664
T. MATSUYA ET AL.
1
amorphous solid (671 mg, 75%). H-NMR (300 MHz, CDCl3) d0.48 (3H, s),
1.16–1.37 (12H, m), 1.41–1.81 (4H, m), 1.82–1.93 (7H, m), 1.89 (3H, s), 1.92–
2.40 (2H, m), 2.44–2.54 (1H, m), 3.58 (1H, q, J¼ 5:8 Hz), 3.87–4.06 (4H, m),
4.20–4.27 (1H, m), 4.43 (1H, s), 6.54 (2H, brs), 7.00 (2H, d, J¼ 8:4 Hz); MS
(ES+) m/e 506.5.
Preparation of 5a-17b-dihydroxy-11b-[4[(N-isopropyl-N-methylamino)phe-
nyl]-17a-ethynyl-esta-9-ene-3-one 3-(cyclic 1,2-ethanediyl acetal) (6). A solu-
tion of 4-(N-isopropyl-N-methylamino)phenyl bromide (10.5 g, 46 mmol) in
THF (10 ml) was added to a suspension of Mg (1.09 g, 44.6 mmol) in THF
(3 ml) dropwise at room temperature. The reaction mixture was stirred at
reflux for 25 min. The Grignard solution was added to a solution of CuCl
(294 mg, 2.97 mmol) in THF (50 ml), at 6–78C. After stirring for 30 min, a
solution of 5a, 10a-epoxy-17a-ethynyl-17b-hydroxy-estr-9(11)-ene-3-one 3-
(cyclic 1,2-ethanediyl acetal) (5.51 g, 14.9 mmol) in THF (50 ml) was added
dropwise at 6–78C. After stirring at 6–78C for 30 min, the mixture was
concentrated in vacuo, the residue was diluted with ethyl acetate and washed
with aqueous 1 N hydrogen chloride solution, saturated aqueous sodium
bicarbonate solution and brine. The extracts were dried over magnesium
sulfate, filtered and concentrated in vacuo. The residue was filtered and washed
1
with IPE to give the desired product as a white powder (11.6 g, 100%). H-
NMR (300 MHz, CDCl3) d0.48–2.07 (3H, s), 1.09–1.17 (6H, m), 1.25–1.40
(2H, m), 1.40–1.60 (2H, m), 1.60–1.64 (1H, m), 1.64–1.78 (3H, m), 1.80 (1H,
brs), 1.82–1.92 (2H, m), 1.88 (3H, s), 1.93–2.07 (4H, m), 2.07–2.39 (5H, m),
2.44–2.55 (1H, m), 2.69 (3H, s), 3.88–4.10 (3H, m), 4.21–4.28 (1H, m), 4.43
(1H, s), 6.69 (2H, d, J¼ 7:7 Hz), 7.04 (2H, d, J¼ 7:7 Hz); MS (ES+) m/e 520.5.
Preparation
of
17-b-hydroxy-11-b-/4-/[1-methylethyl]-aminophenyl/-17a-
[prop-1-ynyl]est a-4-9-diene-3-one (4). A solution of 6 N H2SO4 (4.42 ml,
26.5 mmol) was added to a solution of ketal (3) (670 mg, 1.32 mmol) in acetone
(26 ml) dropwise with cooling on an ice bath. The reaction mixture was stirred
at 08C for 1 h. The mixture was concentrated in vacuo. The residue was diluted
with ethyl acetate and washed with saturated aqueous sodium bicarbonate
solution and brine. The extracts were dried over magnesium sulfate, filtered
and concentrated in vacuo. The residue was purified by silica gel column
chromatography eluted with a mixture of hexane and ethyl acetate (1:1) to give
a gum. The desired product was obtained by freeze-drying from benzene
1
(530 mg, 90%). H-NMR (300 MHz, CDCl3) d0.56 (3H, s), 1.10–2.09 (18H,
m), 2.15–2.52 (6H, m), 2.53–2.63 (2H, m), 2.72–2.84 (1H, m), 3.58 (1H, q,
J¼ 6:2 Hz), 4.33 (1H, d, J¼ 7:0 Hz), 5.75 (1H, s), 6.52 (2H, d, J¼ 8:4 Hz), 6.94
(2H, d, J¼ 8:4 Hz); MS (ES+) m/e 444.5.
Copyright # 2005 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2005; 48: 657–668