= 0.74 mm 1 T = 100 K. Data collection. Refinement. R[F 2 >2(F 2 )] = wr(f 2 ) = S = reflections 423 parameters 1 restraint

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1 organic compounds Acta Crystallographica Section E Structure Reports Online ISSN Cyclohexyl-2-(3-furyl)-1Hbenzimidazole-5-carboxylic acid Sergey Dibrov, Sanjay Dutta and Thomas Hermann* University of California, San Diego, 9500 Gilman Drive # 0358, La Jolla, CA , USA Correspondence tch@ucsd.edu Received 16 July 2009; accepted 6 August 2009 Key indicators: single-crystal X-ray study; T = 100 K; mean (C C) = Å; R factor = 0.052; wr factor = 0.143; data-to-parameter ratio = = 0.74 mm 1 T = 100 K Data collection Bruker APEXII CCD area-detector diffractometer Absorption correction: multi-scan (SADABS; Bruker, 2005) T min = 0.710, T max = Refinement R[F 2 >2(F 2 )] = wr(f 2 ) = S = reflections 423 parameters 1 restraint Table 1 Hydrogen-bond geometry (Å, ) mm 7859 measured reflections 4379 independent reflections 4006 reflections with I > 2(I) R int = H atoms treated by a mixture of independent and constrained refinement max = 0.73 e Å 3 min = 0.29 e Å 3 The asymmetric unit of the title compound, C 18 H 18 N 2 O 3, contains two molecules. The fused rings of both molecules are almost planar, with dihedral angles of 3.1 (1) and 2.8 (2) between the fused rings. The furan rings are rotated by (15) and (9) with respect to the planes of the attached bnzimidazole systems. In the crystal, molecules are linked into infinite chains by intermolecular O HN hydrogen bonds. Related literature For general background, see Beaulieu et al. (2004a). For the synthesis, see Beaulieu et al. (2004b). D HA D H HA DA D HA O2 H2N2 i 0.99 (5) 1.66 (5) (3) 173 (4) O4 H4N4 ii 0.75 (5) 1.94 (5) (4) 159 (5) Symmetry codes: (i) x þ 1; y þ 1 2 ; z þ 1; (ii) x; y þ 1 2 ; z. Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); 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. All authors contributed equally to this paper. We thank Bao Ho and Cody Higginson for help with compound synthesis and James Golen for help with the structural solution. This work was supported in part by the National Institutes of Health, grant R01 AI Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: RK2157). Experimental Crystal data C 18 H 18 N 2 O 3 M r = Monoclinic, P2 1 a = (3) Å b = (3) Å c = (5) Å = (2) V = (8) Å 3 Z =4 Cu K radiation References Beaulieu, P. L., Bös, M., Bousquet, Y., Fazal, G., Gauthier, J., Gillard, J., Goulet, S., LaPlante, S., Poupart, M. A., Lefebvre, S., McKercher, G., Pellerin, C., Austel, V. & Kukolj, G. (2004a). Bioorg. Med. Chem. Lett. 14, Beaulieu, P. L., Bousquet, Y., Gauthier, J., Gillard, J., Marquis, M., McKercher, G., Pellerin, C., Valois, S. & Kukolj, G. (2004b). J. Med. Chem. 47, Bruker (2005). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Sheldrick, G. M. (2008). Acta Cryst. A64, o2136 Dibrov et al. doi: /s

