organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 10| October 2014| Pages o1118-o1119

Crystal structure of 9-(4-bromo­but­yl)-9H-fluorene-9-carb­­oxy­lic acid

aTianjin Medical University, Tianjin 300070, People's Republic of China, and bTianjin Institute of Pharmaceutical Research, Tianjin 300193, People's Republic of China
*Correspondence e-mail: liudk@tjipr.com

Edited by V. V. Chernyshev, Moscow State University, Russia (Received 24 July 2014; accepted 29 August 2014; online 24 September 2014)

The title compound, C18H17BrO2, is a key inter­mediate in the synthesis of lomitapide mesylate, a microsomal triglyceride transfer protein inhibitor. Its asymmetric unit contains two independent mol­ecules with slightly different conformations; the mean planes of the 4-bromo­butyl and carboxyl­ate groups in the two mol­ecules form dihedral angles of 24.54 (12) and 17.10 (18)°. In the crystal, carboxyl­ate groups are involved in O—H⋯O hydrogen bonding, which leads to the formation of two crystallographically independent centrosymmetric dimers. Weak inter­molecular C—H⋯O inter­actions further link these dimers into layers parallel to the bc plane.

1. Related literature

For background to the bioactivity and applications of the microsomal triglyceride transfer protein inhibitor lomitapide mesylate, see: Stein et al. (2009[Stein, E. A. (2009). J. Endocrin. Metabol. Clin. North Am. 38, 99-119.]); Cuchel et al. (2013[Cuchel, M., Meagher, E. A., du Toit Theron, H., Blom, D. J., Marais, A. D., Hegele, R. A., Averna, M. R., Sirtori, C. R., Shah, P. K., Gaudet, D., Stefanutti, C., Vigna, G. B., Du Plessis, A. M., Propert, K. J., Sasiela, W. J., Bloedon, L. T. & Rader, D. J. (2013). Lancet, 381, 40-46.]); Burnett & Watts (2007[Burnett, J. R. & Watts, G. F. (2007). Exp. Opin. Ther. Targets, 11, 181-189.]).

[Scheme 1]

2. Experimental

2.1. Crystal data

  • C18H17BrO2

  • Mr = 345.23

  • Triclinic, [P \overline 1]

  • a = 9.897 (2) Å

  • b = 11.800 (2) Å

  • c = 14.202 (3) Å

  • α = 91.59 (3)°

  • β = 95.32 (3)°

  • γ = 104.70 (3)°

  • V = 1595.1 (6) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 2.58 mm−1

  • T = 113 K

  • 0.20 × 0.18 × 0.12 mm

2.2. Data collection

  • Rigaku Saturn diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.]) Tmin = 0.627, Tmax = 0.747

  • 20422 measured reflections

  • 7599 independent reflections

  • 4010 reflections with I > 2σ(I)

  • Rint = 0.056

2.3. Refinement

  • R[F2 > 2σ(F2)] = 0.041

  • wR(F2) = 0.092

  • S = 0.99

  • 7599 reflections

  • 381 parameters

  • H-atom parameters constrained

  • Δρmax = 0.43 e Å−3

  • Δρmin = −1.27 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O2—H2⋯O1i 0.84 1.81 2.652 (2) 175
O3—H3⋯O4ii 0.84 1.80 2.642 (2) 176
C18—H18B⋯O4iii 0.99 2.54 3.377 (4) 142
C36—H36B⋯O1iv 0.99 2.44 3.386 (4) 159
Symmetry codes: (i) -x, -y+2, -z+1; (ii) -x+2, -y+1, -z; (iii) -x+1, -y+1, -z; (iv) -x+1, -y+1, -z+1.

Data collection: CrystalClear (Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

Lomitapide mesylate is a microsomal triglyceride transfer protein inhibitor which can lower the level of low density lipoprotein cholesterol in plasma. It has a new mechanism on lowering the lipid and mainly used by patients with homozygous familial hypercholesterolemia (Stein et al. (2009); Cuchel et al. (2013); Burnett & Watts (2007). The crystal structure of the title compound, a key intermediate in the synthesis of lomitapide mesylate is reported here.

