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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

Methyl­naltrexone bromide methanol monosolvate

aShenyang Pharmaceutical University, Liaoning 110016, People's Republic of China, and bBeijing Institute of Pharmacology and Toxicology, Beijing 100850, People's Republic of China
*Correspondence e-mail: hapwave@yahoo.cn

(Received 18 October 2011; accepted 8 February 2012; online 24 February 2012)

In the title compound [systematic name: (4R,4aS,7aR,12bS)-3-cyclo­propyl­meth­yl-4a,9-hy­droxy-7-oxo-2,3,4,4a,5,6,7,7a-octa­hydro-1H-4,12-methano­benzofuro[3,2-e]isoquinolin-3-ium bromide methanol monosolvate], C21H26NO4+·Br·CH3OH, two of the three six-membered rings adopt chair conformations while the third, which contains a C=C double bond, adopts an approximate half-boat conformation. The 2,3-dihydro­furan ring adopts an envelope conformation. In the crystal, the components are linked by O—H⋯O and O—H⋯Br hydrogen bonds. The absolute stereochemistry was inferred from one of the starting materials.

Related literature

For general background to methyl­naltrexone (MNTX) bromide, see: Crabtree (1984[Crabtree, B. L. (1984). Clin. Pharm. 3, 273-280.]). For the bioactivity and synthesis of R-MNTX bromide, see: Baker (2009[Baker, D. E. (2009). Rev. Gastroenterol. Disord. 9, E84-E93.]); Doshan & Perez (2006[Doshan, H. D. & Perez, J. (2006). WO Patent WO 2006127899.]).

[Scheme 1]

Experimental

Crystal data
  • C21H26NO4+·Br·CH4O

  • Mr = 468.38

  • Orthorhombic, P 21 21 21

  • a = 7.3335 (11) Å

  • b = 12.956 (2) Å

  • c = 21.506 (3) Å

  • V = 2043.4 (5) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 2.05 mm−1

  • T = 113 K

  • 0.20 × 0.18 × 0.12 mm

Data collection
  • Rigaku Saturn CCD area-detector diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.]) Tmin = 0.685, Tmax = 0.791

  • 15852 measured reflections

  • 4179 independent reflections

  • 3287 reflections with I > 2σ(I)

  • Rint = 0.042

Refinement
  • R[F2 > 2σ(F2)] = 0.024

  • wR(F2) = 0.047

  • S = 0.90

  • 4179 reflections

  • 267 parameters

  • H-atom parameters constrained

  • Δρmax = 0.41 e Å−3

  • Δρmin = −0.23 e Å−3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 1768 Friedel pairs

  • Flack parameter: 0.010 (6)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1⋯O5i 0.84 1.78 2.613 (2) 170
O4—H4⋯Br1 0.84 2.39 3.2272 (16) 175
O5—H5⋯Br1ii 0.84 2.42 3.2376 (16) 165
Symmetry codes: (i) [-x+2, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]; (ii) [x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+2].

Data collection: CrystalClear (Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear. Rigaku/MSC, 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

Methylnaltrexone (MNTX) is a quaternary derivative of the pure opioid antagonist naltrexone, which has greater polarity and lower lipid solubility and does not cross the blood-brain barrier in humans thus enabling reversal of opioid-induced peripheral effects such as constipation without affecting the central effects such as pain relief (Baker, 2009). R-MNTX bromide has been used in clinical applications to counteract addiction caused by meconium drugs. This paper reports the synthesis and crystal structure of the title compound R-MNTX bromide methanol solvate.

In the title compound, C21H26BrNO4.CH3OH, (Fig.1), two of the three six-membered rings adopt chair conformations while the third, which contains a C=C double bond, adopts an approximate half-boat conformation. The 2,3-dihydrofuran ring adopts an envelope conformation. The structure displays OH···O hydrogen bonding (Table 1, Fig. 2).

Related literature top

For general background to methylnaltrexone(MNTX) bromide, see: Crabtree (1984). For the bioactivity and synthesis of R-MNTX bromide, see: Baker (2009); Doshan & Perez (2006).

Experimental top

A solution of (4R,4aS,7aRR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (1 g, 2.94 mmol) and MeI (3.4 g) in 1-methyl-2-pyrrolidinone (12 ml) was stirred at 140 K for 10 h and the solvent was removed under reduced pressure. The residue was dissolved in water and the pH was adjusted to about 9 with 10% Na2CO3 solution and after filtration the crude solid was obtained. Colorless single crystals of the title compound were obtained by recrystallization from a methanol–water solution acidified with HBraq. Anal. Calc. (%) for C21H26BrNO4: C, 57.81; H, 6.01; Br, 18.31; N, 3.21. Found: C, 58.00; H, 6.11; Br, 18.30; N, 3.25.

Refinement top

All H atoms were placed in calculated positions with C—H distances ranging from 0.95 to 1.00 Å and included in the refinement in the riding-model approximation with Uiso = 1.2Ueq (1.5Ueq for methyl) of the attached atom. The absolute configuration was inferred from that of the starting material.

