Z. Chilmonczyk et al. / Il Farmaco 60 (2005) 439–443
441
Ethyl 2-[(4-pyrimidin-2-ylpiperazin-1-yl)carbonyl]-
heptanoate (3). (1.278 g) 77% yield. Rf: 0.64 (hexane-
AcOEt 50:50). 1H NMR (CDCl3, 200 MHz) d (ppm): 0.88 (t,
J = 6.5 Hz, 3H); 1.23–1.32 (m, 9H, CH2); 1.93–1.96 (m, 2H);
3.55–3.92 (m, 9H, CH); 4.19 (k, J = 7.2 Hz, 2H); 6.55 (t,
J = 4.8 Hz, 1H); 8.33 (d, J = 4.8 Hz, 2H). 13C NMR (CDCl3,
50 MHz) d (ppm): 169.77 (C); 167.21 (C); 161.23 (C); 157.53
(CH); 110.29 (CH); 61.04 (CH2); 48.91 (CH); 45.48 (CH2);
43.48 (CH2); 43.26 (CH2); 41.84 (CH2); 31.34 (CH2); 28.82
(CH2); 26.95 (CH2); 22.15 (CH2); 13.95 (CH3); 13.74 (CH3).
IR (CHCl3) m (cm–1): 2960; 2930; 2860; 1731; 1644; 1586;
1552; 1497; 1441; 1393; 1358; 1308; 1263; 1243; 1181; 1115;
1017; 983. GC (min) tR: 12.05. MS (EI, 70 eV) m/z (%): 348
(18, M+); 291 (9); 231 (3); 228 (3); 163 (28); 134 (74); 122
(100); 108 (97); 56 (40); 43 (16). HPLC (min): OJ t1 = 15.88;
t2 = 17.58; AD t1 = 18.98; t2 = 20.20.
Ethyl 2-[(4-pyrimidin-2-ylpiperazin-1-yl)carbonyl]-
octanoate (4). (1.31 g) 80% yield. Rf: 0.61(hexane-AcOEt
50:50). 1H NMR (CDCl3, 200 MHz) d (ppm): 0.87(t,
J = 6.2 Hz, 3H); 1.23–1.30 (m, 11H, CH2); 1.94–1.96 (m,
2H); 3.55–3.92 (m, 9H, CH); 4.19 (k, J = 7.1 Hz, 2H); 6.54
(t, J = 4.7 Hz, 1H); 8.33 (d, J = 4.7 Hz, 2H). 13C NMR
(CDCl3, 50 MHz) d (ppm): 169.87 (C); 167.31 (C); 161.29
(C); 157.62 (CH); 110.37 (CH); 61.15 (CH2); 49.02 (CH);
45.56 (CH2); 43.55 (CH2); 43.34 (CH2); 41.92 (CH2); 31.39
(CH2); 28.95 (CH2); 28.92 (CH2); 27.34 (CH2); 22.37 (CH2);
14.04 (CH3); 13.88 (CH3). IR (CHCl3) m (cm–1): 2959; 2929;
2859; 1731; 1644; 1586; 1552; 1497; 1441; 1393; 1358; 1308;
1263; 1237; 1020; 983. GC (min) tR: 12.31. MS (EI, 70 eV)
m/z (%): 362 (11, M+); 291 (8); 242 (2); 163 (26); 134 (69);
122 (100); 108 (90); 56 (40); 43 (17). HPLC (min): OJ
t1 = 14.84; t2 = 16.45; AD t1 = 19.24; t2 = 19.24.
170.06 (C); 170.04 (C); 167.48 (C); 167.23 (C); 161.94 (C);
157.76 (CH); 110.20 (CH); 61.28 (CH2); 61.22 (CH2); 49.44
(CH); 49.35 (CH); 47.57 (CH2); 47.22 (CH2); 45.77 (CH);
45.55 (CH); 43.43 (CH2); 43.28 (CH2); 40.76 (CH2); 31.58
(CH2); 31.54 (CH2); 29.48 (CH2); 29.24 (CH2); 27.28 (CH2);
27.15 (CH2); 22.38 (CH2); 16.72 (CH3); 15.46 (CH3); 14.83
(CH3); 14.80 (CH3); 13.92 (CH3). IR (CHCl3) m (cm–1): 2960;
2930; 2859; 1732; 1639; 1587; 1552; 1504; 1452; 1433; 1366;
1268; 1179; 1014. GC (min) tR: 11.90. MS (EI, 70 eV) m/z
(%): 362 (19, M+); 228 (7); 177 (36); 163 (9); 134 (53); 122
(100); 108 (34); 56 (11); 43 (15).
HPLC (min): OJ t1 = 11.11; t2 = 11.11; AD t1 = 15.66;
t2 = 18.84.
Ethyl (2RS)-2-{[(2R)-2-methyl-4-pyrimidin-2-ylpipe-
razin-1-yl] carbonyl} heptanoate (7). (0.593 g). 48% yield.