As shown in Fig. 1, it crystallizes with two similar molecules (A and B) in the asymmetric unit. In molecule A, the C2–C14 triple-ring plane and the carbon chain plane defined by C1/C2/C15/C16/C17/C18 formed a dihedral angle of 86.88 (11)°. Molecule B exhibited a similar conformation to molecule A, with the dihedral angle of 86.85 (11)°. In the crystal, the packing is realised by intermolecular C—H···O and O—H···O interactions.

Related literature top

For background to the bioactivity and applications of the microsomal triglyceride transfer protein inhibitor lomitapide mesylate, see: Stein et al. (2009); Cuchel et al. (2013); Burnett & Watts (2007).

Experimental top

9-(4-Bromobutyl)-9H-fluorene-9-carboxylic acid 5.0 g (0.024 mol) 9H-fluorene-9-carboxylic acid was dissolved into 120 ml THF at 273 K, a solution of n-butyllithium (2.5 M, 22 ml, 0.055 mol) in THF was dropwised into the mixture and stirred for 1 h. Then 1,4-dibromobutane (3.2 ml, 0.026 mol) was added dropwise over 30 min. The reaction was stirred at 273 K for 30 min. Then the reaction was warmed to room temperature for 30 h. The reaction was extracted with water (3 × 75 ml), the combined aqueous was extracted with 2-methoxy-2-methylpropane (80 ml). The aqueous was made acidic with HCl (1 N, 50 ml), then extracted with dichloromethane (3 × 75 ml), the combined organic layers ere dried over Na2SO4. Evaporation gave 7.0 g yellow solid as crude product. The solid was dissolved in a mixture of petroleum ether (24 ml) and ethyl acetate (4 ml) at 298 K, then white crystals were generated slowly. 1H NMR (400 MHz, DMSO-d6) δ: 12.53 (br s, 1H, COOH), 7.54 (d, J=7.2 Hz, 2H, ArH), 7.68 (d, J=7.2 Hz, 2 H, Ar H), 7.42–7.38 (m, 2H, ArH), 7.35–7.25 (m, 2H, ArH), 3.31 (t, J=13.2 Hz, 2H, CH2), 2.32–2.28 (m, 2H, CH2), 1.65–1.57 (m, 2H, CH2), 0.80–0.72 (m, 2H, CH2).

Refinement top

All the H atoms were geometrically positioned with O—H=0.84 Å, C—H=0.95 Å (aromatic CH) and 0.99 Å (CH2), Uiso = 1.5 or 1.2Ueq(O or C).

