organic compounds
1-[(1-Methyl-1H-imidazol-5-yl)methyl]-1H-indole-5-carbonitrile
aDepartment of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa
*Correspondence e-mail: jjdj@sun.ac.za
In the title compound, C14H12N4, the dihedral angle between the indole ring system (r.m.s. deviation = 0.010 Å) and the imidazole ring is 77.70 (6)°. In the crystal, molecules are linked by C—H⋯N hydrogen bonds. One set of hydrogen bonds forms an undulating chain running parallel to the b-axis direction, while the other undulating chain is parallel to the c-axis direction. In combination, (100) sheets result.
Related literature
For background to farnesyl transferase, see: Chakrabarti et al. (2002). For the properties of related compounds, see: Bulbule et al. (2008), van Voorhis et al. (2007); de Ruyck & Wouters (2008).
Experimental
Crystal data
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Refinement
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Data collection: APEX2 (Bruker, 2009); cell SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001; Atwood et al., 2003); software used to prepare material for publication: SHELXL97.
Supporting information
10.1107/S1600536812048404/hb7000sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536812048404/hb7000Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536812048404/hb7000Isup3.cml
The structure of the title compound was synthesized by the nucleophillic addition of 1H-indole-5-carbonitrile (195 mg, 1.37 mmol), through the use of NaH (78.6 mg, 3.28 mmol), to the hydrochloric acid salt of 5-(chloromethyl)-1-methyl-1H-imidazole (179 mg, 1.37 mmol) in anhydrous dimethyl formamide (5 ml). The reaction was left to proceeded for 18 h at 0 °C. The solvent was then removed in vacuo, after which the crude material was partitioned between water and ethyl acetate. Purification by
(1% methanol, 1% Et3N, 98% dichloromethane) afforded the product. Recrystallization from 90% dichloromethane, 5% n-hexane and 5% toluene produced pale yellow, block crystals.1H NMR (300 MHz, CDCl3) δ 7.98 - 7.97 (m, 1H, ArH), 7.48 - 7.43 (m, 3H, ArH), 7.17 (s, 1H, ArH), 7.10 (d, J = 3.3 Hz, 1H, ArH), 5.30 (s, 2H), 3.34 (s, 3H, CH3).
H atoms were placed geometrically [C—H = 0.95 - 0.98 Å; with Uiso(H) = 1.2 - 1.5 Ueq(C)] and constrained to ride on their parent atoms.
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001; Atwood et al., 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).Fig. 1. The molecular structure of the title compound with displacement ellipsoids shown at the 50% probability level. | |
Fig. 2. Packing diagram showing the intermolecular C—H···N hydrogen bonds. |
C14H12N4 | F(000) = 496 |
Mr = 236.28 | Dx = 1.329 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 7965 reflections |
a = 10.9624 (16) Å | θ = 3.0–28.6° |
b = 7.8687 (12) Å | µ = 0.08 mm−1 |
c = 14.292 (2) Å | T = 100 K |
β = 106.727 (2)° | Plate, colourless |
V = 1180.6 (3) Å3 | 0.10 × 0.10 × 0.02 mm |
Z = 4 |
Bruker APEXII CCD diffractometer | 3286 independent reflections |
Radiation source: fine-focus sealed tube, Bruker Apex2 | 2643 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.042 |
