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

Wang, N.; Guo, H.-M.; Hou, G.-G.; Hu, X.-Y.; Meng, Q.-G.

doi:10.1107/S1600536811034295

organic compounds

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ISSN: 2056-9890

Volume 67| Part 9| September 2011| Page o2464

doi:10.1107/S1600536811034295

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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

Nan Wang,^a Huan-Mei Guo,^b Gui-Ge Hou,^c Xin-Yue Hu ^a and Qing-Guo Meng ^a ^*

^aSchool of Pharmacy, Yantai University, Yantai 264005, People's Republic of China, ^bMicroscale Science Institute, Weifang University, Weifang 261041, People's Republic of China, and ^cSchool of Pharmacy, Binzhou Medical College, Yantai 264003, People's Republic of China
^*Correspondence e-mail: mqg@ytu.edu.cn

(Received 30 July 2011; accepted 21 August 2011; online 27 August 2011)

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 $[\overline{1}]$ ]. 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).

Related literature

For the applications of azole and triazole compounds as antifungal agents, see: Singh (2001 ); Richardson (2005 ); Hobson (2003 ); Slavin et al. (2002 ); Wingard & Leather (2004 ); Fridkin & Jarvis (1996 ); Gallis et al. (1990 ); Sheehan et al. (1999 ); Denning (2002 ); Aoyama et al. (1984 ); Lamb et al. (1999 ).

Experimental

Crystal data

C₂₁H₂₂F₂N₆O₄·0.62CH₂Cl₂
M_r = 512.93
Triclinic, $[P \overline 1]$
a = 8.474 (2) Å
b = 12.464 (3) Å
c = 13.410 (4) Å
α = 62.942 (4)°
β = 73.187 (4)°
γ = 83.746 (4)°
V = 1207.1 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.24 mm⁻¹
T = 298 K
0.30 × 0.16 × 0.14 mm

Data collection

Bruker SMART APEX diffractometer
6058 measured reflections
4162 independent reflections
3053 reflections with I > 2σ(I)
R_int = 0.022

Refinement

R[F² > 2σ(F²)] = 0.092
wR(F²) = 0.209
S = 1.16
4162 reflections
356 parameters
42 restraints
H-atom parameters constrained
Δρ_max = 0.50 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N6—H6⋯N2ⁱ	0.80	2.11	2.893 (5)	167
O1—H1A⋯O2ⁱⁱ	0.82	2.13	2.903 (4)	158
Symmetry codes: (i) x+1, y, z-1; (ii) -x+2, -y+1, -z+2.

Data collection: SMART (Bruker, 1997 ); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811034295/lh5302sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811034295/lh5302Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811034295/lh5302Isup3.cml

checkCIF report

Comment top

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]-2-propanol compounds. Herein, we report the crystal structure of the title compound (I).

The molecular structure of the title compound is shown in Fig. 1. 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 one-dimensional chains (Fig. 2) along [101].

Related literature top

For the applications of azole and triazole compounds as antifungal agents, see: Singh (2001); Richardson (2005); Hobson (2003); Slavin et al. (2002); Wingard & Leather (2004); Fridkin & Jarvis (1996); Gallis et al. (1990); Sheehan et al. (1999); Denning (2002); Aoyama et al. (1984); Lamb et al. (1999).

Experimental top

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 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.

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of the title compound showing displacement ellipsoids with 30% probability. The solvent molecule is not shown.
	Fig. 2. Part of the crystal structure of the title compound. Dashed lines indicate hydrogen bonds. Only H atoms involved in hydrogen bonds are shown. The solvent molecules are not shown.

N-Cyclopropyl-N-[2-(2,4-difluorophenyl)-2-hydroxy- 3-(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 top

Crystal data top

C₂₁H₂₂F₂N₆O₄·0.62CH₂Cl₂	Z = 2
M_r = 512.93	F(000) = 532.2
Triclinic, P1	D_x = 1.411 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.474 (2) Å	Cell parameters from 1529 reflections
b = 12.464 (3) Å	θ = 2.5–24.6°
c = 13.410 (4) Å	µ = 0.24 mm⁻¹
α = 62.942 (4)°	T = 298 K
β = 73.187 (4)°	Block, colourless
γ = 83.746 (4)°	0.30 × 0.16 × 0.14 mm
V = 1207.1 (6) Å³

