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J. Handzlik et al. / Bioorg. Med. Chem. 20 (2012) 4245–4257
4.00 (q, J = 6.93 Hz, 2H, OCH2CH3), 4.32–4.35 (m, 1H, CH–OH), 6.39
(br s, 1H, OH), 6.53 (s, 1H, Ph-CH@), 6.84–7.00 (m, 4H, PpPh-
3,4,5,6-H), 7.31–7.43 (m, 3H, Ph-3,4,5-H), 7.65 (d, J = 7.18 Hz, 2H,
Ph-2,6-H), 10.30 (br s, 1H, NH+), 10.83 (s, 1H, N1H). IR KBr (cmꢀ1):
3413 (OH), 3239 (N1H), 3062 (@C–H), 2463 (NH+), 1767 (C2@O),
1708 (C4@O), 1660 (ArCH@), 1573 (Ar).
(C2@O), 1715 (C4@O), 1658 (ArCH@), 1608 (Ar).
4.1.2.10. Hydrochloride of (Z)-5-benzylidene-3-(2-hydroxy-3-
(4-(2-methoxyphenyl)piperazin-1-yl)propyl)imidazolidine-2,
4-dione (14a). (Z)-5-Benzylidene-3-(oxiran-2-ylmethyl)imidaz-
olidine-2,4-dione 32 (0.8 mmol, 0.20 g) and N-2-methoxyphenyl-
piperazine 39 (0.88 mmol, 0.14 g) were used. The irradiation:
450 W for 2 min, 600 W for 4 min (2 ꢃ 2 min) and 750 W for
19 min (2 ꢃ 2 min and 3 ꢃ 5 min). White crystals of pure
compound 14 (300 mg, 0.69 mmol). Yield 86%, mp 188–190 °C;
TLC:Rf (V): 0.58; Anal. Calcd; C24H28N4O4 (14): C, 66.04; H, 6.47; N,
12.84. Found: C, 66.24; H, 6.77; N, 12.90. 1H NMR (CDCl3) d (ppm):
2.44–2.57 (m, 2H, Pp-CH2), 2.62–2.65 (m, 2H, Pp-2,6-Ha), 2.82–2.87
(m, 2H, Pp-2,6-He), 3.07 (br s, 4H, Pp-3,5-H), 3.66–3.81 (m, 2H,
N3-CH2), 3.86 (s, 3H, OCH3), 4.06–4.14 (m, 1H, CH–OH), 6.77 (s, 1H,
Ph-CH@), 6.84–7.03 (m, 4H, PpPh-3,4,5,6-H), 7.33–7.47 (m, 5H, Ph-
2,3,4,5,6-H), 8.17 (br s, 1H, N1H). IR KBr (cmꢀ1): 3457 (OH), 3320
(N1H), 3059 (@C–H), 1753 (C2@O), 1709 (C4@O), 1658 (ArCH@),
1593 (Ar). Compound 14 (0.20 g, 0.46 mmol) in dry MeOH (10 mL)
with HCl concd (4 drops) was converted into white crystals of
hydrochloride 14a (0.23 g, 0.46 mmol). Yield 99%, mp 232–236 °C;
TLC: Rf (V): 0.53; Anal. Calcd for C24H28N4O4 ꢃ HCl ꢃ 1.4H2O (14a):
C, 57.86; H, 6.43; N, 11.25. Found: C, 57.74; H, 6.41; N, 11.26. 1H
NMR for 14a (DMSO-d6) d (ppm): 3.00–3.39 (m, 6H, Pp-CH2, Pp-
2,6-H), 3.41–3.67 (m, 6H, Pp-3,5-H, N3-CH2), 3.77 (s, 3H, OCH3),
4.32–4.34 (m, 1H, CH–OH), 6.04 (br s, 1H, OH), 6.53 (s, 1H, Ph-
CH@), 6.85–7.03 (m, 4H, PpPh-3,4,5,6-H), 7.31–7.44 (m, 3H, Ph-
3,4,5-H), 7.64 (d, J = 7.18 Hz, 2H, Ph-2,6-H), 10.32 (br s, 1H, NH+),
10.83 (s, 1H, N1H). IR KBr (cmꢀ1): 3358 (N1H), 3061 (@C–H), 2420
(NH+), 1766 (C2@O), 1714 (C4@O), 1660 (ArCH@), 1614 (Ar).
4.1.2.8. Hydrochloride of (Z)-5-(3,4-dimethoxybenzylidene)-3-
(2-hydroxy-3-(4-phenylpiperazin-1-yl)propyl)imidazolidine-2,
4-dione (12a).
(Z)-5-(3,4-Dimethoxybenzylidene)-3-(oxiran-2-
ylmethyl)imidazolidine-2,4-dione 37 (1 mmol, 0.30 g) and N-
phenylpiperazine 38 (1.1 mmol, 0.18 g) were used. The irradiation:
450 W for 3 min, 600 W for 3 min and 750 W for 15 min (3
ꢃ 5 min). Bright-yellow crystals of pure compound 12 (370 mg,
0.79 mmol). Yield 79.3%, mp 154–158 °C; TLC: Rf (V): 0.63; Anal.
