organic compounds
N-tert-Butyl-3-hydroxy-5-androstene-17-carboxamide monohydrate
aSchool of Chemistry and Biological Engineering, Changsha University of Science & Technology, Changsha 410004, People's Republic of China, bDepartment of Chemistry, University of Otago, PO Box 56, Dunedin, New Zealand, and cSchool of Chemical Engineering, Hebei University of Technology, Tianjin 300130, People's Republic of China
*Correspondence e-mail: js_li@yahoo.com.cn
In the title compound, C24H39NO2·H2O, the A and C rings of the pregnolene derivative sterol adopt chair conformations, with the B ring in a flattened chair conformation and the five-membered ring in an twisted about the C/D ring junction. The N-tert-butylcarboxamide substituent is equatorial. The 3β-hydroxy H atom and one H atom of the water molecule are disordered over two positions with equal occupancies. In the O—H⋯O hydrogen bonds between the 3β-hydroxy groups of neighbouring molecules form dimers in the bc plane and these dimers are stacked along the a axis by additional O—H⋯O hydrogen bonds involving the water molecules. The of the bulky tert-butyl substituent in the carboxamide chain precludes hydrogen-bond formation by the N—H group.
Related literature
The title compound is an intermediate in the synthesis of finasteride (Li et al., 2001). For pharmaceutical applications of finasteride, N-(tert-butyl)-3-oxo-4-aza-5-androst-1-ene-17-carboxamide, see: Rasmusson et al. (1984, 1986); Rasmusson & Reynold (1985); US National Library of Medicine and National Institutes of Health (2008). For pregnenolone and its derivatives, see: Finar (1959). For the preparation of the title compound, see: Rasmusson et al. (1984); Dolling et al. (1999). For related structures, see: Bordner et al. (1978); Lancaster et al. (2007); Duax et al. (1989); Shukla et al. (2008). For ring puckering analysis, see: Cremer & Pople (1975). For a description of the Cambridge Structural Database, see: Allen (2002).
Experimental
Crystal data
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Refinement
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Data collection: SMART (Bruker, 1997); cell SAINT (Bruker, 1997); 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) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL97, enCIFer (Allen et al., 2004), PLATON (Spek, 2009) and publCIF (Westrip, 2009).
Supporting information
10.1107/S1600536809020984/wm2238sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536809020984/wm2238Isup2.hkl
The title compound was prepared from pregnenolone as previously described (Rasmusson et al., 1984; Dolling et al., 1999). A single-crystal of the title compound, suitable for X-ray analysis, was grown by slow evaporation of the solvent DMF/H2O (1:2 v:v).
