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P. Tapolcsanyi et al. / Tetrahedron 58 (2002) 10137–10143
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3.5.10. 9-Chloro-1,3-dimethylpyrimido[5,4-c]cinnoline-
2,4(1H,3H)-dione (12b). 6-(2-Amino-5-chlorophenyl)-1,3-
dimethyluracil (10b) (5 mmol) was dissolved in concen-
trated hydrochloric acid (40 mL) and cooled to 08C with
stirring. Aqueous NaNO2 solution (0.73 g, 10.62 mmol of
NaNO2 in 27 mL of water) was added dropwise at such a
rate that the temperature of the mixture did not exceed 58C.
The mixture was stirred at this temperature for 1.5 h. Then
the mixture was neutralized with saturated Na2CO3 solution
and extracted with dichloromethane (3£50 mL), dried over
Na2SO4, filtered, evaporated and recrystallized from
n-butanol to yield pale yellow prisms (747 mg, 54%); mp
218–2198C; Rf (CHCl3/MeOH, 9:1): 0.63; nmax: 1721,
1668, 1502, 1441, 1363, 1286, 1246, 1216, 1084, 847; dH
(CDCl3): 8.58 (d, J¼9.0 Hz, 1H, H-7), 8.46 (d, J¼1.5 Hz,
1H, H-10), 7.93 (dd, J¼9.0, 1.5 Hz, 1H, H-8), 4.04 (s, 3H,
N–CH3), 3.57 (s, 3H, N–CH3); dC (CDCl3): 159.3 (C-4),
151.3, 149.9, 137.3, 136.3, 133.4 and 132.8 (C-8 and -10),
130.2, 123.3 (C-7), 115.8 (C-10a), 38.0 and 29.2 (1-CH3 and
3-CH3); Anal. calcd for C12H9ClN4O2 (276.78): C, 52.09;
H, 3.28; N, 20.25; Cl, 12.81. Found: C, 52.22; H, 3.26; N,
20.20 Cl, 12.80.
39.5 (N–CH3), 28.9 (N–CH3). Anal. calcd for C13H11N3O2
(241.25): C, 64.72; H, 4.60; N, 17.42. Found: C, 64.74; H,
4.46; N, 17.46.
3.5.14. N-[2-(Pyrazin-2-yl)phenyl]pivalamide (21). The
crude product obtained according to the general procedure
(1.2) was subjected to flash
chromatography
(EtOAc/CHCl3, 5:95) to yield colorless oil (270 mg,
53%); Rf (EtOAc/CHCl3, 1:9): 0.40; nmax: 3342, 2962,
1682, 1584, 1528, 1478, 1440, 1309, 1164, 1073, 1021, 923,
849, 756; dH (CDCl3): 11.6 (br s, 1H, NH), 9.07 (s, 1H,
H-3), 8.64 (d, 1H, H-60), 8.63 (s, 2H, H-5 and -6), 7.72 (d0d,
J¼7.7, 1.4 Hz, 1H, H-30), 7.48 (td, J¼7.7, 1.4 Hz, 1H, H-5 ),
7.21 (t, J¼7.7 Hz, 1H, H-40), 1.31 (s, 9H, C(CH3)3); dC
(CDCl3): 177.4(COC(CH3)3), 153.5(C-2), 144.5 and 142.3
and 141.1(C-3, -5 and -6), 138.3(C-10), 131.1 and 128.6(C-
30 and -50), 123.6 and 122.4(C-40 and -60), 122.9(C-20),
40.1(COC(CH3)3, 27.6(COC(CH3)3. Anal. calcd for
C15H17N3O (255.32): C, 70.56; H, 6.71; N, 16.46. Found:
C, 70.27; H, 6.79; N, 16.35.
3.5.15. 2-(2-Aminophenyl)pyrazine (22). The crude pro-
duct obtained according to the general procedure (1.3) was
subjected to flash chromatography (EtOAc/CHCl3, 1:4) to
yield yellow needles (171 mg, 50%); mp 80–818C; Rf
(EtOAc/CHCl3, 5:95): 0.20; nmax: 3376, 3268, 3156, 3082,
3038, 2924, 2764, 2684, 2342, 1614, 1514, 1482, 1442,
1402, 1354, 1332, 1304, 1260, 1190, 1164, 1140, 1074,
1042, 1018, 954, 926, 844, 764, 698; dH (CDCl3): 8.99 (d,
J¼1.2 Hz, 1H, H-3), 8.52 (dd, J¼2.6, 1.6 Hz, 1H, H-5), 8.43
(d, J¼2.6 Hz, 1H, H-6), 7.60 (dd, J¼2.6, 1.4 Hz, 1H, H-60),
7.22 (t0d, J¼7.3, 1.4 Hz, 1H, H-40), 6.75–6.85 (m, 2H, H-30
and -5 ), 5.70 (br s, 2H, NH2), dC (CDCl3 and DMSO-d6):
154.1(C-2), 146.7 (C-20), 143.1 and0141.5 and 140.7 (C-3,
-5, -6), 130.5 and 128.05 (C-40 and -6 ), 117.9 and 117.3 and
117.1 (C-10, -30 and -5 ). Anal. calcd for C10H9N3 (171.20):
C, 70.16; H, 5.30; N, 24.54. Found: C, 69.81; H, 5.23; N,
24.55.