Data collection top

Bruker SMART APEX diffractometer	3053 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.022
Graphite monochromator	θ_max = 25.0°, θ_min = 1.8°
ϕ and ω scans	h = −10→8
6058 measured reflections	k = −14→11
4162 independent reflections	l = −15→10

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.092	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.209	H-atom parameters constrained
S = 1.16	w = 1/[σ²(F_o²) + (0.0687P)² + 1.6778P] where P = (F_o² + 2F_c²)/3
4162 reflections	(Δ/σ)_max < 0.001
356 parameters	Δρ_max = 0.50 e Å⁻³
42 restraints	Δρ_min = −0.34 e Å⁻³

Crystal data top

C₂₁H₂₂F₂N₆O₄·0.62CH₂Cl₂	γ = 83.746 (4)°
M_r = 512.93	V = 1207.1 (6) Å³
Triclinic, P1	Z = 2
a = 8.474 (2) Å	Mo Kα radiation
b = 12.464 (3) Å	µ = 0.24 mm⁻¹
c = 13.410 (4) Å	T = 298 K
α = 62.942 (4)°	0.30 × 0.16 × 0.14 mm
β = 73.187 (4)°

Data collection top

Bruker SMART APEX diffractometer	3053 reflections with I > 2σ(I)
6058 measured reflections	R_int = 0.022
4162 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.092	42 restraints
wR(F²) = 0.209	H-atom parameters constrained
S = 1.16	Δρ_max = 0.50 e Å⁻³
4162 reflections	Δρ_min = −0.34 e Å⁻³
356 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
C1	0.4568 (7)	0.7140 (5)	1.3061 (5)	0.0602 (15)
H1	0.3778	0.7522	1.3425	0.072*
C2	0.5856 (6)	0.5787 (4)	1.2724 (4)	0.0416 (11)
H2	0.6213	0.5044	1.2752	0.050*
C3	0.7947 (5)	0.7116 (4)	1.0885 (3)	0.0320 (10)
H3A	0.8887	0.6649	1.1106	0.038*
H3B	0.8256	0.7963	1.0532	0.038*
C4	0.7508 (5)	0.6834 (4)	0.9990 (4)	0.0296 (9)
C5	0.5887 (5)	0.7388 (4)	0.9760 (3)	0.0291 (9)
C6	0.5620 (5)	0.8613 (4)	0.9364 (4)	0.0331 (10)
C7	0.4170 (6)	0.9142 (4)	0.9172 (4)	0.0481 (12)
H7	0.4040	0.9968	0.8914	0.058*
C8	0.2910 (6)	0.8396 (5)	0.9378 (5)	0.0537 (14)
C9	0.3077 (6)	0.7182 (4)	0.9764 (4)	0.0476 (12)
H9	0.2210	0.6695	0.9894	0.057*
C10	0.4563 (5)	0.6694 (4)	0.9955 (4)	0.0349 (10)
H10	0.4680	0.5866	1.0227	0.042*
C11	0.8951 (5)	0.7280 (4)	0.8885 (4)	0.0333 (10)
H11A	0.9135	0.8136	0.8603	0.040*
H11B	0.9940	0.6873	0.9079	0.040*
C12	0.7806 (6)	0.7963 (4)	0.7168 (4)	0.0421 (11)
H12	0.6619	0.7806	0.7371	0.051*
C13	0.8329 (10)	0.9254 (5)	0.6618 (5)	0.078 (2)
H13A	0.7476	0.9850	0.6514	0.094*
H13B	0.9264	0.9450	0.6791	0.094*
