F. Herold et al. / European Journal of Medicinal Chemistry 41 (2006) 125–134
131
1
crystals, m.p. 285–288 °C; H-NMR (400 MHz) δ: 1.88 (m,
(C-6′′), 149.9 (C-1), 152.2 (C-2′′), 157.6 (C-2′), 165.9 (C-3).
IR ν: 1641 (C=O), 1700 (C=O). Anal. (C28H31N5O3 × 2 HCl ×
H2O) C, H, N.
4H, C-2xH2, C-3xH2), 2.11 (s, 3H, CH3), 3.37 (m, 4H, C-
4xH2, CαHax), 3.68 (bs, 2H, CβHax), 3.81 (bs, 2H, CαHeq),
4.21 (t, J = 6.4 Hz, C-1xH2), 4.36 (bs, 2H, CβHeq), 6.72 (d,
3
3J = 9.2 Hz, 1H, C-5H), 6.76 (t, J = 7.6 Hz, 1H, C-7H), 7.16
6.1.4.6. 4-(2-Methoxyphenyl)-2-[4-[4-(2-pyrimidinyl)-1-piper-
3
3
3
(t, J = 6.8 Hz, 1H, C-5′′H), 7.20 (d, J = 7.6 Hz, 1H, C-6′H),
azinyl]butyl]-2H-pyrido[1,2-c]pyrimidine-1,3-dione
(11).
7.24 (t, J = 7.2 Hz, 1H, C-6H), 7.36 (t, J = 7.2 Hz, 1H, C-5′
Yield 46%; yellow crystals, m.p. 235–236 °C; 1H-NMR
(400 MHz) δ: 1.83 (m, 4H, C-2xH, C-3xH), 3.20 (pt, 2H, CαH
3
3
H), 7.39 (d, 3J = 9.2 Hz, 1H, C-3′′H), 7.44 (m, 2H, C-3′H, C-4′
H), 8.03 (d, J = 6.0 Hz, 1H, C-6′′H), 8.15 (t, J = 7.6 Hz, 1H,
C-4′′H), 8.45 (d, J = 7.2 Hz, 1H, C-8H).
ax), 3.31 (t, J = 6.8 Hz, 2H, C-4xH2), 3.52 (pt, 2H, CβHax),
3
3
3
3.72 (bs, 2H, CαHeq), 3.75 (s, 3H, OCH3), 4.16 (t, 3J
= 6.8 Hz, 2H, C-1xH2), 4.68 (pd, 2H, CβHeq), 6.72 (t, 3J
3
13C-NMR (100 MHz) δ: 19.7 (CH3), 22.1 (C-3x), 25.1 (C-
2x), 42.9 (C-1x), 44.4 (2C, Cβ), 51.8 (2C, Cα), 57.7 (C-4x),
104.3 (C-4), 114.2 (C-3′′), 114.3 (C-5′′), 116.1 (C-7), 122.3
(C-5), 127.8 (C-5′), 129.1 (C-8), 130.1 (C-4′), 131.7 (C-3′),
133.0 (C-6′), 133.2 (C-2′), 136.3 (C-6), 138.0 (C-4′′), 140.3
(C-1′), 146.6 (C-4a), 146.6 (C-6′′), 151.2 (C-1), 151.2 (C-2′′),
162.8 (C-3). IR ν: 1641 (C=O), 1703 (C=O). Anal.
(C27H30N6O3 × 2 HCl × H2O) C, H, N.
3
= 6.8 Hz, 1H, C-7H), 6.76 (d, J = 9.6 Hz, 1H, C-5H), 7.00
(t, 1H, C-5′′H), 7.13 (t, 3J = 7.2 Hz, 1H, C-6H), 7.17-7.26
3
(m, 3H, C-3′H, C-5′H, C-6′H), 7.50 (t, J = 6.8 Hz, 1H, C-4′
3
3
H), 8.40 (d, J = 7.6 Hz, 1H, C-8H), 8.54 (d, J = 5.2 Hz, 2H,
C-4′′H, C-6′′H).
