N-Cyclopropyl-N-[2-(2,4-difluorophenyl)-2-hydroxy-1-(1H-1,2,4-triazol-1-yl)propyl]-2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetamide dichloromethane 0.62-solvate

In the title compound, C21H22F2N6O4·0.62CH2Cl2, the difluoro-substituted benzene ring forms dihedral angles of 54.6 (3)° with the mean plane of the thymine ring and 50.9 (2)° with the triazole ring. The dihedral angle between the thymine and triazole rings is 7.4 (3)°. In the crystal, intermolecular N—H⋯N and O—H⋯O hydrogen bonds link the main molecules into chains along [10]. The CH2Cl2 solvent molecule was refined as partial occupancy over two sets of sites with refined occupancies of 0.308 (9) and 0.310 (8).

In the title compound, C 21 H 22 F 2 N 6 O 4 Á0.62CH 2 Cl 2 , the difluoro-substituted benzene ring forms dihedral angles of 54.6 (3) with the mean plane of the thymine ring and 50.9 (2) with the triazole ring. The dihedral angle between the thymine and triazole rings is 7.4 (3) . In the crystal, intermolecular N-HÁ Á ÁN and O-HÁ Á ÁO hydrogen bonds link the main molecules into chains along [101]. The CH 2 Cl 2 solvent molecule was refined as partial occupancy over two sets of sites with refined occupancies of 0.308 (9) and 0.310 (8).

Comment
In recent years, fungal infections are prevalent diseases from which a large proportion of the human population suffers (Singh, 2001;Richardson, 2005;Hobson, 2003;Slavin et al., 2002). The increased emergence of both superficial and systemic fungal infections has led to the massive increase in the rate of mortality, especially in immunocompromised individuals i.e. those suffering from tuberculosis, cancer or AIDS (Wingard & Leather, 2004;Fridkin & Jarvis, 1996). There are very few antifungal agents that can be used for life-threatening fungal infections. Several clinical drugs, such as amphotericin B,5-fluorocytosine, azoles (such as fluconazole and itraconazole) and echinocandins (such as caspofungin and micafungin) have been developed to reduce the impact of fungal diseases (Gallis et al., 1990;Sheehan et al., 1999;Denning, 2002).
Among those, azoles, especially triazole antifungal agents, are used widely and efficiently. For over a decade, azoles have been a mainstay of the antifungal armamentarium. They act by competitive inhibition of the lanosterol 1410 which is the key enzyme in sterol biosynthesis of fungi (Aoyama et al., 1984). Selective inhibition of CYP51 would cause depletion of ergosterol and accumulation of lanosterol and other 14-methyl sterols resulting in the growth inhibition of fungal cells (Lamb et al., 1999). We have attempted to prepare some potential antifungal agents with improved activity and broader spectrum, by sythesizing a series of 1-(1H-1,2,4-triazole-1-yl)-(2,4-difluorophenyl)-3-[N-n-alkyl-N-(1-thyminyl)acetyl]-2propanol compounds. Herein, we report the crystal structure of the title compound (I).
The molecular structure of the title compound is shown in Fig. 1

Experimental
The synthesis of thymin-1-yl acetic acid: To a solution of thymine (30.00 g, 237.89 mmol) in water (150 ml) was added potassium hydroxide (51.25 g, 903.79 mmol). The solution was heated to 313 K, and then bromoacetic acid (49.58 g, 356.83 mmol) was added dropwise. The resulting solution was allowed to stir for 2 h at the same temperature. The solution was then brought to pH 5 with 36% HCl at 273 K. The white precipitate was filtered off and discarded. Then the filtrate was brought to pH 1 with 36% HCl. Solid was filtered off and dried and obtained in 83.5% yield, m.p 528-530 K.
The synthesis of the title compound: To a solution of 1-(1H-1,2,4-triazole)-2,2-[oxiranyl-(2,4-difluorophenyl)]ethane mesylate (16.75 g, 50 mmol) in ethanol (240 ml) was added triethylamine (16 ml, 110 mmol) and cyclopropylamine (6.93 ml, 100 mmol). The resulting solution was raised to 318 K and stirred for 10 h at the same temperature. Once concentrated to light yellow oil under vacuum, the residue was taken off with ethyl acetate and was treated with 1 M HCl. The aqueous phase was then brought to pH 8 with sodium carbonate and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. A light yellow oil was obtained in 67.6% yield. A solution of the title compound (9.2 mg,0.02 mmol) in dichloromethane and methanol (4 sup-2 ml, 1:1, v/v) was kept at room temperature. Upon slow evaporation of the solvent over about 10 d, colourless block-shaped crystals suitable for X-ray measurements were obtained.

Refinement
All H atoms were placed in idealized positions and treated as riding,with C-H = 0.97 (CH 2 ), 0.96 (CH 3 ), 0.93 Å (CH aromatic ), 0.98 Å (CH tertiary alkyl ), N-H = 0.80 Å, O-H = 0.82 Å, and U iso (H) = 1.2U eq (N, CH and CH 2 ), U iso (H) = 1.5U eq (OH and CH 3 ). The CH 2 Cl 2 solvent molecule was refined as partial occupancy over two sets of sites with refined occupancies of 0.308 (9) and 0.310 (8). The precision of this structure is lower than normal and this may be the result of the presence of the disordered solvent in the lattice.   supplementary materials sup-9