ϕ and ω scans | θmax = 29.8°, θmin = 2.1° |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | h = −15→15 |
Tmin = 0.992, Tmax = 0.998 | k = −10→10 |
36857 measured reflections | l = −19→19 |
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)] = 0.042 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.06 | w = 1/[σ2(Fo2) + (0.0451P)2 + 0.613P] where P = (Fo2 + 2Fc2)/3 |
3286 reflections | (Δ/σ)max < 0.001 |
164 parameters | Δρmax = 0.32 e Å−3 |
0 restraints | Δρmin = −0.21 e Å−3 |
C14H12N4 | V = 1180.6 (3) Å3 |
Mr = 236.28 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 10.9624 (16) Å | µ = 0.08 mm−1 |
b = 7.8687 (12) Å | T = 100 K |
c = 14.292 (2) Å | 0.10 × 0.10 × 0.02 mm |
β = 106.727 (2)° |
Bruker APEXII CCD diffractometer | 3286 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | 2643 reflections with I > 2σ(I) |
Tmin = 0.992, Tmax = 0.998 | Rint = 0.042 |
36857 measured reflections |
R[F2 > 2σ(F2)] = 0.042 | 0 restraints |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.06 | Δρmax = 0.32 e Å−3 |
3286 reflections | Δρmin = −0.21 e Å−3 |
164 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.74899 (9) | 0.05550 (13) | 0.10401 (7) | 0.0182 (2) | |
C8 | 0.63632 (11) | 0.14156 (15) | 0.06741 (8) | 0.0172 (2) | |
C3 | 0.57779 (11) | 0.15677 (15) | 0.14387 (8) | 0.0182 (2) | |
N3 | 1.05057 (10) | 0.09402 (14) | 0.16447 (8) | 0.0204 (2) | |
N4 | 1.15865 (10) | −0.14899 (14) | 0.18381 (8) | 0.0218 (2) | |
C6 | 0.46523 (12) | 0.28892 (17) | −0.04359 (9) | 0.0222 (3) | |
H6 | 0.4248 | 0.3338 | −0.1066 | 0.027* | |
C9 | 0.28834 (12) | 0.40021 (18) | 0.01344 (10) | 0.0253 (3) | |
C13 | 1.16216 (12) | 0.01364 (17) | 0.20734 (9) | 0.0213 (3) | |
H13 | 1.2346 | 0.0681 | 0.2495 | 0.026* | |
C2 | 0.66051 (12) | 0.07444 (16) | 0.22788 (9) | 0.0202 (2) | |
H2 | 0.6472 | 0.0638 | 0.2904 | 0.024* | |
N2 | 0.19352 (11) | 0.47248 (17) | −0.00085 (10) | 0.0327 (3) | |
C4 | 0.46133 (12) | 0.24195 (16) | 0.12543 (9) | 0.0206 (3) | |
H4 | 0.4203 | 0.2545 | 0.1752 | 0.025* | |
C1 | 0.76221 (12) | 0.01428 (16) | 0.20058 (9) | 0.0201 (2) | |
H1 | 0.8318 | −0.0469 | 0.2419 | 0.024* | |
C12 | 1.03687 (12) | −0.17490 (17) | 0.12259 (9) | 0.0209 (3) | |
H12 | 1.0050 | −0.2807 | 0.0937 | 0.025* | |
C7 | 0.58051 (11) | 0.20564 (16) | −0.02668 (9) | 0.0201 (2) | |
H7 | 0.6205 | 0.1923 | −0.0770 | 0.024* | |
C5 | 0.40688 (11) | 0.30803 (16) | 0.03208 (9) | 0.0213 (3) | |
C10 | 0.83783 (11) | 0.01570 (18) | 0.04742 (9) | 0.0214 (3) | |
H10A | 0.8426 | 0.1144 | 0.0056 | 0.026* | |
H10B | 0.8041 | −0.0819 | 0.0039 | 0.026* | |
C11 | 0.96882 (11) | −0.02628 (16) | 0.10955 (9) | 0.0195 (2) | |
C14 | 1.02309 (13) | 0.27356 (18) | 0.17436 (11) | 0.0296 (3) | |
H14A | 1.0997 | 0.3305 | 0.2147 | 0.044* | |
H14C | 0.9546 | 0.2842 | 0.2054 | 0.044* | |
H14B | 0.9965 | 0.3265 | 0.1096 | 0.044* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0142 (5) | 0.0216 (5) | 0.0177 (5) | 0.0003 (4) | 0.0028 (4) | 0.0016 (4) |
C8 | 0.0135 (5) | 0.0176 (5) | 0.0192 (5) | −0.0028 (4) | 0.0028 (4) | −0.0013 (4) |
C3 | 0.0169 (5) | 0.0178 (5) | 0.0189 (5) | −0.0030 (4) | 0.0035 (4) | −0.0017 (4) |
N3 | 0.0158 (5) | 0.0211 (5) | 0.0230 (5) | 0.0004 (4) | 0.0033 (4) | 0.0003 (4) |
N4 | 0.0183 (5) | 0.0244 (5) | 0.0221 (5) | 0.0015 (4) | 0.0048 (4) | 0.0025 (4) |
