In the crystal structure of the title compound, C
18H
17FN
4O
2S·2H
2O, the organic molecules are linked by intermolecular O—H

O, O—H

N and N—H

O hydrogen bonds with the water molecules, generating a three-dimensional network. The imidazole ring system forms a dihedral angle of 24.9 (2)° with the 4-fluorophenyl ring. The pyridine ring is oriented approximately perpendicular [72.24 (8)°] to the imidazole ring system.
Supporting information
CCDC reference: 766794
Key indicators
- Single-crystal X-ray study
- T = 193 K
- Mean
(C-C) = 0.004 Å
- R factor = 0.046
- wR factor = 0.099
- Data-to-parameter ratio = 18.1
checkCIF/PLATON results
No syntax errors found
Alert level C
ABSTY03_ALERT_1_C The _exptl_absorpt_correction_type has been given as none.
However values have been given for Tmin and Tmax. Remove
these if an absorption correction has not been applied.
From the CIF: _exptl_absorpt_correction_T_min 0.903
From the CIF: _exptl_absorpt_correction_T_max 0.979
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) ..... 1
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L= 0.600 5
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L= 0.600 7
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 27.87
From the CIF: _reflns_number_total 4628
Count of symmetry unique reflns 2691
Completeness (_total/calc) 171.98%
TEST3: Check Friedels for noncentro structure
Estimate of Friedel pairs measured 1937
Fraction of Friedel pairs measured 0.720
Are heavy atom types Z>Si present yes
0 ALERT level A = In general: serious problem
0 ALERT level B = Potentially serious problem
4 ALERT level C = Check and explain
1 ALERT level G = General alerts; check
1 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
2 ALERT type 4 Improvement, methodology, query or suggestion
0 ALERT type 5 Informative message, check
N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylthio)-1H-imidazol-5-yl)pyridin-2- yl)acetamide (3.56 g, 10 mmol) was dissolved in a mixture of
THF (30 ml) and acetone (58 ml), and water (45 ml) was added. The mixture was
stirred at T = 313 K, and an aqueous solution of sodium periodate (4.01 g,
18.4 mmol in 65 ml water) was added dropwise. The reaction mixture was heated
at T = 338 K. The progress was again monitored until HPLC analysis (C8
Betasil, MeOH/ 0.01 M KH2PO4, pH = 2,3) indicated complete
conversion. After cooling to rt, the organic solvents were removed under
reduced pressure and a precipitate dropped down, which was filtered off and
washed with water and isopropylether. The crude product was purified by
recrystallization from ethylacetate to yield 3.02 g (81.2%) of the colorless
racemic product
N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylsulfinyl)-1H-imidazol-5-yl)pyridin-2-yl)acetamide. The both enantiomers were isolated
by enantioselective preparative HPLC (Daicel CHIRALPAK AD, CH2Cl2 / MeOH/
TEA 98: 2: 0.1). Suitable crystals of the first eluted enantiomer I for X-ray
were obtained by slow evaporation at T = 298 K of a solution of ethanol.
Hydrogen atoms attached to carbons were placed at calculated positions with
C—H = 0.95 Å (aromatic) or 0.98–0.99 Å (sp3 C-atom). Hydrogen
atoms attached to nitrogen and oxygen were located in diff. Fourier maps. All
H atoms were refined in the riding-model approximation with isotropic
displacement parameters (set at 1.2–1.5 times of the Ueq of the
parent atom). The absolute structure was determined on the basis of 1949
Friedel pairs.
Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).