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear (Rigaku/MSC, 2005); data reduction: CrystalClear (Rigaku/MSC, 2005); 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 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The content of asymmetric unit of (I) showing the atomic numbering and 50% probability displacement ellipsoids.
9-(4-Bromobutyl)-9H-fluorene-9-carboxylic acid top
Crystal data top
C18H17BrO2Z = 4
Mr = 345.23F(000) = 704
Triclinic, P1Dx = 1.438 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 9.897 (2) ÅCell parameters from 4642 reflections
b = 11.800 (2) Åθ = 1.8–27.9°
c = 14.202 (3) ŵ = 2.58 mm1
α = 91.59 (3)°T = 113 K
β = 95.32 (3)°Cubic, colorless
γ = 104.70 (3)°0.20 × 0.18 × 0.12 mm
V = 1595.1 (6) Å3
Data collection top
Rigaku Saturn
diffractometer
7599 independent reflections
Radiation source: rotating anode4010 reflections with I > 2σ(I)
Confocal monochromatorRint = 0.056
ω scansθmax = 27.9°, θmin = 1.8°
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
h = 1213
Tmin = 0.627, Tmax = 0.747k = 1515
20422 measured reflectionsl = 1818
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.041Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.092H-atom parameters constrained
S = 0.99 w = 1/[σ2(Fo2) + (0.0306P)2]
where P = (Fo2 + 2Fc2)/3
7599 reflections(Δ/σ)max = 0.001
381 parametersΔρmax = 0.43 e Å3
0 restraintsΔρmin = 1.27 e Å3
Crystal data top
C18H17BrO2γ = 104.70 (3)°
Mr = 345.23V = 1595.1 (6) Å3
Triclinic, P1Z = 4
a = 9.897 (2) ÅMo Kα radiation
b = 11.800 (2) ŵ = 2.58 mm1
c = 14.202 (3) ÅT = 113 K
α = 91.59 (3)°0.20 × 0.18 × 0.12 mm
β = 95.32 (3)°
Data collection top
Rigaku Saturn
diffractometer
7599 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
4010 reflections with I > 2σ(I)
Tmin = 0.627, Tmax = 0.747Rint = 0.056
20422 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0410 restraints
wR(F2) = 0.092H-atom parameters constrained
S = 0.99Δρmax = 0.43 e Å3
7599 reflectionsΔρmin = 1.27 e Å3
381 parameters
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
Br10.38791 (3)0.59238 (3)0.04660 (2)0.03473 (11)
Br20.59649 (4)0.07669 (3)0.40874 (3)0.04780 (13)
O10.0453 (2)0.90473 (15)0.43181 (12)0.0218 (5)
O20.0497 (2)1.08986 (16)0.39999 (13)0.0272 (5)
H20.01551.08890.45200.041*
O30.9568 (2)0.57553 (15)0.10428 (13)0.0242 (5)
H30.98560.58720.05070.036*
O40.96586 (19)0.39224 (16)0.06820 (12)0.0215 (5)
C10.0668 (3)0.9857 (2)0.37874 (19)0.0180 (6)
C20.1092 (3)0.9715 (2)0.27999 (18)0.0171 (6)
C30.0231 (3)0.9517 (2)0.21020 (19)0.0164 (6)
C40.1440 (3)0.8610 (2)0.2065 (2)0.0230 (7)