C6 | 0.0197 (6) | 0.0224 (6) | 0.0199 (6) | −0.0009 (5) | −0.0014 (4) | 0.0008 (5) |
C9 | 0.0199 (6) | 0.0251 (6) | 0.0276 (6) | −0.0005 (5) | 0.0013 (5) | −0.0026 (5) |
C13 | 0.0152 (5) | 0.0254 (6) | 0.0222 (6) | 0.0007 (5) | 0.0037 (4) | 0.0019 (5) |
C2 | 0.0197 (6) | 0.0218 (6) | 0.0182 (5) | −0.0017 (5) | 0.0042 (4) | 0.0006 (4) |
N2 | 0.0222 (6) | 0.0324 (7) | 0.0392 (7) | 0.0041 (5) | 0.0019 (5) | −0.0023 (5) |
C4 | 0.0171 (5) | 0.0215 (6) | 0.0222 (6) | −0.0026 (5) | 0.0043 (4) | −0.0040 (5) |
C1 | 0.0188 (6) | 0.0215 (6) | 0.0183 (5) | −0.0001 (5) | 0.0026 (4) | 0.0024 (4) |
C12 | 0.0188 (6) | 0.0235 (6) | 0.0207 (6) | −0.0010 (5) | 0.0063 (4) | −0.0009 (5) |
C7 | 0.0181 (6) | 0.0224 (6) | 0.0187 (5) | −0.0018 (5) | 0.0033 (4) | −0.0001 (5) |
C5 | 0.0150 (5) | 0.0202 (6) | 0.0256 (6) | −0.0004 (5) | 0.0008 (4) | −0.0025 (5) |
C10 | 0.0148 (5) | 0.0305 (7) | 0.0184 (5) | 0.0006 (5) | 0.0041 (4) | 0.0000 (5) |
C11 | 0.0152 (5) | 0.0244 (6) | 0.0185 (5) | −0.0015 (5) | 0.0043 (4) | −0.0003 (4) |
C14 | 0.0233 (6) | 0.0215 (6) | 0.0402 (8) | 0.0016 (5) | 0.0031 (6) | −0.0026 (6) |
N1—C8 | 1.3733 (15) | C9—C5 | 1.4445 (18) |
N1—C1 | 1.3842 (15) | C13—H13 | 0.9500 |
N1—C10 | 1.4676 (15) | C2—C1 | 1.3673 (17) |
C8—C7 | 1.4011 (16) | C2—H2 | 0.9500 |
C8—C3 | 1.4226 (16) | C4—C5 | 1.3958 (18) |
C3—C4 | 1.3982 (17) | C4—H4 | 0.9500 |
C3—C2 | 1.4341 (17) | C1—H1 | 0.9500 |
N3—C13 | 1.3567 (16) | C12—C11 | 1.3707 (18) |
N3—C11 | 1.3822 (16) | C12—H12 | 0.9500 |
N3—C14 | 1.4598 (17) | C7—H7 | 0.9500 |
N4—C13 | 1.3209 (17) | C10—C11 | 1.4918 (17) |
N4—C12 | 1.3845 (16) | C10—H10A | 0.9900 |
C6—C7 | 1.3817 (17) | C10—H10B | 0.9900 |
C6—C5 | 1.4140 (18) | C14—H14A | 0.9800 |
C6—H6 | 0.9500 | C14—H14C | 0.9800 |
C9—N2 | 1.1504 (18) | C14—H14B | 0.9800 |
C8—N1—C1 | 108.65 (10) | C2—C1—H1 | 125.0 |
C8—N1—C10 | 124.20 (10) | N1—C1—H1 | 125.0 |
C1—N1—C10 | 127.14 (10) | C11—C12—N4 | 110.39 (11) |
N1—C8—C7 | 129.75 (11) | C11—C12—H12 | 124.8 |
N1—C8—C3 | 107.70 (10) | N4—C12—H12 | 124.8 |
C7—C8—C3 | 122.55 (11) | C6—C7—C8 | 117.60 (11) |
C4—C3—C8 | 119.00 (11) | C6—C7—H7 | 121.2 |
C4—C3—C2 | 134.22 (11) | C8—C7—H7 | 121.2 |
C8—C3—C2 | 106.78 (10) | C4—C5—C6 | 121.89 (11) |
C13—N3—C11 | 106.87 (11) | C4—C5—C9 | 118.55 (12) |
C13—N3—C14 | 126.29 (11) | C6—C5—C9 | 119.56 (12) |
C11—N3—C14 | 126.84 (11) | N1—C10—C11 | 113.39 (10) |
C13—N4—C12 | 104.82 (11) | N1—C10—H10A | 108.9 |
C7—C6—C5 | 120.60 (11) | C11—C10—H10A | 108.9 |
C7—C6—H6 | 119.7 | N1—C10—H10B | 108.9 |
C5—C6—H6 | 119.7 | C11—C10—H10B | 108.9 |
N2—C9—C5 | 179.32 (16) | H10A—C10—H10B | 107.7 |
N4—C13—N3 | 112.35 (11) | C12—C11—N3 | 105.58 (11) |
N4—C13—H13 | 123.8 | C12—C11—C10 | 131.51 (12) |
N3—C13—H13 | 123.8 | N3—C11—C10 | 122.82 (11) |
C1—C2—C3 | 106.77 (11) | N3—C14—H14A | 109.5 |
C1—C2—H2 | 126.6 | N3—C14—H14C | 109.5 |
C3—C2—H2 | 126.6 | H14A—C14—H14C | 109.5 |
C5—C4—C3 | 118.35 (11) | N3—C14—H14B | 109.5 |
C5—C4—H4 | 120.8 | H14A—C14—H14B | 109.5 |
C3—C4—H4 | 120.8 | H14C—C14—H14B | 109.5 |
C2—C1—N1 | 110.09 (11) | ||
C1—N1—C8—C7 | −178.49 (12) | C13—N4—C12—C11 | 0.44 (14) |
C10—N1—C8—C7 | 1.3 (2) | C5—C6—C7—C8 | 0.08 (18) |