13C-NMR (100 MHz) δ: 20.9 (C-3x), 23.9 (C-2x), 41.6 (Cβ),
41.8 (C-1x), 51.0 (Cα), 55.8 (OCH3), 56.5 (C-4x), 100.0 (C-4),
111.6 (C-5′′), 112.3 (C-7), 113.1 (C-3′), 120.9 (C-1′), 121.3 (C-
5′), 121.8 (C-5), 127.9 (C-8), 130.6 (C-4′), 133.1 (C-6), 135.1
(C-6′), 145.7 (C-4a), 149.9 (C-1), 156.5 (C-2′′), 157.6 (C-2′),
157.8 (C-4′′, C-6′′), 161.7 (C-3). IR ν: 1631(C=O), 1701
(C=O). Anal. (C27H30N6O3 × 2 HCl × H2O) C, H, N.
6.1.4.4. 4-(2-Tolyl)-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]bu-
tyl]-2H-pyrido[1,2-c]pyrimidine-1,3-dione (9). Yield 51%; yel-
1
low crystals, m.p. 267–270 °C; H-NMR (400 MHz) δ: 1.90
(m, 4H, C-2xH2, C-3xH2), 2.11 (s, 3H, CH3), 3.30 (pt, 2H,
CαHax), 3.38 (t, J = 7.6 Hz, 2H, C-4xH2), 3.66 (pt, 2H, CβH
3
ax), 3.83 (pd, 2H, CαHeq), 4.22 (t, J = 6.4 Hz, 2H, C-1xH2),
6.1.4.7. 4-(2-Chlorophenyl)-2-[4-[4-(2-pyridyl)-1-piperazinyl]
3
4.76 (pd, 2H, CβHeq), 6.70 (d, 3J = 9.6 Hz, 1H, C-5H), 6.77 (t,
butyl]-2H-pyrido[1,2-c]pyrimidine-1,3-dione (12). Yield 84%;
1
3J = 7.2 Hz, 1H, C-7H), 7.13 (t, 3J = 5.2 Hz, 1H, C-5′′H), 7.18
yellow crystals, m.p. 273–275 °C (decomposition); H-NMR
(d, J = 7.2 Hz, 1H, C-6′H), 7.24 (t, J = 7.6 Hz, 1H, C-6H),
(400 MHz) δ: 1.89 (s, 4H, C-2xH2, C-3xH2), 3.37 (d, 4H, C-
4xH2, CαHax), 3.69 (t, 2H, CβHax), 3.82 (bs, 2H, CαHeq), 4.22
3
3
3
7.37 (t, J = 6.8 Hz, 1H, C-5′H), 7.45 (m, 2H, C-3′H, C-4′H),
3
8.44 (d, 3J = 7.6 Hz, 1H, C-8H), 8.66 (d, 3J = 5.6 Hz, 2H, C-4′′
H, C-6′′H).
(m, J = 5.6 Hz, 2H, C-1xH2), 4.38 (bs, 2H, CβHeq), 6.79 (q,
3
2H, C-5H, C-7H), 7.18 (t, 1H, C-5′′H), 7.29 (q, J = 7.2 Hz,
13C-NMR (100 MHz) δ: 21.2 (CH3), 23.5 (C-3x), 26.5 (C-
2x), 44.3 (2C, Cβ), 44.3(C-1x), 53.4 (2C, Cα), 59.1 (C-4x),
105.7 (C-4), 114.0 (C-5′′), 115.6 (C-7), 123.7 (C-5), 129.2
(C-5′), 130.5 (C-8), 131.5 (C-4′), 133.2 (C-3′), 134.4 (C-6′),
134.5 (C-2′), 137.7 (C-6), 141.7 (C-1′), 147.9 (C-4a), 152.5
(C-1), 157.6 (C-2′′), 160.1 (C-4′′, C-6′′), 164.1 (C-3). IR ν:
1641 (C=O), 1701 (C=O). Anal. (C27H30N6O3 × 2 HCl × 1.5
H2O) C, H, N.
1H, C-6H), 7.37 (t, 1H, C-3′′H), 7.40 (t, 1H, C-6′H), 7.51 (k,
2H, C-4′H, C-5′H), 7.66 (d, 1H, C-3′H), 8.05 (d, 1H, C-6′′H),
8.17 (t, 1H, C-4′′H), 8.48 (d, J = 7.2 Hz, 1H, C-8H).