N-{4-[4-(4-Fluorophenyl)-1-methyl-2-[(
R)-methylsulfinyl]-
1
H-imidazol-5-yl]-2-pyridyl}acetamide dihydrate
top
Crystal data top
C18H17FN4O2S·2H2O | F(000) = 856 |
Mr = 408.45 | Dx = 1.393 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71069 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 1669 reflections |
a = 5.8178 (2) Å | θ = 2.9–23.5° |
b = 14.3233 (5) Å | µ = 0.21 mm−1 |
c = 23.3694 (9) Å | T = 193 K |
V = 1947.37 (12) Å3 | Needle, colourless |
Z = 4 | 0.50 × 0.10 × 0.10 mm |
Data collection top
Bruker SMART APEXII diffractometer | 2634 reflections with I > 2σ(I) |
Radiation source: sealed Tube | Rint = 0.089 |
Graphite monochromator | θmax = 27.9°, θmin = 1.7° |
CCD scan | h = −7→7 |
10703 measured reflections | k = −18→15 |
4628 independent reflections | l = −24→30 |
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)] = 0.046 | H-atom parameters constrained |
wR(F2) = 0.099 | w = 1/[σ2(Fo2) + (0.0293P)2] where P = (Fo2 + 2Fc2)/3 |
S = 0.84 | (Δ/σ)max = 0.001 |
4628 reflections | Δρmax = 0.27 e Å−3 |
256 parameters | Δρmin = −0.30 e Å−3 |
0 restraints | Absolute structure: Flack (1983), 1949 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.08 (11) |
Crystal data top
C18H17FN4O2S·2H2O | V = 1947.37 (12) Å3 |
Mr = 408.45 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 5.8178 (2) Å | µ = 0.21 mm−1 |
b = 14.3233 (5) Å | T = 193 K |
c = 23.3694 (9) Å | 0.50 × 0.10 × 0.10 mm |
Data collection top
Bruker SMART APEXII diffractometer | 2634 reflections with I > 2σ(I) |
10703 measured reflections | Rint = 0.089 |
4628 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.046 | H-atom parameters constrained |
wR(F2) = 0.099 | Δρmax = 0.27 e Å−3 |
S = 0.84 | Δρmin = −0.30 e Å−3 |
4628 reflections | Absolute structure: Flack (1983), 1949 Friedel pairs |
256 parameters | Absolute structure parameter: −0.08 (11) |
0 restraints | |
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 | Uiso*/Ueq | |
C1 | −0.0028 (5) | 0.38294 (18) | 0.67677 (10) | 0.0247 (6) | |
N2 | 0.0086 (5) | 0.38684 (16) | 0.73573 (9) | 0.0301 (6) | |
C3 | 0.1670 (5) | 0.44957 (18) | 0.74681 (10) | 0.0299 (7) | |
N4 | 0.2625 (4) | 0.48701 (15) | 0.69850 (7) | 0.0276 (5) | |
C5 | 0.1496 (5) | 0.44518 (18) | 0.65318 (10) | 0.0244 (6) | |
C6 | −0.1622 (5) | 0.31718 (18) | 0.64897 (11) | 0.0265 (7) | |
C7 | −0.1212 (6) | 0.2827 (2) | 0.59361 (11) | 0.0334 (7) | |
H7 | 0.0139 | 0.3008 | 0.5736 | 0.040* | |
C8 | −0.2761 (6) | 0.2227 (2) | 0.56802 (13) | 0.0406 (8) | |
H8 | −0.2504 | 0.2003 | 0.5303 | 0.049* | |
