N-Cyclo­pentyl-N-(3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide

Tao Zhang; Tom McCabe; Bartosz Marzec; Neil Frankish; Helen Sheridan

doi:10.1107/S160053681200606X

. 2012 Mar 3;68(Pt 4):o958. doi: 10.1107/S160053681200606X

N-Cyclopentyl-N-(3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide

Tao Zhang ^a,^b, Tom McCabe ^c, Bartosz Marzec ^c, Neil Frankish ^a, Helen Sheridan ^a,^*

PMCID: PMC3343937 PMID: 22590018

Abstract

The title molecule, C₁₆H₁₉NO₂, consists of an indane moiety, which is connected through an N atom to an acetamide group and a cyclopentane ring. The N atom adopts planar triangular geometry. Intermolecular interactions, such as π–π stacking or hydrogen bonding, were not observed.

Related literature

For background information on the indane pharmacophore, see: Vaccva et al. (1994 ▶); Buckle et al. (1973 ▶); Heinzelmann et al. (1940 ▶). For details of the pharmacological activity of the title compound, see: Sheridan et al. (1990 ▶, 1999a ▶,b ▶, 2008 ▶); Frankish et al. (2004 ▶). For ionization characteristics, see: Simplício et al. (2004 ▶).

Experimental

Crystal data

C₁₆H₁₉NO₂
M _r = 257.32
Triclinic,
a = 8.1539 (16) Å
b = 8.9944 (18) Å
c = 10.084 (2) Å
α = 87.97 (3)°
β = 81.29 (3)°
γ = 63.15 (3)°
V = 651.8 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 K
0.60 × 0.50 × 0.30 mm

Data collection

Rigaku Saturn 724 diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2006 ▶) T _min = 0.726, T _max = 1.000
7260 measured reflections
2191 independent reflections
2157 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.100
S = 1.13
2191 reflections
174 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrystalClear (Rigaku, 2006 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 1998 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681200606X/hg5169sup1.cif

e-68-0o958-sup1.cif^{(23.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681200606X/hg5169Isup2.hkl

e-68-0o958-Isup2.hkl^{(107.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681200606X/hg5169Isup3.cml

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

Acknowledgments

We gratefully acknowledge financial support of this study by Enterprise Ireland (grant No. PC/2008/0008) and thank colleagues at the Drug Discovery Group, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, for their input.

supplementary crystallographic information

Comment

The indane pharmacophore occurs in many different bioactive molecules. Indinavir, a HIV-1 inhibitor is a protease inhibitor in clinical use that contains an indane fragment (Vaccva et al., 1994). Nivemedone, a nitro-indanone has anti-allergenic activity (Buckle et al., 1973) while many simple indanols demonstrate bronchodilatory activity (Heinzelmann et al., 1940). We have demonstrated that indanone derivatives possess smooth muscle relaxant activity and inhibit mediator release (Sheridan et al., 1990, 1999a, 1999b; Frankish et al., 2004). In a recent study on bioactivity we evaluated the smooth muscle relaxant activity and mediator release inhibition activities demonstrated by a series of aminoindanones (Simplício et al., 2004; Sheridan et al., 2008).

The asymmetric unit of the compound presented in this paper contains a single molecule of N-cyclopentyl-N-(3-oxo-2,3-dihydro-1H -inden-1-yl)acetamide. The geometry around the nitrogen atom can be best described as trigonal planar. As there are no flexible hydrogen atoms attached to the nitrogen atom N1 or the oxygen atoms (O1 and O2) hydrogen bonding do not prevail in the title compound. The shortest distance between the aromatic rings is 4.150 (9) Å and cannot be considered as the π-π stacking interaction.

The packing diagram of the structure, presented in Fig. 2, shows that the molecules are separated and when viewed along the crystallographic a-axis seem to form a sheet-like structure in the ab-plane. These sheets pack in the direction of the crystallographic c-axis. The shortest separation distance between them is 4.243 (75) Å and a weak Van der Vaals force or an electrostatic interaction may be responsible for holding the sheets together.

Experimental

The title compound was synthesized as reported (Sheridan et al., 2008). N-Bromosuccinimide (672 mg, 3.78 mmol) and a catalytic amount of dibenzoylperoxide were added to a solution of indan-1-one (500 mg, 3.78 mmol) in CCl₄ (15 ml) and the reaction was refluxed for 45 min. After cooling, the reaction was washed with water, dried over Na₂SO₄, filtered and evaporated in vacuo. The resultant was purified by column chromatography over silica gel (eluant, pet. ether:EtOAc, 4:1) to yield 3-bromoindan-1-one as an oil. To this 3-bromoindan-1-one solution (200 mg, 0.95 mmol) in dry DCM was added cyclopentanamine (80 mg, 0.94 mmol) and triethylamine (200 mg, 1.98 mmol). The reaction was stirred at 0°C for 3 h. The solvent was removed in vacuo and the residue was purified directly by flash column chromatography on silica gel (eluant, pet. ether:EtOAc, 4:1). After evaporation of the eluent the secondary amine was isolated as an oil (175 mg, 86%). To this secondary amine solution (700 mg, 3.25 mmol) in DCM (5 ml) was added triethylamine (657 mg, 0.90 ml, 6.51 mmol), acetic anhydride (664 mg, 0.61 ml, 6.51 mmol) and DMAP (476 mg, 3.90 mmol). The reaction was stirred at room temperature for 2 h. The reaction mixture was then washed with water, dried over Na₂SO₄, filtered and evaporated in vacuo. The residue was purified by column chromatography over silica gel (pet. ether:EtOAc, 4:1) to yield the title compound as a white solid (450 mg, 54%). Crystals suitable for X-ray diffraction were obtained after 5 days of slow evaporation of an ethanol solution.