MAI et al.
1534
F 14.37. m/z 270 [M]+. C23H29N3O. Calculated, %:
C 62.22; H 5.97; F 14.06. M 270.27.
4. Mai, A., Artico, M., Rotili, D., Tarantino, D., Clotet-
Codina, I., Armand-Ugon, M., Ragno, R., Simeoni, S.,
Sbardella, G., Nawrozkij, M.B., Samuele, A., Maga, G.,
and Este, J.A., J. Med. Chem., 2007, vol. 50, p. 5412.
5. Quaglia, M., Mai, A., Sbardella, G., Artico, M.,
Ragno, R., Massa, S., del Piano, D., Setzu, G., Dorati-
otto, S., and Cotichini, V., Chirality, 2001, vol. 13,
p. 75.
2-(Cyclopentylsulfanyl)-6-[(1R)-1-(2,6-difluoro-
phenyl)ethyl]-5-methylpyrimidin-4(3H)-one (VII).
A solution of 5.5 g (40.0 mmol) of potassium carbo-
nate in 5.5 ml of water was slowly added to a mixture
of 5 g (18.5 mmol) of compound VI, 9 g (40.0 mmol)
of S-cyclopentylisothiourea hydrobromide, and 25 ml
of 95% ethanol, maintaining the temperature at 10–
15°C. The mixture was stirred for a week at room
temperature, diluted with water, neutralized with acetic
acid, and extracted with ethyl acetate (3×100 ml). The
extracts were washed with water and a saturated aque-
ous solution of sodium chloride, dried over MgSO4,
and mixed with 50 g of silica gel (Macherey–Nagel
Kieselgel). The solvent was removed under reduced
pressure, and the sorbent was applied onto a dry col-
umn for flash chromatography charged with 150 g of
silica gel (for TLC). The column was eluted with pe-
troleum ether (bp 40–70°C)–diethyl ether (0–50 vol %
of the latter). Fractions containing the target product
were combined and evaporated under reduced pres-
sure, and the residue was recrystallized from cyclo-
hexane. Yield 2 g (31%), mp 196–197°C (from cyclo-
hexane) [5]. The optical purity of the product was
checked by HPLC using a chiral stationary phase
according to the procedure described previously [5].
6. Selva, M., Marques, C.A., and Tundo, P., J. Chem. Soc.,
Perkin Trans. 1, 1994, p. 1323.
7. Navrotskii, M.B., Khim.-Farm. Zh., 2004, vol. 38, p. 16.
8. Ojima, I., Kogure, T., and Yoda, Y., Org. Synth., 1985,
vol. 63, p. 18.
9. Larsen, R.D., Corley, E.G., Davis, P., Reider, P.J., and
Grabowski, E.J.J., J. Am. Chem. Soc., 1989, vol. 111,
p. 7650.
10. Novakov, I.A., Orlinson, B.S., and Navrotskii, M.B.,
Russian Patent no. 2238269; Byull. Izobret., 2004,
no. 29.
11. Nawrozkij, M.B., Rotili, D., Tarantino, D., Botta, G.,
Eremiychuk, A.S., Musmuca, I., Ragno, R., Samuele, A.,
Zanoli, M., Armand-Ugon, M., Clotet-Codina, I.,
Novakov, I.A., Orlinson, B.S., Maga, G., Este, J.A.,
Artico, M., and Mai, A., J. Med. Chem., 2008, vol. 51,
p. 4641.
12. Kagan, H.B. and Suen, M.Y.-H., Bull. Soc. Chim. Fr.,
1966, p. 1819.
13. Oikawa, Y., Sugano, K., and Yonemitsu, O., J. Org.
Chem., 1978, vol. 43, p. 2087.
14. Novakov, I.A., Orlinson, B.S., and Navrotskii, M.B.,
Russian Patent no. 2254328, 2005; Byull. Izobret.,
2005, no. 17.
15. Wang, X., Monte, W.T., Napier, J.J., and Ghannam, A.,
Tetrahedron Lett., 1994, vol. 35, p. 9323.
16. Clay, R.J., Collom, T.A., Karrick, G.L., and Wemple, J.,
Synthesis, 1993, p. 290.
17. Simon, I.B. and Kovtunovskaya, I.I., Zh. Obshch.
Khim., 1951, vol. 21, p. 760.
REFERENCES
1. Mai, A., Sbardella, G., Artico, M., Ragno, R., Massa, S.,
Novellino, E., Greco, G., Lavecchia, A., Musiu, C., La
Colla, M., Murgioni, C., La Colla, P., and Loddo, R.,
J. Med. Chem., 2001, vol. 44, p. 2544.
2. Ragno, R., Mai, A., Sbardella, G., Artico, M., Massa, S.,
Musiu, C., Mura, M., Marturana, F., Cadeddu, A., and La
Colla, P., J. Med. Chem., 2004, vol. 47, p. 928.
18. Breslow, D.S., Baumgarten, E., and Hauser, C.R., J. Am.
Chem. Soc., 1944, vol. 66, p. 1286.
19. Riegel, B. and Lilienfeld, W.M., J. Am. Chem. Soc.,
3. Mai, A., Artico, M., Ragno, R., Sbardella, G., Massa, S.,
Musiu, C., Mura, M., Marturana, F., Cadeddu, A.,
Maga, G., and La Colla, P., Bioorg. Med. Chem., 2005,
vol. 13, p. 2065.
1945, vol. 67, p. 1273.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009