The H atoms bound to C were positioned geometrically and constrained to ride on their parent atoms [C—H distances are 0.97–0.98Å for CH2 and CH groups with Uiso(H) = 1.2 Ueq(C), and 0.96 Å for CH3 groups. The O—H and N—H hydrogen atoms were refined with their isotropic displacement parameters 1.2 Ueq(O,N) for the O—H and N—H groups and 1.5 Ueq(O) for the water molecule. Distances were constrained to 0.82 (1) Å for the O—H bond 0.85 (1) Å in the water molecule and 0.90 (1)Å for the N—H bond. The H1O atom on O1 and the H2W atom of the water molecule are each disordered over two positions with equal occupancies. This disorder leads to a close approach of the O1 atoms and their hydrogen atoms on adjacent molecules. The
of (I) could not be determined and Friedel equivalents were averaged in the The chosen configuration was based on that of the pregnenolone precursor with C3 S, C8 R, C9 S, C10 R, C13 S and C14 S.Data collection: SMART (Bruker, 1997); cell
SAINT (Bruker, 1997); data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008), enCIFer (Allen et al., 2004), PLATON (Spek, 2009) and publCIF (Westrip, 2009).C24H39NO2·H2O | F(000) = 864 |
Mr = 391.58 | Dx = 1.144 Mg m−3 |
Monoclinic, C2 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: C 2y | Cell parameters from 734 reflections |
a = 9.934 (6) Å | θ = 3.3–26.2° |
b = 7.469 (5) Å | µ = 0.07 mm−1 |
c = 30.647 (18) Å | T = 293 K |
β = 91.547 (10)° | Block, colourless |
V = 2273 (2) Å3 | 0.40 × 0.30 × 0.15 mm |
Z = 4 |
Bruker SMART 1K CCD diffractometer | 2146 independent reflections |
Radiation source: fine-focus sealed tube | 1735 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.035 |
ϕ and ω scans | θmax = 25.0°, θmin = 2.0° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −11→11 |
Tmin = 0.971, Tmax = 0.989 | k = −5→8 |
4186 measured reflections | l = −32→36 |
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)] = 0.048 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.114 | w = 1/[σ2(Fo2) + (0.0584P)2 + 0.5179P] where P = (Fo2 + 2Fc2)/3 |
S = 1.07 | (Δ/σ)max = 0.003 |
2146 reflections | Δρmax = 0.18 e Å−3 |
277 parameters | Δρmin = −0.15 e Å−3 |
7 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0095 (13) |
C24H39NO2·H2O | V = 2273 (2) Å3 |
Mr = 391.58 | Z = 4 |
Monoclinic, C2 | Mo Kα radiation |
a = 9.934 (6) Å | µ = 0.07 mm−1 |
b = 7.469 (5) Å | T = 293 K |
c = 30.647 (18) Å | 0.40 × 0.30 × 0.15 mm |
β = 91.547 (10)° |
Bruker SMART 1K CCD diffractometer | 2146 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 1735 reflections with I > 2σ(I) |
Tmin = 0.971, Tmax = 0.989 | Rint = 0.035 |
4186 measured reflections |
R[F2 > 2σ(F2)] = 0.048 | 7 restraints |
wR(F2) = 0.114 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.07 | Δρmax = 0.18 e Å−3 |
2146 reflections | Δρmin = −0.15 e Å−3 |
277 parameters |
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 | Occ. (<1) | |
C1 | 0.4428 (4) | 0.2304 (5) | 0.35592 (10) | 0.0384 (9) | |
H1A | 0.4627 | 0.3396 | 0.3403 | 0.046* | |
