ꢂꢁꢁꢁ
P. Żmudzki et al.: New 5-HT6 and D2 receptors ligandsꢀ
ꢀ17
3
1
3
3.23 (t, J ꢁ=ꢁ 6.2 Hz, 2H), 3.24 (s, 3H), 3.43–3.46 (m, 4H), 3.45 (s, 3H), 0.28; H NMR: δ 2.50 (t, J ꢁ=ꢁ 6.3 Hz, 2H), 2.54–2.64 (m, 4H), 2.87–3.01
3
3
4
4.82 (s, 2H), 7.25 (ddd, J ꢁ=ꢁ 8.3 Hz, J ꢁ=ꢁ 6.8 Hz, J ꢁ=ꢁ 1.2 Hz, 1H), 7.37 (m, 4H), 3.28–3.32 (m, 2H), 3.45 (s, 3H), 3.85 (s, 3H), 4.55 (s, 2H), 6.85
3
4
(ddd, 3J ꢁ=ꢁ 8.0 Hz, 3J ꢁ=ꢁ 7.0 Hz, 4J ꢁ=ꢁ 1.2 Hz, 1H), 7.50–7.52 (m, 1H), 7.67 (s, (dd, J ꢁ=ꢁ 5.4 Hz, J ꢁ=ꢁ 4.1 Hz, 1H), 6.97–7.10 (m, 2H), 7.51–7.53 (m, 2H);
1H), 7.68–7.69 (m, 1H), 7.78 (dd, 3J ꢁ=ꢁ 6.8 Hz, 4J ꢁ=ꢁ 1.2 Hz, 1H); 13C NMR: δ 13C NMR: δ 29.6, 33.4, 36.0, 43.2, 50.8, 52.9, 56.6, 107.5, 118.5, 124.7,
23.5, 26.8, 27.8, 29.6, 39.3, 48.8, 49.6, 52.7, 57.9, 106.9, 120.4, 123.7, 124.0, 127.3, 127.4, 133.9, 142.0, 148.7, 150.7, 151.4, 154.8, 167.7. Anal. Calcd for
127.6, 127.7, 142.9, 148.5, 151.6, 152.4, 155.3, 163.3, 166.0. Anal. Calcd for C21H25N7O3Cl2: C, 51.02; H, 5.10; N, 19.83. Found: C, 51.12; H, 5.19; N,
C24H30N8SO3: C, 56.45; H, 5.92; N, 21.94. Found: C, 56.55; H, 5.87; N, 19.69. LC/MS: calcd m/z 494.15, found m/z 494.29.
21.81. LC/MS: calcd m/z 511.22, found m/z 511.37.
N-[3-(4-(2,3-Dichlorophenyl)piperazino)propyl]-2-(3,7-dimethyl-
N-[4-(4-(Benzo[d]isoxazol-3-yl)piperazino)butyl]-2-(1,3-dimethyl-
2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetamide (7):ꢂThis com-
pound was obtained from I in 94% yield; mp 146–147°C; Rf ꢁ=ꢁ 0.38; 1H
NMR: δ 1.50–1.58 (m, 4H), 2.40 (t, 3J ꢁ=ꢁ 6.9 Hz, 2H), 2.60–2.63 (m, 4H),
3.24–3.30 (m, 2H), 3.37 (s, 3H), 3.55–3.58 (m, 4H), 3.57 (s, 3H), 4.86
(s, 2H), 7.20 (ddd, 3J ꢁ=ꢁ 8.1 Hz, 3J ꢁ=ꢁ 6.4 Hz, 4J ꢁ=ꢁ 1.7 Hz, 1H), 7.37 (t, 3J ꢁ=ꢁ
5.4 Hz, 1H), 7.40–7.50 (m, 2H), 7.66–7.69 (m, 1H), 7.72 (s, 1H); 13C NMR:
δ 23.9, 27.1, 28.1, 29.9, 39.7, 48.1, 50.1, 52.4, 57.9, 106.7, 110.5, 116.1, 122.1,
