Y. Sun et al. / European Journal of Medicinal Chemistry 46 (2011) 5146e5153
5151
TMS, ppm):
d
2.29(s, 3H, CH3Ph),
d
3.68(s, 4H, CH2 of azetidine),
were filtered off, washed with a little of chilled water, and then
dried at 40 ꢁC in vacuo.
The preparation of compounds 2e13 was the similar to that of
compound 1 described above.
d
3.73(s, 2H, NCH2Ph), d7.26e7.27(m, 4H, CH of Ph); ESI-MS: m/z
[M ꢀ 2Na þ H]ꢀ ¼ 248 (100%).
L-9: Yield 81%. White powder. Anal. calcd. for C13H13NO4Na2: C,
53.25; H, 4.47; N, 4.78. Found: C, 53.33; H, 4.62; N, 4.58. IR (KBr,
cmꢀ1): 3420(br), 2853, 1607, 1433, 1334, 857, 781, 690; 1H NMR
Complex 1: Yield 55%. Yellow crystals. Anal. calcd. for
C18H27N3O4Pt: C, 39.70; H, 5.00; N, 7.72. Found: C, 39.62; H, 5.09;
N, 7.85. IR (KBr, cmꢀ1): 3420(br), 3208, 3123, 2931, 2854, 1616,
1451, 1384, 747, 699; 1H NMR (d6-D2O/TMS, ppm):
(d6-D2O/TMS, ppm):
d
2.34(s, 3H, CH3Ph),
d3.59(s, 4H, CH2 of
azetidine), d3.63(s, 2H, NCH2Ph), d7.14e7.30(m, 4H, CH of Ph);
ESI-MS: m/z [M ꢀ 2Na þ H]ꢀ ¼ 248 (100%).
L-10: Yield 83%. White powder. Anal. calcd. for C13H13NO4Na2: C,
53.25; H, 4.47; N, 4.78. Found: C, 53.29; H, 4.52; N, 4.70. IR (KBr,
cmꢀ1): 3426(br), 2848, 1609, 1435, 1333, 805; 1H NMR (d6-D2O/
d0.81e2.61(m, 11H, CH2 and CH of cyclohexyl), d3.90e4.32(m,
6H, CH2N),
d7.37e7.45(m, 5H, CH of Ph); ESI-MS: m/z
[M þ H]þ ¼ 545(100%).
TMS, ppm):
d
2.16(s, 3H, CH3Ph),
d
3.56(s, 4H, CH2 of azetidine),
Complex 2: Yield 60%. Yellow crystals. Anal. calcd. for
C18H26FN3O4Pt: C, 38.43; H, 4.66; N, 7.47; Found: C, 38.50; H,
4.62; N, 7.39. IR (KBr, cmꢀ1): 3404(br), 3195, 3105, 2932, 2855,
1616, 1453, 1383, 762; 1H NMR (d6-D2O/TMS, ppm):
d
3.61(s, 2H, NCH2Ph), d7.09 (m, 4H, CH of Ph); ESI-MS: m/z
[M ꢀ 2Na þ H]ꢀ ¼ 248 (100%).
L-11: Yield 79%. White powder. Anal. calcd. for C13H13NO5Na2: C,
50.49; H, 4.24; N, 4.53. Found: C, 50.54; H, 4.29; N, 4.48. IR (KBr,
cmꢀ1): 3425(br), 2855, 1611, 1433, 1333, 770; 1H NMR (d6-D2O/
d0.82e2.27(m, 11H, CH2 and CH of cyclohexyl), d3.80e4.23(m,
6H, CH2N),
d7.17e7.22(m, 4H, CH of Ph); ESI-MS: m/z
[M þ H]þ ¼ 563(100%).
TMS, ppm):
d3.55(s, 4H, CH2 of azetidine),
d3.62(s, 2H, NCH2Ph),
d
3.75(s, 3H, PhOCH3), d7.11(s, 4H, CH of Ph); ESI-MS: m/z
Complex 3: Yield 51%. Yellow crystals. Anal. calcd. for
C18H26FN3O4Pt: C, 38.43; H, 4.66; N, 7.47; Found: C, 38.52; H,
4.71; N, 7.43. IR (KBr, cmꢀ1): 3410 (br), 3196, 3106, 2932, 2856,
1614, 1449, 1384, 788, 686; 1H NMR (d6-D2O/TMS, ppm):
[M ꢀ 2Na þ H]ꢀ ¼ 264 (100%).
L-12: Yield 85%. White powder. Anal. calcd. for C13H13NO5Na2: C,
50.49; H, 4.24; N, 4.53. Found: C, 50.60; H, 4.32; N, 4.45. IR (KBr,
cmꢀ1): 3420(br), 2830, 1604, 1434, 1334, 850, 771, 689; 1H NMR
d1.08e2.27(m, 11H, CH2 and CH of cyclohexyl), d3.80e4.52(m,
(d6-D2O/TMS, ppm):
d
3.59(s, 4H, CH2 of azetidine),
d
3.65(s, 2H,
6H, CH2N),
d7.15e7.30(m, 4H, CH of Ph); ESI-MS: m/z
[M þ H]þ ¼ 563(100%).
NCH2Ph), d3.82(s, 3H, PhOCH3), d6.91e7.34(m, 4H, CH of Ph);
ESI-MS: m/z [M ꢀ 2Na þ H]ꢀ ¼ 264 (100%).
