3β-Chloro-N-methoxy-N-methyl-cholest-5-ene-24-carboxamide.

The title compound, C26H42ClNO2, is a 3β-chloro steroid with a Weinreb amide at the C-24 position. The two cyclo-hexane and the cyclo-hexene rings adopt chair and boat conformations, respectively. The cyclo-pentane 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 ▶). 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

Crystal data

C26H42ClNO2

M = 436.06

Orthorhombic,

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 ▶) T min = 0.949, T max = 0.987

23203 measured reflections

6244 independent reflections

3307 reflections with I > 2σ(I)

R int = 0.035

Refinement

R[F 2 > 2σ(F 2)] = 0.056

wR(F 2) = 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 ▶), 2662 Friedel pairs

Flack parameter: −0.04 (9)

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; 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.

Click here for additional data file.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681204679X/fy2071sup1.cif

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S160053681204679X/fy2071Isup2.cdx

Click here for additional data file.

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681204679X/fy2071Isup3.hkl

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

C26H42ClNO2	F(000) = 952
Mr = 436.06	Dx = 1.136 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 5845 reflections
a = 7.5263 (2) Å	θ = 2.7–20.9°
b = 16.2157 (4) Å	µ = 0.17 mm−1
c = 20.8850 (5) Å	T = 296 K
V = 2548.89 (11) Å3	Needle, colourless
Z = 4	0.31 × 0.09 × 0.08 mm

Bruker APEXII CCD diffractometer	6244 independent reflections
Radiation source: fine-focus sealed tube	3307 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.035
φ and ω scans	θmax = 28.3°, θmin = 1.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 2008a)	h = −9→10
Tmin = 0.949, Tmax = 0.987	k = −19→21
23203 measured reflections	l = −27→25

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.056	H-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 reflections	Δρmax = 0.19 e Å−3
276 parameters	Δρmin = −0.14 e Å−3
0 restraints	Absolute structure: Flack (1983), 2662 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: −0.04 (9)

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.