3
13C-NMR (100 MHz) δ: 23.5 (C-3x), 26.5 (C-2x), 44.3 (C-
1x), 45.8 (Cβ), 53.2 (Cα), 59.1 (C-4x), 104.1 (C-4), 115.8 (C-
7), 115.8 (C-3′′), 117.6 (C-5′′), 123.5 (C-5), 130.6 (C-5′), 130.7
(C-6′), 132.6 (C-4′), 133.1 (C-3′), 133.9 (C-1′), 136.2 (C-6),
138.0 (C-2′), 138.3 (C-8), 139.4 (C-4′′), 148.1 (C-6′′), 148.3
(C-4a), 152.4 (C-1), 154.8 (C-2′′), 164.0 (C-3). IR ν: 1649
(C=O), 1701 (C=O). Anal. (C27H28ClN5O2 × 2 HCl) C, H, N.
6.1.4.5. 4-(2-Methoxyphenyl)-2-[4-[4-(2-pyridyl)-1-piperazi-
nyl]butyl]-2H-pyrido[1,2-c]pyrimidine-1,3-dione (10). Yield
1
45%; yellow crystals, m.p. 250–251 °C; H-NMR (400 MHz)
6.1.4.8. 4-(2-Chlorophenyl)-2-[4-[4-(2-pyrimidinyl)-1-pipera-
δ: 1.83 (q, 2H, C-2xH2), 1.87 (q, 2H, C-3xH2), 3.34 (t, J
zinyl]butyl]-2H-pyrido[1,2- c]pyrimidine-1,3-dione (13). Yield
3
= 8.4 Hz, 2H, C-4xH2), 3.66 (bs, 2H, Cαax), 3.74 (s, 3H,
70%; yellow crystals, m.p. 268–270 °C (decomposition); H-
1
3
OCH3), 3.79 (bs, 4H, CαHeq, CβHax), 4.15 (t, J = 6.8 Hz,
NMR (400 MHz) δ: 1.76 (s, 2H, C-3xH2), 1.88 (s, 2H, C-
2xH2), 3.27 (t, 2H, CαHax), 3.36 (d, 3J = 6.8 Hz, 2H, C-
2H, C-1xH2], 4.33 (bs, 2H, CβHeq), 6.71 (t, J = 6.8 Hz, 1H,
3
3
3
3
C-7H), 6.74 (d, J = 10.0 Hz, 1H, C-5H), 7.11 (t, J = 7.6 Hz,
1H, C-6H), 7.14 (d, 3J = 6.4 Hz, 1H, C-3′H), 7.19 (m, 3H, C-5′
H, C-6′H, C-5′′H), 7.37 (d, 3J = 9.6 Hz, 1H, C-3′′H), 7.49 (t, 3J
4xH2), 3.62 (t, 2H, CβHax), 3.80 (d, 2H, CαHeq), 4.21 (d, J
= 5.2 Hz, 2H, C-1xH2), 4.74 (d, 2H, CβHeq), 6.78 (q, 2H, C-
3
5H, C-7H), 7.10 (d, 1H, C-5′′H), 7.28 (t, J = 7.2 Hz, 1H, C-
3
= 7.6 Hz, 1H, C-4′H), 8.00 (d, J = 6.0 Hz, 1H, C-6′′H), 8.12
6H), 7.36 (t, 1H, C-6′H), 7.50 (k, 2H, C-4′H, C-5′H), 7.64 (d,
1H, C-3′H), 8.47 (d, 3J = 7.2 Hz, 1H, C-8H), 8.62 (d, 2H, C-4′′
H, C-6′′H).
3
3
(t, J = 7.6 Hz, 1H, C-4′′H), 8.38 (d, J = 7.6 Hz, 1H, C-8H).
13C-NMR (100 MHz) δ: 21.0 (C-3x), 23.9 (C-2x), 41.8 (C-
1x), 43.3 (Cβ), 50.6 (Cα), 55.8 (OCH3), 56.6 (C-4x), 100.0 (C-
4), 112.3 (C-7), 113.1 (C-3′), 113.3 (C-3′′), 115.0 (C-5′′), 120.9
(C-1′), 121.3 (C-5′), 121.7 (C-5), 127.9 (C-8), 130.6 (C-4′),
133.1 (C-6), 135.0 (C-6′), 136.7 (C-4′′), 145.6 (C-4a), 145.6
13C-NMR (100 MHz) δ: 23.5 (C-3x), 26.5 (C-2x), 44.3 (C-
1x, Cβ), 53.4 (Cα), 59.1 (C-4x), 104.1 (C-4), 114.1 (C-5′′),
115.8 (C-7), 123.5 (C-5), 130.6 (C-5′), 130.7 (C-6′), 132.6
(C-4′), 133.1 (C-3′), 133.8 (C-1′), 136.2 (C-6), 138.0 (C-2′),