C14	0.8650 (8)	0.8592 (5)	0.5897 (4)	0.0644 (16)
H14A	0.9779	0.8385	0.5633	0.077*
H14B	0.7991	0.8785	0.5357	0.077*
C15	0.9161 (5)	0.6029 (4)	0.7912 (4)	0.0315 (10)
C16	0.8534 (5)	0.5732 (4)	0.7112 (4)	0.0375 (11)
H16A	0.7435	0.5370	0.7513	0.045*
H16B	0.8459	0.6471	0.6432	0.045*
C17	0.9241 (6)	0.3704 (4)	0.7248 (4)	0.0440 (12)
H17	0.8292	0.3407	0.7861	0.053*
C18	1.0177 (6)	0.2925 (4)	0.6907 (4)	0.0468 (12)
C19	0.9756 (9)	0.1617 (5)	0.7452 (6)	0.086 (2)
H19A	0.8814	0.1425	0.8114	0.129*
H19B	1.0675	0.1158	0.7697	0.129*
H19C	0.9508	0.1422	0.6898	0.129*
C20	1.1630 (6)	0.3403 (4)	0.5940 (4)	0.0430 (11)
C21	1.1004 (5)	0.5404 (4)	0.5851 (4)	0.0376 (10)
F1	0.6869 (3)	0.9347 (2)	0.9153 (3)	0.0508 (7)
F2	0.1460 (4)	0.8888 (3)	0.9206 (4)	0.0897 (12)
N1	0.5731 (5)	0.7741 (4)	1.2121 (4)	0.0512 (11)
N2	0.4584 (5)	0.5937 (4)	1.3470 (3)	0.0525 (11)
N3	0.6572 (4)	0.6839 (3)	1.1920 (3)	0.0322 (8)
N4	0.8680 (4)	0.7077 (3)	0.7957 (3)	0.0298 (8)
N5	0.9609 (4)	0.4908 (3)	0.6742 (3)	0.0351 (9)
N6	1.1926 (4)	0.4609 (3)	0.5494 (3)	0.0411 (9)
H6	1.2754	0.4935	0.5005	0.049*
O1	0.7269 (3)	0.5572 (2)	1.0449 (3)	0.0351 (7)
H1A	0.8101	0.5229	1.0622	0.053*
O2	0.9993 (4)	0.5299 (3)	0.8517 (3)	0.0455 (8)
O3	1.1376 (4)	0.6464 (3)	0.5414 (3)	0.0573 (10)
O4	1.2549 (5)	0.2801 (3)	0.5518 (3)	0.0655 (11)
C1A	0.332 (3)	0.799 (2)	0.626 (4)	0.104 (10)	0.308 (9)
H1AA	0.2307	0.7586	0.6801	0.125*	0.308 (9)
H1AB	0.3205	0.8252	0.5492	0.125*	0.308 (9)
Cl1	0.4739 (16)	0.7045 (11)	0.6375 (13)	0.193 (7)	0.308 (9)
Cl2	0.350 (3)	0.920 (2)	0.633 (2)	0.371 (15)	0.308 (9)
C1B	0.401 (4)	0.803 (2)	0.5671 (15)	0.103 (9)	0.310 (8)
H1BA	0.3007	0.7941	0.5521	0.123*	0.310 (8)
H1BB	0.4728	0.7448	0.5497	0.123*	0.310 (8)
Cl1'	0.3513 (16)	0.7336 (13)	0.7053 (12)	0.177 (6)	0.310 (8)
Cl2'	0.477 (3)	0.9237 (19)	0.453 (2)	0.340 (13)	0.310 (8)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.051 (3)	0.067 (4)	0.056 (4)	0.010 (3)	0.005 (3)	−0.036 (3)
C2	0.045 (3)	0.046 (3)	0.030 (2)	0.003 (2)	−0.003 (2)	−0.017 (2)
C3	0.028 (2)	0.041 (2)	0.032 (2)	0.0028 (18)	−0.0105 (18)	−0.019 (2)
C4	0.027 (2)	0.030 (2)	0.032 (2)	0.0003 (17)	−0.0059 (18)	−0.0146 (18)
C5	0.027 (2)	0.036 (2)	0.024 (2)	−0.0010 (18)	−0.0036 (17)	−0.0159 (18)
C6	0.027 (2)	0.034 (2)	0.043 (3)	−0.0028 (18)	−0.0070 (19)	−0.021 (2)
