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7.54 7.59 (m, 3 arom. H); 7.86 7.92 (m, 2 arom. H); 8.87 (br. s, 1 H, NH2); 8.96 (br. s, 1 H, NH2). Anal. calc. for
C12H10ClN5O2S (323.73): C 46.22, H 3.58, Cl 10.49, N 20.73, S 9.49; found: C 46.50, H 3.43, Cl 10.35, N 20.88,
S 9.30.
1-Methyl-7-phenyl-1H-pyrazino[2,3-c][1,2,6]thiadiazine-4,6-diamine 2,2-Dioxide (3). Compound 1 was
treated with an excess of liquid NH3 in a sealed tube at 808 for 6 d. Then, NH3 was evaporated and the residue
purified by CC (SiO2, CH2Cl2/MeOH): 0.13 g (44%) of 3. 1H-NMR: 3.33 (t, Me); 6.16 (s, NH2); 7.44 7.70 (m,
3 arom. H); 7.86 7.88 (m, 2 arom. H); 8.09 (br. s, 1 H, NH2); 8.67 (br. s, 1 H, NH2). Anal. calc. for C12H12N6O2S
(303.33): C 49.82, H 3.83, N 24.20, S 11.08; found: C 49.47, H 4.04, N 23.97, S 11.17.
6-Chloro-1-ethyl-N4-methyl-7-phenyl-1H-pyrazino[2,3-c][1,2,6]thiadiazin-4-amine 2,2-Dioxide (4). From 2
(0.80 g, 2.4 mmol) in dry EtOH (80 ml) and MeNH2 (33% in EtOH; 0.30 ml, 2.4 mmol) in a sealed tube at 808
for 48h. The solvent was evaporated and the residue recrystallized from EtOH/H 2O: 0.48g (60%) of 4.
1H-NMR: 1.32 (t, Me); 2.94 (d, Me); 4.06 (q, CH2); 7.40 7.67 (m, 3 arom. H); 7.75 7.93 (m, 2 arom. H); 9.39 (m,
NH). Anal. calc. for C14H14ClN5O2S (351.81): C 47.79, H 4.01, Cl 10.08, N 19.91, S 9.11; found: C 47.69, H 4.21,
Cl 10.03, N 19.71, S 9.21.
1-Ethyl-N4,N6-dimethyl-7-phenyl-1H-pyrazino[2,3-c][1,2,6]thiadiazine-4,6-diamine 2,2-Dioxide (5). From
2 (0.50 g, 1.5 mmol) in dry EtOH (50 ml) and MeNH2 (33% in EtOH; 1.80 ml, 2.4 mmol) in a sealed tube at 808
for 6 d. The solvent was evaporated and the residue recrystallized from H2O: 0.27 g (54%) of 5. 1H-NMR: 1.26
(m, NH); 2.88 (d, Me); 2.95 (s, Me); 3.95 (q, CH2); 6.60 (m, NH); 7.53 7.67 (m, 3 arom. H); 7.78 7.81 ( m,
2 arom. H); 8.70 (br. s, NH). Anal. calc. for C15H18N6O2S (346.41): C 52.01, H 5.24, N 24.26, S 9.26; found:
C 52.11, H 5.41, N 24.60, S 9.21.
6-Bromo-1-methyl-1H-pyrazino[2,3-c][1,2,6]thiadiazin-4-amine 2,2-Dioxide (6). From 6-bromo-1H-pyra-
zino[2,3-c][1,2,6]thiadiazin-4-amine 2,2-dioxide (3.00 g, 10.1 mmol), acetone (150 ml), Et3N (1.4 ml,
1
10.1 mmol), and MeI (1.7 ml, 30.3 mmol), reaction time 24 h: 2.40 g (82%) of 6. H-NMR: 3.37 (s, Me); 8.86
(br. s, NH2); 8.90 (br. s, 1 H, NH2); 8.97 (br. s, 1 H, NH2). Anal. calc. for C6H6BrN5O2 (292.11): C 24.67, H 2.07,
Br 27.35, N 23.97, S 10.97; found: C 24.80, H 2.24, Br 27.12, N 24.06, S 11.85.
6-Bromo-1-methyl-1H-pyrazino[2,3-c][1,2,6]thiadiazin-4,7-diamine 2,2-Dioxide (7). From
6 (0.60 g,
1.0 mmol) with an excess of liquid NH3 in a sealed tube at r.t. for 10 d. NH3 was evaporated and the residue
recrystallized from H2O/MeOH: 0.37 g (60%) of 7. 1H-NMR: 3.25 (s, Me); 8.10 (br. s, NH2); 8.10 (s, HÀC(7));
.