C9 | −0.4667 (6) | 0.1961 (2) | 0.59797 (14) | 0.0428 (9) | |
C10 | −0.5117 (6) | 0.2250 (2) | 0.65250 (13) | 0.0391 (8) | |
H10 | −0.6438 | 0.2036 | 0.6725 | 0.047* | |
C11 | −0.3591 (5) | 0.2864 (2) | 0.67776 (12) | 0.0326 (7) | |
H11 | −0.3885 | 0.3082 | 0.7154 | 0.039* | |
F13 | −0.6195 (4) | 0.13680 (13) | 0.57211 (9) | 0.0687 (6) | |
S14 | 0.25518 (17) | 0.48524 (5) | 0.81652 (3) | 0.0404 (2) | |
O15 | 0.3625 (4) | 0.40219 (16) | 0.84497 (7) | 0.0490 (6) | |
C16 | −0.0249 (7) | 0.4982 (3) | 0.84489 (11) | 0.0636 (12) | |
H16C | −0.0151 | 0.5104 | 0.8861 | 0.095* | |
H16B | −0.1127 | 0.4408 | 0.8383 | 0.095* | |
H16A | −0.1020 | 0.5506 | 0.8260 | 0.095* | |
C17 | 0.4374 (6) | 0.5604 (2) | 0.69480 (12) | 0.0439 (9) | |
H17A | 0.4180 | 0.6041 | 0.7267 | 0.066* | |
H17B | 0.4205 | 0.5940 | 0.6585 | 0.066* | |
H17C | 0.5906 | 0.5321 | 0.6967 | 0.066* | |
C18 | 0.2057 (5) | 0.47072 (17) | 0.59317 (9) | 0.0244 (6) | |
C19 | 0.4114 (5) | 0.44302 (19) | 0.56902 (11) | 0.0285 (7) | |
H19 | 0.5209 | 0.4092 | 0.5909 | 0.034* | |
C20 | 0.4555 (6) | 0.4653 (2) | 0.51252 (11) | 0.0331 (7) | |
H20 | 0.5962 | 0.4448 | 0.4961 | 0.040* | |
N21 | 0.3106 (4) | 0.51404 (17) | 0.47977 (8) | 0.0294 (6) | |
C22 | 0.1152 (5) | 0.54307 (19) | 0.50371 (11) | 0.0262 (7) | |
C23 | 0.0530 (5) | 0.52212 (19) | 0.56027 (10) | 0.0264 (6) | |
H23 | −0.0896 | 0.5426 | 0.5756 | 0.032* | |
N24 | −0.0213 (4) | 0.59582 (16) | 0.46634 (9) | 0.0314 (6) | |
H24 | 0.0221 | 0.5970 | 0.4291 | 0.047* | |
C25 | −0.1937 (6) | 0.65639 (19) | 0.47982 (12) | 0.0327 (7) | |
O26 | −0.2713 (4) | 0.66543 (13) | 0.52821 (8) | 0.0405 (5) | |
C27 | −0.2867 (7) | 0.7123 (2) | 0.43046 (12) | 0.0530 (10) | |
H27A | −0.2501 | 0.7784 | 0.4361 | 0.080* | |
H27C | −0.4538 | 0.7044 | 0.4284 | 0.080* | |
H27B | −0.2166 | 0.6904 | 0.3948 | 0.080* | |
O1L | 0.2647 (6) | 0.21319 (16) | 0.85452 (9) | 0.0726 (8) | |
H1L | 0.2717 | 0.2057 | 0.8945 | 0.109* | |
H2L | 0.2448 | 0.2723 | 0.8557 | 0.109* | |
O2L | 0.0400 (5) | 0.16661 (18) | 0.75536 (11) | 0.0795 (9) | |
H3L | 0.1051 | 0.1806 | 0.7863 | 0.119* | |
H4L | −0.0357 | 0.2127 | 0.7435 | 0.119* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0296 (16) | 0.0238 (15) | 0.0207 (13) | 0.0027 (13) | −0.0021 (14) | 0.0000 (11) |
N2 | 0.0400 (16) | 0.0291 (14) | 0.0211 (11) | −0.0024 (12) | −0.0021 (12) | 0.0038 (10) |
C3 | 0.0408 (19) | 0.0302 (15) | 0.0186 (13) | −0.0020 (14) | −0.0058 (14) | 0.0009 (11) |
N4 | 0.0324 (13) | 0.0299 (12) | 0.0206 (10) | −0.0038 (13) | −0.0037 (12) | 0.0004 (9) |
