888
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Ryabova et al.
H, 5.86; N, 19.59. C22H34N8O2S4. Calculated (%): C, 46.29;
H, 6.00; N, 19.63. MS, m/z (Irel (%)): 570 [M]+ (64), 470
[M – CONEt2]+ (37), 438 [M – SCONEt2]+ (30), 285 [0.5 M]+
(100), 253 [0.5 M – S]+ (36), 241 [0.5 M – NMe2]+ (43), 100
[O=C=N+Et2]+ (760). IR (Nujol mulls), ν/cm–1: 1668 (C=O),
1550, 1256, 1218, 1170, 1116, 993, 852.
6ꢀRꢀ4ꢀDialkylaminoꢀ5ꢀnitropyrimidines (15a—d). A solution
of the corresponding sodium monoalkyldithiocarbamate
(10.7 mmol) was added to a solution of pyrimidine 2 (10.5 mmol)
in EtOH (50 mL) and the reaction mixture was kept at ~20 °C
for 2—5 h. The course of the reaction was monitored by TLC
(CHCl3—MeOH, 9 : 1, as the eluent). The reaction mixture was
concentrated in vacuo and the residue was treated with cold
water (10 mL). The paleꢀyellow precipitate of dialkylaminoꢀ
pyrimidine 15 that formed was filtered off (see Table 1).
Bis(4ꢀdiethylcarbamoylthioꢀ6ꢀmethoxypyrimidinꢀ5ꢀyl) disulꢀ
fide (12b). A. A solution of pyrimidine 3e (0.5 g, 1.62 mmol)
in xylene (40 mL) was refluxed for 1 h, concentrated, and
treated with diethyl ether (30 mL). Large white crystals of
disulfide 12b were filtered off in a yield of 0.37 g (84%).
M.p. 189—191 °C (EtOH). Found (%): C, 43.98; H, 5.07;
N, 15.52. C20H28N6O4S4. Calculated (%): C, 44.10; H, 5.18;
N, 15.43. MS, m/z (Irel (%)): 544 [M]+ (32), 444 [M – CONEt2]+
(44), 412 [M – SCONEt2]+ (31), 372 [M – CONEt2 – NEt2]+
(17), 272 [0.5 M]+ (83), 240 [0.5 M – S]+ (55), 225 [0.5 M – S –
References
1. M. Marinovich, B. Viviani, V. Capra, E. Corsini, L. Anselmi,
G. D'Agostino, A. Di Nucci, M. Binaglia, M. Tonini, and
C. L. Galli, Chem. Res. Toxicol., 2002, 15, 26.
2. A. Easton, K. Guven, and D. I. de Pomerai, J. Biochem.
Mol. Toxicol., 2001, 15, 15.
Me]+ (27), 100 [O=C=N+Et2]+ (100). IR (Nujol mulls), ν/cm–1
:
1664 (C=O), 1520, 1244, 1212, 1110, 1025.
3. Pat. BRD3016767; Chem. Abstrs, 1981, 96, P52327.
4. E. Halbova, E. Sidova, and R. Spaldonova, Chem. Pap.,
1986, 4, 127.
5. R. Sh. Erkasov, A. B. Tosherov, and A. M. Shaikina, Dokl.
Khim. Fak. MGU [Dokl. Dept. Chem., Moscow State Univerꢀ
sity], 1981, 137 (in Russian).
6. V. G. Granik and N. B. Grigor´ev, Izv. Akad. Nauk, Ser.
Khim., 2002, 1819 [Russ. Chem. Bull., Int. Ed., 2002,
51, 1973].
7. V. A. Makarov, A. L. Sedov, M. P. Nemeryuk, N. P.
Solov´eva, O. S. Anisimova, and T. S. Safonova, Khim.
Geterotsikl. Soedin., 1994, 1420 [Chem. Heterocycl. Compd.,
1994, 30, 1231 (Engl. Transl.)].
8. J. Clark, J. Gelling, J. W. Southon, and M. S. Morton,
J. Chem. Soc., C, 1970, 494.
9. K. Rasheed and J. D. Warkentin, J. Org. Chem., 1977,
42, 1265.