8.26 (br. s). EI-MS: 306 (M ). Anal. calc. for C6H7BrN5O2S (307.12): C 23.46, H 2.30, Br 26.02, N 27.36, S 10.44;
found: C 23.40, H 2.49, Br 26.10, N 27.60, S 10.54.
6-Bromo-N4,1-dimethyl-1H-pyrazino[2,3-c][1,2,6]thiadiazin-4-amine 2,2-Dioxide (8). From 6 (0.30 g,
1.0 mmol) in dry EtOH (15 ml) and MeNH2 (33% in EtOH; 0.4 ml, 3.0 mmol) in a sealed tube at r.t. for
48h. The solvent was evaporated and the residue recrystallized from MeOH: 0.13 g (44%) of 8. 1H-NMR: 2.93
.
(br. s, Me); 3.29 (s, Me); 8.89 (s, HÀC(7)); 9.39 (br. s, NH). EI-MS: 307 (M ). Anal. calc. for C7H8BrN5O2S
(306.14): C 27.46, H 2.63, Br 26.10, N 22.87, S 10.47; found: C 27.51, H 2.72, Br 26.44, N 22.67, S 10.21.
Compounds 10a c: General Procedure. To
a soln. of the corresponding 7-methyl-1H-pyrazino-
[2,3-c][1,2,6]thiadiazin-4-amine 2,2-dioxide 9a c (1.0 mmol) in H2O (50 ml), benzaldehyde (2.0 mmol) and
NaOH (2.0 mmol) in EtOH (10 ml) were added, and the mixture was refluxed for 72 h. The soln. was acidified
with conc. HCl soln., and the precipitate was filtered and recrystallized from the appropriate solvent (Table 1).
7-(2-Phenylethenyl)-1H-pyrazino[2,3-c][1,2,6]thiadiazin-4-amine 2,2-Dioxide (10a). From 9a (0.50 g,
2.5 mmol), NaOH (0.19 g, 5.0 mmol), H2O (125 ml), benzaldehyde (0.8ml , 5.0 mmol), and EtOH (10.0 ml):
1
0.21 g (40%) of 10a. H-NMR: 7.39 7.47 (m, CHCH, 1 arom. H); 7.39 7.47 (m, 2 arom. H); 7.70 7.73 (m,
2 arom. H); 7.86 (d, J 16.2, CHCH); 8.56 (s, HÀC(6)); 8.57 (br. s, NH2); 12.16 (br. s, NH). Anal. calc. for
C13H11N5O2S (301.33): C 51.82, H 3.68, N 23.24, S 10.64; found: C 51.59, H 3.86, N 23.17, S 10.44.
7-[2-(4-Chlorophenyl)ethenyl]-6-methyl-1H-pyrazino[2,3-c][1,2,6]thiadiazin-4-amine 2,2-Dioxide (10b).
From 9b (2.00 g, 8.8 mmol), NaOH (0.70 g, 17.6 mmol), H2O (200 ml), 4-chlorobenzaldehyde (2.50 g,
17.6 mmol), and EtOH (20 ml): 1.52 g (50 %) of 10b. 1H-NMR: 2.67 (s, Me); 7.50 (d, 2 arom. H); 7.56 (d,
J 18.7, CHCH,); 7.74 (d, CHCH); 7.81 (d, 2 arom. H); 8.36 (br. s, 1 H, NH2); 8.52 (br. s, 1 H, NH2); 11.96
(br. s, 1 H, NH). Anal. calc. for C14H14ClN5O2S (349.79): C 48.07, H 3.46, Cl 10.14, N 20.02, S 9.17; found:
C 48.03, H 3.75, Cl 10.22, N 20.12, S 9.21.
6-Phenyl-7-(2-phenylethenyl)-1H-pyrazino[2,3-c][1,2,6]thiadiazin-4-amine 2,2-Dioxide (10c). From 9c
(0.40 g, 1.9 mmol) in NaOH (38ml, 0.05 n) and benzaldehyde (1.20 g, 7.6 mmol): 0.12 g (28%) of 10c.
1H-NMR: 7.24 (d, CHCH, 1 arom. H); 7.39 7.42 (m, 3 arom. H); 7.53 7.56 (m, 5 arom. H); 7.70 7.76 (m,
2 arom. H); 7.85 (d, J 14.8, CHCH); 8.38 (br. s, 1 H, NH2); 8.51 (br. s, 1 H, NH2). Anal. calc. for
C19H15N5O2S (377.00): C 60.46, H 4.00, N 18.55, S 8.49; found: C 60.31, H 3.95, N 18.31, S 8.32.