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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

3β-Chloro-N-meth­oxy-N-methyl­cholest-5-ene-24-carboxamide

aDepartment of Chemistry, University of Puerto Rico, PO Box 23346, San Juan 00931-3346, Puerto Rico
*Correspondence e-mail: karilysgn@yahoo.com

(Received 11 September 2012; accepted 13 November 2012; online 28 November 2012)

The title compound, C26H42ClNO2, is a 3β-chloro steroid with a Weinreb amide at the C-24 position. The two cyclo­hexane and the cyclo­hexene rings adopt chair and boat conformations, respectively. The cyclo­pentane ring has an envelope conformation.

Related literature

The title compound was obtained as part of our studies on the synthesis of chlorinated steroids as anti­malarial agents. For chlorination of 3β-hydroxyl-5-Δ steroids, see: Liu et al. (2005[Liu, F.-W., Liu, H.-M., Zhang, Y.-B., Zhang, J.-Y. & Tian, L.-H. (2005). Steroids, 70, 825-830.]). For anti­malarial steroids, see: Corrales et al. (2011[Corrales, R. C. N. R., de Souza, N. B., Pinheiro, L. S., Abramo, C., Coimbra, E. S. & Da Silva, A. D. (2011). Biomed. Pharmacother. 65, 198-203.]); Sharma et al. (2008[Sharma, U., Srivastava, K., Puri, S. K. & Singh, C. (2008). Med. Chem. Res. 17, 326-334.]). For the emerging role of chlorinated lipids and fatty acids in pathology, see: Spickett (2007[Spickett, C. M. (2007). Pharmacol. Ther. 115, 400-409.]). For the use of steryl chlorides as synthetic inter­mediates, see: Ochi et al. (1977[Ochi, K., Matsunaga, I. & Shindo, M. (1977). Steroids, 30, 795-803.]). For liquid crystal properties of steryl chlorides, see: Leder (1971[Leder, L. B. (1971). J. Chem. Phys. 54, 4671-4675.]). For chloro­quine-resistant malaria, see: Wellems & Plowe (2001[Wellems, T. E. & Plowe, C. V. (2001). J. Infect. Dis. 184, 770-776.]). For drug resistance in malaria, see: Bloland (2001[Bloland, P. B. (2001). World Health Organization, WHO/CDS/CSR/DRS/2001.4. http://www.who.int/emc .]).

[Scheme 1]

Experimental

Crystal data
  • C26H42ClNO2

  • Mr = 436.06

  • Orthorhombic, P 21 21 21

  • a = 7.5263 (2) Å

  • b = 16.2157 (4) Å

  • c = 20.8850 (5) Å

  • V = 2548.89 (11) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.17 mm−1

  • T = 296 K

  • 0.31 × 0.09 × 0.08 mm

Data collection
  • Bruker APEXII CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2008a[Sheldrick, G. M. (2008a). SADABS. University of Göttingen, Germany.]) Tmin = 0.949, Tmax = 0.987

  • 23203 measured reflections

  • 6244 independent reflections

  • 3307 reflections with I > 2σ(I)

  • Rint = 0.035

Refinement
  • R[F2 > 2σ(F2)] = 0.056

  • wR(F2) = 0.157

  • S = 1.01

  • 6244 reflections

  • 276 parameters

  • H-atom parameters constrained

  • Δρmax = 0.19 e Å−3

  • Δρmin = −0.14 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 2662 Friedel pairs

  • Flack parameter: −0.04 (9)

Data collection: APEX2 (Bruker, 2005[Bruker (2005). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 1999[Bruker (1999). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

The synthesis of the title compound started with the alcohol protection of 5-cholenic acid 3β-ol methyl ester with tert-butyldimethyl silyl chloride. Then it was derivatized to the Weinreb amide in the presence of N-methoxy N-methyl hydroxylamine hydrochloride and dimethyl aluminium chloride with the concomitant chlorination of the 3β-silyl ether to afford compound 1 with retention of configuration at the C-3 position.

