4-Methyl-N-(9-methyl-9-aza­bicyclo­[3.3.1]non-3-yl)benzamide

Diya Lv; Yan Cao; Xin Dong; Ziyang Lou; Yifeng Chai

doi:10.1107/S1600536812017795

. 2012 May 19;68(Pt 6):o1781. doi: 10.1107/S1600536812017795

4-Methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)benzamide

Diya Lv ^a, Yan Cao ^a, Xin Dong ^a, Ziyang Lou ^a, Yifeng Chai ^a,^*

PMCID: PMC3379360 PMID: 22719558

Abstract

The asymmetric unit of the title compound, C₁₇H₂₄N₂O, contains three independent molecules. In the crystal, molecules are linked by weak N—H⋯O hydrogen bonds into chains parallel to the c axis.

Related literature

For background to our work to design and synthesize a series of potent 5-HT₃ receptor antagonists, see: Bermudez et al. (1990 ▶); Vernekar et al. (2010 ▶); Yang et al. (2010 ▶).

Experimental

Crystal data

C₁₇H₂₄N₂O
M _r = 272.38
Monoclinic,
a = 38.68 (2) Å
b = 12.300 (7) Å
c = 9.975 (5) Å
β = 101.263 (7)°
V = 4654 (4) Å³
Z = 12
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 293 K
0.25 × 0.15 × 0.10 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1999 ▶) T _min = 0.982, T _max = 0.993
10320 measured reflections
6399 independent reflections
4035 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.151
S = 0.96
6399 reflections
556 parameters
5 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: SMART (Bruker, 1999 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812017795/vm2165sup1.cif

e-68-o1781-sup1.cif^{(33KB, cif)}

Supplementary material file. DOI: 10.1107/S1600536812017795/vm2165Isup2.cdx

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812017795/vm2165Isup3.hkl

e-68-o1781-Isup3.hkl^{(313.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812017795/vm2165Isup4.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
N2—H2′⋯O1ⁱ	0.85 (2)	2.10 (2)	2.935 (5)	171 (4)
N4—H4′⋯O2ⁱⁱ	0.86 (2)	2.05 (2)	2.894 (5)	166 (4)
N6—H6′⋯O3ⁱⁱⁱ	0.86 (2)	2.30 (2)	3.164 (5)	174 (4)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

supplementary crystallographic information

Comment

Motion sickness is common in the population, especially with children. In our laboratory, we have designed and synthesized a novel series of potent 5-HT₃ receptor antagonists (Bermudez et al., 1990; Vernekar et al., 2010; Yang et al., 2010). Furthermore, we find that the candidate has the anti-motion sickness effect. Here, we report the crystal structure of the title compound.

As shown in Fig.1, the asymmetric unit of the title compound contains three molecules. H-bonding interactions do play a decisive role in the crystal packing arrangement (Fig. 2). The molecules are linked by weak intermolecular N2—H2···O1, N4—H4···O2 and N6—H6···O3 hydrogen bonds (Table 1) linking the molecules into chains parallel to the c axis.

Experimental

A solution of 9-methyl-9-azabicyclo[3.3.1]nonan-3-one (0.03 mol) in ethanol (150 ml) was added dropwise to a solution of sodium acetate (0.06 mol) and hydroxylamine hydrochloride (0.06 mol) in ethanol (200 ml) under stirring, and refluxed for 4 hr to get crude products, which was recrystallized from ethyl acetate to give pure 9-methyl-9-azabicyclo[3.3.1]nonan-3-one (3.8 g, yield 75.2%). To a solution of LiAlH₄ (0.066 mol) in anhydrous tetrahydrofuran (THF, 50 ml) a solution of concentrated sulfuric acid (3.0 ml) and THF (12 ml) was added dropwise at -10°C and stirred for 1 hr. To thisabove reaction mixture, a solution of 9-methyl-9-azbicyclo[3.3.1]non-3-ylamine (0.022 mol) in anhydrous THF (70 ml) was added dropwise at 30-35°C and stirred. After reaction, the reaction mixture was evaporated at vacuum to remove solvent to give 3-amine-9-methyl-9-azabicyclo[3.3.1]nonane (2.9 g, yield 78.3%). To a solution of 3-amine-9-methyl-9-azabicyclo[3.3.1]nonane (0.013 mol) and triethylamine (0.013 mol) in dichloromethane (20 ml), a mixture of 4-methylbenzoyl chloride (0.016 mol) and dichloromethane (5 ml) was added dropwise and stirred to obtain crude product, which was recrystallized from ethyl acetate to give pure 4-methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-benzenecarboxamide (2.9 g, yield 81%).