	x	y	z	Uiso*/Ueq
C1	0.4754 (4)	0.8660 (2)	0.82833 (14)	0.0888 (8)
H1A	0.5059	0.8075	0.8234	0.107*
C2	0.3024 (4)	0.8823 (2)	0.79438 (14)	0.0873 (8)
H2A	0.2679	0.9395	0.8001	0.105*
H2B	0.2095	0.8476	0.8120	0.105*
C3	0.3269 (3)	0.86371 (18)	0.72355 (14)	0.0786 (7)
H3A	0.2150	0.8735	0.7018	0.094*
H3B	0.3551	0.8057	0.7188	0.094*
C4	0.4729 (3)	0.91473 (15)	0.69012 (13)	0.0666 (6)
C5	0.6421 (3)	0.90625 (15)	0.72909 (14)	0.0721 (7)
C6	0.6235 (4)	0.9177 (2)	0.80067 (14)	0.0901 (9)
H6A	0.7345	0.9028	0.8213	0.108*
H6B	0.6005	0.9753	0.8098	0.108*
C7	0.4179 (4)	1.00624 (17)	0.68853 (16)	0.0969 (9)
H7A	0.4991	1.0365	0.6620	0.145*
H7B	0.4205	1.0283	0.7312	0.145*
H7C	0.2999	1.0110	0.6715	0.145*
C8	0.7984 (3)	0.89137 (17)	0.70284 (15)	0.0805 (7)
H8	0.8945	0.8844	0.7303	0.097*
C9	0.8336 (3)	0.88485 (18)	0.63301 (14)	0.0823 (8)
H9A	0.8636	0.8282	0.6228	0.099*
H9B	0.9354	0.9189	0.6224	0.099*
C10	0.6762 (3)	0.91138 (15)	0.59167 (13)	0.0655 (6)
H10	0.6733	0.9718	0.5903	0.079*
C11	0.5021 (3)	0.88085 (15)	0.62200 (13)	0.0653 (6)
H11	0.5154	0.8211	0.6268	0.078*
C12	0.3419 (3)	0.8934 (2)	0.57734 (13)	0.0838 (8)
H12A	0.3119	0.9516	0.5768	0.101*
H12B	0.2410	0.8640	0.5950	0.101*
C13	0.3702 (3)	0.86456 (19)	0.50792 (14)	0.0820 (8)
H13A	0.3805	0.8049	0.5071	0.098*
H13B	0.2676	0.8798	0.4824	0.098*
C14	0.5371 (3)	0.90269 (14)	0.47859 (13)	0.0650 (6)
C15	0.6915 (3)	0.87954 (15)	0.52369 (13)	0.0661 (6)
H15	0.6880	0.8193	0.5272	0.079*
C16	0.8581 (3)	0.89897 (19)	0.48523 (13)	0.0841 (8)
H16A	0.9568	0.8647	0.4989	0.101*
H16B	0.8911	0.9565	0.4899	0.101*
C17	0.8063 (3)	0.87974 (18)	0.41608 (15)	0.0838 (8)
H17A	0.8700	0.8315	0.4010	0.101*
H17B	0.8355	0.9259	0.3885	0.101*
C18	0.6013 (3)	0.86341 (15)	0.41517 (13)	0.0683 (7)
H18	0.5847	0.8037	0.4193	0.082*
C19	0.5143 (4)	0.88930 (16)	0.35166 (13)	0.0748 (7)
H19	0.5342	0.9486	0.3463	0.090*
C20	0.3108 (4)	0.8747 (2)	0.35159 (16)	0.0934 (9)
H20A	0.2551	0.9125	0.3807	0.140*
H20B	0.2863	0.8191	0.3648	0.140*
H20C	0.2650	0.8834	0.3092	0.140*
C21	0.6022 (4)	0.84559 (17)	0.29503 (14)	0.0828 (8)
H21A	0.7299	0.8516	0.2989	0.099*
H21B	0.5753	0.7872	0.2978	0.099*
C22	0.5466 (4)	0.87628 (18)	0.22971 (15)	0.0924 (9)
H22A	0.4238	0.8610	0.2222	0.111*
H22B	0.5535	0.9360	0.2292	0.111*
C23	0.6578 (5)	0.84295 (18)	0.17692 (17)	0.0880 (9)
C24	0.6782 (7)	0.8149 (3)	0.06221 (17)	0.169 (2)
H24A	0.6617	0.8600	0.0331	0.253*
H24B	0.6373	0.7648	0.0426	0.253*
H24C	0.8021	0.8098	0.0725	0.253*
C25	0.2820 (7)	0.8083 (4)	0.1041 (3)	0.206 (3)
H25A	0.2553	0.7869	0.1459	0.308*
H25B	0.3244	0.7644	0.0773	0.308*
H25C	0.1766	0.8316	0.0857	0.308*
C26	0.5199 (4)	0.99713 (16)	0.47055 (16)	0.0927 (9)
H26A	0.4993	1.0220	0.5116	0.139*
H26B	0.4221	1.0092	0.4426	0.139*
H26C	0.6275	1.0187	0.4525	0.139*
Cl1	0.45336 (14)	0.88904 (7)	0.91266 (4)	0.1218 (4)
N1	0.5778 (4)	0.83019 (19)	0.12042 (14)	0.1117 (10)
O1	0.8116 (3)	0.82332 (15)	0.18387 (12)	0.1129 (7)
O2	0.4135 (4)	0.86944 (18)	0.10918 (12)	0.1320 (10)