Calcd for C25H30N4O5 (12): C, 64.36; H, 6.48; N, 12.01. Found: C,
64.01; H, 6.72; N, 12.03. 1H NMR (CDCl3) d (ppm): 2.43–2.51 (m,
2H, Pp-CH2), 2.53–2.62 (m, 2H, Pp-2,6-Ha), 2.75–2.81 (m, 2H, Pp-
2,6-He), 3.13–3.22 (m, 4H, Pp-3,5-H), 3.60–3.80 (m, 2H, N3-CH2),
3.92 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 4.05–4.13 (m, 1H, CH–OH),
6.72 (s, 1H, Ph-CH@), 6.83–6.93 (m, 5H, PpPh-2,4,6-H, Ph-2,5-H),
7.04 (dd, J1 = 8.47 Hz, J2 = 1.8 Hz, 1H, Ph-6-H), 7.23–7.28 (m, 2H,
PpPh-3,5-H), 8.19 (s, 1H, N1H). Compound 12 (0.20 g, 0.43 mmol)
in dry MeOH (10 mL) with HCl concd (4 drops) was converted into
white crystals of hydrochloride 12a (0.18 g, 0.34 mmol). Yield 79%,
mp230–235 °C; TLC: Rf (V): 0.58; Anal. Calcd for C25H30N4O5 ꢃ HCl
ꢃ 1.5H2O (12a): C, 56.65; H, 6.47; N, 10.57. Found: C, 56.65; H,
6.79; N, 10.62. 1H NMR for 12a (DMSO-d6) d (ppm): 3.11–3.34 (m,
6H, Pp-CH2, Pp-2,6-H), 3.41–3.68 (m, 6H, Pp-3,5-H, N3-CH2), 3.78
(s, 3H, OCH3), 3.82 (s, 3H, OCH3), 4.32–4.34 (m, 1H, CH–OH), 6.23
(br s, 1H, OH), 6.50 (s, 1H, Ph-CH@), 6.84 (t, J = 7.18 Hz, 1H, PpPh-4-
H), 6.97 (d, J = 8.21 Hz, 3H, PpPh-2,6-H, Ph-5-H), 7.15 (d, J = 2,05 Hz,
1H, Ph-2-H), 7.21–7.27 (m, 3H, PpPh-3,5-H, Ph-6-H), 10.35 (br s,
1H, NH+), 10.79 (s, 1H, N1H). IR KBr (cmꢀ1): 3413 (OH), 2446 (NH+),
1766 (C2@O), 1709 (C4@O), 1656 (ArCH@), 1598 (Ar).
4.1.2.11. Hydrochloride of (Z)-5-(2,3-dimethoxybenzylidene)-3-
(2-hydroxy-3-(4-phenylpiperazin-1-yl)propyl)imidazolidine-2,
4-dione (15a).
(Z)-5-(2,3-Dimethoxybenzylidene)-3-(oxiran-2-
ylmethyl)imidazolidine-2,4-dione 35 (1 mmol, 0.30 g) and N-
phenylpiperazine 38 (1.1 mmol, 0.18 g) were used. The irradiation:
450 W for 3 min, 600 W for 4 min (2 ꢃ 2 min) and 750 W for
15 min (3 ꢃ 5 min). White crystals of pure compound 15 (300 mg,
0.64 mmol). Yield 64.4%, mp 180–182 °C; TLC: Rf (V): 0.59; Anal.
Calcd for C25H30N4O5 (15): C, 64.36; H, 6.48; N, 12.01. Found: C,
64.38; H, 6.72; N, 12.02. 1H NMR (CDCl3) d (ppm): 2.45–2.55 (m,
2H, Pp-CH2), 2.58–2.65 (m, 2H, Pp-2,6-Ha), 2.77–2.84 (m, 2H, Pp-
2,6-He), 3.18–3.24 (m, 4H, Pp-3,5-H), 3.59–3.78 (m, 2H, N3-CH2),
3.80 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 4.05–4.12 (m, 1H, CH–OH),
6.65 (s, 1H, Ph-CH@), 6.83–6.97 (m, 5H, PpPh-2,4,6-H, Ph-4,5-H),
7.09–7.14 (m, 1H, Ph-6-H), 7.23–7.28 (m, 2H, PpPh-3,5-H), 8.22 (s,
1H, N1H). IR KBr (cmꢀ1): 3482 (OH), 3329 (N1H), 1762 (C2@O),
1710 (C4@O), 1660 (ArCH@), 1599 (Ar).Compound 15 (0.20 g,
0.43 mmol) in dry MeOH (10 mL) with HCl concd (4 drops) was
converted into white crystals of hydrochloride 15a (0.23 g,
0.34 mmol). Yield 79%, mp 215–218 °C; TLC: Rf (V): 0.65; Anal.
