Synthesis of Novel Tricyclic Pyrimido[4,5-b][1,4]benzothiazepines
4-(Phenylthio)-6-p-tolylpyrimido[4,5-b][1,4]-
benzothiazepine (2.3): 97%; yellow solid; mp 164-167 °C;
1H NMR (CDCl3) δ 8.44 (s, 1 H), 7.82 (d, J ) 8.1 Hz, 2 H),
7.65-7.25 (m, 11 H), 2.45 (s, 3 H); 13C NMR (CDCl3) δ 170.8,
166.4, 154.0, 152.7, 142.3, 137.8, 137.2, 137.1, 136.7, 135.5,
133.7, 132.3, 131.2, 130.2, 129.5, 129.3, 129.2, 128.3, 21.6; ES-
MS 412.1 [M + H+].
4-(Phenylthio)-6-(o-nitrophenyl)pyrimido[4,5-b][1,4]-
benzothiazepine (2.4): 70%; yellow solid; mp 190-192 °C;
1H NMR (CDCl3) δ 8.49 (s, 1 H), 8.07 (dd, J ) 8.1, 1.2 Hz, 1
H), 7.97 (dd, J ) 7.8, 1.2 Hz, 1 H), 7.81 (td, J ) 7.8, 1.2 Hz, 1
H), 7.68 (td, J ) 8.1, 1.5 Hz, 1 H), 7.62-7.54 (m, 3 H), 7.52
(dd, J ) 7.5, 1.5 Hz, 1 H), 7.49-7.43 (m, 3 H), 7.29 (td, J )
8.1, 1.4 Hz, 1 H), 7.09 (dd, J ) 7.5, 1.2 Hz, 1 H); 13C NMR
(CDCl3) δ 170.1, 167.6, 155.5, 153.7, 149.1, 137.6, 137.5, 137.1,
136.7, 135.9, 134.0, 133.7, 133.4, 132.7, 131.3, 129.9, 129.6,
129.5, 129.0, 128.1, 125.0; ES-MS 443.1 [M + H+].
4-(Phenylthio)-6-(p-fluorophenyl)pyrimido[4,5-b][1,4]-
benzothiazepine (2.7): 52%; yellow solid; mp 197-198 °C;
1H NMR (CDCl3) δ 8.46 (s, 1 H), 7.97-7.92 (m, 2 H), 7.65 (dd,
J ) 8.0, 1.4 Hz, 1 H), 7.61-7.57 (m, 2 H), 7.54 (dd, J ) 7.5,
1.5 Hz, 1 H), 7.48-7.43 (m, 3 H), 7.40 (dd, J ) 7.2, 1.2 Hz, 1
H), 7.33 (dd, J ) 7.7, 1.7 Hz, 1 H), 7.22-7.14 (m, 2 H); 13C
NMR (CDCl3) δ 169.8, 166.9, 165.1 (J ) 235.8 Hz), 154.5,
152.9, 137.5, 137.0, 135.8, 135.5, 134.2, 132.8, 132.7 (J ) 9.2
Hz), 131.2, 129.9, 129.6, 129.5, 128.7, 128.3, 115.8 (J ) 20.6
Hz); ES-MS 416.1 [M + H+].
4-(Phenylthio)-6-methylpyrimido[4,5-b][1,4]benzo-
thiazepine (2.8): 45%; yellow oil; 1H NMR (CDCl3) δ 8.42 (s,
1 H), 7.55-7.52 (m, 4 H), 7.46-7.42 (m, 5 H), 2.77 (s, 3 H);
13C NMR (CDCl3) δ 173.5, 165.9, 153.9, 153.2, 138.9, 137.5,
136.2, 135.5, 133.5, 132.0, 129.5, 129.3, 129.0, 128.2, 29.1; ES-
MS 336.0 [M + H+].
133.1, 131.5, 130.1, 129.1, 124.6, 21.5, 21.4, 21.0; ES-MS 440.3
[M + H+].