10. J. J. D’Amico, C. C. Tung, W. E. Dahl, and D. J. Dahm,
J. Org. Chem., 1976, 41, 3564.
11. K. Rasheed and J. D. Warkentin, J. Org. Chem., 1979, 44, 267.
12. B. Ya. Adamsone, B. Zh. Tilka, and I. K. Raiskuma, Abstrs
of Papers, Int. Conf. on Chemistry of Dicarbonyl Compounds,
Riga, 1991, Pꢀ42.
13. W. Hanefeld and G. Glaeske, Liebigs Ann. Chem., 1981,
8, 1388.
14. S. N. Singh and M. V. George, J. Org. Chem., 1971, 36, 615.
15. E. H. Hoffmeister and D. S. Tarbell, Tetrahedron, 1965,
21, 2857.
16. V. V. Chernyshev, K. A. Paseshnichenko, V. A. Makarov,
E. J. Sonneveld, and H. Schenk, Acta Cryst., Sect. C, 2001,
C57, 72.
17. P. Vallance and J. Leiper, Nature Reviews, Drug Disc.,
2002, 1, 939.
B. Pyrimidine 3e (0.5 g, 1.62 mmol) was dried in a vacuum
desiccator over P2O5 for 1 day and heated in vacuo (~40 Torr) to
135—140 °C for 15 min. The resulting black resinous mixture
was dissolved in acetone and filtered through a layer of activated
carbon and aluminum oxide. The filtrate was concentrated and
treated with a mixture of anhydrous EtOH (20 mL) and diethyl
ether (10 mL). White crystalline compound 12b was filtered off
in a yield of 0.32 g (73%). A mixture of samples prepared by the
methods A and B showed no melting point depression. The IR
spectra of both samples are identical.
2ꢀDiethylaminoꢀ2ꢀhydroxyꢀ7ꢀmethoxyꢀ1,3ꢀdithioꢀ
lo[4,5ꢀd]pyrimidine (13). Sodium borohydride (0.18 g,
4.73 mmol) was added to a solution of disulfide 14b (0.7 g,
1.28 mmol) in refluxing EtOH (30 mL). The resulting suspenꢀ
sion was refluxed for 2.5 h. The reaction mixture was concenꢀ
trated. The residue was dissolved in water (20 mL), acidified
with 10% HCl to pH ~5, and kept at 6—8 °C for 16 h. The white
precipitate of pyrimidine 13 (0.51 g, 73%) that formed was filꢀ
tered off. M.p. 152—153 °C (benzene). Found (%): C, 43.91;
H, 5.43; N, 15.29. C10H15N3O2S2. Calculated (%): C, 43.93;
H, 5.53; N, 15.37. MS, m/z (Irel (%)): 273 [M]+ (27), 200
[M – HNEt2]+ (36), 172 [M – COHNEt2]+ (86), 108
[M – SSCONEt2]+ (100). IR (KBr, ν/cm–1): 3600—3200, 3109
(HO assoc.), 1648, 1580, 1555, 1288, 1214, 1150, 1113, 1032.
1H NMR (DMSOꢀd6), δ: 1.15 (t, 6 H, 2 CH2CH3); 3.34 (q, 4 H,
2 CH2Me); 3.91 (s, 3 H, OMe); 8.35 (s, 1 H, H of pyrimidine);
14.10 (br.s, 1 H, OH).
4ꢀDialkylaminoꢀ6ꢀmethylaminoꢀ5ꢀnitropyrimidine hydrochloꢀ
rides (14a,b). A solution of pyrimidine 3 (10.5 mmol) in acetone
(or isopropyl alcohol) (50 mL) was refluxed for 4—8 h until the
starting dithiocarbamate was completely consumed (TLC). The
reaction mixture was concentrated in vacuo and the residue was
treated with a 9% methanolic solution of HCl to pH ~3, again
concentrated, and triturated with diethyl ether. The beige preꢀ
cipitate of hydrochloride 14 that formed was recrystallized from
MeOH (see Table 1).
Received December 18, 2003;
in revised form January 22, 2004