This synthetic route is part of our studies on the synthesis of 3β-chloro steroids as antimalarial agents. There is an urgent need to develop new classes of antimalarial drugs due to the development of resistance by the parasite to the commonly used drugs, such as chloroquine [Bloland (2001) and Wellems and Plowe (2001)]. Compound 1 was screened against Plasmodium falciparum, but unfortunely, it showed negligible activity (37.4% inhibition). Our future plans include the synthesis of additional derivatives with different functional groups at C-24. The structure of the title compound was determined by one-dimensional and two-dimensional NMR spectra. To confirm the structure of compound 1, X-ray crystallography was performed.

Related literature top

For chlorination of 3β-hydroxyl-5-Δ steroids, see: Liu et al. (2005). For antimalarial steroids, see: Corrales et al. (2011); Sharma et al. (2008). For the emerging role of chlorinated lipids and fatty acids in pathology, see: Spickett (2007). For the use of steryl chlorides as synthetic intermediates, see: Ochi et al. (1977). For liquid crystal properties of steryl chlorides, see: Leder (1971). For chloroquine-resistant malaria, see: Wellems & Plowe (2001). For drug resistance in malaria, see: Bloland (2001).

Experimental top

Compound 1 was synthesized by the reaction of 5-cholenic acid 3β-ol methyl ester (259 mg, 0.67 mmol) and imidazole (114 mg, 1.68 mmol) in 15 ml of CH2Cl2/DMF (2:1) with 1.0 M tert-butyldimethylsilyl chloride (TBSCl) in CH2Cl2 (1.0 ml, 1.0 mmol). The reaction mixture was stirred for 24 h at room temperature, quenched with NH4Cl (aq) (20 ml), and extracted with CH2Cl2 (3 x 15 ml). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude (378.1 mg) was dissolved in CH2Cl2 (10 ml), then (OMe)NH(Me).HCl (87.8 mg, 0.9 mmol) and 1.0 M Me2AlCl in hexane (1.5 ml, 1.5 mmol) were added. The reaction mixture was stirred at room temperature for 24 h, quenched with a solution of 1.0 M NaOH(aq), and extracted with CH2Cl2 (3 x 10 ml). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Purification by flash-Silica Gel column chromatography [Hex/EtOAc (4:1)] afforded the chlorinated steroid 1 as a white solid in 75% yield (217 mg). Crystals of 1 were obtained by slow evaporation from Hex/CH2Cl2 (2:1) at room temperature. Mp 111–113°C; [α]D20 -27.0 (c 1.0, CHCl3); IR (film) νmax 2948, 1662, 1386, 994 cm-1; 1H NMR (500 MHz, CDCl3) δ 5.33 (br d, 1H), 3.71 (m, 1H), 3.65 (s, 3H), 3.13 (s, 3H), 2.53–2.25 (broad envelope, 4H), 2.04–1.71 (broad envelope, 7H), 1.58–0.82 (broad envelope, 14H), 0.98 (s, 3H), 0.91 (d, J = 6.5 Hz, 3H), 0.64 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 175.1 (C),140.6 (C), 122.3 (CH), 61.1 (CH3), 60.1 (CH), 56.5 (CH), 55.8 (CH), 49.9(CH), 43.3 (CH2), 42.2 (C), 39.5 (CH2), 39.0 (CH2), 36.2 (C), 35.4 (CH), 33.2 (CH2), 32.1 (CH3), 31.7 (CH2), 31.6 (CH), 30.6 (CH2), 28.7 (CH3), 28.0 (CH2), 24.1 (CH2), 20.8 (CH2), 19.1 (CH3), 18.4 (CH3), 11.7 (CH3); HRESIMS m/z [M+ H]+ 436.2977 (calcd for C26H43NO2Cl, 436.2982).

Refinement top

All non-H atoms were refined anisotropically. H atoms were positioned geometrically with C—H=0.96 (CH3), 0.97 (CH2), 0.98 (CH) Å and constrained with Uiso(H) = 1.5 Ueq(parent) for methyl H and Uiso(H) = 1.2 Ueq(parent) for all other atoms.