H40.15280.80120.25060.028*
C50.2520 (3)0.8600 (3)0.1364 (2)0.0299 (8)
H50.33570.79830.13190.036*
C60.2388 (3)0.9486 (3)0.0728 (2)0.0309 (8)
H60.31480.94740.02640.037*
C70.1180 (3)1.0380 (3)0.07561 (19)0.0267 (7)
H70.10941.09740.03110.032*
C80.0079 (3)1.0394 (2)0.14550 (18)0.0177 (6)
C90.1317 (3)1.1203 (2)0.16555 (19)0.0191 (7)
C100.2006 (3)1.2164 (2)0.1180 (2)0.0277 (7)
H100.15541.24050.06310.033*
C110.3360 (3)1.2758 (3)0.1524 (2)0.0339 (8)
H110.38531.34020.11980.041*
C120.4013 (3)1.2424 (3)0.2345 (2)0.0337 (8)
H120.49311.28600.25860.040*
C130.3334 (3)1.1463 (2)0.2813 (2)0.0258 (7)
H130.37861.12260.33650.031*
C140.1997 (3)1.0857 (2)0.24656 (19)0.0179 (6)
C150.1813 (3)0.8696 (2)0.27546 (18)0.0196 (6)
H15A0.26450.88650.32310.024*
H15B0.11540.79640.29180.024*
C160.2273 (3)0.8515 (2)0.17776 (19)0.0232 (7)
H16A0.14470.83820.13000.028*
H16B0.29600.92390.16270.028*
C170.2932 (3)0.7488 (2)0.17017 (19)0.0216 (7)
H17A0.37790.76200.21610.026*
H17B0.22570.67560.18500.026*
C180.3326 (3)0.7377 (2)0.0703 (2)0.0234 (7)
H18A0.41140.80550.05990.028*
H18B0.25160.73980.02450.028*
C190.9441 (3)0.4653 (2)0.12332 (18)0.0173 (6)
C200.9030 (3)0.4356 (2)0.22235 (18)0.0163 (6)
C210.8124 (3)0.5103 (2)0.26096 (18)0.0177 (6)
C220.6789 (3)0.5146 (2)0.2272 (2)0.0229 (7)
H220.63450.47420.16930.027*
C230.6111 (3)0.5795 (3)0.2798 (2)0.0315 (8)
H230.51910.58370.25750.038*
C240.6753 (4)0.6384 (2)0.3645 (2)0.0340 (8)
H240.62550.68000.40060.041*
C250.8112 (3)0.6373 (2)0.3970 (2)0.0300 (8)
H250.85630.67960.45400.036*
C260.8800 (3)0.5728 (2)0.34435 (19)0.0202 (7)
C271.0206 (3)0.5536 (2)0.36167 (19)0.0213 (7)
C281.1289 (3)0.5984 (3)0.4320 (2)0.0313 (8)
H281.11920.65340.47940.038*
C291.2500 (4)0.5630 (3)0.4328 (2)0.0372 (8)
H291.32530.59520.48020.045*
C301.2649 (3)0.4797 (3)0.3648 (2)0.0339 (8)
H301.34870.45410.36730.041*
C311.1569 (3)0.4349 (3)0.2937 (2)0.0261 (7)
H311.16650.37920.24690.031*
C321.0353 (3)0.4722 (2)0.29201 (18)0.0174 (6)
C330.8311 (3)0.3036 (2)0.22100 (18)0.0187 (6)
H33A0.74390.28660.17700.022*
H33B0.89400.25940.19610.022*
C340.7946 (3)0.2601 (2)0.31781 (18)0.0197 (6)
H34A0.73320.30500.34380.024*
H34B0.88180.27420.36160.024*
C350.7200 (3)0.1295 (2)0.31216 (19)0.0202 (7)
H35A0.63570.11400.26560.024*
H35B0.78350.08350.29070.024*
C360.6774 (3)0.0922 (2)0.4085 (2)0.0241 (7)
H36A0.60790.13370.42710.029*
H36B0.76080.11510.45590.029*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.0455 (2)0.03137 (19)0.0336 (2)0.02173 (17)0.00528 (16)0.00455 (15)
Br20.0734 (3)0.02000 (18)0.0541 (3)0.00884 (18)0.0332 (2)0.01456 (16)
O10.0330 (12)0.0178 (10)0.0172 (11)0.0085 (9)0.0088 (9)0.0051 (9)