2 [doi: /s ] 1-Cyclohexyl-2-(3-furyl)-1H-benzimidazole-5-carboxylic acid Sergey Dibrov, Sanjay Dutta and Thomas Hermann S1. Comment The title compound is an allosteric inhibitor of the RNA dependent RNA polymerase NS5B of hepatitis C virus (HCV) (Beaulieu et al., 2004a). The inhibitor binds with low micromolar affinity (4.3 mm) to the NS5B polymerase and prevents replication of subgenomic HCV replicon in human cells (Beaulieu et al., 2004b). The title compound was synthesized following the route described by Beaulieu et al., (2004b). We report here the single crystal X ray structure. Asymmetric unit of the title compound is composed of molecule 1 and molecule 2 (Fig. 1). They are linked together into infinite non interacting chains by the intermolecular O2 H2 N2 i and O4 H4 N4 ii hydrogen bonds along the b axis (Fig. 2). Symmetry codes: (i) -x + 1, y + 1/2, -z + 1 and (ii) -x, y + 1/2, -z. S2. Experimental 1-Cyclohexyl-2-(furan-3-yl)-1H-benzo[d]imidazole-5-carboxylic acid was prepared according to the literature procedure (Beaulieu et al., 2004b). In a sample vial, 15 mg of compound was taken and dissolved in CH 2 Cl 2 DMSO/ 9:1 mixture. Upon slow evaporation at 273 K within 2 months the crystals are formed as colourless blocks. S3. Refinement Acidic H2 and H4 hydrgen atoms were located in a Fourier difference map and refined freely with distances obtained for O2 H2 = 1.00 (5) and O4 H4 = 0.76 (5). Other H atoms were positioned geometrically and refined using a riding model with C H = Å and with U iso (H) = 1.2 U eq (C). The highest density value is peak with a value of 0.73 e Å -3 at coordinates that is 1.21Å from atom H6 and 1.24Å from atom C Friedel pairs were merged. sup-1

3 Figure 1 The asymmetric units of structure of title compound, with the atom numbering scheme. The displacement ellipsoids are drawn at 50% probability level. H atoms are presented as a small spheres of arbitrary radius. Figure 2 The crystal packing of one of the two molecules, viewed down the a axis, showing the molecules are linked along the b axis. Intermolecular hydrogen bonds are shown as dashed lines. Symmetry codes: (i) -x + 1, y + 1/2, -z + 1 and (ii) -x + 1, y - 1/2, -z + 1. Second molecule behaves similarly. 1-Cyclohexyl-2-(3-furyl)-1H-benzimidazole-5-carboxylic acid Crystal data C 18 H 18 N 2 O 3 M r = Monoclinic, P2 1 Hall symbol: P 2yb a = (3) Å b = (3) Å c = (5) Å β = (2) sup-2

4 V = (8) Å 3 Z = 4 F(000) = 656 D x = Mg m 3 Cu Kα radiation, λ = Å Cell parameters from 5005 reflections Data collection Bruker APEXII CCD area-detector diffractometer Radiation source: fine-focus sealed tube Graphite monochromator φ and ω scans Absorption correction: multi-scan (SADABS; Bruker, 2005) T min = 0.710, T max = Refinement Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = wr(f 2 ) = S = reflections 423 parameters 1 restraint Primary atom site location: structure-invariant direct methods θ = µ = 0.74 mm 1 T = 100 K Block, colourless mm 7859 measured reflections 4379 independent reflections 4006 reflections with I > 2σ(I) R int = θ max = 66.4, θ min = 2.9 h = k = l = Secondary atom site location: difference Fourier map Hydrogen site location: inferred from neighbouring sites H atoms treated by a mixture of independent and constrained refinement w = 1/[σ 2 (F o2 ) + (0.0919P) P] where P = (F o 2 + 2F c2 )/3 (Δ/σ) max = Δρ max = 0.73 e Å 3 Δρ min = 0.29 e Å 3 Special details Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R factor wr and goodness of fit S are based on F 2, conventional R factors R are based on F, with F set to zero for negative F 2. The threshold expression of F 2 > σ(f 2 ) is used only for calculating R factors(gt) etc. and is not relevant to the choice of reflections for refinement. R factors based on F 2 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 (Å 2 ) x y z U iso */U eq O (3) (19) (16) (6) O (3) (2) (14) (5) H (5) (4) (3) (13)* O (3) (2) (17) (7) N (3) (3) (17) (6) N (3) (2) (17) (6) C (3) (3) (2) (7) C (4) (3) (2) (7) C (4) (3) (2) (8) H * sup-3

5 C (4) (3) (2) (8) H4B * C (4) (3) (2) (7) C (5) (4) (2) (9) H * C (4) (4) (2) (9) H7A * H7B * C (6) (6) (3) (15) H8A * H8B * C (6) (8) (3) (2) H9A * H9B * C (4) (3) (2) (7) C (3) (3) (2) (7) C (3) (3) (2) (7) H * C (4) (3) (2) (8) C (5) (3) (3) (9) H * C (5) (4) (3) (10) H * C (4) (3) (2) (9) H * C (5) (5) (3) (12) H17A * H17B * C (5) (6) (3) (17) H18A * H18B * O (4) (2) (16) (7) H (5) (4) (3) (13)* O (3) (2) (15) (6) O (3) (2) (17) (7) N (3) (2) (16) (6) N (3) (2) (17) (6) C (4) (3) (2) (7) C (4) (3) (2) (7) C (4) (3) (2) (8) H * C (4) (3) (2) (8) H * C (4) (3) (2) (7) C (4) (3) (2) (8) H * C (4) (4) (2) (9) H25A * sup-4