C1—N1—C8—C3 | 0.78 (13) | N1—C8—C7—C6 | −179.67 (12) |
C10—N1—C8—C3 | −179.46 (11) | C3—C8—C7—C6 | 1.15 (18) |
N1—C8—C3—C4 | 179.29 (11) | C3—C4—C5—C6 | 0.89 (18) |
C7—C8—C3—C4 | −1.37 (18) | C3—C4—C5—C9 | −178.31 (11) |
N1—C8—C3—C2 | −0.42 (13) | C7—C6—C5—C4 | −1.11 (19) |
C7—C8—C3—C2 | 178.91 (11) | C7—C6—C5—C9 | 178.07 (12) |
C12—N4—C13—N3 | −0.46 (14) | C8—N1—C10—C11 | 161.26 (11) |
C11—N3—C13—N4 | 0.31 (14) | C1—N1—C10—C11 | −19.02 (18) |
C14—N3—C13—N4 | −179.36 (12) | N4—C12—C11—N3 | −0.26 (14) |
C4—C3—C2—C1 | −179.75 (14) | N4—C12—C11—C10 | 176.39 (12) |
C8—C3—C2—C1 | −0.09 (14) | C13—N3—C11—C12 | −0.02 (13) |
C8—C3—C4—C5 | 0.32 (17) | C14—N3—C11—C12 | 179.65 (12) |
C2—C3—C4—C5 | 179.95 (13) | C13—N3—C11—C10 | −177.03 (11) |
C3—C2—C1—N1 | 0.58 (14) | C14—N3—C11—C10 | 2.63 (19) |
C8—N1—C1—C2 | −0.86 (14) | N1—C10—C11—C12 | 112.73 (15) |
C10—N1—C1—C2 | 179.39 (11) | N1—C10—C11—N3 | −71.12 (15) |
D—H···A | D—H | H···A | D···A | D—H···A |
C4—H4···N4i | 0.95 | 2.53 | 3.4588 (18) | 167 |
C13—H13···N4ii | 0.95 | 2.57 | 3.4010 (18) | 147 |
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+5/2, y+1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C14H12N4 |
Mr | 236.28 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 100 |
a, b, c (Å) | 10.9624 (16), 7.8687 (12), 14.292 (2) |
β (°) | 106.727 (2) |
V (Å3) | 1180.6 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.10 × 0.10 × 0.02 |
Data collection | |
Diffractometer | Bruker APEXII CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2009) |
Tmin, Tmax | 0.992, 0.998 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 36857, 3286, 2643 |
Rint | 0.042 |
(sin θ/λ)max (Å−1) | 0.700 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.113, 1.06 |
No. of reflections | 3286 |
No. of parameters | 164 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.32, −0.21 |
Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), X-SEED (Barbour, 2001; Atwood et al., 2003).
D—H···A | D—H | H···A | D···A | D—H···A |
C4—H4···N4i | 0.95 | 2.53 | 3.4588 (18) | 167 |
C13—H13···N4ii | 0.95 | 2.57 | 3.4010 (18) | 147 |
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) −x+5/2, y+1/2, −z+1/2. |
Acknowledgements
The authors wish to thank W. A. L. van Otterlo, S. C. Pelly and the National Research Foundation for financial assistance and academic guidance.
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Protein farnesyl transferase has been identified as a drug target for its role as the sole prenylating agent in Plasmodium falciparum (Chakrabarti et al. 2002). The title compound is designed to fill some of the active site and importantly, to facilitate co-ordination to the zinc within this site via the imidazole side chain.
Crystalizing from a mixture of dichloromethane, toluene and n-hexane in a 18: 1: 1 ratio, crystals suitable for single-crystal X-ray diffraction were obtained. The space group was determined as P21/n from the systematic absences while the unit-cell dimensions were recorded as: a = 10.9624 (16), b = 7.8687 (12), c = 14.2915 (21) and β = 106.727 (2). In the crystal packing the molecules associate via intermolecular C—H···N hydrogen bonds that form undulating chains parallel to the axial directions b and c.