4-(p-Tolylthio)-6-(p-fluorophenyl)-8-methylpyrimido-
[4,5-b][1,4]benzothiazepine (2.14): 80%; yellow solid; mp
152-153 °C; 1H NMR (CDCl3) δ 8.45 (s, 1 H), 7.98-7.93 (m, 2
H), 7.51 (d, J ) 7.8 Hz, 1 H), 7.45 (d, J ) 8.1 Hz, 2 H), 7.34
(dd, J ) 8.1, 1.8 Hz, 1 H), 7.25 (d, J ) 8.1 Hz, 2 H), 7.21-7.15
(m, 2 H), 7.11 (d, J ) 1.5 Hz, 1 H), 2.40 (s, 3 H), 2.33 (s, 3 H);
13C NMR (CDCl3) δ 169.8, 166.9, 165.2 (J ) 251.9 Hz), 154.5,
153.1, 140.1, 139.1, 137.8, 136.8, 136.0, 135.9, 135.7, 134.2,
134.0, 133.7, 132.6 (J ) 8.6 Hz), 131.6, 130.5, 124.7, 115.8 (J
) 21.8 Hz), 21.7, 21.4; ES-MS 444.1 [M + H+].
4-(p-Tolylthio)-6-propyl-8-methylpyrimido[4,5-b][1,4]-
benzothiazepine (2.15): 67%; yellow solid; mp 164-166 °C;
1H NMR (CDCl3) δ 8.40 (s, 1 H), 7.43-7.39 (m, 3 H), 7.30-
7.22 (m, 4 H), 3.01 (t, J ) 7.2 Hz, 2 H), 2.39 (s, 3 H), 2.38 (s,
3 H), 1.90-1.78 (m, 2 H), 1.10 (t, J ) 7.8 Hz, 3 H); 13C NMR
(CDCl3) δ 176.7, 166.1, 153.7, 153.3, 139.6, 139.1, 138.3, 137.5,
135.4, 133.3, 133.2, 132.4, 130.0, 128.4, 124.6, 43.5, 21.3, 21.1,
20.4, 13.8; ES-MS 392.1 [M + H+]. Anal. Calcd for C22H21-
N3S2: C, 67.48; H, 5.41; N, 10.73. Found: C, 69.39; H, 5.43;
N, 10.66.
4-(p-Tolylthio)-6-benzyl-8-methylpyrimido[4,5-b][1,4]-
benzothiazepine (2.16): 60%; yellow solid; mp 179-181 °C;
1H NMR (CDCl3) δ 8.40 (s, 1 H), 7.42 (d, J ) 8.1 Hz, 4 H),
7.35-7.18 (m, 8 H), 4.37 (s, 2 H), 2.39 (s, 3 H), 2.34 (s, 3 H);
13C NMR (CDCl3) δ 174.7, 166.2, 154.0, 153.6, 139.7, 139.1,
137.8, 137.4, 136.2, 135.4, 133.7, 133.3, 132.6, 130.1, 129.4,
128.5, 128.4, 126.8, 124.5, 48.1, 21.4, 21.2; ES-MS 440.1 [M +
H+].
4-(p-Chlorophenylthio)-6-phenyl-8-chloropyrimido-
[4,5-b][1,4]benzothiazepine (2.17): 98%; yellow solid; mp
203-205 °C; 1H NMR (CDCl3) δ 8.46 (s, 1 H), 7.94-7.90 (m, 2
H), 7.61-7.49 (m, 7 H), 7.44-7.40 (m, 2 H), 7.31 (d, J ) 2.4
Hz, 1 H); 13C NMR (CDCl3) δ 169.9, 166.3, 154.6, 152.7, 139.0,
138.3, 137.8, 137.1, 136.3, 125.7, 135.3, 135.2, 132.7, 132.3,
131.0, 130.3, 129.9, 128.9, 126.7; ES-MS 466.0 [M + H+].