H1B | 0.3577 | 0.1847 | 0.3443 | 0.046* | |
C3 | 0.3985 (3) | 0.1094 (5) | 0.42947 (10) | 0.0379 (9) | |
H3 | 0.3143 | 0.0565 | 0.4181 | 0.045* | |
O1 | 0.3816 (3) | 0.1542 (4) | 0.47468 (8) | 0.0467 (7) | |
H1OA | 0.450 (6) | 0.128 (13) | 0.489 (3) | 0.070* | 0.50 |
H1OB | 0.358 (10) | 0.052 (5) | 0.480 (3) | 0.070* | 0.50 |
C4 | 0.5102 (4) | −0.0249 (5) | 0.42418 (11) | 0.0374 (9) | |
H4A | 0.5926 | 0.0222 | 0.4374 | 0.045* | |
H4B | 0.4877 | −0.1344 | 0.4394 | 0.045* | |
C5 | 0.5333 (3) | −0.0670 (5) | 0.37715 (10) | 0.0300 (8) | |
C6 | 0.5374 (3) | −0.2341 (5) | 0.36342 (11) | 0.0350 (8) | |
H6 | 0.5238 | −0.3239 | 0.3838 | 0.042* | |
C7 | 0.5621 (3) | −0.2899 (5) | 0.31783 (11) | 0.0346 (8) | |
H7A | 0.4788 | −0.3350 | 0.3048 | 0.042* | |
H7B | 0.6269 | −0.3871 | 0.3183 | 0.042* | |
C8 | 0.6145 (3) | −0.1399 (5) | 0.28958 (10) | 0.0273 (7) | |
H8 | 0.7102 | −0.1216 | 0.2968 | 0.033* | |
C9 | 0.5391 (3) | 0.0331 (4) | 0.29865 (10) | 0.0264 (7) | |
H9 | 0.4435 | 0.0065 | 0.2933 | 0.032* | |
C10 | 0.5527 (3) | 0.0933 (4) | 0.34704 (10) | 0.0268 (7) | |
C19 | 0.6913 (3) | 0.1751 (5) | 0.35760 (10) | 0.0388 (9) | |
H19A | 0.7037 | 0.1859 | 0.3887 | 0.058* | |
H19B | 0.6969 | 0.2914 | 0.3444 | 0.058* | |
H19C | 0.7602 | 0.0992 | 0.3463 | 0.058* | |
C11 | 0.5739 (4) | 0.1816 (5) | 0.26685 (10) | 0.0365 (8) | |
H11A | 0.6649 | 0.2223 | 0.2735 | 0.044* | |
H11B | 0.5138 | 0.2819 | 0.2713 | 0.044* | |
C12 | 0.5642 (4) | 0.1268 (5) | 0.21887 (10) | 0.0372 (9) | |
H12A | 0.4708 | 0.1039 | 0.2106 | 0.045* | |
H12B | 0.5963 | 0.2239 | 0.2009 | 0.045* | |
C13 | 0.6473 (3) | −0.0400 (5) | 0.21091 (10) | 0.0292 (8) | |
C18 | 0.7972 (3) | 0.0009 (5) | 0.21675 (12) | 0.0404 (9) | |
H18A | 0.8486 | −0.1026 | 0.2090 | 0.061* | |
H18B | 0.8169 | 0.0317 | 0.2467 | 0.061* | |
H18C | 0.8204 | 0.0994 | 0.1983 | 0.061* | |
C14 | 0.5993 (3) | −0.1847 (4) | 0.24156 (10) | 0.0288 (8) | |
H14 | 0.5022 | −0.1957 | 0.2357 | 0.035* | |
C15 | 0.6607 (4) | −0.3561 (5) | 0.22482 (12) | 0.0451 (10) | |
H15A | 0.6081 | −0.4594 | 0.2331 | 0.054* | |
H15B | 0.7524 | −0.3708 | 0.2360 | 0.054* | |
C16 | 0.6573 (4) | −0.3311 (6) | 0.17535 (12) | 0.0553 (11) | |
H16A | 0.5903 | −0.4094 | 0.1618 | 0.066* | |
H16B | 0.7444 | −0.3592 | 0.1635 | 0.066* | |
C17 | 0.6212 (4) | −0.1340 (6) | 0.16646 (11) | 0.0389 (9) | |
H17 | 0.5244 | −0.1277 | 0.1596 | 0.047* | |
C20 | 0.6943 (4) | −0.0543 (6) | 0.12881 (12) | 0.0448 (10) | |
O2 | 0.8041 (3) | −0.1105 (5) | 0.11812 (9) | 0.0679 (10) | |
N1 | 0.6348 (3) | 0.0865 (5) | 0.10950 (9) | 0.0459 (9) | |
H1N | 0.553 (2) | 0.120 (6) | 0.1186 (12) | 0.055* | |
C21 | 0.6855 (4) | 0.1911 (7) | 0.07302 (11) | 0.0499 (11) | |
C22 | 0.8179 (5) | 0.2794 (9) | 0.08648 (17) | 0.0811 (16) | |
H22A | 0.8044 | 0.3557 | 0.1112 | 0.122* | |
H22B | 0.8501 | 0.3494 | 0.0626 | 0.122* | |
H22C | 0.8830 | 0.1889 | 0.0941 | 0.122* | |
