1-Isobutyl-4-meth­oxy-1H-imidazo[4,5-c]quinoline

Hoong-Kun Fun; Wan-Sin Loh; Dinesha; Reshma Kayarmar; G K Nagaraja

doi:10.1107/S1600536811031801

. 2011 Aug 11;67(Pt 9):o2331. doi: 10.1107/S1600536811031801

1-Isobutyl-4-methoxy-1H-imidazo[4,5-c]quinoline

Hoong-Kun Fun ^a,^*,^‡, Wan-Sin Loh ^a,^§, Dinesha ^b, Reshma Kayarmar ^c, G K Nagaraja ^b

PMCID: PMC3200859 PMID: 22058955

Abstract

In the title compound, C₁₅H₁₇N₃O, the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.036 (1) Å. The C—N—C—C torsion angles formed between this ring system and the isobutyl unit are −99.77 (16) and 79.71 (17)°. In the crystal, intermolecular C—H⋯O hydrogen bonds link the molecules into chains along the c axis.

Related literature

For background to quinolines and their microbial activity, see: Crozat & Beutler (2004 ▶); Stringfellow & Glasgow (1972 ▶); Miller et al. (1999 ▶); Hemmi et al. (2002 ▶). For related structures, see: Loh et al. (2011a ▶,b ▶).

Experimental

Crystal data

C₁₅H₁₇N₃O
M _r = 255.32
Monoclinic,
a = 7.4196 (8) Å
b = 18.910 (2) Å
c = 10.4112 (14) Å
β = 110.568 (2)°
V = 1367.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 297 K
0.40 × 0.31 × 0.13 mm

Data collection

Bruker SMART APEXII DUO CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.969, T _max = 0.989
12741 measured reflections
3463 independent reflections
2386 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.127
S = 1.04
3463 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 0.12 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811031801/wn2444sup1.cif

e-67-o2331-sup1.cif^{(18.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811031801/wn2444Isup2.hkl

e-67-o2331-Isup2.hkl^{(169.9KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811031801/wn2444Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C10—H10A⋯O1ⁱ	0.93	2.39	3.3052 (16)	169

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Symmetry code: (i) Inline graphic .

Acknowledgments

HKF and WSL thank Universiti Sains Malaysia (USM) for the Research University Grant (1001/PFIZIK/811160). WSL thanks the Malaysian Government and USM for the award of a Research Fellowship.

supplementary crystallographic information

Comment

The quinoline scaffold is prevalent in a variety of pharmacologically active synthetic and natural products. Long before endosomal TLR7 was discovered to serve as the primary sensor for short, single-stranded, GU-rich RNA sequences (ssRNA), mainly of viral origin (Crozat & Beutler, 2004), a number of small molecules were synthesized and evaluated in the 1970's and 1980's for antiviral activities owing to their pronounced type I interferon (IFN-R and -β) inducing properties (Stringfellow & Glasgow, 1972). Although the mechanisms of innate immune stimulation of several of these compounds (such as tilorone14 and bromopirone16) remain yet to be formally elucidated, the members of the 1H-imidazo[4,5-c]quinolines were found to be good type I IFN inducers in human cell-derived assays and FDA approval was obtained in 1997 for imiquimod for the treatment of basal cell carcinoma and actinic keratosis (Miller et al., 1999). It was not until 2002, however, that the mechanistic basis of IFN induction by the imidazoquinolines was found to be a consequence of TLR7 engagement and activation (Hemmi et al., 2002). We have earlier reported the crystal structures of 1-isobutyl-N,N-dimethyl-1H-imidazo[4,5-c]quinolin- 4-amine and 4-hydrazinyl-1-isobutyl-1H-imidazo[4,5-c]quinoline (Loh et al., 2011a,b). Following on from these, we have synthesized 1-isobutyl-4-methoxy-1H-imidazo[4,5-c]quinoline.

In the title compound (Fig. 1), the 1H-imidazo[4,5-c]quinoline ring system (C1–C7/N3/C10/N2/C8/C9/N1) is approximately planar with a maximum deviation of 0.036 (1) Å at atom C8. The torsion angle, C10—N3—C11—C12, formed between this ring system and the isobutyl unit is -99.77 (16)°; the torsion angle C7—N3—C11—C12 is 79.71 (17)°. Bond lengths and angles are within the normal ranges and are comparable to those in the related crystal structures (Loh et al., 2011a,b).

In the crystal packing (Fig. 2), the intermolecular C10—H10A···O1 hydrogen bonds (Table 1) link the molecules into chains along the c axis.

Experimental

To a solution of 4-chloro-1-(2-methylpropyl)-1H-imidazo[4,5-c] quinoline (0.1 mol) in methanol (30 ml) was added a solution of sodium methoxide (0.01 mol) in methanol (10 ml) and the mixture was stirred for 1 h. The reaction mixture was heated under reflux for 12 h, concentrated and poured into crushed ice. The resultant solid was filtered, dried and recrystallized using a mixture of DMF and water (1:1). M. p. = 493–495 K.