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008b); molecular graphics: SHELXTL (Sheldrick, 2008b); software used to prepare material for publication: SHELXTL (Sheldrick, 2008b.

Figures top
[Figure 1] Fig. 1. Reaction scheme showing the synthesis of compound 1 from 5-cholenic acid 3β-ol methyl ester with tert-butyldimethyl silyl chloride, N-methoxy N-methyl hydroxylamine hydrochloride, and dimethyl aluminium chloride.
[Figure 2] Fig. 2. Asymmetric unit of compound 1 with 50% probability displacement ellipsoid for non-hydrogen atoms.
[Figure 3] Fig. 3. Packing diagram of compound 1.
3β-Chloro-N-methoxy-N-methylcholest-5-ene-24-carboxamide top
Crystal data top
C26H42ClNO2F(000) = 952
Mr = 436.06Dx = 1.136 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 5845 reflections
a = 7.5263 (2) Åθ = 2.7–20.9°
b = 16.2157 (4) ŵ = 0.17 mm1
c = 20.8850 (5) ÅT = 296 K
V = 2548.89 (11) Å3Needle, colourless
Z = 40.31 × 0.09 × 0.08 mm
Data collection top
Bruker APEXII CCD
diffractometer
6244 independent reflections
Radiation source: fine-focus sealed tube3307 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.035
ϕ and ω scansθmax = 28.3°, θmin = 1.6°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
h = 910
Tmin = 0.949, Tmax = 0.987k = 1921
23203 measured reflectionsl = 2725
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.056H-atom parameters constrained
wR(F2) = 0.157 w = 1/[σ2(Fo2) + (0.0698P)2 + 0.2353P]
where P = (Fo2 + 2Fc2)/3
S = 1.01(Δ/σ)max = 0.001
6244 reflectionsΔρmax = 0.19 e Å3
276 parametersΔρmin = 0.14 e Å3
0 restraintsAbsolute structure: Flack (1983), 2662 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.04 (9)
Crystal data top
C26H42ClNO2V = 2548.89 (11) Å3
Mr = 436.06Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.5263 (2) ŵ = 0.17 mm1
b = 16.2157 (4) ÅT = 296 K
c = 20.8850 (5) Å0.31 × 0.09 × 0.08 mm
Data collection top
Bruker APEXII CCD
diffractometer
6244 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
3307 reflections with I > 2σ(I)
Tmin = 0.949, Tmax = 0.987Rint = 0.035
23203 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.056H-atom parameters constrained
wR(F2) = 0.157Δρmax = 0.19 e Å3
S = 1.01Δρmin = 0.14 e Å3
6244 reflectionsAbsolute structure: Flack (1983), 2662 Friedel pairs
276 parametersAbsolute structure parameter: 0.04 (9)
0 restraints
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.4754 (4)0.8660 (2)0.82833 (14)0.0888 (8)
H1A0.50590.80750.82340.107*
C20.3024 (4)0.8823 (2)0.79438 (14)0.0873 (8)
H2A0.26790.93950.80010.105*
H2B0.20950.84760.81200.105*
C30.3269 (3)0.86371 (18)0.72355 (14)0.0786 (7)
H3A0.21500.87350.70180.094*
H3B0.35510.80570.71880.094*
C40.4729 (3)0.91473 (15)0.69012 (13)0.0666 (6)