3.5.11. 5-Amino-6-chloro-1,3-dimethyluracil (15). 6-
Chloro-5-nitro-1,3-dimethyluracil (880 mg, 4 mmol) was
dissolved in acetic acid (99.5 %) (20 mL), iron powder
(2.4 g) was added and stirred at 258C for 4 h. The reaction
mixture was then poured onto ice-water (100 g), neutralised
with Na2CO3, extracted with ethyl acetate (5£50 mL), dried
over Na2SO4 and evaporated to give yellow prisms (588 mg,
77%); Rf (EtOAc): 0.70; mp 120–1228C (lit.4a 118–1208C,
lit.4b 120–1218C); nmax: 3459, 3363, 1651, 1570, 1480,
1415, 1338, 1085; dH (CDCl3): 3.71 (br s, 2H, NH2), 3.55 (s,
3H, N–CH3), 3.39 (s, 3H, N–CH3), dC (CDCl3): 158.4
(C-4), 149.4 (C-2), 121.7 and 119.7 (C-5 and -6), 33.3
(1-CH3), 28.7 (3-CH3).
3.5.12. 5-Amino-6-phenyl-1,3-dimethyluracil (17). The
crude product obtained according to the general procedure
(1.2) was purified by flash chromatography (EtOAc/CHCl3,
5:95) to yield orange prisms (360 mg, 77%); mp 104–
1078C; Rf (EtOAc/CHCl3, 1:1): 0.50; nmax: 3449, 3347,
1682, 1623, 1575, 1482, 1439, 1354, 1309, 1188, 1084, 7805,
722, 697, 541. dH (CDCl3): 7.40–7.60 (m, 3H, H-30, -40, -5 ),
7.33 (d, J¼7.8 Hz, 2H, H-20 and -60), 3.47 (s, 3H, N–CH3),
3.15 (br s, 2H, NH2), 3.09 (s, 3H, N–CH3); dC (CDCl3):
160.20(C-04), 150.6 (C-2), 131.0 and 129.8 and 128.9 (C-6,
-10, -2 , -3 , -40, -50 and -60), 119.7 (C-5), 34.1 (N–CH3), 28.5
(N–CH3). Anal. calcd for C12H13N3O2 (231.25): C, 62.33;
H, 5.57; N, 18.19. Found: C, 61.98; H, 5.57; N, 18.29.
3.5.16. 2-(2-Azidophenyl)pyrazine (24). The crude pro-
duct obtained according to the general procedure (1.4) was
not further purified (955 mg, 97%); Rf (CHCl3/MeOH, 9:1):
0.85; nmax: 3442, 2130, 2096, 1600, 1580, 1492, 1462, 1446,
1396, 1288, 1152, 1072, 1016, 766, 742; dH (CDCl3): 9.03
(s, 1H, H-3), 8.67 (s, 1H, H-5), 8.53 (s, 1H, H-6), 7.73 (d0d,
J¼8.4, 1.7 Hz, 1H, H-60),07.50 (td, J¼8.0, 1.7 Hz, 1H, H-4 ),
7.29 (m, 2H, H-30 and -5 ).
3.5.17. Pyrazino[1,2-b]indazole (25). The crude product
obtained according to the general procedure was filtered
through silicagel, eluted first with CHCl3 (50 mL), then
ethyl acetate (250 mL). The ethyl acetate fraction was
evaporated to dryness to yield gray crystals (71 mg, 42%),
which were further purified by flash chromatography using
ethyl acetate/chloroform (1:9) as the eluent (65 mg, 38%)
and recrystallized from methanol to get white needles; mp
146–1478C; Rf (EtOAc/CHCl3, 1:9): 0.25; nmax: 3055,
3010, 1725, 1588, 1510, 1427, 1333, 1273, 1204, 1154, 990,
889, 811, 752; dH (DMSO-d6): 9.82 (d, J¼1.4 Hz, 1H, H-1),
9.06 (dd, J¼4.7, 1.5 Hz, 1H, H-3), 8.44 (d, J¼8.2 Hz, 1H,
H-10), 8.34 (d, J¼4.7 Hz, 1H, H-4), 7.93 (d, J¼8.6 Hz, 1H,
H-7), 7.67 (dd, J¼8.3, 6.8 Hz, 1H, H-8), 7.44 (dd, J¼7.6,
7.5 Hz, 1H, H-9); dC (DMSO-d6): 148.8 (C-6a), 144.1
3.5.13. 1,3-Dimethylpyrimido[5,4-c]isoquinoline-2,
4(1H,3H)-dione (19). The crude product obtained accord-
ing to the general procedure (1.2) was subjected to flash
chromatography (EtOAc/CHCl3, 1:1), and crystallized from
a mixture of acetone and methanol to yield yellow needles
(120 mg, 25%); mp 283–2848C; Rf (EtOAc/CHCl3, 1:1):
0.26; nmax: 1693, 1654, 1483, 1335, 1287, 1070, 776; dH
(CDCl3): 9.13 (s, 1H, H-6); 8.42 (m, 1H) and 8.10 (m, 1H):
(H-7 and -10), 7.83 (m, 2H, H-8 and -9), 3.95 (s, 3H,
N–CH3): 3.55 (s, 3H, N–CH3), dC (CDCl3): 161.1 (C-4),
152.5 (C-2), 149.1 (C-6), 136.6 (C-10b), 131.5 (C-4a),
130.3, 130.0, 128.8, 127.0 and 126.0 (C-6a and -10a), 124.8,