O20.0465 (14)0.0209 (11)0.0210 (12)0.0163 (10)0.0155 (11)0.0054 (9)
O30.0395 (13)0.0197 (11)0.0137 (11)0.0036 (10)0.0134 (10)0.0048 (9)
O40.0307 (12)0.0228 (11)0.0141 (10)0.0096 (10)0.0101 (9)0.0029 (9)
C10.0188 (16)0.0206 (15)0.0163 (15)0.0071 (13)0.0039 (13)0.0048 (13)
C20.0225 (17)0.0175 (15)0.0143 (15)0.0088 (13)0.0046 (13)0.0061 (12)
C30.0196 (16)0.0161 (15)0.0152 (15)0.0070 (13)0.0038 (12)0.0021 (12)
C40.0243 (18)0.0231 (16)0.0215 (16)0.0049 (14)0.0043 (14)0.0035 (13)
C50.0242 (18)0.0299 (18)0.0324 (19)0.0023 (15)0.0014 (15)0.0035 (15)
C60.0304 (19)0.041 (2)0.0225 (18)0.0154 (17)0.0065 (15)0.0037 (15)
C70.038 (2)0.0330 (18)0.0142 (16)0.0183 (16)0.0020 (14)0.0054 (14)
C80.0261 (17)0.0177 (15)0.0131 (15)0.0115 (13)0.0054 (13)0.0032 (12)
C90.0253 (18)0.0186 (15)0.0196 (16)0.0123 (13)0.0136 (13)0.0066 (12)
C100.041 (2)0.0217 (16)0.0285 (18)0.0168 (15)0.0164 (16)0.0126 (14)
C110.032 (2)0.0185 (16)0.054 (2)0.0038 (15)0.0239 (18)0.0115 (16)
C120.0244 (19)0.0214 (17)0.054 (2)0.0011 (14)0.0112 (17)0.0044 (16)
C130.0217 (18)0.0260 (17)0.0325 (19)0.0103 (14)0.0046 (15)0.0058 (14)
C140.0195 (16)0.0151 (14)0.0225 (16)0.0073 (13)0.0113 (13)0.0035 (12)
C150.0243 (17)0.0190 (15)0.0185 (15)0.0091 (13)0.0061 (13)0.0060 (12)
C160.0277 (18)0.0244 (16)0.0230 (16)0.0136 (14)0.0099 (14)0.0063 (13)
C170.0255 (17)0.0196 (15)0.0218 (16)0.0090 (13)0.0049 (14)0.0005 (13)
C180.0265 (18)0.0156 (15)0.0310 (18)0.0099 (13)0.0051 (14)0.0010 (13)
C190.0170 (16)0.0195 (15)0.0140 (15)0.0021 (13)0.0009 (12)0.0032 (12)
C200.0207 (16)0.0164 (15)0.0111 (14)0.0013 (13)0.0082 (12)0.0008 (12)
C210.0250 (17)0.0133 (14)0.0146 (15)0.0016 (13)0.0086 (13)0.0040 (12)
C220.0290 (18)0.0192 (15)0.0201 (16)0.0029 (14)0.0081 (14)0.0054 (13)
C230.034 (2)0.0291 (18)0.038 (2)0.0138 (16)0.0166 (17)0.0171 (16)
C240.054 (2)0.0190 (17)0.038 (2)0.0170 (16)0.0279 (18)0.0100 (15)
C250.051 (2)0.0172 (16)0.0234 (18)0.0083 (16)0.0149 (16)0.0016 (13)
C260.0321 (18)0.0114 (14)0.0166 (15)0.0014 (13)0.0105 (14)0.0039 (12)
C270.0308 (18)0.0146 (14)0.0151 (15)0.0025 (13)0.0068 (14)0.0045 (12)
C280.043 (2)0.0282 (18)0.0154 (16)0.0042 (16)0.0020 (15)0.0005 (14)
C290.036 (2)0.045 (2)0.0208 (18)0.0044 (18)0.0052 (15)0.0095 (16)
C300.0180 (18)0.048 (2)0.0325 (19)0.0017 (16)0.0013 (15)0.0132 (17)
C310.0258 (18)0.0309 (18)0.0212 (17)0.0051 (15)0.0064 (14)0.0045 (14)
C320.0210 (17)0.0164 (14)0.0125 (14)0.0012 (13)0.0058 (12)0.0033 (12)
C330.0235 (17)0.0170 (15)0.0152 (15)0.0021 (13)0.0083 (13)0.0015 (12)
C340.0243 (17)0.0190 (15)0.0152 (15)0.0026 (13)0.0058 (13)0.0029 (12)
