Voriconazole, an anti­fungal drug

Voriconazole [systematic name 2-(2,4-difluoro­phen­yl)-3-(5-fluoro­pyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol], C₁₆H₁₄F₃N₅O, (I), is a triazole anti­fungal medication used to treat serious fungal infections. The dihedral angle between the planes of the fluoro­pyrimidine and triazole rings is 32.0 (2)° and that between the difluoro­phenyl and triazole rings is 47.7 (2)°. In addition to the O—H...N intra­molecular hydrogen bond, C—H...O and C—H...N inter­actions contribute to the mol­ecular arrangement in the crystal packing.

Key indicators

• Single-crystal X-ray study
• T = 294 K
• Mean [sigma](C-C) = 0.006 Å
• R factor = 0.059
• wR factor = 0.161
• Data-to-parameter ratio = 6.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       6.62
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          6

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.00
           From the CIF: _reflns_number_total               1529
           Count of symmetry unique reflns         1529
           Completeness (_total/calc)            100.00%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C2     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3     = .          S

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   3 ALERT level G = General alerts; check

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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Computing details

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL/PC (Sheldrick, 1990), DIAMOND (Brandenburg & Putz, 2005) and Mercury (Bruno et al., 2002); software used to prepare material for publication: SHELXL97.

2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol

Crystal data

C16H14F3N5O	F(000) = 360
Mr = 349.32	Dx = 1.442 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 3871 reflections
a = 7.5332 (19) Å	θ = 2.4–27.7°
b = 8.349 (2) Å	µ = 0.12 mm^−1
c = 12.989 (3) Å	T = 294 K
β = 100.062 (4)°	Block, colorless
V = 804.4 (3) Å^3	0.15 × 0.12 × 0.10 mm
Z = 2

Data collection

Bruker SMART APEX CCD area-detector diffractometer	1398 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.040
Graphite monochromator	θmax = 25.0°, θmin = 1.6°
ω scan	h = −8→8
7364 measured reflections	k = −9→9
1529 independent reflections	l = −15→15

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.059	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.161	H atoms treated by a mixture of independent and constrained refinement
S = 1.20	w = 1/[σ^2(Fo^2) + (0.1192P)^2 + 0.0109P] where P = (Fo^2 + 2Fc^2)/3
1529 reflections	(Δ/σ)max < 0.001
231 parameters	Δρmax = 0.41 e Å^−3
1 restraint	Δρmin = −0.31 e Å^−3

