2′-Methyl­pyrazolo[4′,3′:16,17]androst-5-en-3β-ol

Hu-ling Zheng; Peng Xia; Ying Chen

doi:10.1107/S1600536809019539

. 2009 May 29;65(Pt 6):o1436. doi: 10.1107/S1600536809019539

2′-Methylpyrazolo[4′,3′:16,17]androst-5-en-3β-ol

Hu-ling Zheng ^a, Peng Xia ^a, Ying Chen ^a,^*

PMCID: PMC2969823 PMID: 21583276

Abstract

In the title compound, C₂₁H₃₀N₂O, there are five fused rings. The A and C rings adopt chair conformations, ring B adopts an 8β,9α-half-chair conformation and ring D adopts a 14α-envelope conformation. The pyrazole ring is planar. Intermolecular O—H⋯N hydrogen bonds [H⋯N = 1.88 (5) Å] help to stabilize the crystal structure. The absolute structure was deduced from those of the starting materials.

Related literature

For general background, see: Kashiwada et al. (1996 ▶); Spek (2009 ▶).

Experimental

Crystal data

C₂₁H₃₀N₂O
M _r = 326.47
Orthorhombic,
a = 11.779 (4) Å
b = 27.996 (10) Å
c = 6.361 (2) Å
V = 2097.6 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.06 mm⁻¹
T = 293 K
0.20 × 0.10 × 0.08 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.988, T _max = 0.995
10038 measured reflections
2633 independent reflections
1670 reflections with I > 2σ(I)
R _int = 0.089

Refinement

R[F ² > 2σ(F ²)] = 0.065
wR(F ²) = 0.178
S = 0.99
2633 reflections
224 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); 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: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809019539/rk2148sup1.cif

e-65-o1436-sup1.cif^{(20KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809019539/rk2148Isup2.hkl

e-65-o1436-Isup2.hkl^{(129.4KB, 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
O1—H1⋯N2ⁱ	0.96 (5)	1.88 (6)	2.813 (5)	163 (5)

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

The authors acknowledge Miss Wang Jingmei, Center of Analysis and Measurement, Fudan University, for her help with the crystal structure analysis.

supplementary crystallographic information

Comment

The 3-O-(2',2'-dimethylsuccinyl)-betulinic acid, a derivative of natural product betulinic acid, was identified as a potent anti-HIV (human immunodificiency virus) agent with remarkable active value (Kashiwada et al., 1996). Based on the structure and bioactivity of 3-O-(2',2'-dimethylsuccinyl)-betulinic acid, we tried to synthesize some of its steroidal analogs with a heterocycle fused E ring. During synthesizing a target compound 3β-O-(2'',2''-dimethylsuccinyl)-4,4-dimethyl-androst-[17,16- c]-(2'-methyl)pyrazole, an important intermediate, 3β-hydroxy-androst-5-en-[17,16-c]-(2'-methyl)pyrazole, was obtained and its molecular structure was reported here.

Fig.1 shows the molecular structure of the title compound. This compound is a five-ring-fused compound. Ring A and ring C adopt chair conformations in each molecule. The C5–C6 distance of 1.340 (5) Å conform the localization of a double bond at this position. As a result of this double bond, the geometry around C5 is planar and hence ring B adopt 8β,9α-half-chair conformation. The ring D assumes 14α-envelope conformation. The pyrazole E ring is essentially planar. Intermolecular O1–H1···N2ⁱ hydrogen bond with parameters O1–H1 = 0.96 (5)Å, H1···N2ⁱ = 1.88 (6)Å, O1···N2ⁱ = 2.813 (5)Å and angle O1–H1···N2ⁱ = 163 (5)° (symmetry code: (i) -x+3/2, y+1/2, -z) help to stablize the crystal structure.

Experimental

3β-Hydroxy-16-hydroxymethylene-androst-5-en-17-one (500 mg, 1.58 mmol) was dissolved in 10 ml EtOH, and methylhydrazine (120 mg, 2.61 mmol) was added. The resulting mixture was stirred for 2 h at room temperature, and 100 ml H₂O was added. After filtered, washed with water and dried, crude product of title compound (520 mg) was got. The crude product was purified by chromatography with petroleum ether/ EtOAc (10:3) as eluent and recrystallized from tetrahydrofuran to obtain its single-crystal for X-ray diffraction analysis.