Nov-Dec 2001
Synthesis of (S)-3-Heteroaryl-2-hydroxy-1-propyl Benzoates
1311
13.4 Hz, H–C(3)); 2.92 (1H, dd, J = 5.3, 13.6 Hz, H–C(3));
4.18–4.26 (3H, m, 2 H–C(1) and H–C(2)); 5.14 (1H, br d, J = 5.3
Hz, OH); 7.37–51 (3H, m, H–C(7') and 2H of Ph); 7.62 (1H, tt, J =
1.3, 7.5 Hz, 1H of Ph); 7.87–7.94 (4H, m, 2H of Ph, H–C(8'), and
H–C(9)); 8.06 (1H, s, H–C(2')); 9.10 (1H, d, J = 7.15 Hz, H–C(6')).
(ethyl acetate/petroleum ether, 2:1). Yield: 0.145 g (37%), m.p.
21
87–90 °C (from ethyl acetate). [α ]
–23.7° (c = 0.19,
D
–1
1
dichloromethane). IR(cm ): 3502 (OH), 1724 (C=O). H nmr
(deuteriochloroform): δ 2.61 (1H, br s, HO–C(2)); 2.81 (1H, dd,
J = 7.5, 14.3 Hz, H–C(3)); 2.94 (1H, dd, J = 3.0, 14.3 Hz,
H–C(3)); 4.37–4.41 (2H, m, H–C(1) and H–C(2)); 4.46–4.53
(1H, m, H–C(1)); 7.36–7.47 (4H, m, 2H of Ph, H–C(7'), and
H–C(9')); 7.56 (1H, tt, J = 1.3, 7.5 Hz, 1H of Ph); 7.63–7.72 (1H,
m, H–C(8')); 7.96 (1H, s, H–C(4')); 8.01–8.07 (2H, m, 2H of Ph).
Anal. Calcd. for C
H N O (348.36): C, 68.96; H, 4.63; N,
20 16 2 4
8.04. Found: C, 68.69; H, 4.63; N, 7.93.
(S)-3-(7,7-Dimethyl-2,5-dioxo-5,6,7,8-tetrahydro-2H-
benzo[b]pyran-3-yl)-2-hydroxy-1-pyropyl Benzoate (15).
Anal. Calcd. for C
H O (392.37): C, 67.35; H, 4.11. Found:
22 16 7
This compound was prepared from 5,5-dimethylcyclohexane-
C, 66.98; H, 4.01.
1,3-dione (9), heating for 7 hours, column chromatography (ethyl
(S)-2-Hydroxy-3-[5-hydroxy-1-(pyridin-2-yl)-1H-pyrazol-4-yl]-
1-pyropyl Benzoate (23).
21
acetate/petroleum ether, 1:1). Yield: 0.299 g (81%), oil. [α]
D
+
1
+25.0° (c = 0.10, dichloromethane). MS (EI): m/z = 370 (M ). H
nmr (dimethyl sulfoxide–d ): δ 1.14 (6H, s, 2 Me–C(7')); 2.40,
This compound was prepared from 2-hydrazinopyridine (19),
6
2.70 (2 x 2H, 2s, 2 H–C(6') and 2 H–C(8')); 2.71 (1H, dd, J = 7.9,
12.6 Hz, H–C(3)); 2.84 (1H, dd, J = 2.8, 14.5 Hz, H–C(3));
4.29–4.47 (3H, m, 2 H–C(1) and H–C(2)); 7.42–7.50 (2H, m, 2H
of Ph); 7.59 (1H, tt, J = 1.3, 7.5 Hz, 1H of Ph); 7.81 (1H, s,
H–C(4')); 8.02–8.08 (2H, m, 2H of Ph). C nmr (deuteriochloro-
form): δ 28.6, 28.7, 33.0, 41.8, 50.8, 68.5, 68.8, 114.1, 123.6,
heating for 2 hours, trituration with ethyl acetate. Yield: 0.064 g
22
(19%), m.p. 149–151 °C (from ethyl acetate). [α] –3.9° (c =
D
–1
1
0.33, dichloromethane). IR(cm ): 3287 (OH), 1714 (C=O). H
nmr (deuteriochloroform): δ 2.64 (1H, br s, HO–C(2)); 2.71 (1H,
dd, J = 6.9, 14.7 Hz, H–C(3)); 2.78 (1H, dd, J = 5.3, 14.7 Hz,
H–C(3)); 4.20–4.28 (1H, m, H–C(2)); 4.35 (1H, dd, J = 6.2, 11.5
Hz, H–C(1)); 4.44 (1H, dd, J = 3.9, 11.3 Hz, H–C(1)); 7.15–7.20
(1H, m, H–C(5'')); 7.40–7.47 (3H, m, 2H of Ph, H–C(3'))); 7.56
(1H, tt, J = 1.3, 7.2 Hz, 1H of Ph); 7.84–7.93 (2H, m, 2H of Ph);
8.04–8.10 (2H, m, H–C(3''), H–C(4'')); 8.23–8.29 (1H, m,
H–C(6'')); 12.69 (1H, br s, HO–C(5')).