	U11	U22	U33	U12	U13	U23
C1	0.0777 (19)	0.097 (2)	0.091 (2)	−0.0030 (17)	−0.0064 (16)	−0.0126 (16)
C2	0.0667 (16)	0.102 (2)	0.093 (2)	−0.0062 (16)	0.0050 (15)	0.0007 (17)
C3	0.0428 (12)	0.1019 (19)	0.091 (2)	−0.0067 (12)	0.0009 (12)	0.0023 (15)
C4	0.0453 (12)	0.0642 (14)	0.0902 (18)	0.0023 (10)	0.0011 (12)	−0.0030 (13)
C5	0.0516 (14)	0.0700 (15)	0.0948 (19)	−0.0081 (11)	−0.0044 (13)	−0.0106 (14)
C6	0.0706 (17)	0.107 (2)	0.092 (2)	−0.0107 (16)	−0.0056 (15)	−0.0163 (17)
C7	0.094 (2)	0.0828 (19)	0.114 (2)	0.0204 (16)	0.0149 (19)	−0.0036 (16)
C8	0.0492 (14)	0.0975 (19)	0.095 (2)	−0.0045 (14)	−0.0098 (13)	−0.0044 (16)
C9	0.0358 (12)	0.0944 (19)	0.117 (2)	0.0002 (12)	−0.0061 (13)	−0.0015 (17)
C10	0.0367 (11)	0.0642 (13)	0.0956 (18)	−0.0018 (10)	0.0029 (11)	−0.0019 (13)
C11	0.0356 (11)	0.0671 (14)	0.0932 (17)	−0.0009 (11)	0.0039 (11)	0.0005 (13)
C12	0.0402 (12)	0.121 (2)	0.0902 (19)	0.0062 (13)	0.0041 (12)	−0.0024 (18)
C13	0.0367 (11)	0.111 (2)	0.098 (2)	−0.0021 (13)	−0.0015 (12)	0.0061 (16)
C14	0.0389 (11)	0.0667 (14)	0.0894 (17)	0.0043 (10)	0.0049 (11)	0.0033 (13)
C15	0.0379 (11)	0.0656 (13)	0.0947 (18)	0.0012 (10)	0.0050 (11)	0.0048 (14)
C16	0.0430 (12)	0.110 (2)	0.099 (2)	−0.0041 (13)	0.0065 (13)	0.0074 (17)
C17	0.0508 (13)	0.0987 (19)	0.102 (2)	0.0067 (14)	0.0164 (14)	0.0180 (17)
C18	0.0510 (13)	0.0613 (14)	0.0927 (18)	0.0052 (10)	0.0045 (13)	0.0092 (13)
C19	0.0675 (15)	0.0658 (15)	0.0912 (19)	0.0138 (13)	0.0064 (14)	0.0027 (14)
C20	0.0644 (16)	0.110 (2)	0.106 (2)	0.0140 (17)	−0.0067 (16)	0.0072 (18)
C21	0.0738 (17)	0.0792 (18)	0.095 (2)	0.0127 (14)	0.0052 (16)	0.0098 (14)
C22	0.092 (2)	0.0893 (19)	0.096 (2)	0.0216 (18)	−0.0097 (18)	−0.0166 (18)
C23	0.089 (2)	0.0821 (19)	0.093 (2)	0.0076 (16)	0.0044 (19)	0.0093 (16)
C24	0.187 (5)	0.238 (5)	0.080 (3)	0.081 (4)	0.019 (3)	0.009 (3)
C25	0.130 (4)	0.230 (6)	0.257 (7)	−0.053 (4)	−0.007 (4)	−0.138 (6)
C26	0.091 (2)	0.0758 (17)	0.112 (2)	0.0209 (15)	−0.0037 (18)	−0.0001 (16)
Cl1	0.1189 (7)	0.1578 (9)	0.0887 (5)	−0.0178 (6)	−0.0027 (5)	−0.0117 (6)
N1	0.111 (2)	0.138 (2)	0.0864 (19)	0.045 (2)	0.0087 (18)	−0.0013 (17)
O1	0.0845 (16)	0.1295 (17)	0.1247 (19)	0.0151 (14)	0.0060 (14)	−0.0026 (15)
O2	0.140 (2)	0.146 (2)	0.1100 (18)	0.051 (2)	−0.0210 (16)	−0.0116 (15)