C5 | 0.0266 (17) | 0.0261 (14) | 0.0206 (13) | 0.0042 (13) | −0.0028 (13) | 0.0002 (11) |
C6 | 0.0312 (19) | 0.0238 (14) | 0.0245 (13) | 0.0029 (13) | −0.0061 (14) | 0.0038 (11) |
C7 | 0.0332 (18) | 0.0328 (17) | 0.0341 (16) | 0.0031 (16) | −0.0017 (15) | −0.0034 (13) |
C8 | 0.044 (2) | 0.0349 (17) | 0.0434 (16) | 0.0021 (19) | −0.0093 (19) | −0.0141 (14) |
C9 | 0.036 (2) | 0.0325 (19) | 0.060 (2) | −0.0051 (17) | −0.0175 (19) | −0.0050 (16) |
C10 | 0.0320 (19) | 0.0342 (18) | 0.0512 (19) | −0.0045 (16) | −0.0054 (17) | 0.0131 (15) |
C11 | 0.0333 (18) | 0.0325 (17) | 0.0318 (15) | 0.0013 (15) | −0.0020 (15) | 0.0071 (13) |
F13 | 0.0562 (14) | 0.0548 (13) | 0.0950 (15) | −0.0195 (12) | −0.0165 (14) | −0.0227 (12) |
S14 | 0.0586 (5) | 0.0411 (4) | 0.0215 (3) | −0.0017 (5) | −0.0099 (4) | −0.0032 (3) |
O15 | 0.0636 (17) | 0.0592 (15) | 0.0243 (10) | 0.0236 (14) | −0.0124 (11) | −0.0030 (10) |
C16 | 0.072 (3) | 0.091 (3) | 0.0272 (15) | 0.030 (3) | −0.0050 (18) | −0.0117 (18) |
C17 | 0.048 (2) | 0.046 (2) | 0.0385 (17) | −0.0163 (17) | −0.0022 (17) | 0.0006 (14) |
C18 | 0.0316 (18) | 0.0237 (14) | 0.0180 (12) | −0.0032 (14) | −0.0011 (12) | −0.0002 (10) |
C19 | 0.0288 (17) | 0.0322 (17) | 0.0243 (14) | 0.0034 (14) | −0.0031 (14) | 0.0050 (12) |
C20 | 0.0310 (18) | 0.040 (2) | 0.0288 (15) | 0.0034 (15) | 0.0038 (14) | 0.0011 (13) |
N21 | 0.0311 (15) | 0.0318 (13) | 0.0254 (11) | 0.0066 (12) | 0.0012 (11) | 0.0013 (10) |
C22 | 0.0313 (18) | 0.0258 (16) | 0.0214 (13) | −0.0029 (14) | −0.0005 (13) | −0.0007 (11) |
C23 | 0.0289 (17) | 0.0288 (16) | 0.0214 (13) | 0.0013 (14) | 0.0018 (12) | −0.0020 (12) |
N24 | 0.0385 (16) | 0.0373 (15) | 0.0185 (11) | 0.0101 (14) | 0.0004 (12) | 0.0032 (10) |
C25 | 0.037 (2) | 0.0295 (16) | 0.0318 (15) | 0.0049 (15) | −0.0035 (15) | −0.0010 (12) |
O26 | 0.0463 (14) | 0.0462 (12) | 0.0289 (10) | 0.0108 (13) | 0.0015 (12) | −0.0037 (9) |
C27 | 0.065 (3) | 0.052 (2) | 0.0415 (17) | 0.026 (2) | −0.006 (2) | 0.0082 (15) |
O1L | 0.105 (2) | 0.0615 (16) | 0.0516 (13) | 0.0245 (19) | 0.0045 (17) | −0.0070 (12) |
O2L | 0.086 (2) | 0.0676 (18) | 0.0850 (18) | −0.0002 (17) | −0.0200 (19) | 0.0271 (15) |
Geometric parameters (Å, º) top
C1—C5 | 1.373 (4) | C17—H17A | 0.9800 |
C1—N2 | 1.380 (3) | C17—H17B | 0.9800 |
C1—C6 | 1.473 (4) | C17—H17C | 0.9800 |
N2—C3 | 1.313 (4) | C18—C19 | 1.381 (4) |
C3—N4 | 1.368 (3) | C18—C23 | 1.386 (4) |
C3—S14 | 1.783 (3) | C19—C20 | 1.382 (3) |
N4—C5 | 1.383 (3) | C19—H19 | 0.9500 |
N4—C17 | 1.465 (4) | C20—N21 | 1.336 (3) |