Rf: 0.70 (hexane-AcOEt 50:50). 1H NMR (CDCl3, 200 MHz)
d (ppm): 0.88 (t, J = 6.7 Hz, 3H, CH3); 1.15–1.31 (m, 12H,
CH2, CH3); 1.95–2.05 (m, 2H, CH2); 2.96–3.78 (m, 5H, CH,
CH2); 4.13–4.18 (m, 2H, CH2); 4.52–4.65 (m, 2H, CH2);
4.71–4.91 (m, 1H, CH); 6.54 (t, J = 4.7 Hz, 1H, CH); 8.31 (d,
J = 4.7 Hz, 2H, CH). 13C NMR (CDCl3, 50 MHz) d (ppm):
170.08 (C); 170.04 (C); 167.52 (C); 167.20 (C); 161.99 (C);
157.72 (CH); 110.24 (CH); 61.26 (CH2); 61.18 (CH2); 49.43
(CH); 49.31 (CH); 47.50 (CH2); 47.26 (CH2); 45.72 (CH);
45.51 (CH); 43.49 (CH2); 43.26 (CH2); 40.79 (CH2); 31.57
(CH2); 31.54 (CH2); 29.45 (CH2); 29.04 (CH2); 27.24 (CH2);
27.10 (CH2); 22.37 (CH2); 16.78 (CH3); 15.44 (CH3); 14.87
(CH3); 14.87 (CH3); 13.94 (CH3).
IR (CHCl3) m (cm–1): 2961; 2931; 2859; 1731; 1639; 1587;
1552; 1504; 1452; 1378; 1366; 1325; 1268; 1049; 1014. GC
(min) tR: 11.97. MS (EI, 70 eV) m/z (%): 362 (11, M+); 228
(9); 177 (42); 163 (10); 134 (57); 122 (100); 108 (37); 56
(11); 43 (13).
Ethyl 2-[(4-pyrimidin-2-ylpiperazin-1-yl)carbonyl]-
nonanoate (5). (1.2 g) 75% yield. Rf: 0.60 (hexane-AcOEt
HPLC (min): OJ t1 = 10.91; t2 = 10.91; AD t1 = 15.20;
t2 = 17.52.
1
50:50). H NMR (CDCl3, 200 MHz) d (ppm): 0.87 (t,
J = 6.22 Hz, 3H); 1.22–1.30 (m, 13H, CH2); 1.94 (m, 2H);
3.55–3.92 (m, 9H, CH); 4.19 (k, J = 7.1 Hz, 2H); 6.55 (t,
J = 4.8 Hz, 1H); 8.33 (d, J = 4.8 Hz, 2H). 13C NMR (CDCl3,
50 MHz) d (ppm): 169.74 (C); 167.18 (C); 161.20 (C); 157.50
(CH); 110.26 (CH); 61.01 (CH2); 48.88 (CH); 45.46 (CH2);
43.45 (CH2); 43.24 (CH2); 41.81 (CH2); 31.47 (CH2); 29.11
(CH2); 28.84 (CH2); 28.76 (CH2); 27.27 (CH2); 22.31 (CH2);
13.93 (CH3); 13.80 (CH3). IR (CHCl3,) m (cm–1): 2959; 2928;
2857; 1732; 1644; 1586; 1552; 1497; 1441; 1393; 1358; 1308;
1236; 983. GC (min) tR: 12.69. MS (EI, 70 eV) m/z (%): 377
(12); 291 (9); 256 (3); 163 (26); 134 (66); 122 (100); 108
(84); 56 (34); 43 (19). HPLC (min): OJ t1=13.20; t2 = 15.17;
AD t1 = 18.63; t2 = 18.63.
Ethyl (2RS)-2-{[(2S)-2-methyl-4-pyrimidin-2-ylpipe-
razin-1-yl] carbonyl} heptanoate (6). (0.239 g). 36% yield.
Rf: 0.64 (hexane-AcOEt 50:50). 1H NMR (CDCl3, 200 MHz)
d (ppm): 0.88 (t, J = 6.7 Hz, 3H, CH3); 1.19–1.31 (m, 12H,
CH2, CH3); 1.99–2.05 (m, 2H, CH2); 2.97–3.81 (m, 5H, CH,
CH2); 4.14–4.18 (m, 2H, CH2); 4.52–4.65 (m, 2H, CH2);
4.71–4.91 (m, 1H, CH); 6.53 (t, J = 4.7 Hz, 1H, CH); 8.31 (d,
J = 4.7 Hz, 2H, CH). 13C NMR (CDCl3, 50 MHz) d (ppm):
2.3. Chromatography
The HPLC analyses were performed using a Shimadzu liq-
uid chromatograph consisting of a LC-10AS pump, variable
wavelength UV SPD-10A detector and Valco (Cincinatti,
Ohio) valve injector equipped with 20 µl loop. Daicel Chiral-
cel OJ (10 µ, 4,6 mm × 250 mm) column packed with silica
coated with cellulose tris(4-methylbenzoate) and Daicel
ChiralpakAD (10 µ, 4,6 mm × 250 mm) column packed with
on silica coated with amylose tris(3,5-dimethylphenyl-
carbamate) were used and were obtained from Daccol Indus-
tries (Tokyo, Japan). The mobile phases were the mixtures of
hexane/propan-2-ol [80:20; 90:10; 95:5; 99:1 (v/v)].All chro-
matograms were recorded at room temperature with a flow
rate of 1 ml min–1 [100:0 (v/v); 0,22 ml min–1 ], using a UV
detector set at 242 nm. The system hold-up time (tm) was
determined as the first baseline disturbance due to the elution
of 1,3,5 tert-butyl benzene. The reported retention factors are
the means of three replicate determinations.