Calcd for C24H27N4O4Cl ꢃ HClꢃ 2.67H2O (15a): C, 54.49; H, 6.65; N,
10.17. Found: C, 54.79; H, 6.62; N, 10.23. 1H NMR for 15a (DMSO-
d6) d (ppm): 3.07–3.41 (m, 6H, Pp-CH2, Pp-2,6-H), 3.43–3.68 (m,
6H, Pp-3,5-H, N3-CH2), 3.74 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 4.32–
4.34 (m, 1H, CH–OH), 5.91 (br s, 1H, OH), 6.69 (s, 1H, Ph-CH@), 6.84
(t, J = 7.18 Hz, 1H, PpPh-4-H), 6.97 (d, J = 7.95 Hz, 2H, PpPh-2,6-H),
7.04–7.13 (m, 2H, Ph-4,5-H), 7.21–7.29 (m, 3H, PpPh-3,5-H, Ph-
6H), 10.33 (br s, 1H, NH+), 10.72 (s, 1H, N1H). IR KBr (cmꢀ1): 3359
(N1H), 2582 (NH+), 1765 (C2@O), 1714 (C4@O), 1665 (ArCH@),
1599 (Ar).
4.1.2.9. Hydrochloride of (Z)-5-(2,4-dimethoxybenzylidene)-3-
(3-(4-(2-ethoxyphenyl)piperazin-1-yl)-2-hydroxypropyl)imidaz
olidine-2,4-dione (13a).
(Z)-5-(2,4-Dimethoxybenzylidene)-3-
(oxiran-2-ylmethyl)imidazolidine-2,4-dione 36 (1 mmol, 0.30 g)
and N-2-ethoxyphenylpiperazine 40 (1.1 mmol, 0.23 g) were used.
The irradiation: 450 W for 3 min, 600 W for 4 min (2 ꢃ 2 min) and
750 W for 10 min (5 ꢃ 2 min). Bright-yellow crystals of pure
compound 13 (370 mg, 0.72 mmol). Yield 72.5%, mp 174–178 °C;
TLC:Rf (V): 0.69; Anal. Calcd for C27H34N4O6 (13): C, 63.51; H, 6.71;
N, 10.98. Found: C, 63.66; H, 6.79; N, 10.78. 1H NMR (CDCl3) d
(ppm): 1.44 (t, J = 6.92 Hz, 3H, OCH2CH3), 2.44–2.56 (m, 2H, Pp-
CH2), 2.63–2.65 (m, 2H, Pp-2,6-Ha), 2.81–2.87 (m, 2H, Pp-2,6-He),
3.10 (br s, 4H, Pp-3,5-H), 3.66–3.77 (m, 2H, N3-CH2), 3.83 (s, 3H,
OCH3), 3.93 (s, 3H, OCH3), 4.02–4.13 (m, 3H, OCH2CH3, CH –OH),
6.51–6.58 (m, 2H, Ph-3,5-H), 6.70 (s, 1H, Ph-CH@), 6.82–6.99 (m,
4H, PpPh-3,4,5,6-H), 7.26 (d, J = 8.72 Hz, 1H, Ph-6-H), 7.83 (s, 1H,
N1H). IR KBr (cmꢀ1): 3420 (OH), 3246 (N1H), 3056 (@C–H), 1759
(C2@O), 1711 (C4@O), 1662 (ArCH@), 1607 (Ar). Compound 13
(0.20 g, 0.39 mmol) in dry MeOH (10 mL) with HCl concd (4 drops)
was converted into white crystals of hydrochloride 13a (0.21 g,
0.36 mmol). Yield 92%, mp 235–241 °C; TLC: Rf (V): 0.57; Anal.
Calcd for C27H34N4O6 ꢃ HCl ꢃ 2H2O (13a): C, 55.62; H, 6.74; N,
9.61. Found: C, 55.87; H, 6.55; N, 9.57. 1H NMR for 13a (DMSO-d6) d
(ppm): 1,34 (t, J = 6.92 Hz, 3H, OCH2CH3), 2.97–3.38 (m, 6H, Pp-
CH2, Pp-2,6-H), 3.40–3.65 (m, 6H, Pp-3,5-H, N3-CH2), 3.80 (s, 3H,
OCH3), 3.84 (s, 3H, OCH3), 4.00 (q, J = 6.92 Hz, 2H, OCH2CH3), 4.29–
4.31 (m, 1H, CH–OH), 5.93 (br s, 1H, OH), 6.54–6.61 (m, 2H, Ph-3,5-
H), 6.72 (s, 1H, Ph-CH@), 6.84–7.00 (m, 4H, PpPh-3,4,5,6-H), 7.59
(d, J = 8.72 Hz, 1H, Ph-6-H), 10.11 (br s, 1H, NH+), 10.59 (s, 1H,
N1H). IR KBr (cmꢀ1): 3414 (OH), 3232 (N1H), 2500 (NH+), 1755
4.1.2.12. Hydrochloride of (Z)-5-(4-(dimethylamino)benzyli-
dene)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)pro
pyl)imidazolidine-2,4-dione (16a).
benzylidene)-3-(oxiran-2-ylmethyl)imidazolidine-2,4-dione
(Z)-5-((4-Dimethylamino)
34