C50.6421 (3)0.90625 (15)0.72909 (14)0.0721 (7)
C60.6235 (4)0.9177 (2)0.80067 (14)0.0901 (9)
H6A0.73450.90280.82130.108*
H6B0.60050.97530.80980.108*
C70.4179 (4)1.00624 (17)0.68853 (16)0.0969 (9)
H7A0.49911.03650.66200.145*
H7B0.42051.02830.73120.145*
H7C0.29991.01100.67150.145*
C80.7984 (3)0.89137 (17)0.70284 (15)0.0805 (7)
H80.89450.88440.73030.097*
C90.8336 (3)0.88485 (18)0.63301 (14)0.0823 (8)
H9A0.86360.82820.62280.099*
H9B0.93540.91890.62240.099*
C100.6762 (3)0.91138 (15)0.59167 (13)0.0655 (6)
H100.67330.97180.59030.079*
C110.5021 (3)0.88085 (15)0.62200 (13)0.0653 (6)
H110.51540.82110.62680.078*
C120.3419 (3)0.8934 (2)0.57734 (13)0.0838 (8)
H12A0.31190.95160.57680.101*
H12B0.24100.86400.59500.101*
C130.3702 (3)0.86456 (19)0.50792 (14)0.0820 (8)
H13A0.38050.80490.50710.098*
H13B0.26760.87980.48240.098*
C140.5371 (3)0.90269 (14)0.47859 (13)0.0650 (6)
C150.6915 (3)0.87954 (15)0.52369 (13)0.0661 (6)
H150.68800.81930.52720.079*
C160.8581 (3)0.89897 (19)0.48523 (13)0.0841 (8)
H16A0.95680.86470.49890.101*
H16B0.89110.95650.48990.101*
C170.8063 (3)0.87974 (18)0.41608 (15)0.0838 (8)
H17A0.87000.83150.40100.101*
H17B0.83550.92590.38850.101*
C180.6013 (3)0.86341 (15)0.41517 (13)0.0683 (7)
H180.58470.80370.41930.082*
C190.5143 (4)0.88930 (16)0.35166 (13)0.0748 (7)
H190.53420.94860.34630.090*
C200.3108 (4)0.8747 (2)0.35159 (16)0.0934 (9)
H20A0.25510.91250.38070.140*
H20B0.28630.81910.36480.140*
H20C0.26500.88340.30920.140*
C210.6022 (4)0.84559 (17)0.29503 (14)0.0828 (8)
H21A0.72990.85160.29890.099*
H21B0.57530.78720.29780.099*
C220.5466 (4)0.87628 (18)0.22971 (15)0.0924 (9)
H22A0.42380.86100.22220.111*
H22B0.55350.93600.22920.111*
C230.6578 (5)0.84295 (18)0.17692 (17)0.0880 (9)
C240.6782 (7)0.8149 (3)0.06221 (17)0.169 (2)
H24A0.66170.86000.03310.253*
H24B0.63730.76480.04260.253*
H24C0.80210.80980.07250.253*
C250.2820 (7)0.8083 (4)0.1041 (3)0.206 (3)
H25A0.25530.78690.14590.308*
H25B0.32440.76440.07730.308*
H25C0.17660.83160.08570.308*
C260.5199 (4)0.99713 (16)0.47055 (16)0.0927 (9)
H26A0.49931.02200.51160.139*
H26B0.42211.00920.44260.139*
H26C0.62751.01870.45250.139*
Cl10.45336 (14)0.88904 (7)0.91266 (4)0.1218 (4)
N10.5778 (4)0.83019 (19)0.12042 (14)0.1117 (10)
O10.8116 (3)0.82332 (15)0.18387 (12)0.1129 (7)
O20.4135 (4)0.86944 (18)0.10918 (12)0.1320 (10)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0777 (19)0.097 (2)0.091 (2)0.0030 (17)0.0064 (16)0.0126 (16)
C20.0667 (16)0.102 (2)0.093 (2)0.0062 (16)0.0050 (15)0.0007 (17)
C30.0428 (12)0.1019 (19)0.091 (2)0.0067 (12)0.0009 (12)0.0023 (15)
C40.0453 (12)0.0642 (14)0.0902 (18)0.0023 (10)0.0011 (12)0.0030 (13)
C50.0516 (14)0.0700 (15)0.0948 (19)0.0081 (11)0.0044 (13)0.0106 (14)