4-(p-Chlorophenylthio)-6-p-tolyl-8-chloropyrimido[4,5-
b][1,4]benzothiazepine (2.18): 95%; yellow solid; mp 192-
4-(Phenylthio)-6-propylpyrimido[4,5-b][1,4]benzo-
thiazepine (2.9): 47%; yellow solid; mp 166-168 °C; 1H NMR
(CDCl3) δ 8.41 (s, 1 H), 7.55-7.46 (m, 4 H), 7.45-7.39 (m, 4
H), 3.01 (t, J ) 7.5 Hz, 2 H), 1.90-1.78 (m, 2 H), 1.10 (t, J )
7.5 Hz, 3 H); 13C NMR (CDCl3) δ 176.8, 165.9, 153.8, 153.2,
138.5, 137.6, 136.7, 135.5, 133.5, 131.7, 129.5, 129.2, 129.0,
128.3, 128.1, 43.7, 20.4, 13.9; ES-MS 364.1 [M + H+].
1
193 °C; H NMR (CDCl3) δ 8.44 (s, 1 H), 7.81 (d, J ) 8.1 Hz,
2 H), 7.58-7.47 (m, 4 H), 7.43-7.39 (m, 2 H), 7.33-7.30 (m, 3
H), 2.46 (s, 3 H); 13C NMR (CDCl3) δ 169.4, 165.9, 154.1, 152.4,
138.1, 137.6, 137.0, 136.8, 136.0, 135.3, 134.9, 134.8, 132.3,
130.7, 130.1, 129.6, 129.5, 129.4, 126.6, 21.6; ES-MS 480.1 [M
+ H+].
4-(Phenylthio)-6-benzylpyrimido[4,5-b][1,4]benzo-
thiazepine (2.10): 65%; yellow solid; mp 149-151 °C; 1H
NMR (CDCl3) δ 8.42 (s, 1 H), 7.57-7.52 (m, 3 H), 7.48-7.36
(m, 8 H), 7.35-7.20 (m, 3 H), 4.38 (s, 2 H); 13C NMR (CDCl3)
δ 175.1, 166.2, 154.4, 153.7, 138.3, 137.7, 137.3, 136.4, 135.8,
133.8, 132.1, 129.8, 129.6, 129.5, 129.2, 128.9, 128.5, 128.3,
127.2, 48.6; ES-MS 412.1 [M + H+].
4-(p-Chlorophenylthio)-6-(pyridin-3-yl)-8-chloropyrim-
ido[4,5-b][1,4]benzothiazepine (2.19): 12%; yellow solid; mp
264-266 °C; 1H NMR (CDCl3) δ 9.07 (s, 1 H), 8.82 (d, J ) 3.6
Hz, 1 H), 8.49 (s, 1 H), 8.32 (dt, J ) 8.1, 1.8 Hz, 1 H), 7.61 (d,
J ) 8.4 Hz, 1 H), 7.56 (d, J ) 2.1 Hz, 1 H), 7.54-7.48 (m, 3
H), 7.45-7.41 (m, 2 H), 7.31 (d, J ) 2.1 Hz, 1 H); 13C NMR
(CDCl3) δ 167.3, 166.2, 154.7, 152.5, 152.4, 151.0, 137.1, 136.9,
136.7, 136.1, 135.5, 135.2, 135.1, 134.4, 132.9, 130.2, 129.6,
126.1, 123.5; ES-MS 467.0 [M + H+].
4-(p-Chlorophenylthio)-6-benzyl-8-chloropyrimido[4,5-
b][1,4]benzothiazepine (2.20): 30%; yellow solid; mp 177-
179 °C; 1H NMR (CDCl3) δ 8.42 (s, 1 H), 7.51-7.25 (m, 12 H),
4.35 (s, 2 H); 13C NMR (CDCl3) δ 173.9, 166.0, 154.5, 153.4,
139.3, 137.1, 136.8, 136.3, 135.8, 135.5, 135.0, 132.2, 129.8,
129.6, 129.0, 128.6, 128.2, 127.5, 126.7, 48.4; ES-MS 480.0 [M
+ H+].
