G. Blanco et al. / Tetrahedron 62 (2006) 11124–11135
11133
(C]O), 1538, 1502, 1404 cmꢀ1
;
1H NMR (300 MHz,
C17H14N6O3S: C, 53.40; H, 3.69; N, 21.98; S, 8.39. Found:
C, 53.49; H, 3.53; N, 21.76; S, 8.25.
CDCl3) d 1.06 (t, J¼7.3 Hz, 3H), 1.48–1.63 (m, 2H),
1.80–1.96 (m, 2H), 4.34 (t, J¼7.7 Hz, 2H), 7.03 (s, 1H,
NH), 7.30–7.37 (m, 2H), 7.87–7.99 (m, 2H), 8.71 (d,
J¼2.3 Hz, 1H), 8.84 (d, J¼2.3 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 13.7, 20.2, 30.1, 42.1, 120.1, 125.3,
142.7, 143.5, 144.2, 158.3; MS (EI) m/z 396 (M+, 15),
339 (25). Anal. Calcd for C18H16N6O3S: C, 54.54; H,
4.07; N, 21.20; S, 8.09. Found: C, 54.31; H, 4.21; N,
21.45; S, 8.14.
3.4.13. 2-Isopropylamino-3-N-(4-methylphenyl)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8c2). Yield
98%; mp 217–219 ꢁC; IR (KBr) n 3414 (NH), 1676
(C]O), 1665, 1552, 1547, 1522, 1507, 1482, 1466, 1422,
1
1409 cmꢀ1; H NMR (300 MHz, CDCl3) d 1.16 (d, J¼
6.5 Hz, 6H), 2.46 (s, 3H), 4.18 (d, J¼7.9 Hz, 1H, NH),
4.45–4.75 (m, 1H), 7.17–7.25 (m, 2H), 7.40–7.45 (m, 2H),
8.65 (d, J¼2.3 Hz, 1H), 8.81 (d, J¼2.3 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 21.3, 22.7, 43.9, 115.2, 128.2, 131.2,
132.5, 140.5, 142.2, 143.7, 144.1, 150.2, 152.9, 158.6,
158.8; MS (EI) m/z 351 (M+, 40), 308 (100), 91 (25).
Anal. Calcd for C18H17N5OS: C, 61.52; H, 4.88; N, 19.93;
S, 9.12. Found: C, 61.45; H, 4.97; N, 20.03; S, 9.17.
3.4.9. 2-n-Butylamino-3-N-(4-methylphenyl)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8a2). Yield
89%; mp 163–165 ꢁC; IR (KBr) n 3256 (NH), 1611
(C]O), 1562, 1524, 1509, 1480, 1464, 1435 cmꢀ1 1H
;
NMR (300 MHz, CDCl3) d 0.88 (t, J¼7.3 Hz, 3H), 1.22–
1.34 (m, 2H), 1.44–1.54 (m, 2H), 2.45 (s, 3H), 3.53–3.60
(m, 2H), 4.35 (t, J¼5.1 Hz, 1H, NH), 7.21–7.23 (m, 2H),
7.39–7.42 (m, 2H), 8.65 (d, J¼2.3 Hz, 1H), 8.80 (d,
J¼2.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 13.7, 19.9,
21.3, 31.1, 42.0, 115.3, 128.2, 131.2, 131.5, 140.5, 142.1,
143.7, 144.1, 150.1, 153.6, 158.5, 158.7; MS (EI) m/z 365
(M+, 10), 308 (30). Anal. Calcd for C19H19N5OS: C,
62.44; H, 5.24; N, 19.16; S, 8.77. Found: C, 62.51; H,
5.39; N, 19.02; S, 8.75.
3.4.14. 2-Cyclohexylylamino-3-N-(4-nitrophenyl)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8d1). Yield
84%; mp 246–248 ꢁC; IR (KBr) n 3429 (NH), 1690
(C]O), 1547, 1530, 1346 cmꢀ1 1H NMR (300 MHz,
;
CDCl3) d 1.06–1.24 (m, 3H), 1.35–1.50 (m, 3H), 1.73–
1.92 (m, 2H), 1.99–2.04 (m, 2H), 3.97 (d, J¼8.0 Hz, 1H,
NH), 4.25–4.38 (m, 1H), 7.57–7.65 (m, 2H), 8.48–8.56
(m, 2H), 8.71 (d, J¼2.3 Hz, 1H), 8.86 (d, J¼2.3 Hz, 1H);
13C NMR (75 MHz, CDCl3) d 24.3, 25.3, 32.8, 50.4,
126.1, 130.4, 140.0, 142.5, 144.1, 148.8, 150.6, 151.7; MS
(EI) m/z 422 (M+, 5), 339 (30), 203 (30), 123 (30), 99
(52). Anal. Calcd for C20H18N6O3S: C, 56.86; H, 4.29; N,
19.89; S, 7.59. Found: C, 56.69; H, 4.13; N, 19.76; S, 7.46.