C60.0706 (17)0.107 (2)0.092 (2)0.0107 (16)0.0056 (15)0.0163 (17)
C70.094 (2)0.0828 (19)0.114 (2)0.0204 (16)0.0149 (19)0.0036 (16)
C80.0492 (14)0.0975 (19)0.095 (2)0.0045 (14)0.0098 (13)0.0044 (16)
C90.0358 (12)0.0944 (19)0.117 (2)0.0002 (12)0.0061 (13)0.0015 (17)
C100.0367 (11)0.0642 (13)0.0956 (18)0.0018 (10)0.0029 (11)0.0019 (13)
C110.0356 (11)0.0671 (14)0.0932 (17)0.0009 (11)0.0039 (11)0.0005 (13)
C120.0402 (12)0.121 (2)0.0902 (19)0.0062 (13)0.0041 (12)0.0024 (18)
C130.0367 (11)0.111 (2)0.098 (2)0.0021 (13)0.0015 (12)0.0061 (16)
C140.0389 (11)0.0667 (14)0.0894 (17)0.0043 (10)0.0049 (11)0.0033 (13)
C150.0379 (11)0.0656 (13)0.0947 (18)0.0012 (10)0.0050 (11)0.0048 (14)
C160.0430 (12)0.110 (2)0.099 (2)0.0041 (13)0.0065 (13)0.0074 (17)
C170.0508 (13)0.0987 (19)0.102 (2)0.0067 (14)0.0164 (14)0.0180 (17)
C180.0510 (13)0.0613 (14)0.0927 (18)0.0052 (10)0.0045 (13)0.0092 (13)
C190.0675 (15)0.0658 (15)0.0912 (19)0.0138 (13)0.0064 (14)0.0027 (14)
C200.0644 (16)0.110 (2)0.106 (2)0.0140 (17)0.0067 (16)0.0072 (18)
C210.0738 (17)0.0792 (18)0.095 (2)0.0127 (14)0.0052 (16)0.0098 (14)
C220.092 (2)0.0893 (19)0.096 (2)0.0216 (18)0.0097 (18)0.0166 (18)
C230.089 (2)0.0821 (19)0.093 (2)0.0076 (16)0.0044 (19)0.0093 (16)
C240.187 (5)0.238 (5)0.080 (3)0.081 (4)0.019 (3)0.009 (3)
C250.130 (4)0.230 (6)0.257 (7)0.053 (4)0.007 (4)0.138 (6)
C260.091 (2)0.0758 (17)0.112 (2)0.0209 (15)0.0037 (18)0.0001 (16)
Cl10.1189 (7)0.1578 (9)0.0887 (5)0.0178 (6)0.0027 (5)0.0117 (6)
N10.111 (2)0.138 (2)0.0864 (19)0.045 (2)0.0087 (18)0.0013 (17)
O10.0845 (16)0.1295 (17)0.1247 (19)0.0151 (14)0.0060 (14)0.0026 (15)
O20.140 (2)0.146 (2)0.1100 (18)0.051 (2)0.0210 (16)0.0116 (15)
Geometric parameters (Å, º) top
C1—C21.506 (4)C14—C181.547 (4)
C1—C61.510 (4)C15—C161.522 (3)
C1—Cl11.808 (3)C15—H150.9800
C1—H1A0.9800C16—C171.528 (4)
C2—C31.521 (4)C16—H16A0.9700
C2—H2A0.9700C16—H16B0.9700
C2—H2B0.9700C17—C181.566 (4)
C3—C41.543 (4)C17—H17A0.9700
C3—H3A0.9700C17—H17B0.9700
C3—H3B0.9700C18—C191.538 (4)
C4—C51.518 (3)C18—H180.9800
C4—C71.541 (4)C19—C211.529 (4)
C4—C111.541 (4)C19—C201.550 (4)
C5—C81.320 (4)C19—H190.9800
C5—C61.513 (4)C20—H20A0.9600
C6—H6A0.9700C20—H20B0.9600
C6—H6B0.9700C20—H20C0.9600
C7—H7A0.9600C21—C221.511 (4)
C7—H7B0.9600C21—H21A0.9700
C7—H7C0.9600C21—H21B0.9700
C8—C91.486 (4)C22—C231.486 (4)
C8—H80.9300C22—H22A0.9700
C9—C101.527 (3)C22—H22B0.9700
C9—H9A0.9700C23—O11.209 (4)
C9—H9B0.9700C23—N11.341 (4)
C10—C151.515 (4)C24—N11.453 (4)
C10—C111.537 (3)C24—H24A0.9600
C10—H100.9800C24—H24B0.9600
C11—C121.538 (3)C24—H24C0.9600
C11—H110.9800C25—O21.405 (5)
C12—C131.538 (4)C25—H25A0.9600
C12—H12A0.9700C25—H25B0.9600
C12—H12B0.9700C25—H25C0.9600
C13—C141.529 (3)C26—H26A0.9600
C13—H13A0.9700C26—H26B0.9600
C13—H13B0.9700C26—H26C0.9600
