S. Gobec et al. / European Journal of Medicinal Chemistry 42 (2007) 54e63
61
OeCH eCH ), 1.15e1.40 (m, 4H, PeCH e(CH ) eCH ),
mide (0.43 g, 2.45 mmol), afforded compound 5f (0.168 g,
1
2
3
2
2 2
3
ꢀ
1
.48e1.68 (m, 2H, PeCH e(CH ) e), 3.77e4.04 (m, 4H,
22.1%). mp ¼ 65e70 C. H NMR (DMSO-d ) d 0.89 (t,
2
2 2
6
Oe(CH ) eN), 4.06e4.23 (m, 2H, PeOeCH eCH ),
J ¼ 6.60 Hz, 3H, eCH eCH eCH ), 1.15e1.42 (m, 25H,
2
2
2
3
2
2
3
3
1
7.79e7.93 (m, 4H, ArH ). P NMR (DMSO-d ) d 33.90.
IR (KBr)
Pe(CH ) e(CH ) eCH and PeOeCH eCH ), 1.50e1.67
2 2 2 11 3 2 3
6
n
3473, 2959, 1774, 1715, 1394, 1246,
þ
(m, 2H, PeCH eCH e(CH ) e), 1.73e1.87 (m, 2H, Pe
2 2 2 11
CH e(CH ) e), 4.06e4.23 (m, 2H, PeOeCH eCH ),
2 2 12 2 3
ꢃ1
1
(
035, 960 cm . MS (FAB) m/z 340 (M þ H) . Anal
C H NO P$0.25H O) (C, H, N).
1
5.58e5.68 (m, 2H, OeCH eN), 7.70e7.98 (m, 4H, ArH ).
2
6
22
5
2
3
1
P NMR (DMSO-d ) d 33.80. IR (KBr) n 3491, 2917,
6
6
.1.4.8. (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-methyl ethyl
2848, 1778, 1722, 1466, 1378, 1246, 1044, 982, 844, 720,
ꢃ1
þ
heptylphosphonate (5c). The general procedure described
above, using ethyl hydrogen heptylphosphonate (3c) (0.50 g,
616, 532 cm . MS (FAB) m/z 488 (M þ Na) . Anal.
(C H NO P$0.5H O) (C, H, N).
2
5
40
5
2
2
3
.40 mmol) and N-(2-hydroxymethyl)phthalimide (0.64 g,
.61 mmol), afforded compound 5c (0.88 g, 54.3%). R 0.33
f
1
6.1.4.12. Ethyl 3,4,5-trimethoxybenzyl hexylphosphonate
6). The general procedure described above, using mono-
phosphonate 3b (0.96 g, 4.95 mmol) and (3,4,5-trimethoxy)-
(
EtOAcehexane 2:1).
H NMR (CDCl3) d 0.87 (t,
(
J ¼ 6.78 Hz, 3H, eCH eCH eCH ), 1.19e1.65 (m, 15H,
2
2
3
Pe(CH ) eCH and PeOeCH eCH ), 4.11e4.26 (m, 2H,
2
6
3
2
3
phenylmethanol (1.07 mL, 4.52 mmol), afforded compound 6
1
0.12 (EtOAcehexane 1:1). H NMR
PeOeCH eCH ), 5.58e5.68 (m, 2H, OeCH eN), 7.77e
7
2
3
2
3
.83 (m, 2H, ArH ), 7.92e7.98 (m, 2H, ArH ). P NMR
1
(0.200 g, 11.0%). R
f
(
DMSO-d ) d 0.85 (t, J ¼ 6.78 Hz, 3H, eCH eCH eCH ),
6
2
2
3
(
CDCl ) d 33.81. IR (KBr) n 2930, 2857, 1783, 1731, 1375,
3
ꢃ1
þ
1.18e1.26 (m, 3H, PeOeCH
eCH ), 1.26e1.52 (m, 8H,
2 3
1256, 1048, 1002, 724 cm . MS (FAB) m/z 368 (M þ H) .
Anal. (C H NO P$0.5H O) (C, H); N: calcd, 3.72; found,
18 26 5 2
PeCH e(CH ) eCH ), 1.67e1.80 (m, 2H, PeOeCH e
2
2 4
3
2
CH ), 3.66 (s, 3H, CH eOeAr), 3.78 (s, 6H, 2 ꢂ CH eOe
3
3
3
4
.28.
Ar), 3.90e4.08 (m, 2H, CH eCH eOeP), 4.86e4.98 (m,
3
2
3
1
2
H, PheCH eOe), 6.71 (s, 2H, ArH ). P NMR (DMSO-
2
6
.1.4.9. (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-methyl ethyl
d ) d 33.80. IR (KBr) n 2935, 1594, 1508, 1460, 1424,
6
nonylphosphonate (5d). The general procedure described
above, using ethyl hydrogen nonylphosphonate (3d) (0.50 g,
3
4
ꢃ1
1
(
334, 1237, 1129, 1047, 1013, 967 cm . MS (EI) m/z 374
M ). Anal. (C H O P$0.2H O) (C, H).
31
þ
1
8
6
2
.01 mmol) and N-(2-hydroxymethyl)phthalimide (0.80 g,
.52 mmol), afforded compound 5d (0.188 g, 15.8%). R 0.39
f
ꢀ
1
(
EtOAcehexane 4:1). mp ¼ 55e59 C. H NMR (DMSO-d )
2 2 3
6
6.1.4.13.
