M. Ono et al. / Bioorg. Med. Chem. 15 (2007) 6802–6809
6807
4
1
.1.4. (E)-3-(4-Aminophenyl)-1-(4-iodophenyl)prop-2-en-
-one (4). To a solution of 3 (80 mg, 0.16 mmol) in
(50 mL). The organic phase was dried over Na SO
2 4
and filtered. The solvent was removed, and the residue
was purified by silica gel chromatography (hexane/ethyl
acetate = 12:1) to give 236 mg of 8 (86.1%). H NMR
CHCl3 (10 mL) was added a solution of iodine in
CHCl3 (2 mL, 50 mg/mL) at room temperature. The
mixture was stirred at room temperature for 30 min,
1
(300 MHz, CDCl ) d 3.06 (s, 6H), 6.70 (d, J = 8.7 Hz,
3
and NaHSO solution (10 mL) was added. The mixture
3
2H), 7.27 (d, J = 15.3 Hz, 1H), 7.54 (d, J = 8.7 Hz,
2H), 7.59 (d, J = 8.7 Hz, 2H), 7.74 (d, J = 15.3 Hz,
1H), 7.87 (d, J = 7.8 Hz, 2H).
was stirred for 5 min, and the organic phase was sepa-
rated, dried over Na SO , and filtered. The solvent was
removed, and the residue was purified by preparative
2
4
TLC (3:2 hexane/ethyl acetate) to give 26 mg of 4
(
4.1.9. (E)-1-(4-(Tributylstannyl)phenyl)-3-(4-(dimethyl-
amino)phenyl)prop-2-en-1-one (9). The same reaction as
described above to prepare 3 was used, and 43 mg of 9
1
46.5%). H NMR (300 MHz, CDCl ) d 4.03 (s, 2H),
3
6
7
7
.68 (d, J = 8.7 Hz, 2H), 7.28 (d, J = 15.6 Hz, 1H),
.48 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 8.7 Hz, 2H),
.76 (d, J = 15.3 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H).
1
was obtained in a 11.9% yield from 8. H NMR
(300 MHz, CDCl ) d 0.87–1.57 (m, 27H), 3.05 (s, 6H),
3
+
MS m/z 349 (M ). Anal. Calcd for C H INO: C,
1
6.70 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 15.3 Hz, 1H),
7.55 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.7 Hz, 2H), 7.79
5
12
5
4
1.60; H, 3.46; N, 4.01. Found: C, 51.30; H, 3.85; N,
.26.
(d, J = 15.6 Hz, 1H), 7.92 (d, J = 7.8 Hz, 2H). MS m/z
5
+
41 (MH ).
4
.1.5. (E)-1-(4-Bromophenyl)-3-(4-(methylamino)phenyl)
prop-2-en-1-one (5). To a solution of 2 (200 mg,
.66 mmol) in DMSO (anhydrous, 5 mL) were added
4.1.10. (E)-3-(4-(Dimethylamino)phenyl)-1-(4-iodophenyl)
prop-2-en-1-one (10). The same reaction as described
above to prepare 4 was used, and 13 mg of 10 was ob-
0
methyl iodide (228 mg, 1.60 mmol) and anhydrous
K CO (500 mg, 3.75 mmol). The reaction mixture was
1
tained in a 46.6% yield from 9. H NMR (300 MHz,
CDCl ) d 3.05 (s, 6H), 6.69 (d, J = 9.0 Hz, 2H), 7.26
2
3
stirred at room temperature for 3 h. After it was poured
into water (30 mL), the mixture was extracted with ethyl
acetate (2 · 30 mL). The organic layers were combined
and dried over Na SO . Evaporation of the solvent
3
(d, J = 15.6 Hz, 1H), 7.54 (d, J = 9.0 Hz, 2H), 7.72 (d,
J = 8.7 Hz, 2H), 7.79 (d, J = 15.6 Hz, 1H), 7.84 (d,
+
J = 8.4 Hz, 2H). MS m/z 377 (M ). Anal. Calcd for
2
4
afforded a residue, which was purified by silica gel chro-
matography (hexane/ethyl acetate = 6:1) to give 74 mg
C H INO: C, 54.13; H, 4.28; N, 3.71. Found: C,
1
53.92; H, 4.40; N, 3.53.
