{(3S,5R)-5-(2,4-Di­fluoro­phen­yl)-5-[(1H-1,2,4-triazol-1-yl)meth­yl]tetra­hydro­furan-3-yl}methyl 4-methyl­benzene­sulfonate

Ma, Q.-S.; Wang, X.-G.; Xu, L.; Bin, S.; Xia, D.-H.; Zheng, G.-X.

doi:10.1107/S2414314617002425

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 2| February 2017| x170242

https://doi.org/10.1107/S2414314617002425

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access

{(3S,5R)-5-(2,4-Difluorophenyl)-5-[(1H-1,2,4-triazol-1-yl)methyl]tetrahydrofuran-3-yl}methyl 4-methylbenzenesulfonate

Qing-Shuang Ma,^a,^b Xiao-Guang Wang,^a,^b Lei Xu,^a Sun Bin,^a Dao-Hong Xia ^b ^* and Geng-Xiu Zheng ^a

^aShandong Jincheng Pharmaceutical Co. Ltd, No. 26, Kunxin Road, Zichuan District, Zibo 255130, People's Republic of China, and ^bCollege of Chemical Engineering, China University of Petroleum, Qingdao 266580, People's Republic of China
^*Correspondence e-mail: maqingshuang@163.com

Edited by J. Simpson, University of Otago, New Zealand (Received 20 January 2017; accepted 13 February 2017; online 17 February 2017)

In the title compound, C₂₁H₂₁F₂N₃O₄S, the tetrahydrofuran ring adopts an envelope conformation with the β-C atom positioned at the flap. The triazole, difluorophenyl and tolyl rings of the various substituents on the tetrahydrofuran ring are inclined at 77.88 (12), 83.81 (10) and 81.00 (10)°, respectively, to the best-fit mean plane through the five atoms of the tetrahydrofuran ring. In the crystal, weak C—H⋯O and C—H⋯F hydrogen bonds link the molecules into a three-dimensional structure, with molecules stacked along the a-axis direction.

Keywords: crystal structure; triazole derivative; antifungal agent.

CCDC reference: 1532447

Structure description

Derivatives of triazole exhibit a broad spectrum of pharmaceutical applications, particularly as antifungal agents (Sheehan et al., 1999 ). The title compound is a key intermediate in the synthesis of the antifungal agent Posaconazole. Compared with the existing antifungal drugs, it has a higher potency against a broad range of fungal pathogens including Asperigillus, Candida and Cryptococcus (Oakley et al., 1997 ; Koltin & Hitchcock, 1997 ). We report herein the synthesis and crystal structure of the title compound (Fig. 1).

Figure 1
The molecular structure of the title compound, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

The molecule contains a central tetrahydrofuran ring with a 2–4-difluorophenyl ring in an R-configuration and a methyl 1,2,4-triazole substituent at C8 with a methyl 4-methylbenzenesulfonate substituent in an S-configuration at C10. The tetrahydrofuran ring O1/C8–C11 adopts an envelope conformation with the C9 atom at the flap. The best-fit mean plane through atoms O1,C8–C11 of the tetrahydrofuran ring is inclined at 77.88 (12)° to the triazole ring, 83.81 (10)° to the difluorophenyl ring and 81.00 (10)° to the tolyl ring. The triazole ring is inclined at angles of 14.32 (7) and 17.73 (9)° to the tolyl and fluorobenzene rings, respectively. The tolyl and fluorobenzene rings are almost parallel, as indicated by the interplanar angle of 3.89 (9)°. Bond lengths and angles in the molecule are generally within the normal ranges and are similar to those observed in the related compounds N′-[(E)-(1S,3R)-(3-isopropyl-1-methyl-2-oxocyclopentyl)methylidene]-4-methylbenzenesulfonohydrazide (Tymann et al., 2015 ) and 3-O-benzyl-4(R)-C-(1-benzyl-1H-1,2,3-triazol-4-yl)-1,2-O- isopropylidene-α-D-erythrofuranose (Semjonovs et al., 2015 ).