C7	0.047 (3)	0.038 (3)	0.059 (3)	0.010 (2)	−0.016 (2)	−0.022 (2)
C8	0.035 (3)	0.054 (3)	0.074 (4)	0.009 (2)	−0.022 (3)	−0.027 (3)
C9	0.033 (3)	0.050 (3)	0.062 (3)	−0.006 (2)	−0.015 (2)	−0.024 (3)
C10	0.033 (2)	0.037 (2)	0.034 (2)	−0.0029 (19)	−0.0070 (19)	−0.016 (2)
C11	0.025 (2)	0.044 (3)	0.038 (3)	0.0033 (18)	−0.0082 (19)	−0.026 (2)
C12	0.048 (3)	0.040 (3)	0.036 (3)	0.008 (2)	−0.012 (2)	−0.016 (2)
C13	0.137 (6)	0.041 (3)	0.054 (4)	0.002 (3)	−0.031 (4)	−0.015 (3)
C14	0.093 (4)	0.051 (3)	0.037 (3)	0.001 (3)	−0.014 (3)	−0.011 (3)
C15	0.020 (2)	0.042 (2)	0.029 (2)	0.0004 (18)	−0.0021 (18)	−0.016 (2)
C16	0.035 (2)	0.050 (3)	0.035 (2)	0.005 (2)	−0.009 (2)	−0.026 (2)
C17	0.048 (3)	0.052 (3)	0.031 (2)	−0.013 (2)	−0.005 (2)	−0.017 (2)
C18	0.058 (3)	0.043 (3)	0.044 (3)	−0.001 (2)	−0.012 (2)	−0.025 (2)
C19	0.107 (5)	0.048 (3)	0.094 (5)	−0.012 (3)	−0.007 (4)	−0.034 (4)
C20	0.050 (3)	0.051 (3)	0.046 (3)	0.012 (2)	−0.023 (2)	−0.032 (2)
C21	0.042 (3)	0.040 (3)	0.033 (2)	−0.001 (2)	−0.011 (2)	−0.017 (2)
F1	0.0455 (16)	0.0343 (14)	0.075 (2)	−0.0060 (12)	−0.0167 (14)	−0.0245 (14)
F2	0.0437 (18)	0.082 (2)	0.143 (4)	0.0242 (17)	−0.048 (2)	−0.041 (2)
N1	0.057 (3)	0.048 (2)	0.049 (3)	0.008 (2)	−0.002 (2)	−0.030 (2)
N2	0.050 (3)	0.060 (3)	0.036 (2)	−0.005 (2)	0.003 (2)	−0.019 (2)
N3	0.0328 (19)	0.043 (2)	0.0258 (19)	0.0026 (16)	−0.0049 (15)	−0.0214 (17)
N4	0.0309 (19)	0.036 (2)	0.0232 (18)	0.0019 (15)	−0.0046 (15)	−0.0153 (15)
N5	0.036 (2)	0.043 (2)	0.030 (2)	−0.0042 (16)	−0.0038 (16)	−0.0212 (17)
N6	0.039 (2)	0.050 (2)	0.033 (2)	−0.0022 (18)	−0.0007 (17)	−0.0214 (18)
O1	0.0352 (17)	0.0327 (16)	0.0405 (18)	0.0086 (13)	−0.0139 (14)	−0.0183 (14)
O2	0.0464 (19)	0.057 (2)	0.047 (2)	0.0239 (16)	−0.0270 (16)	−0.0315 (17)
O3	0.060 (2)	0.045 (2)	0.054 (2)	−0.0065 (17)	0.0030 (18)	−0.0210 (18)
O4	0.071 (3)	0.071 (2)	0.074 (3)	0.018 (2)	−0.018 (2)	−0.052 (2)
C1A	0.102 (13)	0.108 (13)	0.095 (12)	−0.001 (9)	−0.034 (9)	−0.034 (9)
Cl1	0.178 (9)	0.167 (9)	0.210 (10)	0.003 (6)	0.005 (7)	−0.096 (7)
Cl2	0.363 (17)	0.382 (18)	0.371 (18)	0.015 (10)	−0.130 (10)	−0.153 (11)
C1B	0.073 (11)	0.102 (12)	0.104 (13)	0.007 (8)	−0.023 (9)	−0.022 (9)
Cl1'	0.162 (9)	0.207 (9)	0.181 (9)	−0.023 (6)	−0.020 (6)	−0.112 (7)
Cl2'	0.310 (15)	0.319 (15)	0.367 (16)	0.024 (9)	−0.121 (10)	−0.119 (10)

