1108
S. Safarov, M. A. Kukaniev, H. Kolshorn and H. Meier
Vol. 42
extracted with CHCl (3 x 60 mL). Evaporation of the CHCl
gave a solid residue which was recrystallized from methanol.
This compound was obtained in 65 % yield (165 mg), mp 227
3
3
1
°C (CHCl ). H NMR (CDCl ): δ 2.37 (s, 1 H, CH ), 3.41 (m, 4
3
3
3
H, NCH ), 3.76 (m, 4 H, OCH ), 6.10 (s, 1 H, 6-H); FD MS: m/z
2
2
5-Methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-one (3a).
+•
+
252 (100 %) [M ]; HR MS (ESI): Calc. for [C
H N O S] :
10 13 4 2
The obtained colorless crystals (1.34 g, 80 %), mp 195 °C cor-
respond to an authentic sample [13a].
253.0759; found: 253.0754.
2-Bromo-6-chloro-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrim-
idin-7-one (14a).
2-Bromo-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-one
(3b).
To 3 mL glacial acetic acid, 492 mg (2.0 mmol) 3b and 534 mg
(4.0 mmol) N-chlorosuccinimide (12) were added. After 1 h stir-
ring at 95 °C, 2 mL petroleum (bp 40 – 70 °C) was added. The
This compound was obtained in 80 % yield (2.09 g), mp
1
181 °C. H NMR (CDCl ): δ 2.48 (s, 3 H, CH ), 6.09 (s, 1 H, 6-
3
3
+•
H); FD MS: m/z 245 (92 %), 247 (100 %) [M , Br isotope pat-
tern].
precipitate formed at 6 °C was washed with H O and recrystal-
2
1
lized from CH OH. Yield 449 mg (80 %), mp 215 °C. H NMR
3
Anal. Calcd. for C H BrN OS (246.1): C, 29.28; H, 1.61; N,
17.08; S, 13.03. Found: C, 29.23; H, 1.70; N, 17.23; S, 13.12.
(CD SOCD ): δ 2.59 (s, 3 H, CH ); FD MS: m/z 279 (70 %), 281
6
4
3
3
3
3
+•
(100 %), 283 (16 %) [M , BrCl isotope pattern].
Anal. Calcd. for C H BrClN OS (280.5): C, 25.69; H, 1.08; N,
14.98. Found: C, 25.47; H, 1.00; N, 15.13.
6
3
3
General Procedure for the Preparation of the 2-Amino-5-methyl-
7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-ones (11a – e).
2,6-Dibromo-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-
one (14b).
To 246 mg (1.0 mmol) 3b in 5 – 7 mL ethanol, 4.0 – 8.0 mmol
[21] of amine 10a-e was added. After 1 – 4 h refluxing (moni-
tored by TLC), the volatile parts were evaporated, 10 mL H O
To 2.4 mL glacial acetic acid, 246 mg (1.0 mmol) 3b and 356
mg (2.0 mmol) NBS (13) were added. After 0.5 h stirring at 90
°C, 2.5 mL petroleum (bp 40 – 70 °C) was added. The precipitate
2
was added and the product extracted with 3 x 20 mL CHCl .
3
Further purification was achieved by recrystallization from the
solvent described for each compound.
formed at 6 °C was washed with H O and recrystallized from
2
1
CH OH. Yield 276 mg (85 %), mp 217 °C. H NMR
3
2-Propylamino-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-
7-one (11a).
(CD SOCD ): δ 2.63 (s, 3 H, CH ); FD MS: m/z 323 (46 %), 325
3
3
3
+•
(100 %), 327 (44 %) [M , Br isotope pattern].
2
Instead of ethanol, methanol was used. Recrystallization from
Anal. Calcd. for C H Br N OS (325.0): C, 22.18; H, 0.93; N,
6
3
2 3
1
methanol yielded 162 mg (72 %) crystals, mp 222 °C. H NMR
12.93; S, 9.87. Found: C, 22.52; H, 0.94; N, 12.95; S, 9.93.
(CD OD): δ 1.04 (t, 3 H, CH ), 1.71 (m, 2 H, CH ), 2.52 (s, 3 H,
3
3
2
6-Chloro-2-dimethylamino-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]-
pyrimidin-7-one (15).