6 H25B * C (4) (4) (2) (10) H26A * H26B * C (4) (4) (2) (9) H27A * H27B * C (4) (4) (2) (10) H28A * H28B * C (4) (4) (2) (9) H29A * H29B * C (4) (3) (2) (7) C (4) (3) (2) (7) C (4) (3) (2) (7) H * C (4) (3) (2) (8) C (5) (3) (2) (9) H * C (4) (3) (2) (9) H * C (4) (3) (2) (9) H * Atomic displacement parameters (Å 2 ) U 11 U 22 U 33 U 12 U 13 U 23 O (15) (11) (13) (11) (11) (10) O (14) (11) (12) (10) (10) (10) O (19) (14) (15) (13) (13) (12) N (15) (15) (13) (13) (11) (12) N (14) (13) (14) (11) (11) (11) C (16) (17) (17) (13) (13) (13) C (16) (15) (16) (13) (13) (13) C (19) (16) (17) (15) (14) (15) C (2) (19) (17) (16) (14) (15) C (17) (17) (16) (14) (13) (14) C (2) (2) (18) (2) (16) (18) C (2) (3) (18) (19) (15) (18) C (3) (4) (2) (3) (2) (3) C (3) (7) (2) (4) (2) (3) C (17) (17) (18) (14) (14) (14) C (15) (15) (16) (13) (12) (13) C (17) (15) (15) (13) (13) (13) C (19) (18) (18) (16) (14) (15) C (2) (19) (2) (18) (17) (16) C (2) (2) (2) (19) (18) (18) sup-5

7 C (2) (2) (19) (16) (16) (16) C (2) (3) (2) (2) (19) (2) C (2) (5) (2) (3) (18) (3) O (2) (12) (14) (13) (13) (11) O (15) (12) (13) (11) (10) (10) O (17) (13) (16) (12) (13) (12) N (13) (13) (13) (11) (11) (11) N (15) (13) (14) (11) (11) (11) C (19) (18) (17) (15) (14) (14) C (18) (15) (16) (14) (13) (13) C (2) (17) (18) (14) (15) (14) C (2) (17) (16) (15) (14) (15) C (17) (16) (16) (13) (13) (13) C (19) (18) (16) (16) (14) (15) C (19) (2) (2) (18) (15) (18) C (2) (3) (2) (2) (17) (2) C (2) (2) (18) (19) (16) (18) C (2) (3) (19) (2) (16) (18) C (19) (2) (19) (17) (15) (17) C (16) (16) (16) (13) (13) (13) C (17) (15) (16) (13) (13) (13) C (19) (16) (16) (15) (13) (13) C (17) (17) (18) (14) (14) (15) C (2) (18) (2) (17) (17) (16) C (19) (2) (2) (15) (16) (17) C (2) (2) (19) (16) (15) (17) Geometric parameters (Å, º) O1 C (4) O4 C (4) O2 C (4) O4 H (5) O2 H (5) O5 C (4) O3 C (5) O6 C (4) O3 C (5) O6 C (5) N1 C (4) N3 C (4) N1 C (4) N3 C (4) N1 C (4) N3 C (4) N2 C (4) N4 C (4) N2 C (4) N4 C (4) C1 C (5) C19 C (5) C2 C (4) C20 C (5) C2 C (4) C20 C (5) C3 C (5) C21 C (5) C3 H C21 H C4 C (5) C22 C (5) C4 H4B C22 H C5 C (4) C23 C (4) C6 C (6) C24 C (5) sup-6