Geometric parameters (Å, º) top

C1—N1	1.306 (6)	C15—O2	1.226 (5)
C1—N2	1.342 (6)	C15—N4	1.348 (5)
C1—H1	0.9300	C15—C16	1.519 (6)
C2—N2	1.304 (6)	C16—N5	1.460 (5)
C2—N3	1.326 (5)	C16—H16A	0.9700
C2—H2	0.9300	C16—H16B	0.9700
C3—N3	1.455 (5)	C17—C18	1.345 (6)
C3—C4	1.541 (6)	C17—N5	1.364 (6)
C3—H3A	0.9700	C17—H17	0.9300
C3—H3B	0.9700	C18—C20	1.444 (7)
C4—O1	1.418 (5)	C18—C19	1.487 (7)
C4—C5	1.517 (6)	C19—H19A	0.9600
C4—C11	1.533 (6)	C19—H19B	0.9600
C5—C10	1.383 (6)	C19—H19C	0.9600
C5—C6	1.386 (6)	C20—O4	1.222 (5)
C6—F1	1.356 (4)	C20—N6	1.362 (6)
C6—C7	1.364 (6)	C21—O3	1.211 (5)
C7—C8	1.376 (7)	C21—N6	1.366 (6)
C7—H7	0.9300	C21—N5	1.370 (5)
C8—F2	1.346 (5)	N1—N3	1.355 (5)
C8—C9	1.364 (7)	N6—H6	0.8013
C9—C10	1.378 (6)	O1—H1A	0.8200
C9—H9	0.9300	C1A—Cl1	1.580 (12)
C10—H10	0.9300	C1A—Cl2	1.581 (12)
C11—N4	1.460 (5)	C1A—H1AA	0.9600
C11—H11A	0.9700	C1A—H1AB	0.9601
C11—H11B	0.9700	C1A—H1BA	1.1262
C12—N4	1.448 (5)	Cl1—H1BB	1.0513
C12—C13	1.489 (7)	C1B—Cl1'	1.590 (12)
C12—C14	1.495 (7)	C1B—Cl2'	1.599 (12)
C12—H12	0.9800	C1B—H1AB	0.7735
C13—C14	1.488 (8)	C1B—H1BA	0.9600
C13—H13A	0.9700	C1B—H1BB	0.9601
C13—H13B	0.9700	Cl1'—H1AA	1.1355
C14—H14A	0.9700	Cl2'—H1AB	1.6877
C14—H14B	0.9700

