Voriconazole [systematic name 2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1
H-1,2,4-triazol-1-yl)butan-2-ol], C
16H
14F
3N
5O, (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.
Supporting information
CCDC reference: 636166
Key indicators
- Single-crystal X-ray study
- T = 294 K
- Mean (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
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-(1
H-1,2,4-triazol-1-yl) butan-2-ol
top
Crystal data top
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) Å3 | 0.15 × 0.12 × 0.10 mm |
Z = 2 | |
Data collection top
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 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)] = 0.059 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.161 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.20 | w = 1/[σ2(Fo2) + (0.1192P)2 + 0.0109P] where P = (Fo2 + 2Fc2)/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 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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | 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 (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
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) top
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) top
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···N3i | 0.97 | 2.47 | 3.382 (6) | 156 |
C6—H6···O1ii | 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. |