C23 | 0.5815 (5) | 0.3306 (8) | 0.06214 (15) | 0.0794 (17) | |
H23A | 0.4980 | 0.2733 | 0.0540 | 0.119* | |
H23B | 0.6112 | 0.4024 | 0.0383 | 0.119* | |
H23C | 0.5686 | 0.4054 | 0.0871 | 0.119* | |
C24 | 0.7039 (5) | 0.0700 (9) | 0.03397 (13) | 0.0816 (17) | |
H24A | 0.7758 | −0.0129 | 0.0402 | 0.122* | |
H24B | 0.7255 | 0.1410 | 0.0090 | 0.122* | |
H24C | 0.6221 | 0.0050 | 0.0280 | 0.122* | |
O1W | 0.3597 (4) | 0.5303 (7) | 0.49476 (16) | 0.1038 (14) | |
H1W | 0.416 (6) | 0.553 (13) | 0.5152 (16) | 0.156* | |
H2WA | 0.288 (15) | 0.55 (3) | 0.508 (7) | 0.156* | 0.50 |
H2WB | 0.299 (18) | 0.60 (2) | 0.503 (8) | 0.156* | 0.50 |
C2 | 0.4264 (4) | 0.2760 (5) | 0.40398 (11) | 0.0408 (9) | |
H2A | 0.5080 | 0.3323 | 0.4154 | 0.049* | |
H2B | 0.3527 | 0.3599 | 0.4070 | 0.049* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.049 (2) | 0.037 (2) | 0.0293 (18) | 0.0108 (17) | 0.0050 (15) | 0.0067 (17) |
C3 | 0.0364 (19) | 0.046 (2) | 0.0312 (18) | −0.0048 (18) | −0.0004 (13) | −0.0004 (17) |
O1 | 0.0488 (17) | 0.061 (2) | 0.0309 (14) | −0.0033 (15) | 0.0086 (11) | −0.0015 (14) |
C4 | 0.048 (2) | 0.036 (2) | 0.0277 (18) | −0.0011 (17) | 0.0005 (15) | 0.0079 (16) |
C5 | 0.0281 (17) | 0.032 (2) | 0.0299 (17) | −0.0031 (15) | −0.0014 (13) | 0.0066 (16) |
C6 | 0.038 (2) | 0.033 (2) | 0.0345 (19) | −0.0038 (16) | 0.0023 (14) | 0.0095 (17) |
C7 | 0.0400 (19) | 0.0231 (19) | 0.041 (2) | −0.0042 (15) | 0.0028 (15) | 0.0031 (16) |
C8 | 0.0254 (16) | 0.0282 (18) | 0.0286 (17) | −0.0008 (15) | 0.0034 (12) | 0.0023 (15) |
C9 | 0.0237 (15) | 0.0247 (17) | 0.0306 (17) | 0.0005 (13) | 0.0002 (12) | 0.0023 (14) |
C10 | 0.0296 (17) | 0.0271 (18) | 0.0237 (16) | 0.0045 (14) | 0.0023 (12) | 0.0027 (14) |
C19 | 0.0403 (19) | 0.043 (2) | 0.0332 (18) | −0.0118 (18) | 0.0021 (14) | 0.0019 (18) |
C11 | 0.054 (2) | 0.0279 (19) | 0.0284 (18) | 0.0077 (18) | 0.0066 (15) | 0.0042 (16) |
C12 | 0.043 (2) | 0.041 (2) | 0.0278 (18) | 0.0085 (17) | 0.0038 (14) | 0.0069 (17) |
C13 | 0.0269 (17) | 0.032 (2) | 0.0288 (18) | −0.0008 (15) | 0.0037 (13) | −0.0001 (16) |
C18 | 0.0337 (19) | 0.044 (2) | 0.044 (2) | −0.0035 (17) | 0.0026 (15) | 0.0073 (18) |
C14 | 0.0256 (16) | 0.0274 (19) | 0.0335 (18) | −0.0029 (14) | 0.0020 (13) | −0.0041 (15) |
C15 | 0.056 (2) | 0.036 (2) | 0.043 (2) | −0.0040 (19) | 0.0084 (17) | −0.0065 (18) |
C16 | 0.068 (3) | 0.051 (3) | 0.048 (2) | −0.007 (2) | 0.0149 (19) | −0.014 (2) |
C17 | 0.0376 (19) | 0.049 (2) | 0.0301 (18) | −0.0050 (18) | 0.0024 (14) | −0.0062 (18) |
C20 | 0.044 (2) | 0.057 (3) | 0.033 (2) | −0.001 (2) | 0.0091 (16) | −0.007 (2) |
O2 | 0.062 (2) | 0.089 (3) | 0.0546 (18) | 0.0252 (18) | 0.0296 (14) | 0.0116 (18) |
N1 | 0.0422 (17) | 0.064 (2) | 0.0315 (16) | 0.0094 (17) | 0.0086 (13) | 0.0049 (17) |
C21 | 0.052 (2) | 0.066 (3) | 0.032 (2) | 0.009 (2) | 0.0086 (16) | 0.004 (2) |
C22 | 0.068 (3) | 0.096 (4) | 0.079 (3) | −0.017 (3) | 0.000 (3) | 0.010 (3) |