In the crystal, weak C—H⋯O and C—H⋯F hydrogen bonds generate a three-dimensional structure, with molecules stacked along the a-axis direction (Table 1, Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12—H12A⋯O3ⁱ	0.97	2.48	3.128 (3)	124
C14—H14⋯F1ⁱⁱ	0.93	2.60	3.222 (3)	125
C12—H12B⋯F2ⁱⁱⁱ	0.97	2.54	3.492 (4)	168
Symmetry codes: (i) x+1, y, z; (ii) x, y, z-1; (iii) $[-x+2, y-{\script{1\over 2}}, -z+1]$ .

Figure 2
Packing of the title compound viewed along the a axis, with hydrogen bonds drawn as dashed lines.

Synthesis and crystallization

The title compound was prepared according to a literature procedure (Saksena et al., 1995 ). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a methanol solution at room temperature over a period of 10 d.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₂₁H₂₁F₂N₃O₄S
M_r	449.47
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	293
a, b, c (Å)	5.93718 (11), 16.9484 (3), 10.8841 (2)
β (°)	103.7973 (19)
V (Å³)	1063.62 (3)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	1.81
Crystal size (mm)	0.36 × 0.12 × 0.02

Data collection
Diffractometer	Agilent Xcalibur Eos Gemini
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2014 )
T_min, T_max	0.721, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	11514, 3732, 3465
R_int	0.036
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.085, 1.05
No. of reflections	3732
No. of parameters	281
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.16
Absolute structure	Flack (1983 )
Absolute structure parameter	−0.014 (16)
Computer programs: CrysAlis PRO (Agilent, 2014), SUPERFLIP (Palatinus et al., 2012 ), SHELXL96 (Sheldrick, 2008 ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1532447

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314617002425/sj4084sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617002425/sj4084Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617002425/sj4084Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SUPERFLIP (Palatinus et al., 2012); program(s) used to refine structure: SHELXL96 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

{(3S,5R)-5-(2,4-Difluorophenyl)-5-[(1H-1,2,4-triazol-1-yl)methyl]tetrahydrofuran-3-yl}methyl 4-methylbenzenesulfonate top

Crystal data top

C₂₁H₂₁F₂N₃O₄S	F(000) = 468
M_r = 449.47	D_x = 1.403 Mg m⁻³
Monoclinic, P2₁	Cu Kα radiation, λ = 1.54184 Å
a = 5.93718 (11) Å	Cell parameters from 5053 reflections
b = 16.9484 (3) Å	θ = 4.2–72.3°
c = 10.8841 (2) Å	µ = 1.81 mm⁻¹
β = 103.7973 (19)°	T = 293 K
V = 1063.62 (3) Å³	, colourless
Z = 2	0.36 × 0.12 × 0.02 mm