C14—C151.542 (3)N1—O21.410 (4)
C14—C261.546 (3)
C2—C1—C6111.1 (2)C15—C14—C18100.81 (18)
C2—C1—Cl1110.1 (2)C26—C14—C18109.9 (2)
C6—C1—Cl1109.0 (2)C10—C15—C16119.1 (2)
C2—C1—H1A108.9C10—C15—C14115.59 (19)
C6—C1—H1A108.9C16—C15—C14104.4 (2)
Cl1—C1—H1A108.9C10—C15—H15105.5
C1—C2—C3108.6 (2)C16—C15—H15105.5
C1—C2—H2A110.0C14—C15—H15105.5
C3—C2—H2A110.0C15—C16—C17104.3 (2)
C1—C2—H2B110.0C15—C16—H16A110.9
C3—C2—H2B110.0C17—C16—H16A110.9
H2A—C2—H2B108.4C15—C16—H16B110.9
C2—C3—C4114.8 (2)C17—C16—H16B110.9
C2—C3—H3A108.6H16A—C16—H16B108.9
C4—C3—H3A108.6C16—C17—C18107.3 (2)
C2—C3—H3B108.6C16—C17—H17A110.3
C4—C3—H3B108.6C18—C17—H17A110.3
H3A—C3—H3B107.5C16—C17—H17B110.3
C5—C4—C7108.9 (2)C18—C17—H17B110.3
C5—C4—C11110.07 (19)H17A—C17—H17B108.5
C7—C4—C11111.2 (2)C19—C18—C14119.5 (2)
C5—C4—C3107.8 (2)C19—C18—C17112.6 (2)
C7—C4—C3109.6 (2)C14—C18—C17103.2 (2)
C11—C4—C3109.2 (2)C19—C18—H18106.9
C8—C5—C6121.0 (2)C14—C18—H18106.9
C8—C5—C4122.8 (3)C17—C18—H18106.9
C6—C5—C4116.2 (2)C21—C19—C18110.9 (2)
C1—C6—C5112.2 (2)C21—C19—C20110.9 (2)
C1—C6—H6A109.2C18—C19—C20112.3 (2)
C5—C6—H6A109.2C21—C19—H19107.5
C1—C6—H6B109.2C18—C19—H19107.5
C5—C6—H6B109.2C20—C19—H19107.5
H6A—C6—H6B107.9C19—C20—H20A109.5
C4—C7—H7A109.5C19—C20—H20B109.5
C4—C7—H7B109.5H20A—C20—H20B109.5
H7A—C7—H7B109.5C19—C20—H20C109.5
C4—C7—H7C109.5H20A—C20—H20C109.5
H7A—C7—H7C109.5H20B—C20—H20C109.5
H7B—C7—H7C109.5C22—C21—C19115.2 (2)
C5—C8—C9125.4 (2)C22—C21—H21A108.5
C5—C8—H8117.3C19—C21—H21A108.5
C9—C8—H8117.3C22—C21—H21B108.5
C8—C9—C10113.4 (2)C19—C21—H21B108.5
C8—C9—H9A108.9H21A—C21—H21B107.5
C10—C9—H9A108.9C23—C22—C21113.2 (2)
C8—C9—H9B108.9C23—C22—H22A108.9
C10—C9—H9B108.9C21—C22—H22A108.9
H9A—C9—H9B107.7C23—C22—H22B108.9
C15—C10—C9112.0 (2)C21—C22—H22B108.9
C15—C10—C11109.96 (19)H22A—C22—H22B107.7
C9—C10—C11109.7 (2)O1—C23—N1119.7 (3)
C15—C10—H10108.4O1—C23—C22123.1 (3)
C9—C10—H10108.4N1—C23—C22117.1 (3)
C11—C10—H10108.4N1—C24—H24A109.5
C10—C11—C12112.1 (2)N1—C24—H24B109.5
C10—C11—C4112.8 (2)H24A—C24—H24B109.5
C12—C11—C4113.62 (19)N1—C24—H24C109.5
C10—C11—H11105.9H24A—C24—H24C109.5
C12—C11—H11105.9H24B—C24—H24C109.5
C4—C11—H11105.9O2—C25—H25A109.5
C11—C12—C13115.00 (19)O2—C25—H25B109.5
C11—C12—H12A108.5H25A—C25—H25B109.5
C13—C12—H12A108.5O2—C25—H25C109.5
C11—C12—H12B108.5H25A—C25—H25C109.5
C13—C12—H12B108.5H25B—C25—H25C109.5
H12A—C12—H12B107.5C14—C26—H26A109.5
C14—C13—C12111.6 (2)C14—C26—H26B109.5
C14—C13—H13A109.3H26A—C26—H26B109.5
C12—C13—H13A109.3C14—C26—H26C109.5
C14—C13—H13B109.3H26A—C26—H26C109.5
C12—C13—H13B109.3H26B—C26—H26C109.5
H13A—C13—H13B108.0C23—N1—O2118.1 (3)
C13—C14—C15106.0 (2)C23—N1—C24121.9 (3)
C13—C14—C26112.0 (2)O2—N1—C24113.2 (3)
C15—C14—C26111.8 (2)C25—O2—N1108.1 (3)
C13—C14—C18115.7 (2)