122.3, 129.5, 142.5, 149.0, 151.4, 155.8, 161.2, 163.9, 165.5. Anal. Calcd
for C24H30N8O4: C, 58.29; H, 6.11; N, 22.66. Found: C, 58.48; H, 6.05; N,
22.55. LC/MS: calcd m/z 495.25, found m/z 495.42.
2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide
(12):ꢂThis
compound was obtained from II in 75% yield; mp 222–224°C; Rf ꢁ=ꢁ
1
3
3
0.30; H NMR: δ 1.68 (quin, J ꢁ=ꢁ 6.9 Hz, 2H), 2.46 (t, J ꢁ=ꢁ 7.0 Hz, 2H),
3
2.54–2.72 (m, 4H), 2.92–3.09 (m, 4H), 3.27 (t, J ꢁ=ꢁ 6.4 Hz, 2H), 3.48 (s,
3
4
3H), 3.89 (s, 3H), 4.56 (s, 2H), 6.88 (dd, J ꢁ=ꢁ 6.2 Hz, J ꢁ=ꢁ 3.3 Hz, 1H),
7.05–7.10 (m, 2H), 7.51–7.53 (m, 2H); 13C NMR: δ 25.3, 29.7, 33.5, 38.2,
43.3, 50.9, 53.0, 56.1, 107.5, 118.5, 124.7, 127.3, 127.5, 133.9, 141.9, 148.9,
150.7, 151.5, 154.8, 167.6. Anal. Calcd for C22H27N7O3Cl2: C, 51.97; H, 5.35;
N, 19.29. Found: C, 52.05; H, 5.21; N, 19.11. LC/MS: calcd m/z 508.16,
found m/z 508.32.
N-[4-(4-(Benzo[d]isothiazol-3-yl)piperazino)butyl]-2-(3,7-dimethyl-
N-[4-(4-(2,3-Dichlorophenyl)piperazino)butyl]-2-(1,3-dimethyl-
2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetamide (8):ꢂThis com-
pound was obtained from I in 50% yield; mp 167–169°C; Rf ꢁ=ꢁ 0.14;
2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide
(13):ꢂThis
compound was obtained from II in 57% yield; mp 183–185°C; Rf ꢁ=ꢁ
1
0.24; H NMR: δ 1.58–1.64 (m, 4H), 2.45–2.49 (m, 2H), 2.68–2.71 (m,
3
1H NMR: δ 1.54–1.58 (m, 4H), 2.44 (t, J ꢁ=ꢁ 6.7 Hz, 2H), 2.55–2.73 (m,
4H), 3.29–3.35 (m, 2H), 3.56 (s, 3H), 3.56–3.59 (m, 4H), 3.95 (s, 3H), 4.65
(s, 2H), 6.45–6.49 (m, 1H), 7.33–7.36 (m, 1H), 7.45 (ddd, 3J ꢁ=ꢁ 8.1 Hz, 3J ꢁ=ꢁ
7.0 Hz, 4J ꢁ=ꢁ 1.7 Hz, 1H), 7.50 (s, 1H), 7.78–7.81 (m, 1H), 7.86–7.90 (m, 1H);
13C NMR: δ 24.1, 27.2, 29.8, 33.6, 39.5, 43.6, 49.9, 52.9, 57.9, 107.5, 120.5,
123.8, 123.9, 127.5, 127.9, 141.7, 149.1, 151.4, 152.7, 154.8, 163.8, 167.1. Anal.
Calcd for C24H30N8SO3: C, 56.45; H, 5.92; N, 21.94. Found: C, 56.63; H,
5.99; N, 21.83. LC/MS: calcd m/z 511.22, found m/z 511.37.
