1-[(1-Methyl-1H-imidazol-5-yl)meth­yl]-1H-indole-5-carbonitrile

de Jager, J.J.; Smith, V.J.

doi:10.1107/S1600536812048404

organic compounds

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Volume 68| Part 12| December 2012| Page o3486

doi:10.1107/S1600536812048404

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1-[(1-Methyl-1H-imidazol-5-yl)methyl]-1H-indole-5-carbonitrile

Josephus Jacobus de Jager ^a ^* and Vincent J. Smith ^a

^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 ). For the properties of related compounds, see: Bulbule et al. (2008 ), van Voorhis et al. (2007 ); de Ruyck & Wouters (2008 ).

Experimental

Crystal data

C₁₄H₁₂N₄
M_r = 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 ) T_min = 0.992, T_max = 0.998
36857 measured reflections
3286 independent reflections
2643 reflections with I > 2σ(I)
R_int = 0.042

Refinement

R[F² > 2σ(F²)] = 0.042
wR(F²) = 0.113
S = 1.06
3286 reflections
164 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

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) $[-x+{\script{3\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[-x+{\script{5\over 2}}, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

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

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812048404/hb7000sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812048404/hb7000Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812048404/hb7000Isup3.cml

checkCIF report

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).

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

	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.

1-[(1-Methyl-1H-imidazol-5-yl)methyl]-1H-indole-5-carbonitrile top

Crystal data top

C₁₄H₁₂N₄	F(000) = 496
M_r = 236.28	D_x = 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

Data collection top

Bruker APEXII CCD diffractometer	3286 independent reflections
Radiation source: fine-focus sealed tube, Bruker Apex2	2643 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.042
ϕ and ω scans	θ_max = 29.8°, θ_min = 2.1°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −15→15
T_min = 0.992, T_max = 0.998	k = −10→10
36857 measured reflections	l = −19→19

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)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.113	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0451P)² + 0.613P] where P = (F_o² + 2F_c²)/3
3286 reflections	(Δ/σ)_max < 0.001
164 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₄H₁₂N₄	V = 1180.6 (3) Å³
M_r = 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)°

Data collection top

Bruker APEXII CCD diffractometer	3286 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2009)	2643 reflections with I > 2σ(I)
T_min = 0.992, T_max = 0.998	R_int = 0.042
36857 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	0 restraints
wR(F²) = 0.113	H-atom parameters constrained
S = 1.06	Δρ_max = 0.32 e Å⁻³
3286 reflections	Δρ_min = −0.21 e Å⁻³
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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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
M_r	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)
T_min, T_max	0.992, 0.998
No. of measured, independent and observed [I > 2σ(I)] reflections	36857, 3286, 2643
R_int	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
Δρ_max, Δρ_min (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).

Hydrogen-bond geometry (Å, º) top

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

Atwood, J. L. & Barbour, L. J. (2003). Cryst. Growth Des. 3, 3-8. Web of Science CrossRef CAS Google Scholar
Barbour, L. J. (2001). Supramol. Chem. 1, 189–191. CrossRef CAS Google Scholar
Bruker (2009). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bulbule, 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 Google Scholar
Chakrabarti, 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 Google Scholar
Ruyck, J. de & Wouters, J. (2008). Curr. Protein Pept. Sci. 9, 117–137. CrossRef PubMed Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
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. Web of Science PubMed Google Scholar