4-(p-Methoxyphenylthio)-6-phenyl-8-methoxypyrimido-
[4,5-b][1,4]benzothiazepine (2.21): 80%; yellow solid; mp
206-209 °C; 1H NMR (CDCl3) δ 8.45 (s, 1 H), 7.99-7.96 (m, 2
H), 7.58-7.48 (m, 6 H), 7.06 (dd, J ) 8.4, 3.0 Hz, 1 H), 7.00-
6.95 (m, 2 H), 6.83 (d, J ) 2.7 Hz, 1 H), 3.85 (s, 3 H), 3.74(s,
3 H); 13C NMR (CDCl3) δ 170.6, 167.2, 161.0, 159.8, 154.4,
153.4, 139.5, 138.2, 137.9, 137.4, 135.2, 131.9, 130.4, 128.7,
128.3, 118.8, 118.4, 116.5, 115.3, 55.9, 55.6; ES-MS 458.1 [M
+ H+].
4-(p-Tolylthio)-6-phenyl-8-methylpyrimido[4,5-b][1,4]-
benzothiazepine (2.11): 97%; yellow solid; mp 210-211 °C;
1H NMR (CDCl3) δ 8.44 (s, 1 H), 7.96-7.93 (m, 2 H), 7.55-
7.45 (m, 6 H), 7.33 (dd, J ) 7.8, 1.7 Hz, 1 H), 7.25 (d, J ) 7.8
Hz, 2 H), 7.13 (d, J ) 1.5 Hz, 1 H), 2.40 (s, 3 H), 2.32 (s, 3 H);
13C NMR (CDCl3) δ 170.9, 166.6, 154.1, 152.9, 139.7, 139.5,
138.6, 137.6, 136.8, 135.4, 133.9, 133.5, 133.2, 131.5, 131.4,
130.1, 128.4, 124.6, 21.4, 21.0; ES-MS 426.1 [M + H+].
4-(p-Tolylthio)-6-(pyridin-3-yl)-8-methylpyrimido[4,5-
b][1,4]benzothiazepine (2.12): 97%; yellow solid; mp 266-
267 °C; 1H NMR (CDCl3) δ 9.04 (d, J ) 1.8 Hz, 1 H), 8.78 (dd,
J ) 4.8, 1.5 Hz, 1 H), 8.47 (s, 1 H), 8.38 (dt, J ) 8.1, 1.8 Hz,
1 H), 7.55-7.36 (m, 5 H), 7.26 (d, J ) 8.1 Hz, 2 H), 7.12 (d, J
) 1.8 Hz, 1 H), 2.41 (s, 3 H), 2.34 (s, 3 H); 13C NMR (CDCl3)
δ 168.9, 167.1, 154.9, 153.3, 152.3, 151.6, 140.2, 139.4, 137.7,
137.3, 136.2, 135.7, 135.5, 134.3, 134.2, 134.0, 131.4, 130.5,
124.5, 123.7, 21.7, 21.4; ES-MS 427.1 [M + H+].
4-(p-Tolylthio)-6-p-tolyl-8-methylpyrimido[4,5-b][1,4]-
benzothiazepine (2.13): 96%; yellow solid; mp 194-196 °C;
1H NMR (CDCl3) δ 8.43 (s, 1 H), 7.83 (d, J ) 8.1 Hz, 2 H),
7.50 (d, J ) 8.1 Hz, 1 H), 7.46 (d, J ) 8.1 Hz, 2 H), 7.34-7.24
(m, 5 H), 7.13 (d, J ) 1.5 Hz, 1 H), 2.45 (s, 3 H), 2.40 (s, 3 H),
2.31 (s, 3 H); 13C NMR (CDCl3) δ 170.7, 166.5, 153.9, 152.8,
142.1, 139.7, 138.6, 137.7, 136.8, 136.7, 135.4, 133.8, 133.5,
4-(p-Methoxyphenylthio)-6-benzyl-8-methoxypyrimido-
[4,5-b][1,4]benzothiazepine (2.22): 30%; yellow solid; mp
J. Org. Chem, Vol. 70, No. 26, 2005 10815