C23 | 0.088 (3) | 0.095 (4) | 0.056 (3) | 0.027 (3) | 0.019 (2) | 0.021 (3) |
C24 | 0.106 (4) | 0.100 (5) | 0.039 (2) | 0.021 (4) | 0.013 (2) | −0.005 (3) |
O1W | 0.076 (3) | 0.106 (4) | 0.131 (4) | 0.021 (3) | 0.019 (2) | −0.036 (3) |
C2 | 0.049 (2) | 0.041 (2) | 0.0326 (19) | 0.0135 (18) | 0.0085 (15) | −0.0001 (18) |
C1—C2 | 1.525 (5) | C13—C18 | 1.526 (5) |
C1—C10 | 1.527 (5) | C13—C17 | 1.548 (5) |
C1—H1A | 0.9700 | C18—H18A | 0.9600 |
C1—H1B | 0.9700 | C18—H18B | 0.9600 |
C3—O1 | 1.440 (4) | C18—H18C | 0.9600 |
C3—C2 | 1.499 (5) | C14—C15 | 1.514 (5) |
C3—C4 | 1.508 (5) | C14—H14 | 0.9800 |
C3—H3 | 0.9800 | C15—C16 | 1.527 (5) |
O1—H1OA | 0.821 (11) | C15—H15A | 0.9700 |
O1—H1OB | 0.819 (11) | C15—H15B | 0.9700 |
C4—C5 | 1.499 (5) | C16—C17 | 1.537 (6) |
C4—H4A | 0.9700 | C16—H16A | 0.9700 |
C4—H4B | 0.9700 | C16—H16B | 0.9700 |
C5—C6 | 1.318 (5) | C17—C20 | 1.503 (5) |
C5—C10 | 1.527 (5) | C17—H17 | 0.9800 |
C6—C7 | 1.485 (5) | C20—O2 | 1.222 (4) |
C6—H6 | 0.9300 | C20—N1 | 1.337 (5) |
C7—C8 | 1.517 (5) | N1—C21 | 1.465 (5) |
C7—H7A | 0.9700 | N1—H1N | 0.899 (10) |
C7—H7B | 0.9700 | C21—C23 | 1.499 (6) |
C8—C14 | 1.513 (4) | C21—C24 | 1.515 (6) |
C8—C9 | 1.522 (5) | C21—C22 | 1.518 (6) |
C8—H8 | 0.9800 | C22—H22A | 0.9600 |
C9—C11 | 1.523 (5) | C22—H22B | 0.9600 |
C9—C10 | 1.552 (4) | C22—H22C | 0.9600 |
C9—H9 | 0.9800 | C23—H23A | 0.9600 |
C10—C19 | 1.533 (4) | C23—H23B | 0.9600 |
C19—H19A | 0.9600 | C23—H23C | 0.9600 |
C19—H19B | 0.9600 | C24—H24A | 0.9600 |
C19—H19C | 0.9600 | C24—H24B | 0.9600 |
C11—C12 | 1.527 (4) | C24—H24C | 0.9600 |
C11—H11A | 0.9700 | O1W—H1W | 0.847 (11) |
C11—H11B | 0.9700 | O1W—H2WA | 0.850 (11) |
C12—C13 | 1.519 (5) | O1W—H2WB | 0.850 (11) |
C12—H12A | 0.9700 | C2—H2A | 0.9700 |
C12—H12B | 0.9700 | C2—H2B | 0.9700 |
C13—C14 | 1.517 (5) | ||
C2—C1—C10 | 114.7 (3) | C14—C13—C17 | 100.0 (3) |
C2—C1—H1A | 108.6 | C12—C13—C17 | 115.8 (3) |
C10—C1—H1A | 108.6 | C18—C13—C17 | 109.5 (3) |
C2—C1—H1B | 108.6 | C13—C18—H18A | 109.5 |
C10—C1—H1B | 108.6 | C13—C18—H18B | 109.5 |
H1A—C1—H1B | 107.6 | H18A—C18—H18B | 109.5 |
O1—C3—C2 | 109.6 (3) | C13—C18—H18C | 109.5 |
O1—C3—C4 | 111.3 (3) | H18A—C18—H18C | 109.5 |
C2—C3—C4 | 110.4 (3) | H18B—C18—H18C | 109.5 |
O1—C3—H3 | 108.5 | C8—C14—C15 | 119.1 (3) |
C2—C3—H3 | 108.5 | C8—C14—C13 | 114.8 (3) |
C4—C3—H3 | 108.5 | C15—C14—C13 | 104.9 (3) |
C3—O1—H1OA | 110 (7) | C8—C14—H14 | 105.7 |
C3—O1—H1OB | 92 (7) | C15—C14—H14 | 105.7 |
H1OA—O1—H1OB | 85 (9) | C13—C14—H14 | 105.7 |
C5—C4—C3 | 112.0 (3) | C14—C15—C16 | 103.6 (3) |
C5—C4—H4A | 109.2 | C14—C15—H15A | 111.0 |
C3—C4—H4A | 109.2 | C16—C15—H15A | 111.0 |
C5—C4—H4B | 109.2 | C14—C15—H15B | 111.0 |
C3—C4—H4B | 109.2 | C16—C15—H15B | 111.0 |
H4A—C4—H4B | 107.9 | H15A—C15—H15B | 109.0 |
C6—C5—C4 | 120.8 (3) | C15—C16—C17 | 107.0 (3) |
C6—C5—C10 | 122.9 (3) | C15—C16—H16A | 110.3 |