N1—C1—N2	115.8 (4)	N5—C16—C15	112.0 (3)
N1—C1—H1	122.1	N5—C16—H16A	109.2
N2—C1—H1	122.1	C15—C16—H16A	109.2
N2—C2—N3	110.8 (4)	N5—C16—H16B	109.2
N2—C2—H2	124.6	C15—C16—H16B	109.2
N3—C2—H2	124.6	H16A—C16—H16B	107.9
N3—C3—C4	111.7 (3)	C18—C17—N5	123.5 (4)
N3—C3—H3A	109.3	C18—C17—H17	118.3
C4—C3—H3A	109.3	N5—C17—H17	118.3
N3—C3—H3B	109.3	C17—C18—C20	117.6 (4)
C4—C3—H3B	109.3	C17—C18—C19	123.2 (5)
H3A—C3—H3B	107.9	C20—C18—C19	119.2 (5)
O1—C4—C5	106.0 (3)	C18—C19—H19A	109.5
O1—C4—C11	109.8 (3)	C18—C19—H19B	109.5
C5—C4—C11	112.6 (3)	H19A—C19—H19B	109.5
O1—C4—C3	109.4 (3)	C18—C19—H19C	109.5
C5—C4—C3	111.1 (3)	H19A—C19—H19C	109.5
C11—C4—C3	107.9 (3)	H19B—C19—H19C	109.5
C10—C5—C6	115.5 (4)	O4—C20—N6	120.5 (5)
C10—C5—C4	121.8 (4)	O4—C20—C18	124.1 (5)
C6—C5—C4	122.7 (4)	N6—C20—C18	115.3 (4)
F1—C6—C7	117.1 (4)	O3—C21—N6	123.1 (4)
F1—C6—C5	118.6 (4)	O3—C21—N5	122.3 (4)
C7—C6—C5	124.4 (4)	N6—C21—N5	114.5 (4)
C6—C7—C8	116.9 (4)	C1—N1—N3	101.6 (4)
C6—C7—H7	121.6	C2—N2—C1	102.3 (4)
C8—C7—H7	121.6	C2—N3—N1	109.6 (3)
F2—C8—C9	119.3 (4)	C2—N3—C3	130.1 (4)
F2—C8—C7	118.3 (4)	N1—N3—C3	120.2 (3)
C9—C8—C7	122.3 (4)	C15—N4—C12	122.2 (3)
C8—C9—C10	118.4 (4)	C15—N4—C11	118.4 (3)
C8—C9—H9	120.8	C12—N4—C11	119.2 (3)
C10—C9—H9	120.8	C17—N5—C21	121.4 (4)
C9—C10—C5	122.6 (4)	C17—N5—C16	121.9 (4)
C9—C10—H10	118.7	C21—N5—C16	116.7 (4)
C5—C10—H10	118.7	C20—N6—C21	127.5 (4)
N4—C11—C4	113.4 (3)	C20—N6—H6	121.9
N4—C11—H11A	108.9	C21—N6—H6	110.3
C4—C11—H11A	108.9	C4—O1—H1A	109.5
N4—C11—H11B	108.9	Cl1—C1A—Cl2	122 (2)
C4—C11—H11B	108.9	Cl1—C1A—H1AA	108.7
H11A—C11—H11B	107.7	Cl2—C1A—H1AA	108.8
N4—C12—C13	118.6 (4)	Cl1—C1A—H1AB	104.8
N4—C12—C14	119.8 (4)	Cl2—C1A—H1AB	104.5
C13—C12—C14	59.8 (3)	H1AA—C1A—H1AB	107.3
N4—C12—H12	115.7	Cl1—C1A—H1BA	96.4
C13—C12—H12	115.7	Cl2—C1A—H1BA	124.6
C14—C12—H12	115.7	H1AA—C1A—H1BA	92.2
C14—C13—C12	60.3 (3)	H1AB—C1A—H1BA	21.3
C14—C13—H13A	117.7	C1A—Cl1—H1BB	73.9
C12—C13—H13A	117.7	Cl1'—C1B—Cl2'	147 (2)
C14—C13—H13B	117.7	Cl1'—C1B—H1AB	106.6
C12—C13—H13B	117.7	Cl2'—C1B—H1AB	82.9
H13A—C13—H13B	114.9	Cl1'—C1B—H1BA	100.4
C13—C14—C12	59.9 (3)	Cl2'—C1B—H1BA	100.3
C13—C14—H14A	117.8	H1AB—C1B—H1BA	25.2
C12—C14—H14A	117.8	Cl1'—C1B—H1BB	99.5
C13—C14—H14B	117.8	Cl2'—C1B—H1BB	100.0
C12—C14—H14B	117.8	H1AB—C1B—H1BB	125.7
H14A—C14—H14B	114.9	H1BA—C1B—H1BB	104.4
O2—C15—N4	123.6 (4)	C1B—Cl1'—H1AA	74.3
O2—C15—C16	119.6 (4)	C1B—Cl2'—H1AB	27.0
N4—C15—C16	116.7 (4)

