N. Todorovic et al. / Tetrahedron Letters 51 (2010) 6037–6040
6039
Figure 1. X-ray crystal structures of (A) 6-(1-methyl-2-(4-iodobenzyl)hydrazinyl)-3-methylpyrimidine-2,4(1H,3H)-dione and (B) 3-(4-bromophenyl)-1,6-dimethyl-1,2-
dihydropyrimido [5,4-e][1,2,4]triazine-5,7(6H,8H)-dione.
130 °C; 1H NMR (200 MHz, DMSO-d6) d 11.32 (s, 1H), 3.58 (s, 2H), 3.05 (s, 3H);
Acknowledgments
13C NMR (50 MHz) d 167.1, 166.6, 151.9, 39.8, 26.9; MS [EI+] m/z (RI%) 142 [M]+
(100); HRMS for C5H6N2O3 calcd m/e 142.0378, observed m/e 142.0377. 6-
The authors thank the Institute for Infectious Disease Research
(McMaster University), the Natural Sciences and Engineering
Research Council of Canada, the Canadian Foundation for Innova-
tion, and the Ontario Innovation Trust for their financial support.
Chloro-3-methylpyrimidine-2,4(1H,3H)-dione (4, with R1 = CH3): A mixture of 6-
hydroxy-3-methylpyrimidine-2,4(1H,3H)-dione (0.2 g, 1.4 mmol) and
phosphorous oxychloride (0.26 mL, 2.8 mmol) in 5 mL acetonitrile was
microwave heated at 120 °C for 20 min. The solution was cooled to room
temperature and methanol was added. The resulting precipitate was filtered
and dried to afford the product as an orange solid in 80% yield (0.18 g,
1.1 mmol); 1H NMR (200 MHz, DMSO-d6) d 12.36 (s, 1H), 5.89 (s, 1H), 3.09 (s,
3H); 13C NMR (50 MHz) 161.8, 150.6, 143.3, 99.2, 26.7; MS [EI+] m/z (RI%) 160
[M]+ (100); HRMS for C5H5ClN2O2 calcd m/e 160.0040, observed m/e 160.0030.
References and notes
1. Van Veen, A. G.; Mertens, W. K. Recl. Trav. Chim. 1934, 53, 257–268.
2. Daves, G. D.; Robins, R. K.; Cheng, C. C. J. Am. Chem. Soc. 1961, 83, 3904–3905.
3. Nagamatsu, T.; Yamasaki, H.; Hirota, T.; Yamato, M.; Kido, Y.; Shibata, M.;
Yoneda, F. Chem. Pharm. Bull. 1993, 41, 362–368.
4. Yoneda, F.; Sakuma, Y.; Nagamatsu, T.; Mizumoto, S. J. Chem. Soc., Perkin Trans.
1 1976, 2398–2402.
5. Devi, I.; Bhuyan, P. J. Tetrahedron Lett. 2005, 46, 5727–5729.
6. Goldner, H.; Dietz, G.; Carstens, E. Justus Liebigs Ann. Chem. 1966, 691, 142–158.
7. Yanada, R.; Yoneda, Y.; Yazaki, M.; Mimura, N.; Taga, T.; Yoneda, F.; Yanada, K.
Tetrahedron: Asymmetry 1997, 8, 2319–2323.
8. The structure has been deposited with the Cambridge Crystallographic Data
Centre (deposition number 788119).
3-Methyl-6-(1-methylhydrazinyl)pyrimidine-2,4(1H,3H)-dione
(6,
with
R
1 = R2 = CH3): To mixture of 6-chloro-3-methylpyrimidine-2,4(1H,3H)-
a
dione (1.56 g, 9.9 mmol) dissolved in ethanol (25 mL) was added
methylhydrazine (1.15 mL, 21.9 mmol) and microwave heated at 100 °C for
10 min. The solution was cooled to room temperature and stirred overnight.
The resulting precipitate was filtered and dried to afford the product as a pale
orange solid in 60% yield (1.01 g, 5.9 mmol); 1H NMR (200 MHz, CDCl3) d 8.93
(s, 1H), 4.78 (s, 1H), 3.29 (s, 3H), 3.17 (s, 3H); 13C NMR (50 MHz, DMSO) d 162.9,
153.9, 150.4, 72.3, 40.6, 26.1; MS [EI+] m/z (RI%) 170 [M]+ (100); HRMS for
C6H10N4O2 calcd m/e 170.0804, observed m/e 170.0808. 6-(2-(4-
Chlorobenzylidene)-1-methylhydrazinyl)-3-methylpyrimidine-2,4(1H,3H)-dione
(8, with R1 = CH3, R2 = CH3, and R3 = p-C6H4Cl; Table 1, entry 3): A mixture of 3-
9. Pearson, R. J. Chem. Sci. 2005, 117, 369–377.
methyl-6-(1-methylhydrazinyl)pyrimidine-2,4(1H,3H)-dione
(0.22 g,
10. Typical experimental procedures. Microwave reactions were performed using a
CEM Discover microwave equipped with an IR sensor which allowed for
monitoring and control of both temperature and pressure. 6-Hydroxy-3-
methylpyrimidine-2,4(1H,3H)-dione (3, with R1 = CH3): A mixture of malonic
acid (5.0 g, 48.0 mmol) and methyl urea (3.6 g, 48.0 mmol) was dissolved in
acetic anhydride (9.08 mL, 96.1 mmol). The solution was microwave heated at
60 °C for 15 min and the resulting acetic acid was removed under a reduced
pressure. The viscous liquid was crystallized in ethanol and filtered to afford
the product as a pale peach solid in 80% yield (5.86 g, 43.3 mmol); mp 125–
1.3 mmol) and 4-chlorobenzaldehyde (0.3 g, 2.1 mmol) in 5 mL ethanol was
microwave heated at 50 °C for 10 min and cooled to room temperature. The
resulting precipitate was filtered and dried to afford the product as a yellow
solid in 91% yield (0.35 g, 1.2 mmol); 1H NMR (200 MHz, CDCl3) d 9.18 (s, 1H),
7.69 (s, 1H), 7.62 (d, J = 8.8 Hz, 2 H), 7.41 (d, J = 8.5 Hz, 2 H), 5.14 (d, J = 2.5 Hz,
1H), 3.34 (s, 3H), 3.32 (s, 3H); 13C NMR (50 MHz) 164.4, 150.7, 149.5, 138.0,
136.3, 132.0, 129.4, 128.5, 77.9, 31.4, 27.1; MS [EI+] m/z (RI%) 292 [M]+ (20);
HRMS for C13H13ClN4O2 calcd m/e 292.0727, observed m/e 292.0726. 3-(4-
Chlorophenyl)-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione
(9