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 molecular structure of the title compound, with 50% displacement ellipsoids.
[Figure 2] Fig. 2. Packing of the title compound viewed down the a axis showing the C—H···O interactions.
(4R,4aS,7aR,12bS)-3-cyclopropylmethyl- 4a,9-hydroxy-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12- methanobenzofuro[3,2-e]isoquinolin-3-ium bromide methanol monosolvate top
Crystal data top
C21H26NO4+·Br·CH4OF(000) = 976
Mr = 468.38Dx = 1.523 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 7107 reflections
a = 7.3335 (11) Åθ = 1.6–27.9°
b = 12.956 (2) ŵ = 2.05 mm1
c = 21.506 (3) ÅT = 113 K
V = 2043.4 (5) Å3Prism, colorless
Z = 40.20 × 0.18 × 0.12 mm
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
4179 independent reflections
Radiation source: fine-focus sealed tube3287 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.042
Detector resolution: 14.63 pixels mm-1θmax = 26.4°, θmin = 1.8°
ω and ϕ scansh = 98
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
k = 1615
Tmin = 0.685, Tmax = 0.791l = 2326
15852 measured reflections
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)] = 0.024H-atom parameters constrained
wR(F2) = 0.047 w = 1/[σ2(Fo2) + (0.0141P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.90(Δ/σ)max = 0.001
4179 reflectionsΔρmax = 0.41 e Å3
267 parametersΔρmin = 0.23 e Å3
0 restraintsAbsolute structure: Flack (1983), 1768 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.010 (6)
Crystal data top
C21H26NO4+·Br·CH4OV = 2043.4 (5) Å3
Mr = 468.38Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.3335 (11) ŵ = 2.05 mm1
b = 12.956 (2) ÅT = 113 K
c = 21.506 (3) Å0.20 × 0.18 × 0.12 mm
Data collection top
Rigaku Saturn CCD area-detector
diffractometer
4179 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
3287 reflections with I > 2σ(I)
Tmin = 0.685, Tmax = 0.791Rint = 0.042
15852 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.024H-atom parameters constrained
wR(F2) = 0.047Δρmax = 0.41 e Å3
S = 0.90Δρmin = 0.23 e Å3
4179 reflectionsAbsolute structure: Flack (1983), 1768 Friedel pairs
267 parametersAbsolute structure parameter: 0.010 (6)
0 restraints
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
Br10.29599 (3)0.501662 (19)0.961583 (10)0.02197 (6)
O11.2501 (2)0.34387 (12)0.65333 (8)0.0234 (4)
H11.25470.31890.61730.035*
O21.1484 (2)0.42585 (12)0.77342 (7)0.0182 (4)
O30.9456 (2)0.58534 (12)0.73226 (8)0.0238 (4)
O40.6957 (2)0.43437 (11)0.91369 (7)0.0165 (4)
H40.58950.44800.92580.025*
N10.6665 (2)0.21015 (13)0.88781 (9)0.0144 (5)
C11.0882 (3)0.31810 (16)0.68032 (11)0.0164 (6)
C20.9548 (3)0.25521 (16)0.65245 (11)0.0174 (6)
H20.97790.22730.61240.021*
C30.7903 (3)0.23257 (15)0.68151 (10)0.0164 (5)
H30.70210.19180.66050.020*
C40.7533 (3)0.26886 (15)0.74100 (11)0.0142 (5)
C50.8893 (3)0.32771 (16)0.76833 (11)0.0135 (5)
C61.0473 (3)0.35531 (17)0.73832 (11)0.0158 (5)
C71.0143 (3)0.46915 (16)0.81590 (11)0.0170 (6)
H71.07400.49690.85420.020*
C80.9052 (3)0.55228 (17)0.78292 (11)0.0180 (6)
C90.7271 (3)0.58009 (16)0.81494 (11)0.0201 (6)
H9A0.66850.63940.79380.024*
H9B0.74940.59880.85890.024*
C100.6045 (3)0.48386 (16)0.81087 (11)0.0171 (6)
H10A0.48050.50030.82610.021*
H10B0.59510.46040.76720.021*
C110.6899 (3)0.39893 (15)0.85102 (11)0.0144 (5)
C120.8869 (3)0.37669 (16)0.83171 (11)0.0143 (5)
C130.9708 (3)0.30462 (16)0.88064 (11)0.0164 (5)