Data collection top

Agilent Xcalibur Eos Gemini diffractometer	3732 independent reflections
Radiation source: Enhance (Cu) X-ray Source	3465 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.036
Detector resolution: 16.0355 pixels mm^-1	θ_max = 66.6°, θ_min = 4.2°
ω scans	h = −5→7
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	k = −20→20
T_min = 0.721, T_max = 1.000	l = −12→11
11514 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.033	H-atom parameters constrained
wR(F²) = 0.085	w = 1/[σ²(F_o²) + (0.0438P)² + 0.0885P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.001
3732 reflections	Δρ_max = 0.18 e Å⁻³
281 parameters	Δρ_min = −0.16 e Å⁻³
1 restraint	Absolute structure: Flack (1983) ???? Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.014 (16)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
S1	0.56836 (9)	0.48540 (3)	0.07225 (5)	0.04259 (14)
O2	0.7081 (2)	0.48578 (12)	0.21565 (13)	0.0479 (4)
O4	0.6463 (4)	0.54834 (10)	0.00697 (17)	0.0564 (5)
F1	0.8681 (3)	0.51345 (9)	0.72967 (13)	0.0568 (4)
O1	1.4023 (2)	0.51967 (10)	0.52970 (13)	0.0424 (4)
O3	0.3339 (3)	0.48282 (15)	0.08029 (18)	0.0686 (5)
N1	1.3532 (3)	0.36806 (11)	0.65236 (18)	0.0456 (5)
C4	1.1446 (4)	0.58104 (14)	0.64476 (18)	0.0380 (5)
F2	0.9096 (5)	0.78712 (12)	0.7749 (2)	0.1063 (8)
C13	0.6451 (4)	0.39536 (13)	0.01338 (19)	0.0359 (5)
C14	0.8229 (4)	0.39399 (13)	−0.0472 (2)	0.0391 (5)
H14	0.9019	0.4400	−0.0572	0.047*
N2	1.1927 (5)	0.31089 (14)	0.6471 (3)	0.0650 (7)
C5	0.9697 (4)	0.58272 (15)	0.7095 (2)	0.0446 (5)
C15	0.8825 (4)	0.32311 (15)	−0.0929 (2)	0.0490 (6)
H15	1.0031	0.3216	−0.1339	0.059*
C1	0.9917 (6)	0.71952 (18)	0.7334 (3)	0.0690 (8)
C9	1.0182 (3)	0.47417 (13)	0.48126 (17)	0.0377 (4)
H9A	1.0341	0.4181	0.4673	0.045*
H9B	0.8675	0.4842	0.4982	0.045*
C10	1.0532 (4)	0.52271 (13)	0.36911 (18)	0.0384 (5)
H10	0.9879	0.5756	0.3721	0.046*
C12	0.9601 (3)	0.48732 (16)	0.23982 (17)	0.0415 (4)
H12A	1.0079	0.5188	0.1761	0.050*
H12B	1.0196	0.4342	0.2369	0.050*
C8	1.2160 (3)	0.50486 (12)	0.58950 (18)	0.0370 (5)
C16	0.7658 (5)	0.25394 (15)	−0.0789 (3)	0.0571 (7)
C6	0.8899 (5)	0.64998 (19)	0.7559 (3)	0.0608 (7)
H6	0.7736	0.6484	0.7999	0.073*
N3	1.4914 (6)	0.26643 (17)	0.5730 (3)	0.0801 (8)
C2	1.1656 (6)	0.72282 (16)	0.6729 (3)	0.0672 (8)
H2	1.2329	0.7709	0.6612	0.081*
C3	1.2428 (5)	0.65347 (16)	0.6283 (2)	0.0513 (6)
H3	1.3624	0.6556	0.5867	0.062*
C7	1.3139 (4)	0.44595 (14)	0.6970 (2)	0.0424 (5)
H7A	1.4593	0.4663	0.7476	0.051*
H7B	1.2065	0.4420	0.7513	0.051*
C17	0.5868 (6)	0.25747 (16)	−0.0185 (3)	0.0639 (8)
H17	0.5060	0.2117	−0.0095	0.077*
C20	1.5278 (5)	0.33992 (18)	0.6096 (3)	0.0618 (7)
H20	1.6595	0.3686	0.6060	0.074*
C18	0.5253 (5)	0.32757 (17)	0.0289 (3)	0.0540 (6)
H18	0.4056	0.3292	0.0705	0.065*