N3—C3—C4—O1	−66.7 (4)	C17—C18—C20—N6	2.0 (7)
N3—C3—C4—C5	50.0 (4)	C19—C18—C20—N6	−179.9 (5)
N3—C3—C4—C11	173.9 (3)	N2—C1—N1—N3	−0.6 (6)
O1—C4—C5—C10	−2.4 (5)	N3—C2—N2—C1	0.6 (6)
C11—C4—C5—C10	117.7 (4)	N1—C1—N2—C2	0.1 (7)
C3—C4—C5—C10	−121.1 (4)	N2—C2—N3—N1	−1.0 (5)
O1—C4—C5—C6	176.4 (4)	N2—C2—N3—C3	−175.6 (4)
C11—C4—C5—C6	−63.5 (5)	C1—N1—N3—C2	1.0 (5)
C3—C4—C5—C6	57.7 (5)	C1—N1—N3—C3	176.2 (4)
C10—C5—C6—F1	−179.9 (4)	C4—C3—N3—C2	65.9 (6)
C4—C5—C6—F1	1.3 (6)	C4—C3—N3—N1	−108.2 (4)
C10—C5—C6—C7	0.3 (6)	O2—C15—N4—C12	175.1 (4)
C4—C5—C6—C7	−178.5 (4)	C16—C15—N4—C12	−8.5 (5)
F1—C6—C7—C8	179.4 (4)	O2—C15—N4—C11	−9.3 (6)
C5—C6—C7—C8	−0.8 (7)	C16—C15—N4—C11	167.1 (3)
C6—C7—C8—F2	179.5 (5)	C13—C12—N4—C15	−135.1 (5)
C6—C7—C8—C9	0.5 (8)	C14—C12—N4—C15	−65.5 (6)
F2—C8—C9—C10	−178.8 (5)	C13—C12—N4—C11	49.3 (6)
C7—C8—C9—C10	0.2 (8)	C14—C12—N4—C11	118.9 (5)
C8—C9—C10—C5	−0.7 (7)	C4—C11—N4—C15	−89.6 (4)
C6—C5—C10—C9	0.4 (6)	C4—C11—N4—C12	86.1 (5)
C4—C5—C10—C9	179.3 (4)	C18—C17—N5—C21	−1.3 (7)
O1—C4—C11—N4	61.5 (4)	C18—C17—N5—C16	178.0 (4)
C5—C4—C11—N4	−56.3 (5)	O3—C21—N5—C17	−177.8 (4)
C3—C4—C11—N4	−179.4 (3)	N6—C21—N5—C17	2.6 (6)
N4—C12—C13—C14	109.7 (5)	O3—C21—N5—C16	2.8 (6)
N4—C12—C14—C13	−107.7 (5)	N6—C21—N5—C16	−176.7 (4)
O2—C15—C16—N5	−27.8 (6)	C15—C16—N5—C17	100.4 (5)
N4—C15—C16—N5	155.7 (3)	C15—C16—N5—C21	−80.3 (5)
N5—C17—C18—C20	−1.1 (7)	O4—C20—N6—C21	178.6 (4)
N5—C17—C18—C19	−179.2 (5)	C18—C20—N6—C21	−0.6 (7)
C17—C18—C20—O4	−177.2 (5)	O3—C21—N6—C20	178.8 (5)
C19—C18—C20—O4	0.9 (8)	N5—C21—N6—C20	−1.7 (6)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6···N2ⁱ	0.80	2.11	2.893 (5)	167
O1—H1A···O2ⁱⁱ	0.82	2.13	2.903 (4)	158

Symmetry codes: (i) x+1, y, z−1; (ii) −x+2, −y+1, −z+2.

Experimental details

Crystal data
Chemical formula	C₂₁H₂₂F₂N₆O₄·0.62CH₂Cl₂
M_r	512.93
Crystal system, space group	Triclinic, P1
Temperature (K)	298
a, b, c (Å)	8.474 (2), 12.464 (3), 13.410 (4)
α, β, γ (°)	62.942 (4), 73.187 (4), 83.746 (4)
V (Å³)	1207.1 (6)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.24
Crystal size (mm)	0.30 × 0.16 × 0.14

Data collection
Diffractometer	Bruker SMART APEX diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	6058, 4162, 3053
R_int	0.022
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.092, 0.209, 1.16
No. of reflections	4162
No. of parameters	356
No. of restraints	42
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.50, −0.34

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6···N2ⁱ	0.80	2.11	2.893 (5)	167.2
O1—H1A···O2ⁱⁱ	0.82	2.13	2.903 (4)	157.5

Symmetry codes: (i) x+1, y, z−1; (ii) −x+2, −y+1, −z+2.

Acknowledgements

The authors thank Mr Lian-dong Liu (College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, China) for his invaluable support in the X-ray data collection. The authors also thank the National Natural Science Foundation of China for a research grant (No. 81072534).

References

Aoyama, Y., Yoshida, Y. & Sato, R. (1984). J. Biol. Chem. 259, 1661–1666. CAS PubMed Web of Science Google Scholar
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Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
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Volume 67| Part 9| September 2011| Page o2464

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

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