C1—C2	1.506 (4)	C14—C18	1.547 (4)
C1—C6	1.510 (4)	C15—C16	1.522 (3)
C1—Cl1	1.808 (3)	C15—H15	0.9800
C1—H1A	0.9800	C16—C17	1.528 (4)
C2—C3	1.521 (4)	C16—H16A	0.9700
C2—H2A	0.9700	C16—H16B	0.9700
C2—H2B	0.9700	C17—C18	1.566 (4)
C3—C4	1.543 (4)	C17—H17A	0.9700
C3—H3A	0.9700	C17—H17B	0.9700
C3—H3B	0.9700	C18—C19	1.538 (4)
C4—C5	1.518 (3)	C18—H18	0.9800
C4—C7	1.541 (4)	C19—C21	1.529 (4)
C4—C11	1.541 (4)	C19—C20	1.550 (4)
C5—C8	1.320 (4)	C19—H19	0.9800
C5—C6	1.513 (4)	C20—H20A	0.9600
C6—H6A	0.9700	C20—H20B	0.9600
C6—H6B	0.9700	C20—H20C	0.9600
C7—H7A	0.9600	C21—C22	1.511 (4)
C7—H7B	0.9600	C21—H21A	0.9700
C7—H7C	0.9600	C21—H21B	0.9700
C8—C9	1.486 (4)	C22—C23	1.486 (4)
C8—H8	0.9300	C22—H22A	0.9700
C9—C10	1.527 (3)	C22—H22B	0.9700
C9—H9A	0.9700	C23—O1	1.209 (4)
C9—H9B	0.9700	C23—N1	1.341 (4)
C10—C15	1.515 (4)	C24—N1	1.453 (4)
C10—C11	1.537 (3)	C24—H24A	0.9600
C10—H10	0.9800	C24—H24B	0.9600
C11—C12	1.538 (3)	C24—H24C	0.9600
C11—H11	0.9800	C25—O2	1.405 (5)
C12—C13	1.538 (4)	C25—H25A	0.9600
C12—H12A	0.9700	C25—H25B	0.9600
C12—H12B	0.9700	C25—H25C	0.9600
C13—C14	1.529 (3)	C26—H26A	0.9600
C13—H13A	0.9700	C26—H26B	0.9600
C13—H13B	0.9700	C26—H26C	0.9600
C14—C15	1.542 (3)	N1—O2	1.410 (4)
C14—C26	1.546 (3)
C2—C1—C6	111.1 (2)	C15—C14—C18	100.81 (18)
C2—C1—Cl1	110.1 (2)	C26—C14—C18	109.9 (2)
C6—C1—Cl1	109.0 (2)	C10—C15—C16	119.1 (2)
C2—C1—H1A	108.9	C10—C15—C14	115.59 (19)
C6—C1—H1A	108.9	C16—C15—C14	104.4 (2)
Cl1—C1—H1A	108.9	C10—C15—H15	105.5
C1—C2—C3	108.6 (2)	C16—C15—H15	105.5
C1—C2—H2A	110.0	C14—C15—H15	105.5
C3—C2—H2A	110.0	C15—C16—C17	104.3 (2)
C1—C2—H2B	110.0	C15—C16—H16A	110.9
C3—C2—H2B	110.0	C17—C16—H16A	110.9
H2A—C2—H2B	108.4	C15—C16—H16B	110.9
C2—C3—C4	114.8 (2)	C17—C16—H16B	110.9
C2—C3—H3A	108.6	H16A—C16—H16B	108.9
C4—C3—H3A	108.6	C16—C17—C18	107.3 (2)
C2—C3—H3B	108.6	C16—C17—H17A	110.3
C4—C3—H3B	108.6	C18—C17—H17A	110.3
H3A—C3—H3B	107.5	C16—C17—H17B	110.3
C5—C4—C7	108.9 (2)	C18—C17—H17B	110.3
C5—C4—C11	110.07 (19)	H17A—C17—H17B	108.5
C7—C4—C11	111.2 (2)	C19—C18—C14	119.5 (2)
C5—C4—C3	107.8 (2)	C19—C18—C17	112.6 (2)