3
4H), 3.00–3.15 (m, 4H), 3.27 (q, J ꢁ=ꢁ 5.4 Hz, 2H), 3.39 (s, 3H), 3.59 (s,
3
4
3H), 4.86 (s, 2H), 6.96 (dd, J ꢁ=ꢁ 6.5 Hz, J ꢁ=ꢁ 3.2 Hz, 1H), 7.07–7.20 (m,
2H), 7.30–7.45 (m, 1H), 7.73 (s, 1H); 13C NMR: δ 24.0, 27.1, 28.1, 29.9, 39.7,
50.1, 51.1, 53.2, 57.8, 106.6, 118.6, 124.7, 127.4, 127.5, 134.0, 142.4, 149.1,
151.1, 151.4, 155.8, 165.3. Anal. Calcd for C23H29N7O3Cl2: C, 52.88; H, 5.60;
N, 18.77. Found: C, 53.01; H, 5.38; N, 18.73. LC/MS: calcd m/z 522.18,
found m/z 522.34.
N-[4-(4-(Benzo[d]isoxazol-3-yl)piperazino)butyl]-2-(3,7-dimethyl-
N-[2-(4-(Benzo[d]isothiazol-3-yl)piperazino)ethyl]-2-(3,7-dimethyl-
2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide
(14):ꢂThis
2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide
(9):ꢂThis
compound was obtained from II in 60% yield; mp 163–165°C; Rf ꢁ=ꢁ
0.34; 1H NMR: δ 1.57–1.51 (m, 4H), 2.44 (t, 3J ꢁ=ꢁ 6.4 Hz, 2H), 2.63–2.67 (m,
4H), 3.28–3.34 (m, 2H), 3.55 (s, 3H), 3.58–3.60 (m, 4H), 3.94 (s, 3H), 4.64
(s, 2H), 6.45 (t, 3J ꢁ=ꢁ 5.3 Hz, 1H), 7.20 (ddd, 3J ꢁ=ꢁ 8.1 Hz, 3J ꢁ=ꢁ 6.4 Hz, 4J ꢁ=ꢁ 1.7
Hz, 1H), 7.40–7.48 (m, 2H), 7.50 (s, 1H), 7.67 (d, 3J ꢁ=ꢁ 8.0 Hz, 1H); 13C NMR:
δ 24.0, 27.2, 29.8, 33.6, 39.5, 43.6, 48.1, 52.4, 57.9, 107.5, 110.4, 116.1, 122.1,
122.3, 129.5, 141.7, 149.1, 151.5, 154.8, 161.2, 163.9, 167.2. Anal. Calcd for
C24H30N8O4: C, 58.29; H, 6.11; N, 22.66. Found: C, 58.14; H, 6.11; N, 22.71.
LC/MS: calcd m/z 495.25, found m/z 495.42.
compound was obtained from II in 69% yield; mp 235–237°C; Rf ꢁ=ꢁ
1
3
0.33; H NMR: δ 2.54 (t, J ꢁ=ꢁ 6.2 Hz, 2H), 2.64–2.67 (m, 4H), 3.34 (t,
3J ꢁ=ꢁ 6.2 Hz, 2H), 3.43–3.46 (m, 4H), 3.47 (s, 3H), 3.87 (s, 3H), 4.59 (s,
2H), 7.28 (ddd, 3J ꢁ=ꢁ 8.1 Hz, 3J ꢁ=ꢁ 7.0 Hz, 4J ꢁ=ꢁ 1.0 Hz, 1H), 7.39 (ddd, 3J ꢁ=ꢁ
3
8.1 Hz, 3J ꢁ=ꢁ 7.0 Hz, 4J ꢁ=ꢁ 1.0 Hz, 1H), 7.50–7.52 (m, 2H), 7.73 (dt, J ꢁ=ꢁ 8.1
4
3
4
Hz, J ꢁ=ꢁ 1.0 Hz, 1H), 7.80 (dt, J ꢁ=ꢁ 8.2 Hz, J ꢁ=ꢁ 1.0 Hz, 1H); 13C NMR: δ
29.7, 33.5, 35.8, 43.3, 49.6, 52.6, 56.7, 107.5, 120.5, 123.8, 124.1, 127.7, 127.8,
142.0, 148.9, 151.4, 152.4, 154.8, 163.7, 167.7. Anal. Calcd for C22H26N8SO3:
C, 54.76; H, 5.43; N, 23.22. Found: C, 54.73; H, 5.22; N, 23.38. LC/MS:
calcd m/z 483.19, found m/z 483.32.