Experimental details

Crystal data
Chemical formulaC26H42ClNO2
Mr436.06
Crystal system, space groupOrthorhombic, P212121
Temperature (K)296
a, b, c (Å)7.5263 (2), 16.2157 (4), 20.8850 (5)
V3)2548.89 (11)
Z4
Radiation typeMo Kα
µ (mm1)0.17
Crystal size (mm)0.31 × 0.09 × 0.08
Data collection
DiffractometerBruker APEXII CCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 2008a)
Tmin, Tmax0.949, 0.987
No. of measured, independent and
observed [I > 2σ(I)] reflections
23203, 6244, 3307
Rint0.035
(sin θ/λ)max1)0.667
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.056, 0.157, 1.01
No. of reflections6244
No. of parameters276
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.19, 0.14
Absolute structureFlack (1983), 2662 Friedel pairs
Absolute structure parameter0.04 (9)

Computer programs: APEX2 (Bruker, 2005), SAINT (Bruker, 1999), SHELXS97 (Sheldrick, 2008b), SHELXL97 (Sheldrick, 2008b), SHELXTL (Sheldrick, 2008b), SHELXTL (Sheldrick, 2008b.

 

Acknowledgements

The authors thank the Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT) in Panama for the anti­malarial bioassay and Dr Raphel G. Raptis for the use of the X-ray facilitites. Mass spectrometry determinations were provided by the Mass Spectrometry Laboratory of the University of Illinois at Urbana–Champaign. Financial support to KN was provided by the UPR–RISE Fellowship Program (grant 2R25GM061151–11).

References

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First citationSheldrick, G. M. (2008b). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
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