5-CH ), 3.35 (t, 2 H, NCH ), 6.18 (s, 1 H, 6-H) [22]; FD MS: m/z
3
2
+•
+
224 (100 %) [M ]; HR MS (ESI): Calcd. for [C H N OS] :
9
13 4
The solution of 150 mg (0.53 mmol) 14a in 5 mL 1,4-diox-
ane/methanol (1:1) was treated with 180 mg (4.0 mmol) 10c.
After stirring and refluxing, the volatile parts were removed, 4
225.0863. Found 225.0805.
2-Phenylamino-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-
7-one (11b).
mL H O was added to the residue and the mixture extracted with
2
Recrystallization from DMSO yielded 216 mg (84 %), mp 295
9 x 40 mL CHCl . Recrystallization from CH OH yielded 65 mg
3
3
1
1
°C. H NMR (CD SOCD ): δ 2.48 (s, 3 H, CH ), 6.01 (s, 1 H, 6-
(50 %) of 15, mp 260 °C. H NMR (CD OD): δ 2.73 (s, 3 H,
3
3
3
3
H), 7.07 (m, 1 H, p-H), 7.37 (m, 2 H, m-H), 7.51 (m, 2 H, o-H),
CH ), 3.18 (s, 6 H, N(CH ) ); FD MS: m/z 244 (100 %), 246 (44
3
3 2
+•
+•
10.60 (br. s, 1 H, NH); FD MS: m/z 258 (100 %) [M ].
%) [M , Cl isotope pattern]; HR MS (ESI): Calc. for
35
+
Anal. Calcd. for C H N OS (257.3): C, 55.80; H, 3.90; N,
[C H
ClN OS] : 245.0270. Found: 245.0185.
12
9 4
8
10
4
21.69; S, 12.41. Found: C, 55.82; H, 3.94; N, 21.50; S, 12.31.
Acknowledgements.
2-Dimethylamino-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrim-
idin-7-one (11c).
We are grateful to the Volkswagen Foundation for a grant for S.
S. and to the Fonds der chemischen Industrie for financial support.
Recrystallization from 1,4-dioxane yielded 179 mg (85 %), mp
1
202 °C. H NMR (CD OD): δ 2.53 (s, 3 H, 5-CH ), 3.16 (s, 6 H,
3
3
REFERENCES AND NOTES
+•
N(CH ) ), 6.20 (s, 1 H, 6-H); FD MS: m/z 210 (100 %) [M ].
3 2
Anal. Calcd. for C H N OS (210.3): C, 45.70; H, 4.79; N,
26.65; S, 15.25 Found: C, 45.87; H, 4.67; N, 26.61; S, 15.24.
8
10 4
[1] F. Russo, A. Santagati and M. Santagati, J. Heterocyclic
Chem., 22, 297 (1985) and references therein.
2-Diethylamino-5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-
7-one (11d).
[2] B. W. Clare and C. T. Supuran, Eur. J. Med. Chem. Chim.
Ther., 859 (2000).
[3] B. H. Lee, M. F. Clothier, F. E. Dutton, G. A. Conder and S. S.
Johnson, Bioorg. Med. Chem. Lett., 8, 3317 (1998).
[4] A. R. Katritzky, K. C. Caster, T. H. Maren, C. W. Conroy and
A. Bar-Ilan, J. Med. Chem., 30, 2058 (1987).
[5] S. Herling (Grünenthal G.m.b.H.), Ger. Offen. 2712932
(1978); Chem. Abstr., 90, 38957p (1978).
[6] S. Herling (Grünenthal G.m.b.H.), Ger. Offen. 2755615
(1979); Chem. Abstr., 91, 91655k (1979).
Recrystallization from ethyl acetate/petroleum (1:1) yielded
1
195 mg (82 %), mp 113 °C. H NMR (CD OD): δ 1.32 (t, 6 H,
3
CH ), 2.54 (s, 1 H, 5-CH ), 3.57 (q, 4 H, NCH ), 6.22 (s, 1 H,
3
3
2
+•
6-H); FD MS: m/z 238 [M ].
Anal. Calcd. for C N OS (238.3): C, 50.40; H, 5.52; N,
H
10 14
4
23.51; S, 13.45. Found: C, 50.69; H, 5.80; N, 23.80; S, 13.53.
5-Methyl-2-morpholino-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-
7-one (11e).
[7] A. Shafiee and I. Lalezari, J. Heterocyclic Chem., 12, 675
(1975).