organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

(Received 22 November 2012; accepted 26 November 2012; online 30 November 2012)

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[Chakrabarti, D., Da Silva, T., Barger, J., Paquette, S., Patel, H., Patterson, S. & Allen, C. M. (2002). J. Biol. Chem. 277, 42066-42073.]). For the properties of related compounds, see: Bulbule et al. (2008[Bulbule, V. J., Rivas, K., Verlinde, C. L. M. J., Van Voorhis, W. C. & Gelb, M. H. (2008). J. Med. Chem. 51, 384-387.]), van Voorhis et al. (2007[Voorhis, W. C. van, Rivas, K. L., Bendale, P., Nallan, L., Horney, C., Barrett, L. K., Bauer, K. D., Smart, B. P., Ankala, S., Hucke, O., Verlinde, C. L. M. J., Chakrabart, D., Strickland, C., Yokoyama, K., Buckner, F. S., Hamilton, A. D., Williams, D. K., Lombardo, L. J., Floyd, D. & Gelb, H. (2007). Antimicrob. Agents Chemother. 51, 3659-3671.]); de Ruyck & Wouters (2008[Ruyck, J. de & Wouters, J. (2008). Curr. Protein Pept. Sci. 9, 117-137.]).

[Scheme 1]

Experimental

Crystal data
  • C14H12N4

  • Mr = 236.28

  • Monoclinic, P 21 /n

  • a = 10.9624 (16) Å

  • b = 7.8687 (12) Å

  • c = 14.292 (2) Å

  • β = 106.727 (2)°

  • V = 1180.6 (3) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.08 mm−1

  • T = 100 K

  • 0.10 × 0.10 × 0.02 mm

Data collection
  • Bruker APEXII CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.992, Tmax = 0.998

  • 36857 measured reflections

  • 3286 independent reflections

  • 2643 reflections with I > 2σ(I)

  • Rint = 0.042

Refinement
  • R[F2 > 2σ(F2)] = 0.042

  • wR(F2) = 0.113

  • S = 1.06

  • 3286 reflections

  • 164 parameters

  • H-atom parameters constrained

  • Δρmax = 0.32 e Å−3

  • Δρmin = −0.21 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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+{\script{3\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) [-x+{\script{5\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].

Data collection: APEX2 (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2009[Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: X-SEED (Barbour, 2001[Barbour, L. J. (2001). Supramol. Chem. 1, 189-191.]; Atwood et al., 2003[Atwood, J. L. & Barbour, L. J. (2003). Cryst. Growth Des. 3, 3-8.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

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.

Related literature top

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); Ruyck et al. (2008).

Experimental top

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 column chromatography (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).

Refinement top

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.