13
128.8, 130.0, 130.1, 133.6, 137.7, 162.7, 167.0, 171.8, 194.6.
Anal. Calcd. for C
H O (370.40) x 1/2H O: C, 66.48; H,
21 22 6 2
6.11. Found: C, 66.14; H, 6.46. HRMS Calcd. for C
370.141639. Found: 370.142850.
H O :
21 22 6
(S)-2-Hydroxy-3-(10-hydroxy-2-oxo-2H-naphtho[2,1–b]pyran-
3-yl)-1-pyropyl Benzoate (16).
Anal. Calcd. for C
H N O (339.35): C, 63.71; H, 5.05; N,
18 17 3 4
12.38. Found: C, 63.45; H, 5.25; N, 11.99.
This compound was prepared from 2,3-dihydroxynaphthalene
(S)-2-Hydroxy-3-[5-hydroxy-1-(6-phenylpyridazin-3-yl)-1H-
pyrazol-4-yl]-1-pyropyl Benzoate (24).
(10), heating for 5 hours, trituration with dichloromethane. Yield:
22
0.056 g (14%), m.p. 198–200 °C (from dichloromethane). [α]
D
–1
–10° (c = 0.11, ethyl acetate). IR (cm ): 3347 (OH), 1724, 1699
(C=O). H nmr (dimethyl sulfoxide–d ): δ 2.79 (1H, dd, J = 7.5,
This compound was prepared from 3-hydrazino-6-phenylpyri-
dazine (20), heating for 3 hours, trituration with ethyl acetate.
Yield: 0.133 g (32%), m.p. 179–182 °C (from ethyl acetate).
1
6
13.6 Hz, H–C(3)); 2.91 (1H, dd, J = 4.5, 13.5 Hz, H–C(3));
4.28–4.32 (3H, m, 2 H–C(1) and H–C(2)); 5.25 (1H, br s, HO–C(2));
7.42 (1H, s, H–C(9')); 7.46–7.51 (4H, m, 2H of Ph, H–C(6'), and
H–C(7')); 7.64 (1H, tt, J = 1.3, 7.5 Hz, 1H of Ph); 7.79–7.83 (1H, m,
H–C(8')); 7.95–8.00 (2H, m, 2H of Ph); 8.34–8.39 (1H, m, H–C(5'));
8.75 (1H, s, H–C(4')); 10.23 (1H, br s, HO–C(10')).
22
–1
[α] –14.7° (c = 0.30, DMF). IR(cm ): 3525 (OH), 1698
D
1
(C=O). H nmr (dimethyl sulfoxide–d ): δ 2.74 (1H, dd, J = 7.2,
6
15.6 Hz, H–C(3)); 2.81 (1H, dd, J = 5.5, 14.9 Hz, H–C(3));
4.23–4.32 (1H, m, H–C(2)); 4.33–4.41 (1H, m, H–C(1));
4.42–4.50 (1H, m, H–C(1)); 7.40–7.48 (2H, m, 2H of Ph);
7.51–7.60 (5H, m, 4H of Ph, H–C(3'))); 7.99–8.11 (5H, m, 4H of
Ph, H–C(5'')); 8.21 (1H, br d, J = 8.7 Hz; H–C(4'')); 12.00 (1H, br
s, HO–C(5')).