C5—C18 | 1.485 (3) | C20—H20 | 0.9500 |
C6—C11 | 1.400 (4) | N21—C22 | 1.333 (3) |
C6—C7 | 1.405 (4) | C22—N24 | 1.402 (3) |
C7—C8 | 1.382 (4) | C22—C23 | 1.403 (3) |
C7—H7 | 0.9500 | C23—H23 | 0.9500 |
C8—C9 | 1.365 (5) | N24—C25 | 1.363 (4) |
C8—H8 | 0.9500 | N24—H24 | 0.9072 |
C9—C10 | 1.365 (4) | C25—O26 | 1.224 (3) |
C9—F13 | 1.370 (4) | C25—C27 | 1.505 (4) |
C10—C11 | 1.382 (4) | C27—H27A | 0.9800 |
C10—H10 | 0.9500 | C27—H27C | 0.9800 |
C11—H11 | 0.9500 | C27—H27B | 0.9800 |
S14—O15 | 1.499 (2) | O1L—H1L | 0.9410 |
S14—C16 | 1.769 (4) | O1L—H2L | 0.8545 |
C16—H16C | 0.9800 | O2L—H3L | 0.8400 |
C16—H16B | 0.9800 | O2L—H4L | 0.8400 |
C16—H16A | 0.9800 | | |
| | | |
C5—C1—N2 | 110.1 (2) | H16C—C16—H16A | 109.5 |
C5—C1—C6 | 130.1 (2) | H16B—C16—H16A | 109.5 |
N2—C1—C6 | 119.8 (2) | N4—C17—H17A | 109.5 |
C3—N2—C1 | 105.0 (2) | N4—C17—H17B | 109.5 |
N2—C3—N4 | 113.0 (2) | H17A—C17—H17B | 109.5 |
N2—C3—S14 | 125.3 (2) | N4—C17—H17C | 109.5 |
N4—C3—S14 | 121.7 (2) | H17A—C17—H17C | 109.5 |
C3—N4—C5 | 105.6 (2) | H17B—C17—H17C | 109.5 |
C3—N4—C17 | 127.7 (2) | C19—C18—C23 | 118.7 (2) |
C5—N4—C17 | 126.5 (2) | C19—C18—C5 | 120.3 (2) |
C1—C5—N4 | 106.3 (2) | C23—C18—C5 | 120.9 (2) |
C1—C5—C18 | 132.9 (2) | C18—C19—C20 | 119.0 (3) |
N4—C5—C18 | 120.8 (2) | C18—C19—H19 | 120.5 |
C11—C6—C7 | 118.1 (3) | C20—C19—H19 | 120.5 |
C11—C6—C1 | 120.3 (2) | N21—C20—C19 | 123.4 (3) |
C7—C6—C1 | 121.6 (3) | N21—C20—H20 | 118.3 |
C8—C7—C6 | 120.4 (3) | C19—C20—H20 | 118.3 |
C8—C7—H7 | 119.8 | C22—N21—C20 | 117.4 (2) |
C6—C7—H7 | 119.8 | N21—C22—N24 | 112.9 (2) |
C9—C8—C7 | 118.8 (3) | N21—C22—C23 | 123.3 (3) |
C9—C8—H8 | 120.6 | N24—C22—C23 | 123.8 (3) |
C7—C8—H8 | 120.6 | C18—C23—C22 | 118.1 (3) |
C10—C9—C8 | 123.4 (3) | C18—C23—H23 | 121.0 |
C10—C9—F13 | 118.4 (3) | C22—C23—H23 | 121.0 |
C8—C9—F13 | 118.3 (3) | C25—N24—C22 | 128.0 (2) |
C9—C10—C11 | 117.9 (3) | C25—N24—H24 | 114.5 |
C9—C10—H10 | 121.0 | C22—N24—H24 | 116.8 |
C11—C10—H10 | 121.0 | O26—C25—N24 | 123.5 (2) |
C10—C11—C6 | 121.4 (3) | O26—C25—C27 | 121.3 (3) |
C10—C11—H11 | 119.3 | N24—C25—C27 | 115.2 (3) |
C6—C11—H11 | 119.3 | C25—C27—H27A | 109.5 |
O15—S14—C16 | 107.50 (16) | C25—C27—H27C | 109.5 |
O15—S14—C3 | 107.32 (12) | H27A—C27—H27C | 109.5 |
C16—S14—C3 | 96.18 (15) | C25—C27—H27B | 109.5 |
S14—C16—H16C | 109.5 | H27A—C27—H27B | 109.5 |
S14—C16—H16B | 109.5 | H27C—C27—H27B | 109.5 |
H16C—C16—H16B | 109.5 | H1L—O1L—H2L | 94.9 |
S14—C16—H16A | 109.5 | H3L—O2L—H4L | 109.5 |
| | | |
C5—C1—N2—C3 | −0.7 (3) | F13—C9—C10—C11 | −178.6 (3) |