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.1441 (5)	0.6829 (5)	0.6867 (3)	0.0452 (9)
H1A	0.0959	0.7234	0.7462	0.054*
H1B	0.1857	0.7735	0.6507	0.054*
C2	0.3049 (5)	0.5704 (4)	0.7258 (3)	0.0387 (8)
C3	0.4505 (5)	0.6635 (5)	0.8030 (3)	0.0453 (9)
H3	0.3929	0.7058	0.8594	0.054*
C4	0.6074 (6)	0.5546 (6)	0.8526 (4)	0.0608 (12)
H4A	0.6568	0.5014	0.7985	0.091*
H4B	0.5639	0.4762	0.8963	0.091*
H4C	0.6993	0.6182	0.8941	0.091*
C5	0.5291 (5)	0.8045 (5)	0.7513 (3)	0.0451 (8)
C6	0.6361 (6)	0.9132 (7)	0.6130 (4)	0.0636 (12)
H6	0.6581	0.8991	0.5453	0.076*
C7	0.6557 (7)	1.0649 (6)	0.7544 (6)	0.0744 (15)
H7	0.6899	1.1594	0.7903	0.089*
C8	0.5769 (6)	0.9471 (6)	0.8047 (4)	0.0565 (10)
C9	−0.0212 (6)	0.5858 (6)	0.5141 (3)	0.0512 (9)
H9	0.0511	0.6346	0.4721	0.061*
C10	−0.2180 (5)	0.4524 (6)	0.5690 (4)	0.0562 (10)
H10	−0.3163	0.3855	0.5701	0.067*
C11	0.2388 (5)	0.4226 (4)	0.7767 (3)	0.0388 (8)
C12	0.2436 (5)	0.2728 (5)	0.7303 (3)	0.0455 (9)
H12	0.2939	0.2631	0.6702	0.055*
C13	0.1754 (6)	0.1378 (6)	0.7714 (4)	0.0562 (10)
H13	0.1790	0.0385	0.7395	0.067*
C14	0.1029 (6)	0.1543 (6)	0.8599 (3)	0.0542 (10)
C15	0.0937 (7)	0.2965 (7)	0.9095 (3)	0.0578 (10)
H15	0.0442	0.3050	0.9700	0.069*
C16	0.1622 (5)	0.4282 (5)	0.8647 (3)	0.0469 (9)
F1	0.5503 (5)	0.9644 (4)	0.9025 (3)	0.0849 (10)
F2	0.1467 (4)	0.5716 (3)	0.9118 (2)	0.0668 (8)
F3	0.0390 (5)	0.0208 (4)	0.9015 (3)	0.0847 (10)
N1	0.0019 (4)	0.5998 (4)	0.6161 (2)	0.0417 (7)
N2	−0.1247 (4)	0.5139 (6)	0.6539 (3)	0.0555 (9)
N3	−0.1612 (5)	0.4929 (5)	0.4789 (3)	0.0599 (10)
N4	0.5582 (5)	0.7922 (5)	0.6539 (3)	0.0530 (8)
N5	0.6856 (6)	1.0512 (6)	0.6581 (4)	0.0739 (12)
O1	0.3763 (4)	0.5149 (4)	0.63818 (19)	0.0467 (7)
H1O	0.449 (7)	0.579 (9)	0.629 (4)	0.063 (15)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.056 (2)	0.032 (2)	0.0483 (19)	0.0000 (16)	0.0099 (16)	−0.0027 (15)
C2	0.0505 (18)	0.0276 (18)	0.0401 (16)	−0.0008 (15)	0.0137 (14)	−0.0016 (14)
C3	0.051 (2)	0.042 (2)	0.0435 (18)	−0.0044 (18)	0.0096 (14)	−0.0012 (16)
C4	0.061 (2)	0.058 (3)	0.059 (2)	−0.003 (2)	−0.0013 (18)	0.009 (2)
C5	0.0426 (17)	0.0302 (19)	0.061 (2)	−0.0001 (15)	0.0048 (15)	−0.0005 (17)
C6	0.062 (2)	0.052 (3)	0.078 (3)	−0.006 (2)	0.018 (2)	0.013 (2)
C7	0.061 (3)	0.038 (3)	0.120 (5)	−0.014 (2)	0.004 (3)	−0.007 (3)
C8	0.055 (2)	0.041 (2)	0.070 (3)	−0.0047 (19)	0.0018 (18)	−0.011 (2)
C9	0.057 (2)	0.044 (2)	0.053 (2)	−0.0123 (19)	0.0123 (16)	0.0020 (18)
C10	0.0482 (19)	0.044 (2)	0.077 (3)	−0.0010 (18)	0.0109 (18)	0.002 (2)
C11	0.0435 (17)	0.0297 (19)	0.0425 (17)	0.0035 (15)	0.0056 (13)	0.0036 (14)
C12	0.054 (2)	0.035 (2)	0.0493 (19)	0.0002 (17)	0.0140 (15)	−0.0017 (16)
C13	0.068 (2)	0.032 (2)	0.068 (3)	−0.0001 (19)	0.0095 (19)	0.0012 (18)
C14	0.059 (2)	0.043 (2)	0.062 (2)	−0.0052 (19)	0.0162 (18)	0.0149 (19)
C15	0.071 (3)	0.055 (3)	0.051 (2)	−0.004 (2)	0.0207 (18)	0.007 (2)
C16	0.060 (2)	0.039 (2)	0.0442 (19)	0.0003 (18)	0.0142 (15)	−0.0024 (16)
F1	0.109 (2)	0.064 (2)	0.0809 (19)	−0.0181 (18)	0.0120 (16)	−0.0283 (16)
F2	0.105 (2)	0.0416 (14)	0.0641 (14)	−0.0027 (14)	0.0446 (14)	−0.0084 (12)
F3	0.114 (2)	0.0537 (19)	0.092 (2)	−0.0188 (17)	0.0345 (17)	0.0195 (16)
N1	0.0438 (15)	0.0300 (16)	0.0509 (16)	−0.0005 (13)	0.0074 (12)	0.0017 (12)
N2	0.0436 (15)	0.060 (2)	0.0643 (19)	−0.0007 (17)	0.0127 (14)	0.0089 (19)
N3	0.069 (2)	0.048 (2)	0.063 (2)	−0.0120 (18)	0.0101 (16)	−0.0078 (17)
N4	0.0615 (19)	0.0382 (18)	0.0609 (19)	−0.0084 (16)	0.0151 (15)	0.0051 (16)
N5	0.070 (2)	0.047 (3)	0.104 (3)	−0.015 (2)	0.015 (2)	0.011 (2)
O1	0.0587 (15)	0.0381 (15)	0.0472 (14)	−0.0053 (13)	0.0201 (11)	−0.0051 (12)