3.4.10. 3-N-Benzylamino-2-(4-nitrophenylamino)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (9b1). Yield
85%; mp 113–115 ꢁC; IR (KBr) n 3393 (NH), 1676
(C]O), 1610, 1541, 1503, 1464, 1413 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 5.61 (s, 2H), 7.01 (s, 1H, NH), 7.42–
7.57 (m, 5H), 7.58–7.65 (m, 2H), 8.21–8.28 (m, 2H), 8.74
(d, J¼2.3 Hz, 1H), 8.86 (d, J¼2.3 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 45.8, 119.7, 125.3, 127.0, 130.0,
130.2, 133.7, 142.8, 144.3; MS (EI) m/z 430 (M+, 10), 279
(3), 91 (20). Anal. Calcd for C21H14N6O3S: C, 58.60; H,
3.28; N, 19.52; S, 7.45. Found: C, 58.58; H, 3.39; N,
19.43; S, 7.39.
3.4.15. 2-Cyclohexylylamino-3-N-(4-methylphenyl)pyr-
azino[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8d2).
Yield 88%; mp 233–235 ꢁC; IR (KBr) n 3416 (NH), 1686
(C]O), 1546, 1532, 1520, 1485, 1347 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 1.00–1.23 (m, 3H), 1.36–1.65 (m,
5H), 1.90–2.05 (m, 2H), 2.48 (s, 3H), 4.20–4.35 (m, 2H),
7.19–7.26 (m, 2H), 7.39–7.47 (m, 2H), 8.67 (d, J¼2.3 Hz,
1H), 8.82 (d, J¼2.3 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 21.3, 24.2, 25.4, 32.8, 49.9, 115.2, 128.2, 131.3, 131.5,
140.5, 142.2, 143.6, 144.1, 150.2, 153.0, 158.6, 158.9; MS
(EI) m/z 391 (M+, 10), 308 (100). Anal. Calcd for
C21H21N5OS: C, 64.43; H, 5.41; N, 17.89; S, 8.19. Found:
C, 64.33; H, 5.42; N, 17.69; S, 8.12.
3.4.11. 2-Benzylamino-3-N-(4-methylphenyl)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8b2). Yield
82%; mp 218–220 ꢁC; IR (KBr) n 3336 (NH), 1685
(C]O), 1553, 1522, 1509, 1452, 1343 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 2.43 (s, 3H), 4.73 (t, J¼5.2 Hz, 1H,
NH), 4.83 (d, J¼5.2 Hz, 2H), 7.20–7.35 (m, 7H), 7.36–
7.44 (m, 2H), 8.68 (d, J¼2.3 Hz, 1H), 8.81 (d, J¼2.3 Hz,
1H); 13C NMR (75 MHz, CDCl3) d 21.3, 46.2, 115.9,
127.4, 127.6, 128.2, 128.7, 131.0, 131.6, 137.5, 140.7,
142.3, 143.8, 144.1, 150.0, 153.6, 158.6, 158.8; MS (EI)
m/z 399 (M+, 20), 91 (35). Anal. Calcd for C22H17N5OS:
C, 66.15; H, 4.29; N, 17.53; S, 8.03. Found: C, 66.24; H,
4.08; N, 17.64; S, 8.17.
3.4.16. 2-tert-Butylamino-3-N-(4-nitrophenyl)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8e1). Yield
93%; mp 227–229 ꢁC; IR (KBr) n 3415 (NH), 1690
(C]O), 1596, 1556, 1545, 1523, 1518, 1484 cmꢀ1 1H
;
NMR (300 MHz, CDCl3) d 1.50 (s, 9H), 3.99 (s, 1H, NH),
7.58–7.61 (m, 2H), 7.48–7.51 (m, 2H), 8.68 (d, J¼2.3 Hz,
1H), 8.86 (d, J¼2.3 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 29.0, 53.8, 126.0, 130.4, 140.3, 142.6, 143.9, 144.1,
148.7, 150.3, 151.0, 158.4, 158.7; MS (EI) m/z 396 (M+,
15), 339 (90). Anal. Calcd for C18H16N6O3S: C, 54.54; H,
4.07; N, 21.20; S, 8.09. Found: C, 54.43; H, 4.19; N,
21.14; S, 8.19.
3.4.12. 2-Isopropylamino-3-N-(4-nitrophenyl)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8c1). Yield
81%; mp>300 ꢁC; IR (KBr) n 3350 (NH), 1685 (C]O),
1545, 1520, 1480, 1390 cmꢀ1
;
1H NMR (300 MHz,
CDCl3) d 1.21 (d, J¼6.5 Hz, 6H), 3.91 (d, J¼7.8 Hz, 1H,
NH), 4.45–4.70 (m, 1H), 7.58–7.65 (m, 2H), 8.50–8.56
(m, 2H), 8.71 (d, J¼2.3 Hz, 1H), 8.86 (d, J¼2.3 Hz, 1H);
13C NMR (75 MHz, CDCl3) d 22.8, 44.5, 115.1, 126.1,
130.4, 139.9, 142.5, 144.1, 148.8, 151.7; MS (EI) m/z 382
(M+, 63), 339 (100), 324 (17), 203 (33). Anal. Calcd for
3.4.17. 2-tert-Butylamino-3-N-(4-methylphenyl)pyrazino-
[20,30:4,5]thieno[3,2-d]pyrimidin-4(3H)-one (8e2). Yield
85%; mp 224–226 ꢁC; IR (KBr) n 3428 (NH), 1681
(C]O), 1557, 1545, 1520, 1484, 1456 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 1.45 (s, 9H), 2.43 (s, 3H), 4.29 (s,