C7—C4—C3	109.6 (2)	C14—C18—C17	103.2 (2)
C11—C4—C3	109.2 (2)	C19—C18—H18	106.9
C8—C5—C6	121.0 (2)	C14—C18—H18	106.9
C8—C5—C4	122.8 (3)	C17—C18—H18	106.9
C6—C5—C4	116.2 (2)	C21—C19—C18	110.9 (2)
C1—C6—C5	112.2 (2)	C21—C19—C20	110.9 (2)
C1—C6—H6A	109.2	C18—C19—C20	112.3 (2)
C5—C6—H6A	109.2	C21—C19—H19	107.5
C1—C6—H6B	109.2	C18—C19—H19	107.5
C5—C6—H6B	109.2	C20—C19—H19	107.5
H6A—C6—H6B	107.9	C19—C20—H20A	109.5
C4—C7—H7A	109.5	C19—C20—H20B	109.5
C4—C7—H7B	109.5	H20A—C20—H20B	109.5
H7A—C7—H7B	109.5	C19—C20—H20C	109.5
C4—C7—H7C	109.5	H20A—C20—H20C	109.5
H7A—C7—H7C	109.5	H20B—C20—H20C	109.5
H7B—C7—H7C	109.5	C22—C21—C19	115.2 (2)
C5—C8—C9	125.4 (2)	C22—C21—H21A	108.5
C5—C8—H8	117.3	C19—C21—H21A	108.5
C9—C8—H8	117.3	C22—C21—H21B	108.5
C8—C9—C10	113.4 (2)	C19—C21—H21B	108.5
C8—C9—H9A	108.9	H21A—C21—H21B	107.5
C10—C9—H9A	108.9	C23—C22—C21	113.2 (2)
C8—C9—H9B	108.9	C23—C22—H22A	108.9
C10—C9—H9B	108.9	C21—C22—H22A	108.9
H9A—C9—H9B	107.7	C23—C22—H22B	108.9
C15—C10—C9	112.0 (2)	C21—C22—H22B	108.9
C15—C10—C11	109.96 (19)	H22A—C22—H22B	107.7
C9—C10—C11	109.7 (2)	O1—C23—N1	119.7 (3)
C15—C10—H10	108.4	O1—C23—C22	123.1 (3)
C9—C10—H10	108.4	N1—C23—C22	117.1 (3)
C11—C10—H10	108.4	N1—C24—H24A	109.5
C10—C11—C12	112.1 (2)	N1—C24—H24B	109.5
C10—C11—C4	112.8 (2)	H24A—C24—H24B	109.5
C12—C11—C4	113.62 (19)	N1—C24—H24C	109.5
C10—C11—H11	105.9	H24A—C24—H24C	109.5
C12—C11—H11	105.9	H24B—C24—H24C	109.5
C4—C11—H11	105.9	O2—C25—H25A	109.5
C11—C12—C13	115.00 (19)	O2—C25—H25B	109.5
C11—C12—H12A	108.5	H25A—C25—H25B	109.5
C13—C12—H12A	108.5	O2—C25—H25C	109.5
C11—C12—H12B	108.5	H25A—C25—H25C	109.5
C13—C12—H12B	108.5	H25B—C25—H25C	109.5
H12A—C12—H12B	107.5	C14—C26—H26A	109.5
C14—C13—C12	111.6 (2)	C14—C26—H26B	109.5
C14—C13—H13A	109.3	H26A—C26—H26B	109.5
C12—C13—H13A	109.3	C14—C26—H26C	109.5
C14—C13—H13B	109.3	H26A—C26—H26C	109.5
C12—C13—H13B	109.3	H26B—C26—H26C	109.5
H13A—C13—H13B	108.0	C23—N1—O2	118.1 (3)
C13—C14—C15	106.0 (2)	C23—N1—C24	121.9 (3)
C13—C14—C26	112.0 (2)	O2—N1—C24	113.2 (3)
C15—C14—C26	111.8 (2)	C25—O2—N1	108.1 (3)
C13—C14—C18	115.7 (2)