Anal. Calcd. for C
H O (390.39): C, 70.76; H, 4.65. Found:
23 18 6
C, 70.42; H, 4.65.
(S)-3-(2,5-Dioxo-7-methyl-2H,5H-pyrano[4,3–b]pyran-3-yl)-2-
hydroxy-1-pyropyl Benzoate (17).
Anal. Calcd. for C
H N O (416.44): C, 66.34; H, 4.84; N,
23 20 4 4
13.45. Found: C, 65.90; H, 4.63; N, 13.02.
This compound was prepared from 4-hydroxy-6-methyl-2H-
pyran-2-one (11), heating for 5 hours, column chromatography
(S)-5-Benzoyloxymethyl-3-[(pyridin-2-yl)aminomethylidene]-
tetrahydrofuran-2-one (25).
(ethyl acetate/petroleum ether, 2:1). Yield: 0.117 g (33%), m.p.
21
This compound was prepared from 2-aminopyridine (21), heat-
92–96 °C (from ethyl acetate). [α ]
–24.0° (c = 0.20,
D
–1
ing for 3 hours, trituration with ethyl acetate. Yield: 0.144 g (44%),
dichloromethane). IR(cm ): 3517, 3463 (OH), 1748, 1729, 1702
(C=O). H nmr (deuteriochloroform): δ 2.35 (3H, s, Me–C(7'));
22
1
m.p. 177–179 °C (from ethyl acetate). [α] +118° (c = 0.81,
D
–1
1
dichloromethane). IR(cm ): 3447 (OH), 1719 (C=O). H nmr
2.74 (1H, dd, J = 7.9, 14.9 Hz, H–C(3)); 2.87 (1H, dd, J = 2.8, 14.5
Hz, H–C(3)); 4.29–4.49 (3H, m, 2 H–C(1) and H–C(2)); 6.17 (1H,
s, H–C(4')); 7.42–7.49 (2H, m, 2H of Ph); 7.59 (1H, tt, J = 1.3, 7.5
Hz, 1H of Ph); 7.81 (1H, s, H–C(8')); 8.03–8.08 (2H, m, 2H of Ph).
(dimethyl sulfoxide–d ): δ 2.76 (1H, ddd, J = 2.3, 4.9, 16.2 Hz,
6
H–C(4)); 3.09 (1H, ddd, J = 2.3, 9.0, 16.2 Hz, H–C(4)); 4.43 (1H,
dd, J = 5.3, 13.5 Hz, H–C(5')); 4.50 (1H, dd, J = 3.4, 15.3 Hz,
H–C(5')); 4.90–4.98 (1H, m, H–C(5)); 6.92–6.98 (2H, m, H–C(3''),
H–C(5'')); 7.50 (2H, t, J = 7.5 Hz, 2H of Ph); 7.65 (1H, t, J = 7.5
Hz, 1H of Ph); 7.70 (1H, d, J = 1.9 Hz, H–C(4'')); 7.90–7.97 (2H,
m, 2H of Ph); 8.24 (1H, dd, J = 3.4, 4.9 Hz, H–C(6'')); 8.30 (1H, tt,
J = 2.3, 10.2 Hz, H–C(3')); 9.68 (1H, d, HN–C(3')).
Anal. Calcd. for C
H O (356.33): C, 64.04; H, 4.53. Found:
19 16 7
C, 64.04; H, 4.60.
(S)-3-(2,5-Dioxo-2H,5H-benzo[b]pyrano[4,3–b]pyran-3-yl)-2-
hydroxy-1-pyropyl Benzoate (18).
This compound was prepared from 4-hydroxy-2H-benzo[b]-
pyran-2-one (12), heating for 3 hours, column chromatography
Anal. Calcd. for C H N O (324.34): C, 66.66; H, 4.97; N,
8.64. Found: C, 66.53; H, 4.85; N, 8.63.
18 16 2 4