C11	1.3187 (4)	0.5280 (2)	0.3973 (2)	0.0583 (7)
H11A	1.3800	0.4864	0.3534	0.070*
H11B	1.3657	0.5785	0.3696	0.070*
C21	1.2873 (7)	0.25194 (18)	0.5978 (3)	0.0777 (10)
H21	1.2149	0.2031	0.5813	0.093*
C19	0.8364 (7)	0.1771 (2)	−0.1289 (4)	0.0932 (12)
H19A	0.9298	0.1877	−0.1879	0.140*
H19B	0.7003	0.1484	−0.1706	0.140*
H19C	0.9242	0.1463	−0.0599	0.140*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0350 (2)	0.0537 (3)	0.0381 (2)	0.0052 (3)	0.00674 (19)	−0.0099 (3)
O2	0.0406 (7)	0.0715 (10)	0.0349 (7)	−0.0048 (9)	0.0154 (6)	−0.0128 (8)
O4	0.0672 (12)	0.0452 (9)	0.0538 (10)	0.0087 (8)	0.0083 (9)	0.0000 (8)
F1	0.0528 (8)	0.0663 (9)	0.0574 (8)	−0.0105 (7)	0.0253 (7)	0.0048 (7)
O1	0.0333 (7)	0.0616 (9)	0.0329 (7)	−0.0049 (7)	0.0089 (6)	0.0048 (7)
O3	0.0390 (8)	0.0927 (14)	0.0737 (11)	0.0054 (11)	0.0124 (8)	−0.0275 (12)
N1	0.0479 (11)	0.0454 (11)	0.0422 (10)	−0.0014 (9)	0.0081 (9)	0.0089 (8)
C4	0.0367 (11)	0.0465 (11)	0.0277 (9)	−0.0045 (9)	0.0016 (8)	0.0009 (8)
F2	0.1321 (19)	0.0673 (12)	0.1169 (17)	0.0173 (12)	0.0245 (15)	−0.0368 (12)
C13	0.0339 (11)	0.0440 (12)	0.0290 (10)	−0.0007 (9)	0.0061 (9)	−0.0039 (8)
C14	0.0409 (12)	0.0445 (12)	0.0324 (10)	−0.0029 (9)	0.0099 (9)	−0.0023 (9)
N2	0.0620 (14)	0.0535 (14)	0.0801 (17)	−0.0121 (11)	0.0181 (13)	0.0101 (12)
C5	0.0443 (12)	0.0539 (13)	0.0349 (11)	−0.0048 (11)	0.0078 (10)	−0.0001 (10)
C15	0.0506 (14)	0.0571 (14)	0.0425 (12)	0.0079 (11)	0.0173 (11)	−0.0059 (11)
C1	0.083 (2)	0.0554 (16)	0.0629 (17)	0.0069 (15)	0.0050 (16)	−0.0179 (14)
C9	0.0378 (10)	0.0426 (12)	0.0314 (9)	−0.0059 (9)	0.0059 (8)	−0.0014 (9)
C10	0.0428 (12)	0.0413 (10)	0.0291 (10)	−0.0003 (9)	0.0047 (8)	0.0009 (8)
C12	0.0384 (10)	0.0553 (12)	0.0327 (9)	0.0041 (12)	0.0118 (8)	−0.0017 (11)
C8	0.0358 (10)	0.0453 (12)	0.0298 (9)	−0.0050 (8)	0.0073 (8)	0.0023 (8)
C16	0.0651 (17)	0.0480 (14)	0.0524 (14)	0.0021 (12)	0.0027 (13)	−0.0085 (11)
C6	0.0591 (16)	0.0776 (18)	0.0459 (13)	0.0092 (14)	0.0134 (12)	−0.0115 (13)
N3	0.093 (2)	0.0677 (17)	0.0816 (19)	0.0115 (15)	0.0242 (16)	−0.0104 (14)
C2	0.082 (2)	0.0445 (14)	0.0690 (18)	−0.0134 (14)	0.0069 (16)	−0.0077 (13)
C3	0.0539 (15)	0.0528 (14)	0.0453 (12)	−0.0129 (12)	0.0083 (11)	−0.0014 (11)
C7	0.0446 (13)	0.0501 (12)	0.0316 (10)	0.0009 (10)	0.0071 (9)	0.0039 (9)
C17	0.0707 (18)	0.0439 (14)	0.0751 (18)	−0.0189 (13)	0.0135 (16)	−0.0022 (13)
C20	0.0589 (16)	0.0664 (17)	0.0645 (17)	0.0030 (13)	0.0230 (14)	−0.0023 (14)
C18	0.0477 (14)	0.0624 (15)	0.0550 (15)	−0.0129 (12)	0.0184 (12)	−0.0025 (12)
C11	0.0455 (14)	0.094 (2)	0.0359 (11)	−0.0173 (14)	0.0116 (10)	0.0086 (12)
C21	0.095 (3)	0.0499 (16)	0.081 (2)	−0.0096 (16)	0.006 (2)	−0.0034 (15)
C19	0.121 (3)	0.0553 (19)	0.099 (3)	0.0145 (19)	0.017 (2)	−0.0234 (18)