C350.0259 (17)0.0152 (14)0.0201 (16)0.0045 (13)0.0066 (13)0.0056 (12)
C360.0298 (18)0.0159 (15)0.0256 (17)0.0017 (13)0.0083 (14)0.0061 (13)
Geometric parameters (Å, º) top
Br1—C181.958 (2)C17—H17A0.9900
Br2—C361.951 (3)C17—H17B0.9900
O1—C11.221 (3)C18—H18A0.9900
O2—C11.314 (3)C18—H18B0.9900
O2—H20.8400C19—C201.525 (3)
O3—C191.313 (3)C20—C321.525 (4)
O3—H30.8400C20—C211.532 (4)
O4—C191.221 (3)C20—C331.538 (3)
C1—C21.517 (3)C21—C221.377 (4)
C2—C31.530 (4)C21—C261.396 (4)
C2—C141.531 (3)C22—C231.385 (4)
C2—C151.549 (3)C22—H220.9500
C3—C41.383 (4)C23—C241.386 (4)
C3—C81.392 (3)C23—H230.9500
C4—C51.389 (4)C24—C251.384 (4)
C4—H40.9500C24—H240.9500
C5—C61.389 (4)C25—C261.389 (4)
C5—H50.9500C25—H250.9500
C6—C71.376 (4)C26—C271.465 (4)
C6—H60.9500C27—C281.383 (4)
C7—C81.400 (4)C27—C321.402 (3)
C7—H70.9500C28—C291.364 (4)
C8—C91.464 (4)C28—H280.9500
C9—C101.394 (4)C29—C301.404 (4)
C9—C141.402 (4)C29—H290.9500
C10—C111.381 (4)C30—C311.386 (4)
C10—H100.9500C30—H300.9500
C11—C121.396 (4)C31—C321.382 (4)
C11—H110.9500C31—H310.9500
C12—C131.385 (4)C33—C341.524 (3)
C12—H120.9500C33—H33A0.9900
C13—C141.373 (4)C33—H33B0.9900
C13—H130.9500C34—C351.527 (3)
C15—C161.526 (3)C34—H34A0.9900
C15—H15A0.9900C34—H34B0.9900
C15—H15B0.9900C35—C361.513 (3)
C16—C171.520 (3)C35—H35A0.9900
C16—H16A0.9900C35—H35B0.9900
C16—H16B0.9900C36—H36A0.9900
C17—C181.517 (3)C36—H36B0.9900
C1—O2—H2109.5H18A—C18—H18B107.9
C19—O3—H3109.5O4—C19—O3123.7 (2)
O1—C1—O2123.5 (2)O4—C19—C20122.1 (2)
O1—C1—C2122.1 (2)O3—C19—C20114.2 (2)
O2—C1—C2114.3 (2)C19—C20—C32108.3 (2)
C1—C2—C3107.7 (2)C19—C20—C21113.9 (2)
C1—C2—C14112.7 (2)C32—C20—C21101.4 (2)
C3—C2—C14101.3 (2)C19—C20—C33108.3 (2)
C1—C2—C15109.8 (2)C32—C20—C33113.0 (2)
C3—C2—C15112.9 (2)C21—C20—C33112.0 (2)
C14—C2—C15112.2 (2)C22—C21—C26121.1 (2)
C4—C3—C8121.6 (3)C22—C21—C20128.5 (2)
C4—C3—C2127.8 (2)C26—C21—C20110.3 (2)
C8—C3—C2110.6 (2)C21—C22—C23118.3 (3)
C3—C4—C5118.1 (3)C21—C22—H22120.8
C3—C4—H4120.9C23—C22—H22120.8
C5—C4—H4120.9C22—C23—C24121.0 (3)
C4—C5—C6120.6 (3)C22—C23—H23119.5
C4—C5—H5119.7C24—C23—H23119.5
C6—C5—H5119.7C25—C24—C23120.7 (3)
C7—C6—C5121.4 (3)C25—C24—H24119.6
C7—C6—H6119.3C23—C24—H24119.6
C5—C6—H6119.3C24—C25—C26118.5 (3)
C6—C7—C8118.5 (3)C24—C25—H25120.8
C6—C7—H7120.7C26—C25—H25120.8
C8—C7—H7120.7C25—C26—C21120.3 (3)
C3—C8—C7119.7 (3)C25—C26—C27130.7 (3)
C3—C8—C9109.0 (2)C21—C26—C27109.1 (2)
C7—C8—C9131.2 (3)C28—C27—C32120.1 (3)
C10—C9—C14120.0 (3)C28—C27—C26131.5 (3)
C10—C9—C8131.3 (3)C32—C27—C26108.4 (2)
C14—C9—C8108.6 (2)C29—C28—C27119.4 (3)
C11—C10—C9118.7 (3)C29—C28—H28120.3