C6—C1—N2—C3 | 178.7 (3) | C9—C10—C11—C6 | −1.1 (4) |
C1—N2—C3—N4 | −0.4 (3) | C7—C6—C11—C10 | −0.9 (4) |
C1—N2—C3—S14 | 179.4 (2) | C1—C6—C11—C10 | 179.8 (3) |
N2—C3—N4—C5 | 1.4 (3) | N2—C3—S14—O15 | 64.5 (3) |
S14—C3—N4—C5 | −178.5 (2) | N4—C3—S14—O15 | −115.7 (2) |
N2—C3—N4—C17 | 177.9 (3) | N2—C3—S14—C16 | −46.0 (3) |
S14—C3—N4—C17 | −2.0 (4) | N4—C3—S14—C16 | 133.8 (3) |
N2—C1—C5—N4 | 1.5 (3) | C1—C5—C18—C19 | −107.8 (4) |
C6—C1—C5—N4 | −177.8 (3) | N4—C5—C18—C19 | 71.7 (3) |
N2—C1—C5—C18 | −178.9 (3) | C1—C5—C18—C23 | 71.8 (4) |
C6—C1—C5—C18 | 1.8 (5) | N4—C5—C18—C23 | −108.7 (3) |
C3—N4—C5—C1 | −1.7 (3) | C23—C18—C19—C20 | −1.7 (4) |
C17—N4—C5—C1 | −178.2 (3) | C5—C18—C19—C20 | 177.9 (3) |
C3—N4—C5—C18 | 178.7 (2) | C18—C19—C20—N21 | 1.2 (4) |
C17—N4—C5—C18 | 2.1 (4) | C19—C20—N21—C22 | 0.8 (4) |
C5—C1—C6—C11 | −155.5 (3) | C20—N21—C22—N24 | 178.2 (2) |
N2—C1—C6—C11 | 25.2 (4) | C20—N21—C22—C23 | −2.3 (4) |
C5—C1—C6—C7 | 25.2 (5) | C19—C18—C23—C22 | 0.3 (4) |
N2—C1—C6—C7 | −154.0 (3) | C5—C18—C23—C22 | −179.3 (2) |
C11—C6—C7—C8 | 2.1 (4) | N21—C22—C23—C18 | 1.8 (4) |
C1—C6—C7—C8 | −178.6 (3) | N24—C22—C23—C18 | −178.8 (3) |
C6—C7—C8—C9 | −1.3 (4) | N21—C22—N24—C25 | −160.2 (3) |
C7—C8—C9—C10 | −0.8 (5) | C23—C22—N24—C25 | 20.3 (4) |
C7—C8—C9—F13 | 179.8 (3) | C22—N24—C25—O26 | −8.5 (5) |
C8—C9—C10—C11 | 2.0 (5) | C22—N24—C25—C27 | 172.0 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N24—H24···O15i | 0.91 | 2.08 | 2.983 (3) | 177 |
O1L—H2L···O15 | 0.85 | 2.00 | 2.775 (3) | 151 |
O1L—H1L···O26ii | 0.94 | 1.90 | 2.825 (3) | 169 |
O2L—H3L···O1L | 0.84 | 1.90 | 2.743 (4) | 177 |
O2L—H4L···N2 | 0.84 | 2.51 | 3.193 (3) | 138 |
Symmetry codes: (i) −x+1/2, −y+1, z−1/2; (ii) −x, y−1/2, −z+3/2. |
Experimental details
Crystal data |
Chemical formula | C18H17FN4O2S·2H2O |
Mr | 408.45 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 193 |
a, b, c (Å) | 5.8178 (2), 14.3233 (5), 23.3694 (9) |
V (Å3) | 1947.37 (12) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.21 |
Crystal size (mm) | 0.50 × 0.10 × 0.10 |
|
Data collection |
Diffractometer | Bruker SMART APEXII diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 10703, 4628, 2634 |
Rint | 0.089 |
(sin θ/λ)max (Å−1) | 0.658 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.046, 0.099, 0.84 |
No. of reflections | 4628 |
No. of parameters | 256 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.27, −0.30 |
Absolute structure | Flack (1983), 1949 Friedel pairs |