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: 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).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound with displacement ellipsoids shown at the 50% probability level.
[Figure 2] Fig. 2. Packing diagram showing the intermolecular C—H···N hydrogen bonds.
1-[(1-Methyl-1H-imidazol-5-yl)methyl]-1H-indole-5-carbonitrile top
Crystal data top
C14H12N4F(000) = 496
Mr = 236.28Dx = 1.329 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 7965 reflections
a = 10.9624 (16) Åθ = 3.0–28.6°
b = 7.8687 (12) ŵ = 0.08 mm1
c = 14.292 (2) ÅT = 100 K
β = 106.727 (2)°Plate, colourless
V = 1180.6 (3) Å30.10 × 0.10 × 0.02 mm
Z = 4
Data collection top
Bruker APEXII CCD
diffractometer
3286 independent reflections
Radiation source: fine-focus sealed tube, Bruker Apex22643 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.042
ϕ and ω scansθmax = 29.8°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
h = 1515
Tmin = 0.992, Tmax = 0.998k = 1010
36857 measured reflectionsl = 1919
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.113H-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 parametersΔρmax = 0.32 e Å3
0 restraintsΔρmin = 0.21 e Å3
Crystal data top
C14H12N4V = 1180.6 (3) Å3
Mr = 236.28Z = 4
Monoclinic, P21/nMo Kα radiation
a = 10.9624 (16) ŵ = 0.08 mm1
b = 7.8687 (12) ÅT = 100 K
c = 14.292 (2) Å0.10 × 0.10 × 0.02 mm
β = 106.727 (2)°
Data collection top
Bruker APEXII CCD
diffractometer
3286 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
2643 reflections with I > 2σ(I)
Tmin = 0.992, Tmax = 0.998Rint = 0.042
36857 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0420 restraints
wR(F2) = 0.113H-atom parameters constrained
S = 1.06Δρmax = 0.32 e Å3
3286 reflectionsΔρmin = 0.21 e Å3
164 parameters
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
xyzUiso*/Ueq
N10.74899 (9)0.05550 (13)0.10401 (7)0.0182 (2)
C80.63632 (11)0.14156 (15)0.06741 (8)0.0172 (2)
C30.57779 (11)0.15677 (15)0.14387 (8)0.0182 (2)
N31.05057 (10)0.09402 (14)0.16447 (8)0.0204 (2)
N41.15865 (10)0.14899 (14)0.18381 (8)0.0218 (2)
C60.46523 (12)0.28892 (17)0.04359 (9)0.0222 (3)
H60.42480.33380.10660.027*
C90.28834 (12)0.40021 (18)0.01344 (10)0.0253 (3)
C131.16216 (12)0.01364 (17)0.20734 (9)0.0213 (3)
H131.23460.06810.24950.026*
C20.66051 (12)0.07444 (16)0.22788 (9)0.0202 (2)
H20.64720.06380.29040.024*
N20.19352 (11)0.47248 (17)0.00085 (10)0.0327 (3)
C40.46133 (12)0.24195 (16)0.12543 (9)0.0206 (3)
H40.42030.25450.17520.025*
C10.76221 (12)0.01428 (16)0.20058 (9)0.0201 (2)
H10.83180.04690.24190.024*
C121.03687 (12)0.17490 (17)0.12259 (9)0.0209 (3)
H121.00500.28070.09370.025*
C70.58051 (11)0.20564 (16)0.02668 (9)0.0201 (2)
H70.62050.19230.07700.024*
C50.40688 (11)0.30803 (16)0.03208 (9)0.0213 (3)
C100.83783 (11)0.01570 (18)0.04742 (9)0.0214 (3)
H10A0.84260.11440.00560.026*
H10B0.80410.08190.00390.026*
C110.96882 (11)0.02628 (16)0.10955 (9)0.0195 (2)
C141.02309 (13)0.27356 (18)0.17436 (11)0.0296 (3)
H14A1.09970.33050.21470.044*
H14C0.95460.28420.20540.044*
H14B0.99650.32650.10960.044*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0142 (5)0.0216 (5)0.0177 (5)0.0003 (4)0.0028 (4)0.0016 (4)
C80.0135 (5)0.0176 (5)0.0192 (5)0.0028 (4)0.0028 (4)0.0013 (4)
C30.0169 (5)0.0178 (5)0.0189 (5)0.0030 (4)0.0035 (4)0.0017 (4)
N30.0158 (5)0.0211 (5)0.0230 (5)0.0004 (4)0.0033 (4)0.0003 (4)
N40.0183 (5)0.0244 (5)0.0221 (5)0.0015 (4)0.0048 (4)0.0025 (4)
C60.0197 (6)0.0224 (6)0.0199 (6)0.0009 (5)0.0014 (4)0.0008 (5)
C90.0199 (6)0.0251 (6)0.0276 (6)0.0005 (5)0.0013 (5)0.0026 (5)
C130.0152 (5)0.0254 (6)0.0222 (6)0.0007 (5)0.0037 (4)0.0019 (5)
C20.0197 (6)0.0218 (6)0.0182 (5)0.0017 (5)0.0042 (4)0.0006 (4)
N20.0222 (6)0.0324 (7)0.0392 (7)0.0041 (5)0.0019 (5)0.0023 (5)
