m, 10 H, Har) ppm. 13C NMR (50 MHz,
13C NMR (50 MHz, CDCl3): δ = 22.73, 25.86, 26.86, 29.06, 29.10, CDCl3): δ = 25.89, 26.87, 29.13, 30.16, 36.72, 46.32, 67.87, 100.79,
30.15, 46.31, 67.95, 100.78, 109.31, 115.00, 118.21, 119.09, 120.87, 109.31, 114.74, 119.10, 120.88, 121.23, 127.53, 127.73, 128.51,
121.23, 121.50, 127.72, 128.50, 128.98, 135.88, 158.80 ppm. IR 129.86, 135.88, 153.30, 158.26 ppm. IR (neat): ν = 3495, 3387
˜
(neat): ν = 2249 (CN), 1612 (C=C) cm–1.
(NH2), 3208 (OH), 1663 (C=N) cm–1.
˜
{4-[10-(Indol-1-yl)decoxy]phenyl}acetonitrile (2f): 70% (yellow oil):
N-Hydroxy-2-{4-[10-(indol-1-yl)decoxy]phenyl}acetamidine
(3f):
1H NMR (200 MHz, CDCl3): δ = 1.21 (m, 12 H, CH2), 1.68 (m, 4 89%, (yellow oil). 1H NMR (200 MHz, CDCl3): δ = 1.21 (m, 12
H, CH2), 3.55 (s, 2 H, CH2CN), 3.84 (t, J = 6.50 Hz, 2 H, CH2O), H, CH2al), 1.70 (m, 4 H, CH2al), 3.32 (s, 2 H, CH2CN), 3.84 (t, J
4.02 (t, J = 7.10 Hz, 2 H, CH2N), 6.40–7.57 (m, 10 H, Har) ppm. = 6.37 Hz, 2 H, CH2O), 4.03 (t, J = 7.01 Hz, 2 H, CH2N), 4.39 (s,
13C NMR (50 MHz, CDCl3): δ = 22.72, 25.90, 26.93, 29.11, 29.15, 2 H, NH2), 6.40–7.56 (m, 10 H, Har) ppm. 13C NMR (50 MHz,
29.22, 29.33, 30.17, 46.31, 68.02, 100.75, 109.31, 115.00, 118.20, CDCl3): δ = 25.95, 26.95, 29.19, 29.37, 30.19, 36.72, 46.35, 67.97,
119.07, 120.86, 121.21, 121.47, 127.72, 128.50, 128.97, 135.87,
100.76, 109.32, 114.76, 119.08, 120.87, 121.22, 127.42, 127.74,
158.83 ppm. IR (neat): ν = 2249 (CN), 1611 (C=C) cm–1.
128.51, 129.85, 135.89, 153.35, 158.32 ppm. IR (neat): ν = 3487,
˜
˜
3346 (NH2), 3234 (OH), 1663 (C=N) cm–1.
N-Hydroxy-2-{4-[5-(indol-1-yl)pentoxy]phenyl}acetamidine (3b): A
mixture of the nitrile 2b (2.50 g, 7.86 mmol), hydroxylamine hydro-
chloride (3.00 g, 43.2 mmol), and K2CO3 (6.00 g, 43.5 mmol) in ab-
3-{4-[3-(Indol-1-yl)propoxy]benzyl}-4H-1,2,4-oxadiazol-5-one (II):
Phenyl chloroformate (0.38 mL, 2.97 mmol) was added dropwise to
solute EtOH (100 mL) was heated at reflux for 18 h. The salts were a solution of the amide oxime 3a (0.80 g, 2.47 mmol) and Et3N
filtered and washed with hot absolute EtOH (2×30 mL), and the
filtrate was concentrated under reduced pressure. The residue was
chromatographed on a silica gel column with CH2Cl2 as eluent to
(0.52 mL, 3.71 mmol) in CH2Cl2 (50 mL), cooled in an ice bath.
After stirring at 0 °C for 1 h, the solution was washed with water
(2×25 mL), dried (MgSO4), and concentrated in vacuo. The resi-
Eur. J. Org. Chem. 2005, 2747–2757
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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