C11—C10—H10120.7C27—C28—H28120.3
C9—C10—H10120.7C28—C29—C30121.0 (3)
C10—C11—C12120.8 (3)C28—C29—H29119.5
C10—C11—H11119.6C30—C29—H29119.5
C12—C11—H11119.6C31—C30—C29119.8 (3)
C13—C12—C11120.6 (3)C31—C30—H30120.1
C13—C12—H12119.7C29—C30—H30120.1
C11—C12—H12119.7C32—C31—C30119.1 (3)
C14—C13—C12118.9 (3)C32—C31—H31120.4
C14—C13—H13120.6C30—C31—H31120.4
C12—C13—H13120.6C31—C32—C27120.5 (3)
C13—C14—C9121.0 (3)C31—C32—C20128.9 (3)
C13—C14—C2128.5 (3)C27—C32—C20110.7 (2)
C9—C14—C2110.3 (2)C34—C33—C20113.8 (2)
C16—C15—C2112.3 (2)C34—C33—H33A108.8
C16—C15—H15A109.1C20—C33—H33A108.8
C2—C15—H15A109.1C34—C33—H33B108.8
C16—C15—H15B109.1C20—C33—H33B108.8
C2—C15—H15B109.1H33A—C33—H33B107.7
H15A—C15—H15B107.9C33—C34—C35111.7 (2)
C17—C16—C15113.4 (2)C33—C34—H34A109.3
C17—C16—H16A108.9C35—C34—H34A109.3
C15—C16—H16A108.9C33—C34—H34B109.3
C17—C16—H16B108.9C35—C34—H34B109.3
C15—C16—H16B108.9H34A—C34—H34B107.9
H16A—C16—H16B107.7C36—C35—C34109.7 (2)
C18—C17—C16109.0 (2)C36—C35—H35A109.7
C18—C17—H17A109.9C34—C35—H35A109.7
C16—C17—H17A109.9C36—C35—H35B109.7
C18—C17—H17B109.9C34—C35—H35B109.7
C16—C17—H17B109.9H35A—C35—H35B108.2
H17A—C17—H17B108.3C35—C36—Br2111.74 (18)
C17—C18—Br1112.16 (19)C35—C36—H36A109.3
C17—C18—H18A109.2Br2—C36—H36A109.3
Br1—C18—H18A109.2C35—C36—H36B109.3
C17—C18—H18B109.2Br2—C36—H36B109.3
Br1—C18—H18B109.2H36A—C36—H36B107.9
O1—C1—C2—C398.5 (3)O4—C19—C20—C3297.0 (3)
O2—C1—C2—C378.8 (3)O3—C19—C20—C3281.4 (3)
O1—C1—C2—C14150.7 (3)O4—C19—C20—C21151.1 (3)
O2—C1—C2—C1432.1 (3)O3—C19—C20—C2130.5 (3)
O1—C1—C2—C1524.8 (4)O4—C19—C20—C3325.8 (4)
O2—C1—C2—C15158.0 (2)O3—C19—C20—C33155.8 (2)
C1—C2—C3—C460.8 (3)C19—C20—C21—C2264.4 (4)
C14—C2—C3—C4179.3 (2)C32—C20—C21—C22179.6 (3)
C15—C2—C3—C460.6 (3)C33—C20—C21—C2258.9 (4)
C1—C2—C3—C8120.0 (2)C19—C20—C21—C26120.0 (3)
C14—C2—C3—C81.5 (3)C32—C20—C21—C264.0 (3)
C15—C2—C3—C8118.7 (2)C33—C20—C21—C26116.7 (2)
C8—C3—C4—C50.7 (4)C26—C21—C22—C232.2 (4)
C2—C3—C4—C5179.8 (3)C20—C21—C22—C23173.0 (2)
C3—C4—C5—C60.7 (4)C21—C22—C23—C240.2 (4)
C4—C5—C6—C71.6 (4)C22—C23—C24—C252.3 (4)
C5—C6—C7—C81.0 (4)C23—C24—C25—C262.0 (4)
C4—C3—C8—C71.2 (4)C24—C25—C26—C210.4 (4)
C2—C3—C8—C7179.5 (2)C24—C25—C26—C27178.7 (3)
C4—C3—C8—C9178.3 (2)C22—C21—C26—C252.5 (4)
C2—C3—C8—C91.0 (3)C20—C21—C26—C25173.5 (2)
C6—C7—C8—C30.3 (4)C22—C21—C26—C27178.9 (2)
C6—C7—C8—C9179.0 (3)C20—C21—C26—C275.1 (3)
C3—C8—C9—C10175.1 (3)C25—C26—C27—C284.1 (5)
C7—C8—C9—C104.3 (5)C21—C26—C27—C28177.5 (3)
C3—C8—C9—C143.4 (3)C25—C26—C27—C32174.3 (3)
C7—C8—C9—C14177.3 (3)C21—C26—C27—C324.2 (3)
C14—C9—C10—C110.0 (4)C32—C27—C28—C290.1 (4)