8 C6 C (6) C24 C (5) C6 H C24 H C7 C (5) C25 C (5) C7 H7A C25 H25A C7 H7B C25 H25B C8 C (7) C26 C (5) C8 H8A C26 H26A C8 H8B C26 H26B C9 C (8) C27 C (6) C9 H9A C27 H27A C9 H9B C27 H27B C10 C (5) C28 C (5) C11 C (4) C28 H28A C12 H C28 H28B C13 C (5) C29 H29A C13 C (5) C29 H29B C14 H C30 C (5) C15 C (6) C31 C (5) C15 H C32 H C16 H C33 C (5) C17 C (6) C33 C (4) C17 H17A C34 H C17 H17B C35 C (5) C18 H18A C35 H C18 H18B C36 H C1 O2 H2 114 (3) C19 O4 H4 114 (3) C14 O3 C (3) C34 O6 C (3) C10 N1 C (3) C23 N3 C (2) C10 N1 C (3) C23 N3 C (3) C5 N1 C (3) C30 N3 C (3) C10 N2 C (3) C30 N4 C (3) O1 C1 O (3) O5 C19 O (3) O1 C1 C (3) O5 C19 C (3) O2 C1 C (3) O4 C19 C (3) C12 C2 C (3) C32 C20 C (3) C12 C2 C (3) C32 C20 C (3) C3 C2 C (3) C21 C20 C (3) C4 C3 C (3) C22 C21 C (3) C4 C3 H C22 C21 H C2 C3 H C20 C21 H C3 C4 C (3) C21 C22 C (3) C3 C4 H4B C21 C22 H C5 C4 H4B C23 C22 H N1 C5 C (3) N3 C23 C (3) N1 C5 C (3) N3 C23 C (3) C11 C5 C (3) C22 C23 C (3) C17 C6 N (3) N3 C24 C (3) sup-7

9 C17 C6 C (4) N3 C24 C (3) N1 C6 C (3) C29 C24 C (3) C17 C6 H N3 C24 H N1 C6 H C29 C24 H C7 C6 H C25 C24 H C6 C7 C (3) C26 C25 C (3) C6 C7 H7A C26 C25 H25A C8 C7 H7A C24 C25 H25A C6 C7 H7B C26 C25 H25B C8 C7 H7B C24 C25 H25B H7A C7 H7B H25A C25 H25B C9 C8 C (4) C27 C26 C (3) C9 C8 H8A C27 C26 H26A C7 C8 H8A C25 C26 H26A C9 C8 H8B C27 C26 H26B C7 C8 H8B C25 C26 H26B H8A C8 H8B H26A C26 H26B C8 C9 C (5) C26 C27 C (3) C8 C9 H9A C26 C27 H27A C18 C9 H9A C28 C27 H27A C8 C9 H9B C26 C27 H27B C18 C9 H9B C28 C27 H27B H9A C9 H9B H27A C27 H27B N2 C10 N (3) C29 C28 C (3) N2 C10 C (3) C29 C28 H28A N1 C10 C (3) C27 C28 H28A N2 C11 C (3) C29 C28 H28B N2 C11 C (3) C27 C28 H28B C5 C11 C (3) H28A C28 H28B C2 C12 C (3) C24 C29 C (3) C2 C12 H C24 C29 H29A C11 C12 H C28 C29 H29A C14 C13 C (3) C24 C29 H29B C14 C13 C (3) C28 C29 H29B C16 C13 C (3) H29A C29 H29B C13 C14 O (3) N4 C30 N (3) C13 C14 H N4 C30 C (3) O3 C14 H N3 C30 C (3) C16 C15 O (4) N4 C31 C (3) C16 C15 H N4 C31 C (3) O3 C15 H C32 C31 C (3) C15 C16 C (4) C20 C32 C (3) C15 C16 H C20 C32 H C13 C16 H C31 C32 H C6 C17 C (4) C34 C33 C (3) C6 C17 H17A C34 C33 C (3) C18 C17 H17A C36 C33 C (3) C6 C17 H17B O6 C34 C (3) sup-8

10 C18 C17 H17B O6 C34 H H17A C17 H17B C33 C34 H C17 C18 C (4) C36 C35 O (3) C17 C18 H18A C36 C35 H C9 C18 H18A O6 C35 H C17 C18 H18B C35 C36 C (3) C9 C18 H18B C35 C36 H H18A C18 H18B C33 C36 H Hydrogen-bond geometry (Å, º) D H A D H H A D A D H A O2 H2 N2 i 0.99 (5) 1.66 (5) (3) 173 (4) O4 H4 N4 ii 0.75 (5) 1.94 (5) (4) 159 (5) Symmetry codes: (i) x+1, y+1/2, z+1; (ii) x, y+1/2, z. sup-9