C4—C5—C10 | 116.2 (3) | C17—C16—H16A | 110.3 |
C5—C6—C7 | 125.0 (3) | C15—C16—H16B | 110.3 |
C5—C6—H6 | 117.5 | C17—C16—H16B | 110.3 |
C7—C6—H6 | 117.5 | H16A—C16—H16B | 108.6 |
C6—C7—C8 | 113.4 (3) | C20—C17—C16 | 113.6 (3) |
C6—C7—H7A | 108.9 | C20—C17—C13 | 115.0 (3) |
C8—C7—H7A | 108.9 | C16—C17—C13 | 104.2 (3) |
C6—C7—H7B | 108.9 | C20—C17—H17 | 107.9 |
C8—C7—H7B | 108.9 | C16—C17—H17 | 107.9 |
H7A—C7—H7B | 107.7 | C13—C17—H17 | 107.9 |
C14—C8—C7 | 111.4 (3) | O2—C20—N1 | 122.6 (4) |
C14—C8—C9 | 109.2 (3) | O2—C20—C17 | 121.5 (4) |
C7—C8—C9 | 110.2 (2) | N1—C20—C17 | 115.8 (3) |
C14—C8—H8 | 108.7 | C20—N1—C21 | 126.9 (3) |
C7—C8—H8 | 108.7 | C20—N1—H1N | 118 (3) |
C9—C8—H8 | 108.7 | C21—N1—H1N | 115 (3) |
C8—C9—C11 | 112.3 (2) | N1—C21—C23 | 106.9 (3) |
C8—C9—C10 | 112.9 (3) | N1—C21—C24 | 109.6 (4) |
C11—C9—C10 | 112.6 (3) | C23—C21—C24 | 109.7 (4) |
C8—C9—H9 | 106.1 | N1—C21—C22 | 109.7 (3) |
C11—C9—H9 | 106.1 | C23—C21—C22 | 110.2 (5) |
C10—C9—H9 | 106.1 | C24—C21—C22 | 110.6 (4) |
C5—C10—C1 | 108.4 (2) | C21—C22—H22A | 109.5 |
C5—C10—C19 | 108.2 (3) | C21—C22—H22B | 109.5 |
C1—C10—C19 | 109.8 (3) | H22A—C22—H22B | 109.5 |
C5—C10—C9 | 109.9 (3) | C21—C22—H22C | 109.5 |
C1—C10—C9 | 108.7 (2) | H22A—C22—H22C | 109.5 |
C19—C10—C9 | 111.8 (2) | H22B—C22—H22C | 109.5 |
C10—C19—H19A | 109.5 | C21—C23—H23A | 109.5 |
C10—C19—H19B | 109.5 | C21—C23—H23B | 109.5 |
H19A—C19—H19B | 109.5 | H23A—C23—H23B | 109.5 |
C10—C19—H19C | 109.5 | C21—C23—H23C | 109.5 |
H19A—C19—H19C | 109.5 | H23A—C23—H23C | 109.5 |
H19B—C19—H19C | 109.5 | H23B—C23—H23C | 109.5 |
C9—C11—C12 | 114.3 (3) | C21—C24—H24A | 109.5 |
C9—C11—H11A | 108.7 | C21—C24—H24B | 109.5 |
C12—C11—H11A | 108.7 | H24A—C24—H24B | 109.5 |
C9—C11—H11B | 108.7 | C21—C24—H24C | 109.5 |
C12—C11—H11B | 108.7 | H24A—C24—H24C | 109.5 |
H11A—C11—H11B | 107.6 | H24B—C24—H24C | 109.5 |
C13—C12—C11 | 110.7 (3) | H1W—O1W—H2WA | 98 (10) |
C13—C12—H12A | 109.5 | H1W—O1W—H2WB | 96 (10) |
C11—C12—H12A | 109.5 | H2WA—O1W—H2WB | 29 (10) |
C13—C12—H12B | 109.5 | C3—C2—C1 | 110.1 (3) |
C11—C12—H12B | 109.5 | C3—C2—H2A | 109.6 |
H12A—C12—H12B | 108.1 | C1—C2—H2A | 109.6 |
C14—C13—C12 | 107.7 (2) | C3—C2—H2B | 109.6 |
C14—C13—C18 | 113.1 (3) | C1—C2—H2B | 109.6 |
C12—C13—C18 | 110.5 (3) | H2A—C2—H2B | 108.2 |
O1—C3—C4—C5 | −177.4 (3) | C7—C8—C14—C15 | −55.4 (4) |
C2—C3—C4—C5 | −55.4 (4) | C9—C8—C14—C15 | −177.3 (3) |
C3—C4—C5—C6 | −129.1 (4) | C7—C8—C14—C13 | 179.1 (3) |
C3—C4—C5—C10 | 51.6 (4) | C9—C8—C14—C13 | 57.1 (3) |
C4—C5—C6—C7 | −178.8 (3) | C12—C13—C14—C8 | −60.6 (4) |
C10—C5—C6—C7 | 0.5 (5) | C18—C13—C14—C8 | 61.8 (4) |
C5—C6—C7—C8 | 13.3 (5) | C17—C13—C14—C8 | 178.2 (3) |
C6—C7—C8—C14 | −163.2 (3) | C12—C13—C14—C15 | 166.8 (3) |
C6—C7—C8—C9 | −41.8 (4) | C18—C13—C14—C15 | −70.8 (4) |
C14—C8—C9—C11 | −49.4 (3) | C17—C13—C14—C15 | 45.5 (3) |
C7—C8—C9—C11 | −172.1 (3) | C8—C14—C15—C16 | −165.9 (3) |