C40.0171 (5)0.0215 (6)0.0222 (6)0.0026 (5)0.0043 (4)0.0040 (5)
C10.0188 (6)0.0215 (6)0.0183 (5)0.0001 (5)0.0026 (4)0.0024 (4)
C120.0188 (6)0.0235 (6)0.0207 (6)0.0010 (5)0.0063 (4)0.0009 (5)
C70.0181 (6)0.0224 (6)0.0187 (5)0.0018 (5)0.0033 (4)0.0001 (5)
C50.0150 (5)0.0202 (6)0.0256 (6)0.0004 (5)0.0008 (4)0.0025 (5)
C100.0148 (5)0.0305 (7)0.0184 (5)0.0006 (5)0.0041 (4)0.0000 (5)
C110.0152 (5)0.0244 (6)0.0185 (5)0.0015 (5)0.0043 (4)0.0003 (4)
C140.0233 (6)0.0215 (6)0.0402 (8)0.0016 (5)0.0031 (6)0.0026 (6)
Geometric parameters (Å, º) top
N1—C81.3733 (15)C9—C51.4445 (18)
N1—C11.3842 (15)C13—H130.9500
N1—C101.4676 (15)C2—C11.3673 (17)
C8—C71.4011 (16)C2—H20.9500
C8—C31.4226 (16)C4—C51.3958 (18)
C3—C41.3982 (17)C4—H40.9500
C3—C21.4341 (17)C1—H10.9500
N3—C131.3567 (16)C12—C111.3707 (18)
N3—C111.3822 (16)C12—H120.9500
N3—C141.4598 (17)C7—H70.9500
N4—C131.3209 (17)C10—C111.4918 (17)
N4—C121.3845 (16)C10—H10A0.9900
C6—C71.3817 (17)C10—H10B0.9900
C6—C51.4140 (18)C14—H14A0.9800
C6—H60.9500C14—H14C0.9800
C9—N21.1504 (18)C14—H14B0.9800
C8—N1—C1108.65 (10)C2—C1—H1125.0
C8—N1—C10124.20 (10)N1—C1—H1125.0
C1—N1—C10127.14 (10)C11—C12—N4110.39 (11)
N1—C8—C7129.75 (11)C11—C12—H12124.8
N1—C8—C3107.70 (10)N4—C12—H12124.8
C7—C8—C3122.55 (11)C6—C7—C8117.60 (11)
C4—C3—C8119.00 (11)C6—C7—H7121.2
C4—C3—C2134.22 (11)C8—C7—H7121.2
C8—C3—C2106.78 (10)C4—C5—C6121.89 (11)
C13—N3—C11106.87 (11)C4—C5—C9118.55 (12)
C13—N3—C14126.29 (11)C6—C5—C9119.56 (12)
C11—N3—C14126.84 (11)N1—C10—C11113.39 (10)
C13—N4—C12104.82 (11)N1—C10—H10A108.9
C7—C6—C5120.60 (11)C11—C10—H10A108.9
C7—C6—H6119.7N1—C10—H10B108.9
C5—C6—H6119.7C11—C10—H10B108.9
N2—C9—C5179.32 (16)H10A—C10—H10B107.7
N4—C13—N3112.35 (11)C12—C11—N3105.58 (11)
N4—C13—H13123.8C12—C11—C10131.51 (12)
N3—C13—H13123.8N3—C11—C10122.82 (11)
C1—C2—C3106.77 (11)N3—C14—H14A109.5
C1—C2—H2126.6N3—C14—H14C109.5
C3—C2—H2126.6H14A—C14—H14C109.5
C5—C4—C3118.35 (11)N3—C14—H14B109.5
C5—C4—H4120.8H14A—C14—H14B109.5
C3—C4—H4120.8H14C—C14—H14B109.5
C2—C1—N1110.09 (11)
C1—N1—C8—C7178.49 (12)C13—N4—C12—C110.44 (14)
C10—N1—C8—C71.3 (2)C5—C6—C7—C80.08 (18)
C1—N1—C8—C30.78 (13)N1—C8—C7—C6179.67 (12)
C10—N1—C8—C3179.46 (11)C3—C8—C7—C61.15 (18)
N1—C8—C3—C4179.29 (11)C3—C4—C5—C60.89 (18)
C7—C8—C3—C41.37 (18)C3—C4—C5—C9178.31 (11)
N1—C8—C3—C20.42 (13)C7—C6—C5—C41.11 (19)
C7—C8—C3—C2178.91 (11)C7—C6—C5—C9178.07 (12)
C12—N4—C13—N30.46 (14)C8—N1—C10—C11161.26 (11)
C11—N3—C13—N40.31 (14)C1—N1—C10—C1119.02 (18)
C14—N3—C13—N4179.36 (12)N4—C12—C11—N30.26 (14)
C4—C3—C2—C1179.75 (14)N4—C12—C11—C10176.39 (12)
C8—C3—C2—C10.09 (14)C13—N3—C11—C120.02 (13)
C8—C3—C4—C50.32 (17)C14—N3—C11—C12179.65 (12)
C2—C3—C4—C5179.95 (13)C13—N3—C11—C10177.03 (11)
C3—C2—C1—N10.58 (14)C14—N3—C11—C102.63 (19)
C8—N1—C1—C20.86 (14)N1—C10—C11—C12112.73 (15)
C10—N1—C1—C2179.39 (11)N1—C10—C11—N371.12 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4···N4i0.952.533.4588 (18)167
C13—H13···N4ii0.952.573.4010 (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 formulaC14H12N4
Mr236.28
Crystal system, space groupMonoclinic, P21/n
Temperature (K)100
a, b, c (Å)10.9624 (16), 7.8687 (12), 14.292 (2)
β (°) 106.727 (2)
V3)1180.6 (3)
Z4
Radiation typeMo Kα
µ (mm1)0.08
Crystal size (mm)0.10 × 0.10 × 0.02
Data collection
DiffractometerBruker APEXII CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2009)
Tmin, Tmax0.992, 0.998
No. of measured, independent and
observed [I > 2σ(I)] reflections
36857, 3286, 2643
Rint0.042
(sin θ/λ)max1)0.700
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.042, 0.113, 1.06
No. of reflections3286
No. of parameters164
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4···N4i0.952.533.4588 (18)167
C13—H13···N4ii0.952.573.4010 (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