Geometric parameters (Å, º) top

S1—O2	1.5832 (14)	C9—C8	1.542 (3)
S1—O4	1.419 (2)	C10—H10	0.9800
S1—O3	1.4159 (18)	C10—C12	1.508 (3)
S1—C13	1.757 (2)	C10—C11	1.535 (3)
O2—C12	1.456 (2)	C12—H12A	0.9700
F1—C5	1.362 (3)	C12—H12B	0.9700
O1—C8	1.433 (3)	C8—C7	1.542 (3)
O1—C11	1.414 (3)	C16—C17	1.378 (4)
N1—N2	1.351 (3)	C16—C19	1.509 (4)
N1—C7	1.445 (3)	C6—H6	0.9300
N1—C20	1.322 (4)	N3—C20	1.310 (4)
C4—C5	1.388 (3)	N3—C21	1.326 (5)
C4—C8	1.526 (3)	C2—H2	0.9300
C4—C3	1.389 (3)	C2—C3	1.390 (4)
F2—C1	1.363 (3)	C3—H3	0.9300
C13—C14	1.372 (3)	C7—H7A	0.9700
C13—C18	1.382 (3)	C7—H7B	0.9700
C14—H14	0.9300	C17—H17	0.9300
C14—C15	1.378 (3)	C17—C18	1.378 (4)
N2—C21	1.322 (4)	C20—H20	0.9300
C5—C6	1.376 (4)	C18—H18	0.9300
C15—H15	0.9300	C11—H11A	0.9700
C15—C16	1.389 (4)	C11—H11B	0.9700
C1—C6	1.373 (5)	C21—H21	0.9300
C1—C2	1.352 (5)	C19—H19A	0.9600
C9—H9A	0.9700	C19—H19B	0.9600
C9—H9B	0.9700	C19—H19C	0.9600
C9—C10	1.527 (3)