Geometric parameters (Å, º)

C1—N1	1.458 (5)	C8—F1	1.328 (6)
C1—C2	1.546 (5)	C9—N1	1.310 (5)
C1—H1A	0.9700	C9—N3	1.325 (6)
C1—H1B	0.9700	C9—H9	0.9300
C2—O1	1.419 (4)	C10—N2	1.305 (6)
C2—C11	1.524 (5)	C10—N3	1.357 (6)
C2—C3	1.558 (5)	C10—H10	0.9300
C3—C5	1.525 (5)	C11—C16	1.369 (5)
C3—C4	1.541 (6)	C11—C12	1.391 (5)
C3—H3	0.9800	C12—C13	1.383 (6)
C4—H4A	0.9600	C12—H12	0.9300
C4—H4B	0.9600	C13—C14	1.363 (7)
C4—H4C	0.9600	C13—H13	0.9300
C5—N4	1.324 (5)	C14—C15	1.359 (8)
C5—C8	1.393 (6)	C14—F3	1.363 (5)
C6—N5	1.317 (8)	C15—C16	1.385 (6)
C6—N4	1.325 (6)	C15—H15	0.9300
C6—H6	0.9300	C16—F2	1.358 (5)
C7—N5	1.313 (8)	N1—N2	1.353 (5)
C7—C8	1.372 (8)	O1—H1O	0.79 (7)
C7—H7	0.9300
N1—C1—C2	111.4 (3)	F1—C8—C5	120.0 (4)
N1—C1—H1A	109.3	C7—C8—C5	118.1 (5)
C2—C1—H1A	109.3	N1—C9—N3	111.0 (4)
N1—C1—H1B	109.3	N1—C9—H9	124.5
C2—C1—H1B	109.3	N3—C9—H9	124.5
H1A—C1—H1B	108.0	N2—C10—N3	115.3 (4)
O1—C2—C11	106.4 (3)	N2—C10—H10	122.4
O1—C2—C1	108.7 (3)	N3—C10—H10	122.4
C11—C2—C1	109.7 (3)	C16—C11—C12	116.0 (3)
O1—C2—C3	110.8 (3)	C16—C11—C2	123.5 (3)
C11—C2—C3	111.8 (3)	C12—C11—C2	120.4 (3)
C1—C2—C3	109.3 (3)	C13—C12—C11	121.7 (3)
C5—C3—C4	108.2 (3)	C13—C12—H12	119.1
C5—C3—C2	112.7 (3)	C11—C12—H12	119.1
C4—C3—C2	112.2 (3)	C14—C13—C12	118.3 (4)
C5—C3—H3	107.9	C14—C13—H13	120.9
C4—C3—H3	107.9	C12—C13—H13	120.9
C2—C3—H3	107.9	C13—C14—C15	123.3 (4)
C3—C4—H4A	109.5	C13—C14—F3	118.3 (4)
C3—C4—H4B	109.5	C15—C14—F3	118.4 (4)
H4A—C4—H4B	109.5	C14—C15—C16	116.2 (4)
C3—C4—H4C	109.5	C14—C15—H15	121.9
H4A—C4—H4C	109.5	C16—C15—H15	121.9
H4B—C4—H4C	109.5	F2—C16—C11	119.2 (4)
N4—C5—C8	118.0 (4)	F2—C16—C15	116.3 (3)
N4—C5—C3	120.1 (3)	C11—C16—C15	124.5 (4)
C8—C5—C3	121.8 (4)	C9—N1—N2	110.0 (3)