First citationAtwood, J. L. & Barbour, L. J. (2003). Cryst. Growth Des. 3, 3-8.  Web of Science CrossRef CAS
First citationBarbour, L. J. (2001). Supramol. Chem. 1, 189–191.  CrossRef CAS
First citationBruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationBulbule, V. J., Rivas, K., Verlinde, C. L. M. J., Van Voorhis, W. C. & Gelb, M. H. (2008). J. Med. Chem. 51, 384–387.  Web of Science CrossRef PubMed CAS
First citationChakrabarti, D., Da Silva, T., Barger, J., Paquette, S., Patel, H., Patterson, S. & Allen, C. M. (2002). J. Biol. Chem. 277, 42066–42073.  Web of Science CrossRef PubMed CAS
First citationRuyck, J. de & Wouters, J. (2008). Curr. Protein Pept. Sci. 9, 117–137.  CrossRef PubMed
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationVoorhis, W. C. van, Rivas, K. L., Bendale, P., Nallan, L., Horney, C., Barrett, L. K., Bauer, K. D., Smart, B. P., Ankala, S., Hucke, O., Verlinde, C. L. M. J., Chakrabart, D., Strickland, C., Yokoyama, K., Buckner, F. S., Hamilton, A. D., Williams, D. K., Lombardo, L. J., Floyd, D. & Gelb, H. (2007). Antimicrob. Agents Chemother. 51, 3659–3671.  Web of Science PubMed

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