C14—C8—C9—C10 | −178.2 (3) | C13—C14—C15—C16 | −35.7 (4) |
C7—C8—C9—C10 | 59.2 (3) | C14—C15—C16—C17 | 11.1 (4) |
C6—C5—C10—C1 | 133.6 (4) | C15—C16—C17—C20 | 142.5 (3) |
C4—C5—C10—C1 | −47.1 (4) | C15—C16—C17—C13 | 16.6 (4) |
C6—C5—C10—C19 | −107.5 (4) | C14—C13—C17—C20 | −162.4 (3) |
C4—C5—C10—C19 | 71.9 (3) | C12—C13—C17—C20 | 82.3 (4) |
C6—C5—C10—C9 | 14.9 (4) | C18—C13—C17—C20 | −43.4 (4) |
C4—C5—C10—C9 | −165.7 (3) | C14—C13—C17—C16 | −37.4 (3) |
C2—C1—C10—C5 | 49.6 (4) | C12—C13—C17—C16 | −152.7 (3) |
C2—C1—C10—C19 | −68.4 (4) | C18—C13—C17—C16 | 81.6 (4) |
C2—C1—C10—C9 | 169.1 (3) | C16—C17—C20—O2 | −26.9 (5) |
C8—C9—C10—C5 | −44.6 (3) | C13—C17—C20—O2 | 93.0 (5) |
C11—C9—C10—C5 | −173.2 (3) | C16—C17—C20—N1 | 156.3 (3) |
C8—C9—C10—C1 | −163.0 (3) | C13—C17—C20—N1 | −83.7 (4) |
C11—C9—C10—C1 | 68.4 (3) | O2—C20—N1—C21 | 1.8 (6) |
C8—C9—C10—C19 | 75.7 (3) | C17—C20—N1—C21 | 178.5 (4) |
C11—C9—C10—C19 | −52.9 (4) | C20—N1—C21—C23 | 178.2 (4) |
C8—C9—C11—C12 | 50.1 (4) | C20—N1—C21—C24 | 59.4 (5) |
C10—C9—C11—C12 | 179.0 (3) | C20—N1—C21—C22 | −62.2 (6) |
C9—C11—C12—C13 | −53.5 (4) | O1—C3—C2—C1 | −179.3 (3) |
C11—C12—C13—C14 | 55.9 (4) | C4—C3—C2—C1 | 57.7 (4) |
C11—C12—C13—C18 | −68.1 (4) | C10—C1—C2—C3 | −57.1 (4) |
C11—C12—C13—C17 | 166.7 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1OA···O1i | 0.82 (1) | 1.99 (4) | 2.783 (6) | 161 (10) |
O1W—H1W···O1Wi | 0.85 (1) | 2.26 (6) | 2.798 (9) | 121 (6) |
O1—H1OB···O1Wii | 0.82 (1) | 2.31 (9) | 2.756 (5) | 115 (8) |
O1W—H2WA···O1iii | 0.85 (1) | 1.93 (6) | 2.756 (5) | 163 (20) |
Symmetry codes: (i) −x+1, y, −z+1; (ii) −x+1/2, y−1/2, −z+1; (iii) −x+1/2, y+1/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C24H39NO2·H2O |
Mr | 391.58 |
Crystal system, space group | Monoclinic, C2 |
Temperature (K) | 293 |
a, b, c (Å) | 9.934 (6), 7.469 (5), 30.647 (18) |
β (°) | 91.547 (10) |
V (Å3) | 2273 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.07 |
Crystal size (mm) | 0.40 × 0.30 × 0.15 |
Data collection | |
Diffractometer | Bruker SMART 1K CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.971, 0.989 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4186, 2146, 1735 |
Rint | 0.035 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.114, 1.07 |
No. of reflections | 2146 |
No. of parameters | 277 |
No. of restraints | 7 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.18, −0.15 |
Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SHELXS97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006), SHELXL97 (Sheldrick, 2008), enCIFer (Allen et al., 2004), PLATON (Spek, 2009) and publCIF (Westrip, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1OA···O1i | 0.821 (11) | 1.99 (4) | 2.783 (6) | 161 (10) |
O1W—H1W···O1Wi | 0.847 (11) | 2.26 (6) | 2.798 (9) | 121 (6) |
O1—H1OB···O1Wii | 0.819 (11) | 2.31 (9) | 2.756 (5) | 115 (8) |