Complex 4: Yield 58%. Yellow crystals. Anal. calcd. for
C18H26FN3O4Pt: C, 38.43; H, 4.66; N, 7.47; Found: C, 38.34; H,
4.56; N, 7.45. IR (KBr, cmꢀ1): 3408(br), 3200, 3114, 2932, 2855,
1604, 1449, 1384, 829, 769; 1H NMR (d6-D2O/TMS, ppm):
L-13: Yield 76%. White powder. Anal. calcd. for C13H13NO5Na2: C,
50.49; H, 4.24; N, 4.53. Found: C, 50.39; H, 4.34; N, 4.46. IR (KBr,
cmꢀ1): 3426(br), 2843, 1609, 1433, 1334, 803; 1H NMR (d6-D2O/
TMS, ppm):
d3.50(s, 4H, CH2 of azetidine),
d3.54(s, 2H, NCH2Ph),
d0.95e2.29(m, 11H, CH2 and CH of cyclohexyl), d3.77e4.33(m,
d
3.69(s, 3H, PhOCH3), d6.85e7.17(m, 4H, CH of Ph); ESI-MS: m/z
6H, CH2N),
d7.19e7.23(m, 4H, CH of Ph); ESI-MS: m/z
[M ꢀ 2Na þ H]ꢀ ¼ 264 (100%).
[M þ H]þ ¼ 563(100%).
Complex 5: Yield 49%. Yellow crystals. Anal. calcd. for
C18H26ClN3O4Pt: C, 37.34; H, 4.53; N, 7.26. Found: C, 37.37; H,
4.39; N, 7.38. IR (KBr, cmꢀ1): 3406(br), 3187, 3069, 2932, 2855,
1610, 1442, 1390, 757; 1H NMR (d6-D2O/TMS, ppm):
4.1.3. Synthesis of complexes 1e13
The preparation of target complexes 1e13 was carried out as
shown in Scheme 2. The brown yellow intermediate cis-
[Pt(C6H11NH2)(NH3)I2] was synthesized according to the literature
[21]. The corresponding silver 1-(substituted benzyl) azetidine-3,
3-dicarboxylate was prepared by the reaction of sodium 1-
(substituted benzyl) azetidine-3, 3-dicarboxylate related and silver
nitrate in water.
d1.12e2.29(m, 11H, CH2 and CH of cyclohexyl), d3.78e4.30(m,
6H, CH2N),
d7.17e7.22(m, 4H, CH of Ph); ESI-MS: m/z
[M þ H]þ ¼ 580(100%).
Complex 6: Yield 59%. Yellow crystals. Anal. calcd. for
C18H26ClN3O4Pt: C, 37.34; H, 4.53; N, 7.26. Found: C, 37.40; H,
4.42; N, 7.31. IR (KBr, cmꢀ1): 3420(br), 3209, 3124, 2933, 2856,
1623, 1449, 1381, 784, 682; 1H NMR (d6-D2O/TMS, ppm):
Synthesis of complex 1: The intermediate cis-[Pt(C6H11NH2)
(NH3)I2] (2 mmol) was suspended in 100 ml of distilled water, and
d1.26e2.19(m, 11H, CH2 and CH of cyclohexyl), d3.77e4.34(m,
then
the
freshly
prepared
silver
1-benzylazetidine-3,
6H, CH2N),
d7.30e7.38(m, 4H, CH of Ph); ESI-MS: m/z
[M þ H]þ ¼ 580(100%).
3-dicarboxylate (2 mmol) was added. The reaction mixture was
heated to 50 ꢁC and stirred for 24 h in dark under a nitrogen
atmosphere. Then the mixture was cooled to the room tempera-
ture, and AgI deposits were filtered off and washed with water. The
yellow filtrate was concentrated by a rotatory evaporator and then
kept cool at 4 ꢁC for several hours. The resulting yellow crystals
Complex 7: Yield 55%. Yellow crystals. Anal. calcd. for
C18H26ClN3O4Pt: C, 37.34; H, 4.53; N, 7.26. Found: C, 37.43; H,
4.45; N, 7.34. IR (KBr, cmꢀ1): 3385(br), 3184, 3050, 2934, 2856,
1617, 1407, 1348, 844, 802; 1H NMR (d6-D2O/TMS, ppm):
d1.08e2.19(m, 11H, CH2 and CH of cyclohexyl), d3.78e4.32(m,
6H, CH2N),
d7.20e7.25(m, 4H, CH of Ph); ESI-MS: m/z
[M þ H]þ ¼ 580(100%).
Complex 8: Yield 62%. Yellow crystals. Anal. calcd. for
C19H29N3O4Pt: C, 40.86; H, 5.23; N, 7.52. Found: C, 40.77; H, 5.18;
N, 7.66. IR (KBr, cmꢀ1): 3398(br), 3192, 3103, 2932, 2856, 1616,
1450, 1383, 749; 1H NMR (d6-D2O/TMS, ppm):
d
1.10e2.30(m,
2.36(s, 3H, CH3Ph),
4.05e4.52(m, 6H, CH2N), d7.16e7.32(m, 4H, CH of Ph); ESI-MS:
11H, CH2 and CH of cyclohexyl),
d
d
m/z [M þ H]þ ¼ 559(100%).
Complex 9: Yield 57%. Yellow crystals. Anal. calcd. for
C19H29N3O4Pt: C, 40.86; H, 5.23; N, 7.52. Found: C, 40.75; H, 5.15;
N, 7.62. IR (KBr, cmꢀ1): 3399(br), 3197, 3115, 2932, 2855, 1622,
1449, 1380, 784, 683; 1H NMR (d6-D2O/TMS, ppm):
Scheme 2. Synthesis of the complexes (1e13).