N5—C6—N4	126.8 (5)	C9—N1—C1	129.2 (3)
N5—C6—H6	116.6	N2—N1—C1	120.7 (3)
N4—C6—H6	116.6	C10—N2—N1	102.2 (3)
N5—C7—C8	123.4 (5)	C9—N3—C10	101.5 (4)
N5—C7—H7	118.3	C5—N4—C6	118.9 (4)
C8—C7—H7	118.3	C6—N5—C7	114.7 (5)
F1—C8—C7	121.9 (5)	C2—O1—H1O	106 (4)
N1—C1—C2—O1	60.3 (4)	C2—C11—C12—C13	−176.3 (4)
N1—C1—C2—C11	−55.6 (4)	C11—C12—C13—C14	−0.3 (6)
N1—C1—C2—C3	−178.6 (3)	C12—C13—C14—C15	0.2 (7)
O1—C2—C3—C5	57.0 (4)	C12—C13—C14—F3	−178.7 (4)
C11—C2—C3—C5	175.5 (3)	C13—C14—C15—C16	0.3 (7)
C1—C2—C3—C5	−62.7 (4)	F3—C14—C15—C16	179.3 (4)
O1—C2—C3—C4	−65.3 (4)	C12—C11—C16—F2	−177.5 (4)
C11—C2—C3—C4	53.2 (4)	C2—C11—C16—F2	−1.5 (6)
C1—C2—C3—C4	174.9 (3)	C12—C11—C16—C15	0.9 (6)
C4—C3—C5—N4	86.9 (4)	C2—C11—C16—C15	176.9 (4)
C2—C3—C5—N4	−37.7 (5)	C14—C15—C16—F2	177.5 (4)
C4—C3—C5—C8	−91.4 (5)	C14—C15—C16—C11	−1.0 (7)
C2—C3—C5—C8	144.1 (4)	N3—C9—N1—N2	0.3 (5)
N5—C7—C8—F1	179.3 (5)	N3—C9—N1—C1	176.3 (4)
N5—C7—C8—C5	1.2 (8)	C2—C1—N1—C9	−90.4 (5)
N4—C5—C8—F1	−179.9 (4)	C2—C1—N1—N2	85.3 (4)
C3—C5—C8—F1	−1.6 (6)	N3—C10—N2—N1	−0.3 (5)
N4—C5—C8—C7	−1.8 (6)	C9—N1—N2—C10	0.0 (5)
C3—C5—C8—C7	176.5 (4)	C1—N1—N2—C10	−176.4 (3)
O1—C2—C11—C16	179.4 (3)	N1—C9—N3—C10	−0.4 (5)
C1—C2—C11—C16	−63.3 (4)	N2—C10—N3—C9	0.4 (5)
C3—C2—C11—C16	58.2 (4)	C8—C5—N4—C6	2.1 (6)
O1—C2—C11—C12	−4.8 (4)	C3—C5—N4—C6	−176.2 (4)
C1—C2—C11—C12	112.5 (4)	N5—C6—N4—C5	−2.1 (7)
C3—C2—C11—C12	−126.0 (4)	N4—C6—N5—C7	1.4 (8)
C16—C11—C12—C13	−0.3 (6)	C8—C7—N5—C6	−1.0 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···N4	0.79 (7)	1.97 (7)	2.679 (5)	150 (6)
C1—H1B···N3^i	0.97	2.47	3.382 (6)	156
C6—H6···O1^ii	0.93	2.54	3.357 (6)	146

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