O1W—H2WA···O1iii | 0.850 (11) | 1.93 (6) | 2.756 (5) | 163 (20) |
Symmetry codes: (i) −x+1, y, −z+1; (ii) −x+1/2, y−1/2, −z+1; (iii) −x+1/2, y+1/2, −z+1. |
Acknowledgements
We thank Professor J. Song, Professor L. G. Chen and Dr X. J. Wang, Tianjin University, for their help and also thank Professor G. B. Jameson, Massey University, for useful discussions.
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Finasteride, systematic name N-(tert-butyl)-3-oxo-4-aza-5-androst-1-ene-17-carboxamide, is an azasteroid used in the treatment of both Benign Prostatic Hypertrophy and hair loss in the male adults (Rasmusson et al., 1984,1986; Rasmusson & Reynold, 1985; US National Library of Medicine and National Institutes of Health, 2008). The title compound, (I), Fig. 1, is a derivative of pregnenolone (Finar, 1959) which crystallizes with a solvent water molecule and is a key intermediate in the synthesis of finasteride (Li et al., 2001).
The A and C rings of the steroid skeleton (C1—C5, C10 and C8,C9,C11—C14) have chair conformations (Cremer & Pople, 1975) with atoms C3 and C10 - 0.668 (5) and 0.604 (5) Å from the C1,C2,C4,C5 plane (r.m.s. deviation 0.018 Å) and atoms C9 and C13 - 0.601 (4) and 0.701 (4) Å from the C8,C11,C12,C14 plane (r.m.s. deviation 0.011 Å). Ring B (C5—C10) has a flattened chair conformation with an r.m.s. deviation of 0.091 Å from the plane through atoms C5—C7,C9,C10 with atom C8 displaced 0.588 (4) Å from this plane. The five membered ring D (C13—C17) has an envelope conformation twisted about the C/D ring junction with atom C14 - 0.617 (5) Å from the plane through C13,C15—C17 (r.m.s. deviation 0.082 Å).
The close similarity between this molecule and pregnenolone is amply demonstrated by the fact that the structure overlays with that of pregnenolone (Lancaster et al., 2007; refcode PREGOL01 in the Cambridge Structural Database, version 5.30, Feb. 2009; Allen, 2002) with an r.m.s. deviation of 0.111 Å. This deviation drops to 0.045 Å if the carbonyl O2 atom is omitted from the calculation, Fig. 2 (Macrae et al., 2006). The C16—C17—C20—O2 torsion angle which defines the conformation of the carboxamide group with respect to the main skeleton is -26.9 (5) °, significantly greater than the values in the range -3.0 to 0.6 ° reported for pregnenolone itself (Bordner et al., 1978; Lancaster et al., 2007) but more comparable to those found in pregnenolone derivatives with substituents elsewhere on the steroid backbone (Duax et al., 1989; Shukla et al., 2008).
In the crystal structure O1—H1OA···O1 hydrogen bonds form dimers in the bc plane. O1W—H1W···O1W hydrogen bonds link pairs of water molecules, while O1—H1O···O1W and O1W—H2W···O1 interactions stack the dimers along a (Fig. 3). The amide N1—H1 group is not involved in hydrogen bonding interactions, presumably because of the shielding effect of the bulky tert-butyl substituents.