O2—S1—C13	104.04 (10)	O1—C8—C9	104.00 (15)
O4—S1—O2	109.50 (11)	O1—C8—C7	105.41 (16)
O4—S1—C13	109.05 (11)	C4—C8—C9	110.73 (17)
O3—S1—O2	103.35 (10)	C4—C8—C7	109.78 (17)
O3—S1—O4	119.81 (13)	C9—C8—C7	116.22 (18)
O3—S1—C13	109.87 (12)	C15—C16—C19	120.0 (3)
C12—O2—S1	116.90 (11)	C17—C16—C15	118.5 (2)
C11—O1—C8	111.00 (16)	C17—C16—C19	121.5 (3)
N2—N1—C7	120.0 (2)	C5—C6—H6	121.9
C20—N1—N2	109.3 (2)	C1—C6—C5	116.2 (3)
C20—N1—C7	130.6 (2)	C1—C6—H6	121.9
C5—C4—C8	122.0 (2)	C20—N3—C21	101.9 (3)
C5—C4—C3	115.8 (2)	C1—C2—H2	120.4
C3—C4—C8	122.2 (2)	C1—C2—C3	119.3 (3)
C14—C13—S1	119.09 (17)	C3—C2—H2	120.4
C14—C13—C18	121.5 (2)	C4—C3—C2	121.3 (3)
C18—C13—S1	119.45 (18)	C4—C3—H3	119.4
C13—C14—H14	120.6	C2—C3—H3	119.4
C13—C14—C15	118.8 (2)	N1—C7—C8	113.47 (18)
C15—C14—H14	120.6	N1—C7—H7A	108.9
C21—N2—N1	101.2 (3)	N1—C7—H7B	108.9
F1—C5—C4	118.6 (2)	C8—C7—H7A	108.9
F1—C5—C6	116.8 (2)	C8—C7—H7B	108.9
C6—C5—C4	124.6 (3)	H7A—C7—H7B	107.7
C14—C15—H15	119.4	C16—C17—H17	119.4
C14—C15—C16	121.2 (2)	C16—C17—C18	121.3 (2)
C16—C15—H15	119.4	C18—C17—H17	119.4
F2—C1—C6	117.1 (3)	N1—C20—H20	124.3
C2—C1—F2	120.1 (3)	N3—C20—N1	111.3 (3)
C2—C1—C6	122.8 (3)	N3—C20—H20	124.3
H9A—C9—H9B	109.3	C13—C18—H18	120.6
C10—C9—H9A	111.4	C17—C18—C13	118.7 (2)
C10—C9—H9B	111.4	C17—C18—H18	120.6
C10—C9—C8	101.83 (16)	O1—C11—C10	107.01 (18)
C8—C9—H9A	111.4	O1—C11—H11A	110.3
C8—C9—H9B	111.4	O1—C11—H11B	110.3
C9—C10—H10	109.6	C10—C11—H11A	110.3
C9—C10—C11	101.56 (17)	C10—C11—H11B	110.3
C12—C10—C9	116.25 (19)	H11A—C11—H11B	108.6
C12—C10—H10	109.6	N2—C21—N3	116.1 (3)
C12—C10—C11	109.89 (19)	N2—C21—H21	121.9
C11—C10—H10	109.6	N3—C21—H21	121.9
O2—C12—C10	107.92 (16)	C16—C19—H19A	109.5
O2—C12—H12A	110.1	C16—C19—H19B	109.5
O2—C12—H12B	110.1	C16—C19—H19C	109.5
C10—C12—H12A	110.1	H19A—C19—H19B	109.5
C10—C12—H12B	110.1	H19A—C19—H19C	109.5
H12A—C12—H12B	108.4	H19B—C19—H19C	109.5
O1—C8—C4	110.35 (17)