(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-methyl
d 0.85 (t, J ¼ 6.78 Hz, 3H, eCH eCH eCH ), 1.07e1.34 (m,
ethyl phenethylphosphonate (10a). The general procedure de-
scribed above, using ethyl hydrogen 2-phenethylphosphonate
(0.45 g, 2.1 mmol) and N-(hydroxymethyl)phthalimide
(1.39 g, 3.15 mmol), afforded compound 10a as a colorless
1
1
5H, Pe(CH ) e(CH ) eCH and PeOeCH eCH ), 1.35e
2 2 2 6 3 2 3
.51 (m, 2H, PeCH eCH eCH e), 1.68e1.83 (m, 2H, Pe
2
2
2
CH eCH eCH e), 3.94e4.09 (m, 2H, PeOeCH eCH ),
2
2
2
2
3
5
.39e5.52 (m, 2H, OeCH eN), 7.88e8.02 (m, 4H, ArH ).
1
2
liquid (0.564 g, 71.90%). Rf 0.36 (EtOAc). H NMR
(DMSO-d ) d 1.20 (t, J ¼ 6.97 Hz, 3H, OCH CH ), 2.06e
3
1
P NMR (DMSO-d ) d 33.00. IR (KBr) n 2920, 2852, 1778,
6
6
2
3
1
5
720, 1613, 1466, 1381, 1247, 1192, 1044, 847, 722, 616,
ꢃ1
2.21 (m, 2H, CH CH P), 2.70e2.84 (m, 2H, PhCH CH ),
2 2 2 2
þ
31 cm
.
MS (FAB) m/z: 396 (M þ H) . Anal.
3
.95e4.09 (m, 2H, OCH CH ), 5.47 (d, J ¼ 8.66 Hz, 2H,
2
3
(
C H NO P) (C, H, N).
20 30 5
OCH N), 7.12e7.30 (m, 5H, ArH ), 7.88e8.03 (m, 4H,
2
ArH ). IR (KBr) n 3496, 2983, 1783, 1375, 1248, 1049,
þ
6
.1.4.10.
2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-ethyl
ꢃ1
1
003, 869, 713 cm . MS (FAB) m/z 374 (M þ H) . Anal.
ethyl nonylphosphonate (5e). The general procedure described
above, using ethyl hydrogen nonylphosphonate (3d) (0.41 g,
(
C H NO P) (C, H, N).
19 20
5
1
4
.74 mmol) and N-(2-hydroxyethyl)phthalimide (0.80 g,
.52 mmol), afforded compound 5e (0.147 g, 20.6%). R 0.25
f
6.1.4.14. (1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-ethyl ethyl
1
(
EtOAcehexane 4:1). H NMR (DMSO-d ) d 0.86 (t,
6
phenethylphosphonate (10b). The general procedure described
above, using ethyl hydrogen 2-phenethylphosphonate (0.63 g,
J ¼ 6.18 Hz, 3H, eCH eCH eCH ), 1.04e1.40 (m, 17H,
2
2
3
Pe(CH )e(CH ) eCH and PeOeCH eCH ), 1.53e1.68
2
2 7
3
2
3
3
3
.28 mmol) and N-(2-hydroxyethyl)phtalimide (1.45 g,
.28 mmol), afforded compound 10b as a colorless liquid
(
m, 2H, PeCH eCH eCH e), 3.77e3.94 (m, 4H, Ne
2 2 2
CH eCH eO), 4.06e4.23 (m, 2H, CH eCH eO), 7.81e
1
2
2
3
2
(0.67 g, 79.7%). R 0.50 (EtOAc). H NMR (DMSO-d6)
31
f
7.92 (m, 4H, ArH ). P NMR (DMSO-d ) d 33.90. IR (KBr)
n 2927, 2854, 1774, 1716, 1393, 1241, 1034, 844, 720 cm
6
d 1.09 (t, J ¼ 6.97 Hz, 3H, OCH CH ), 1.89e2.04 (m, 2H,
ꢃ1
2
3
.
CH CH P), 2.61e2.73 (m, 2H, OCH CH N), 3.81e3.93
þ
2
2
2
2
MS (FAB) m/z 410 (M þ H) . Anal. (C H NO P$1.67H O)
2
1
32
5
2
(
m, 4H, PhCH CH and OCH CH N), 4.13e4.22 (m, 2H,
2 2 2 2
(
C, H, N).
OCH CH ), 7.13e7.30 (m, 5H, ArH ), 7.81e7.93 (m,
2
3
3
1
6
.1.4.11.
(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-methyl
4H, ArH ). P NMR (DMSO-d ) d 32.3. IR (KBr) n 3478,
6
ethyl tetradecylphosphonate (5f). The general procedure de-
scribed above, using ethyl hydrogen tetradecylphosphonate
2982, 1774, 1714, 1604, 1394, 1245, 1072, 1035, 961,
ꢃ1
þ
720 cm
(C20
.
MS (FAB) m/z 388 (M þ H) . Anal.
(
3e) (0.50 g, 1.63 mmol) and N-(2-hydroxymethyl)phthali-
H22NO
5
) (C, H, N).