Tert-butyl 3-oxo-2,3,4,5,6,7-hexa­hydro-1H-pyrazolo[4,3-c]pyridine-5-carboxyl­ate

Tara Shahani; Hoong-Kun Fun; R Venkat Ragavan; V Vijayakumar; S Sarveswari

doi:10.1107/S1600536809053021

. 2009 Dec 16;66(Pt 1):o142–o143. doi: 10.1107/S1600536809053021

Tert-butyl 3-oxo-2,3,4,5,6,7-hexahydro-1H-pyrazolo[4,3-c]pyridine-5-carboxylate

Tara Shahani ^a, Hoong-Kun Fun ^a,^*,^‡, R Venkat Ragavan ^b, V Vijayakumar ^b, S Sarveswari ^b

PMCID: PMC2980051 PMID: 21580034

Abstract

In the title compound, C₁₁H₁₇N₃O₃, the pyrazole ring is approximately planar, with a maximum deviation of 0.005 (2) Å, and forms a dihedral angle of 5.69 (13)° with the plane through the six atoms of the piperidine ring. In the crystal, pairs of intermolecular N—H⋯O hydrogen bonds form dimers with neighbouring molecules, generating R ₂ ²(8) ring motifs. These dimers are further linked into two-dimensional arrays parallel to the bc plane by intermolecular N—H⋯O and C—H⋯O hydrogen bonds.

Related literature

For the biological activity of pyrazolone derivatives, see: Al-Haiza et al. (2001 ▶); Brogden, (1986 ▶); Coersmeier et al. (1986 ▶); Gursoy et al. (2000 ▶). For myocardial ischemia, see: Wu et al. (2002 ▶). For brain ischemia, see: Watanabe et al. (1984 ▶); Kawai et al. (1997 ▶). For new compounds with the pyrazolone unit, see: Al-Haiza et al. (2001 ▶). For a related structure, see: Shahani et al. (2009 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For bond-length data, see: Allen et al. (1987 ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₁H₁₇N₃O₃
M _r = 239.28
Monoclinic,
a = 18.6250 (12) Å
b = 6.0893 (5) Å
c = 10.7414 (7) Å
β = 104.100 (4)°
V = 1181.51 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.97 × 0.35 × 0.14 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.910, T _max = 0.986
13101 measured reflections
2690 independent reflections
2136 reflections with I > 2σ(I)
R _int = 0.035

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.172
S = 1.24
2690 reflections
222 parameters
All H-atom parameters refined
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.31 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 datablocks global, I. DOI: 10.1107/S1600536809053021/ng2705sup1.cif

e-66-0o142-sup1.cif^{(18.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809053021/ng2705Isup2.hkl

e-66-0o142-Isup2.hkl^{(132.1KB, hkl)}

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
N1—H1N1⋯O2ⁱ	0.99 (3)	1.77 (3)	2.748 (3)	171 (3)
N2—H1N2⋯O2ⁱⁱ	0.94 (3)	1.75 (4)	2.665 (3)	167 (3)
C1—H1B⋯O2ⁱⁱⁱ	0.98 (3)	2.57 (3)	3.492 (3)	157 (3)
C11—H11C⋯O3^iv	0.97 (3)	2.60 (3)	3.504 (3)	156 (3)

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

Acknowledgments

HKF and TSH thank Universiti Sains Malaysia (USM) for the Research University Golden Goose Grant (1001/PFIZIK/811012). VV is grateful to DST-India for funding through the Young Scientist Scheme (Fast Track Proposal).

supplementary crystallographic information

Comment

Pyrazolone derivatives have a broad spectrum of biological activities being used as analgesic, antipyretic and anti-inflammatory therapeutical drugs (Brogden, 1986; Gursoy et al., 2000). A class of new compounds with pyrazolone moiety was synthesized and reported for their antibacterial, antifungal activities by Al-Haiza et al. (2001). A new pyrazolone derivative, edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) is being used as a drug in clinical practice for brain ischemia (Watanabe et al., 1984; Kawai et al., 1997) and the same has been found to be effective against myocardial ischemia (Wu et al., 2002).

In the crystal structure (Fig. 1), the pyrazole ring (C3/N1/N2/C4/C5) is approximately planar, with a maximum deviation of 0.005 (2) Å at atom N2. The piperidine ring (C1/C2/C3/C5/C6/N3) adopts a half-boat conformation (Cremer & Pople, 1975) with puckering of Q = 0.465 (2) Å, Θ = 52.9 (2)° & φ = 39.8 (4)°. The maximum deviation in this piperidine ring is 0.286 Å at atom N3. The dihedral angle formed between the mean planes of pyrazole and piperidine rings is 5.69 (13)°. The bond lengths (Allen et al., 1987) and angles are within normal ranges and comparable to a closely related structure (Shahani et al., 2009).

In the crystal packing (Fig. 2), pairs of intermolecular N2—H1N2···O2 hydrogen bonds form dimers with neighbouring molecules, generating R²₂(8) ring motifs (Bernstein et al., 1995). These dimers are further linked into two-dimensional arrays parallel to the bc plane by intermolecular N1—H1N1···O2, C1—H1B···O2 and C11—H11C···O3 hydrogen bonds.

Experimental

LiHMDS (1.0 M solution in toluene, 11 mmol) was added quickly to a solution of tert-butyl 4-oxopiperidine-1-carboxylate (10 mmol 15 ml of toluene) using syringe at 273 K with stirring for 10 minutes. Ethyl chloro formate (11 mmol) was then added quickly. The reaction mixture was slowly (10 minutes) brought to room temperature and stirred for 10 minutes. Acetic acid (2 ml), ethanol (15 ml), and hydrazine hydrate (30 mmol) were added and refluxed for 15 minutes. The reaction mixture was concentrated to dryness under reduced pressure and re-dissolved in ethyl acetate. The organic layer was washed with saturated brine solution, dried over Na₂SO₄, evaporated under reduced pressure and purified by crystallizing using ethanol (white solid). The recrystallization was done using 1:1 mixture of ethanol and acetone. Yield: 78%. M.p. 498.5–500.5 K. MS calculated for C₁₁H₁₇N₃O₃: 239.126. Found: 239.80 (M+).