S1—O2—C12—C10	155.39 (17)	C9—C10—C11—O1	−25.6 (3)
S1—C13—C14—C15	179.88 (17)	C9—C8—C7—N1	44.5 (3)
S1—C13—C18—C17	179.6 (2)	C10—C9—C8—O1	−35.4 (2)
O2—S1—C13—C14	−94.97 (18)	C10—C9—C8—C4	83.1 (2)
O2—S1—C13—C18	85.1 (2)	C10—C9—C8—C7	−150.75 (19)
O4—S1—O2—C12	−52.0 (2)	C12—C10—C11—O1	−149.2 (2)
O4—S1—C13—C14	21.8 (2)	C8—O1—C11—C10	3.4 (3)
O4—S1—C13—C18	−158.2 (2)	C8—C4—C5—F1	3.5 (3)
F1—C5—C6—C1	−179.2 (2)	C8—C4—C5—C6	−176.6 (2)
O1—C8—C7—N1	−70.0 (2)	C8—C4—C3—C2	176.1 (2)
O3—S1—O2—C12	179.3 (2)	C8—C9—C10—C12	155.55 (19)
O3—S1—C13—C14	154.94 (18)	C8—C9—C10—C11	36.3 (2)
O3—S1—C13—C18	−25.0 (2)	C16—C17—C18—C13	0.8 (4)
N1—N2—C21—N3	0.7 (4)	C6—C1—C2—C3	1.5 (5)
C4—C5—C6—C1	1.0 (4)	C2—C1—C6—C5	−2.0 (5)
C4—C8—C7—N1	171.16 (18)	C3—C4—C5—F1	−179.39 (19)
F2—C1—C6—C5	177.8 (2)	C3—C4—C5—C6	0.5 (3)
F2—C1—C2—C3	−178.3 (3)	C3—C4—C8—O1	4.0 (3)
C13—S1—O2—C12	64.5 (2)	C3—C4—C8—C9	−110.6 (2)
C13—C14—C15—C16	0.2 (4)	C3—C4—C8—C7	119.8 (2)
C14—C13—C18—C17	−0.3 (4)	C7—N1—N2—C21	177.5 (2)
C14—C15—C16—C17	0.3 (4)	C7—N1—C20—N3	−177.1 (2)
C14—C15—C16—C19	−179.4 (3)	C20—N1—N2—C21	−1.1 (3)
N2—N1—C7—C8	−97.1 (3)	C20—N1—C7—C8	81.1 (3)
N2—N1—C20—N3	1.2 (3)	C20—N3—C21—N2	0.0 (4)
C5—C4—C8—O1	−179.07 (17)	C18—C13—C14—C15	−0.2 (3)
C5—C4—C8—C9	66.3 (2)	C11—O1—C8—C4	−98.5 (2)
C5—C4—C8—C7	−63.3 (2)	C11—O1—C8—C9	20.3 (2)
C5—C4—C3—C2	−1.0 (3)	C11—O1—C8—C7	143.0 (2)
C15—C16—C17—C18	−0.8 (4)	C11—C10—C12—O2	−178.2 (2)
C1—C2—C3—C4	0.0 (4)	C21—N3—C20—N1	−0.8 (4)
C9—C10—C12—O2	67.2 (3)	C19—C16—C17—C18	178.9 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12A···O3ⁱ	0.97	2.48	3.128 (3)	124
C14—H14···F1ⁱⁱ	0.93	2.60	3.222 (3)	125
C12—H12B···F2ⁱⁱⁱ	0.97	2.54	3.492 (4)	168

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

Acknowledgements

The authors thank Professor Chen for providing the single-crystal X-ray diffractometer facility.

Funding information

Funding for this research was provided by: Shandong Jincheng Pharmaceutical Co. Ltd

References

Agilent (2014). CrysAlis PRO. Agilent Technologies, Yarnton, England. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Koltin, Y. & Hitchcock, C. A. (1997). Curr. Opin. Chem. Biol. 1, 176–182. Web of Science CrossRef CAS PubMed Google Scholar
Oakley, K. L., Moore, C. B. & Denning, D. W. (1997). Antimicrob. Agents Chemother. 41, 1124–1126. CAS Google Scholar
Palatinus, L., Prathapa, S. J. & van Smaalen, S. (2012). J. Appl. Cryst. 45, 575–580. Web of Science CrossRef CAS IUCr Journals Google Scholar
Saksena, A. K., Montclair, U. & Girijavallabhan, V. M. (1995). US Patent US5661151. Google Scholar
Semjonovs, N., Rjabovs, V., Stepanovs, D. & Turks, M. (2015). Acta Cryst. E71, 1542–1544. CSD CrossRef IUCr Journals Google Scholar
Sheehan, D. J., Hitchcock, C. A. & Sibley, C. M. (1999). Clin. Microbiol. Rev. 12, 40–79. Web of Science CAS PubMed Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tymann, D., Dragon, D. C., Golz, C., Preut, H., Strohmann, C. & Hiersemann, M. (2015). Acta Cryst. E71, o904–o905. CSD CrossRef IUCr Journals Google Scholar

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