Absolute structure parameter | −0.08 (11) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N24—H24···O15i | 0.91 | 2.08 | 2.983 (3) | 177 |
O1L—H2L···O15 | 0.85 | 2.00 | 2.775 (3) | 151 |
O1L—H1L···O26ii | 0.94 | 1.90 | 2.825 (3) | 169 |
O2L—H3L···O1L | 0.84 | 1.90 | 2.743 (4) | 177 |
O2L—H4L···N2 | 0.84 | 2.51 | 3.193 (3) | 138 |
Symmetry codes: (i) −x+1/2, −y+1, z−1/2; (ii) −x, y−1/2, −z+3/2. |
Many chiral sulfoxides exhibit interesting biological activities and show promise as therapeutic agents (Jia et al., 2004). The title compound, N-(4-(4-(4-fluorophenyl)-1-methyl-2-((R)-methylsulfinyl)-1H-imidazol-5-yl) pyridin-2-yl)acetamide, was prepared in the course of our studies on tri- and tetrasubstituted 2-thioimidazoles as p38 mitogen-activated protein (MAP) kinase inhibitors (Wagner et al., 2003, Laufer, Hauser, Domeyer et al.,2008); Laufer, Hauser & Liedtke, 2008). The oxidation of the sulfide N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylthio)-1H-imidazol-5-yl)pyridin-2- yl)acetamide with sodium periodate as oxidant yields the corresponding sulfoxide N-(4-(4-(4-fluorophenyl)-1-methyl-2-(methylsulfinyl)-1H-imidazol-5-yl) pyridin-2-yl)acetamide. This compound has a centre of asymmetry in the sulfur atom meaning that two sulfoxide enantiomers exist, which can differ in pharmacodynamic and/or pharmacokinetic properties (Lu, 2007). The both enantiomers were separated by enantioselective preparative HPLC. To identify the absolute configurations of the enantiomers according to the Cahn-Ingold-Prelog-nomenclature X-ray analysis was used. In this article we present the X-ray data of the first eluted enantiomer I. The analysis of the crystal structure shows that the N24 amino- group of the acetamide moiety of the one imidazole-molecule interact with another imidazole ring system by the building of one intermolecular hydrogen bond N—H···O to the sulfoxide oxygen-atom O15, whereas the O15···H24 distance is 2.08 Å. Furthermore, the carbonyl-oxygen atom O26 of the acetamide-moiety of a third imidazole molecule is linked over two water molecules to the sulfoxide oxygen-atom O15 and to the nitrogen atom N2 of the imidazole core by the building of intermolecular O1L—H1L···O26 (1.90 Å), O1L—H2L···O15 (2.00 Å) and O2L—H4L···N2 (2.51 Å) hydrogen bonds. The imidazole ring system forms a dihedral angle of 24.9 (1)° to the 4-fluorophenyl ring. The pyridine ring is oriented approximately perpendicular (72.24 (8)°) to the imidazole ring system. According to the Cahn-Ingold-Prelog-nomenclature the first eluted enantiomer I is (R)-configurated.