7
16
1
of 5 (35.5%). H NMR (300 MHz, CDCl ) d 2.90 (s,
3
3
H), 4.20 (s, 1H), 6.60 (d, J = 9.0 Hz, 2H), 7.26 (d,
4.1.11. (E)-1-(4-Bromophenyl)-3-(4-methoxyphenyl)prop-
2-en-1-one (11). Equimolar portions of 4-bromoacetoph-
enone (1.99 g, 10 mmol) and 4-anisaldehyde (1.36 g,
10 mmol) were dissolved in 20 mL of ethanol. The mix-
ture was allowed to stir for 15 min in an ice bath. A
20 mL aliquot of 10% aqueous potassium hydroxide solu-
tion was then slowly added dropwise to the reaction mix-
ture. The reaction solution was allowed to stir at room
temperature for 3 h. A precipitate was collected and
J = 15.3 Hz, 1H), 7.51 (d, J = 8.7 Hz, 2H), 7.62 (d,
J = 8.4 Hz, 2H), 7.78 (d, J = 15.9 Hz, 1H), 7.87 (d,
J = 8.7 Hz, 2H).
4
.1.6. (E)-1-(4-(Tributylstannyl)phenyl)-3-(4-(methylami-
no)phenyl)prop-2-en-1-one (6). The same reaction as de-
scribed above to prepare 3 was used, and 64 mg of 6
was obtained in a 55.0% yield from 5. H NMR
1
1
(
300 MHz, CDCl ) d 0.87–1.61 (m, 27H), 2.90 (s, 3H),
washed with ethanol to give 2.97 g of 11 (93.6%). H
NMR (300 MHz, CDCl ) d 3.86 (s, 3H), 6.94 (d,
3
4
.16 (s, 1H), 6.60 (d, J = 8.7 Hz, 2H), 7.33 (d,
3
J = 15.6 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.59 (d,
J = 8.1 Hz, 2H), 7.78 (d, J = 15.6 Hz, 1H), 7.92 (d,
J = 7.8 Hz, 2H). MS m/z 527 (MH ).
J = 8.7 Hz, 2H), 7.36 (d, J = 15.3 Hz, 1H), 7.59–7.65 (m,
4H), 7.80 (d, J = 15.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H).
+
4.1.12. (E)-1-(4-Bromophenyl)-3-(4-hydroxyphenyl)prop-
2-en-1-one (12). BBr (5 mL, 1 M solution in CH Cl )
4
.1.7. (E)-1-(4-Iodophenyl)-3-(4-(methylamino)phenyl)prop-
-en-1-one (7). The same reaction as described above to
3
2
2
2
prepare 4 was used, and 41 mg of 7 was obtained in an
was added to a solution of 11 (500 mg, 1.58 mmol) in
CH Cl (20 mL) dropwise in an ice bath. The mixture
2
2
1
8
0.6% yield from 6. H NMR (300 MHz, CDCl ) d 2.90
was allowed to warm to room temperature and stirred
for 30 min. Water (50 mL) was added while the reaction
mixture was cooled in an ice bath. The mixture was ex-
tracted with chloroform (2 · 30 mL), and the organic
phase was dried over Na SO and filtered. The filtrate
3
(
s, 3H), 4.19 (s, 1H), 6.60 (d, J = 9.0 Hz, 2H), 7.25 (d,
J = 15.6 Hz, 1H), 7.51 (d, J = 8.7 Hz, 2H), 7.71 (d,
J = 8.7 Hz, 2H), 7.77 (d, J = 15.6 Hz, 1H), 7.84 (d,
J = 8.7 Hz, 2H). MS m/z 363 (M ). Anal. Calcd for
+
2
4
C H INO: C, 52.91; H, 3.89; N, 3.86. Found: C,
14
was concentrated and the residue was purified by silica
gel chromatography (hexane/ethyl acetate = 7:2) to give
1
6
5
3.24; H, 4.19; N, 3.44.
1
3
07 mg of 12 (64.1%). H NMR (300 MHz, CDCl ) d
3
4
.1.8. (E)-1-(4-Bromophenyl)-3-(4-(dimethylamino)phenyl)
5.59 (s, 1H), 6.90 (d, J = 8.7 Hz, 2H), 7.35 (d,
J = 15.3 Hz, 1H), 7.56 (d, J = 8.7 Hz, 2H), 7.64 (d,
J = 8.4 Hz, 2H), 7.79 (d, J = 15.6 Hz, 1H), 7.88 (d,
J = 8.4 Hz, 2H).
prop-2-en-1-one (8). To a stirred mixture of 2 (250 mg,
.83 mmol) and paraformaldehyde (400 mg, 13.4 mmol)
in AcOH (15 mL) was added in one portion NaCNBH3
250 mg, 3.98 mmol) at room temperature. The resulting
0
(
mixture was stirred at room temperature for 3 h, 1 M
NaOH (50 mL) was added and extracted with CH Cl
4.1.13. (E)-1-(4-(Tributylstannyl)phenyl)-3-(4-methoxy-
phenyl)prop-2-en-1-one (13). The same reaction as
3