N-[4-(4-(2,3-Dichlorophenyl)piperazino)butyl]-2-(3,7-dimethyl-
2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide
(15):ꢂThis
N-[2-(4-(Benzo[d]isoxazol-3-yl)piperazino)ethyl]-2-(3,7-dimethyl-
compound was obtained from II in 18% yield; mp 214–216°C; Rf ꢁ=ꢁ
2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide
(10):ꢂThis
1
3
0.16; H NMR: δ 1.48–1.55 (m, 4H), 2.42 (t, J ꢁ=ꢁ 7.2 Hz, 2H), 2.55–2.75
compound was obtained from II in 41% yield; mp 208–210°C; Rf ꢁ=ꢁ
0.33; 1H NMR: δ 2.60 (t, 3J ꢁ=ꢁ 6.0 Hz, 2H), 2.67–2.70 (m, 4H), 3.44 (q, 3J ꢁ=ꢁ
5.6 Hz, 2H), 3.53–3.56 (m, 4H), 3.57 (s, 3H), 3.96 (s, 3H), 4.70 (s, 2H),
3
(m, 4H), 2.94–3.11 (m, 4H), 3.21 (t, J ꢁ=ꢁ 6.2 Hz, 2H), 3.49 (s, 3H), 3.90
(s, 3H), 4.58 (s, 2H), 6.91 (dd, 3J ꢁ=ꢁ 6.2 Hz, 4J ꢁ=ꢁ 3.3 Hz, 1H), 7.03–7.13 (m,
2H), 7.52–7.55 (m, 2H); 13C NMR: δ 23.6, 27.0, 29.7, 33.5, 39.1, 43.2, 50.7,
53.0, 57.8, 107.5, 118.6, 124.7, 127.3, 127.5, 133.9, 141.9, 148.9, 150.8, 151.49,
154.9, 167.5. Anal. Calcd for C23H29N7O3Cl2: C, 52.88; H, 5.60; N, 18.77.
Found: C, 52.95; H, 5.44; N, 18.62. LC/MS: calcd m/z 522.18, found m/z
522.34.
3
3
4
6.35–6.45 (m, 1H), 7.22 (ddd, J ꢁ=ꢁ 8.1 Hz, J ꢁ=ꢁ 6.3 Hz, J ꢁ=ꢁ 1.5 Hz, 1H),
7.41–7.54 (m, 3H), 7.66–7.69 (m, 1H); 13C NMR: δ 29.8, 33.6, 35.9, 43.6,
48.2, 52.1, 56.4, 107.5, 110.5, 116.1, 122.1, 122.4, 129.6, 141.8, 149.2, 151.4,
154.8, 161.2, 164.0, 167.2. Anal. Calcd for C22H26N8O4: C, 56.64; H, 5.62;
N, 24.02. Found: C, 56.58; H, 5.71; N, 23.92. LC/MS: calcd m/z 467.21,
found m/z 4 6 7. 3 7.
Acknowledgments: This study was supported by the
project ‘Prokog,’ UDAPOIG.01.03.01-12-063/09-00, co-
financed by the European Union from the European Fund
N-[2-(4-(2,3-Dichlorophenyl)piperazino)ethyl]-2-(3,7-dimethyl-
2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)acetamide
(11):ꢂThis
compound was obtained from II in 58% yield; mp 245–247°C; Rf ꢁ=ꢁ of Regional Development (EFRD).
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 2/13/15 8:19 PM