C8—C9—C10—C11178.2 (3)C26—C27—C28—C29178.3 (3)
C9—C10—C11—C121.7 (4)C27—C28—C29—C301.5 (5)
C10—C11—C12—C132.4 (5)C28—C29—C30—C311.9 (5)
C11—C12—C13—C141.2 (4)C29—C30—C31—C320.8 (4)
C12—C13—C14—C90.4 (4)C30—C31—C32—C270.6 (4)
C12—C13—C14—C2174.0 (2)C30—C31—C32—C20179.6 (3)
C10—C9—C14—C131.1 (4)C28—C27—C32—C310.9 (4)
C8—C9—C14—C13179.7 (2)C26—C27—C32—C31177.6 (2)
C10—C9—C14—C2174.3 (2)C28—C27—C32—C20179.9 (2)
C8—C9—C14—C24.4 (3)C26—C27—C32—C201.5 (3)
C1—C2—C14—C1366.8 (3)C19—C20—C32—C3159.4 (4)
C3—C2—C14—C13178.5 (3)C21—C20—C32—C31179.6 (3)
C15—C2—C14—C1357.8 (4)C33—C20—C32—C3160.5 (4)
C1—C2—C14—C9118.3 (3)C19—C20—C32—C27121.5 (2)
C3—C2—C14—C93.6 (3)C21—C20—C32—C271.4 (3)
C15—C2—C14—C9117.1 (2)C33—C20—C32—C27118.6 (2)
C1—C2—C15—C16179.7 (2)C19—C20—C33—C34175.5 (2)
C3—C2—C15—C1660.2 (3)C32—C20—C33—C3455.6 (3)
C14—C2—C15—C1653.5 (3)C21—C20—C33—C3458.1 (3)
C2—C15—C16—C17177.7 (2)C20—C33—C34—C35178.4 (2)
C15—C16—C17—C18179.1 (2)C33—C34—C35—C36176.3 (2)
C16—C17—C18—Br1170.04 (19)C34—C35—C36—Br2174.89 (18)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2···O1i0.841.812.652 (2)175
O3—H3···O4ii0.841.802.642 (2)176
C18—H18B···O4iii0.992.543.377 (4)142
C36—H36B···O1iv0.992.443.386 (4)159
Symmetry codes: (i) x, y+2, z+1; (ii) x+2, y+1, z; (iii) x+1, y+1, z; (iv) x+1, y+1, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2···O1i0.841.812.652 (2)175
O3—H3···O4ii0.841.802.642 (2)176
C18—H18B···O4iii0.992.543.377 (4)142
C36—H36B···O1iv0.992.443.386 (4)159
Symmetry codes: (i) x, y+2, z+1; (ii) x+2, y+1, z; (iii) x+1, y+1, z; (iv) x+1, y+1, z+1.
 

Acknowledgements

The authors thank Mr Hai-Bin Song of Nankai University for helpful suggestions.

References

First citationBurnett, J. R. & Watts, G. F. (2007). Exp. Opin. Ther. Targets, 11, 181–189.  Web of Science CrossRef CAS Google Scholar
First citationCuchel, M., Meagher, E. A., du Toit Theron, H., Blom, D. J., Marais, A. D., Hegele, R. A., Averna, M. R., Sirtori, C. R., Shah, P. K., Gaudet, D., Stefanutti, C., Vigna, G. B., Du Plessis, A. M., Propert, K. J., Sasiela, W. J., Bloedon, L. T. & Rader, D. J. (2013). Lancet, 381, 40–46.  Web of Science CrossRef CAS PubMed Google Scholar
First citationRigaku/MSC (2005). CrystalClear. Rigaku/MSC Inc., The Woodlands, Texas, USA.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationStein, E. A. (2009). J. Endocrin. Metabol. Clin. North Am. 38, 99–119.  Web of Science CrossRef CAS Google Scholar

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Volume 70| Part 10| October 2014| Pages o1118-o1119
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