H13A1.10130.29330.87100.020*
H13B0.96290.33740.92210.020*
C140.8727 (3)0.20165 (16)0.88195 (11)0.0163 (5)
H14A0.91960.16070.91740.020*
H14B0.90190.16350.84330.020*
C150.5739 (3)0.25964 (17)0.77574 (10)0.0153 (6)
H15A0.53310.18680.77430.018*
H15B0.48100.30180.75410.018*
C160.5843 (3)0.29442 (16)0.84432 (11)0.0144 (5)
H160.45640.30710.85850.017*
C170.6162 (3)0.23066 (16)0.95469 (11)0.0188 (6)
H17A0.65190.17150.98030.028*
H17B0.48420.24120.95790.028*
H17C0.67980.29260.96930.028*
C180.5965 (3)0.10122 (15)0.87173 (11)0.0172 (6)
H18A0.63650.08390.82900.021*
H18B0.65450.05120.90030.021*
C190.3938 (3)0.08794 (16)0.87549 (11)0.0181 (6)
H190.31780.13690.85060.022*
C200.3307 (3)0.02288 (15)0.87791 (11)0.0210 (6)
H20A0.21930.04140.85440.025*
H20B0.42520.07740.87940.025*
C210.3093 (4)0.04501 (16)0.93415 (11)0.0220 (6)
H21A0.39060.03210.97010.026*
H21B0.18470.06820.94510.026*
O50.7189 (2)0.78677 (11)0.96273 (8)0.0307 (4)
H50.75860.83640.98390.046*
C220.7505 (3)0.69215 (17)0.99537 (12)0.0289 (7)
H22A0.82280.64560.96930.043*
H22B0.63340.65961.00520.043*
H22C0.81680.70651.03400.043*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.02033 (12)0.02373 (11)0.02185 (12)0.00216 (15)0.00200 (12)0.00233 (15)
O10.0236 (12)0.0294 (9)0.0171 (10)0.0052 (8)0.0075 (8)0.0035 (8)
O20.0148 (9)0.0231 (9)0.0169 (10)0.0047 (7)0.0025 (8)0.0034 (7)
O30.0346 (11)0.0213 (9)0.0155 (11)0.0085 (8)0.0031 (9)0.0025 (8)
O40.0165 (9)0.0177 (8)0.0153 (9)0.0016 (8)0.0013 (8)0.0026 (7)
N10.0169 (12)0.0148 (10)0.0114 (11)0.0002 (8)0.0007 (9)0.0000 (8)
C10.0150 (14)0.0170 (13)0.0172 (15)0.0022 (10)0.0027 (11)0.0026 (11)
C20.0275 (15)0.0153 (12)0.0093 (14)0.0040 (11)0.0002 (12)0.0001 (10)
C30.0191 (13)0.0142 (11)0.0158 (14)0.0027 (11)0.0030 (13)0.0005 (9)
C40.0161 (15)0.0121 (11)0.0144 (13)0.0006 (9)0.0013 (10)0.0029 (9)
C50.0157 (13)0.0138 (12)0.0111 (14)0.0020 (10)0.0003 (11)0.0027 (10)
C60.0154 (14)0.0162 (12)0.0157 (14)0.0021 (10)0.0036 (12)0.0016 (10)
C70.0162 (13)0.0227 (15)0.0121 (14)0.0058 (10)0.0005 (11)0.0005 (10)
C80.0202 (15)0.0163 (13)0.0176 (16)0.0120 (11)0.0052 (12)0.0024 (11)
C90.0256 (15)0.0139 (12)0.0208 (14)0.0021 (11)0.0072 (13)0.0042 (10)
C100.0141 (12)0.0189 (15)0.0183 (13)0.0018 (11)0.0052 (11)0.0007 (11)
C110.0177 (13)0.0163 (12)0.0092 (13)0.0001 (11)0.0029 (12)0.0000 (9)
C120.0132 (13)0.0175 (13)0.0121 (14)0.0032 (11)0.0008 (11)0.0013 (10)
C130.0136 (13)0.0215 (13)0.0142 (14)0.0001 (10)0.0005 (11)0.0031 (11)
C140.0154 (13)0.0201 (13)0.0133 (14)0.0018 (11)0.0021 (11)0.0024 (11)
C150.0164 (14)0.0168 (13)0.0128 (14)0.0034 (10)0.0038 (12)0.0008 (10)
C160.0099 (13)0.0170 (12)0.0162 (14)0.0023 (10)0.0004 (11)0.0027 (10)
C170.0260 (14)0.0182 (12)0.0122 (14)0.0003 (11)0.0047 (13)0.0005 (11)
C180.0239 (15)0.0102 (12)0.0174 (15)0.0020 (10)0.0025 (12)0.0007 (10)
C190.0184 (14)0.0143 (12)0.0217 (16)0.0016 (11)0.0004 (12)0.0023 (11)
C200.0199 (14)0.0162 (15)0.0269 (15)0.0058 (10)0.0042 (11)0.0027 (10)
C210.0221 (14)0.0217 (12)0.0222 (15)0.0019 (11)0.0024 (13)0.0037 (10)
O50.0504 (12)0.0223 (9)0.0193 (10)0.0031 (9)0.0040 (11)0.0007 (8)
C220.0353 (18)0.0246 (13)0.0267 (16)0.0003 (11)0.0002 (13)0.0039 (11)
Geometric parameters (Å, º) top
O1—C11.363 (3)C11—C121.531 (3)
O1—H10.8400C11—C161.567 (3)
O2—C61.398 (3)C12—C131.536 (3)
O2—C71.455 (3)C13—C141.516 (3)
O3—C81.208 (3)C13—H13A0.9900
O4—C111.424 (2)C13—H13B0.9900
O4—H40.8400C14—H14A0.9900
N1—C171.508 (3)C14—H14B0.9900
N1—C141.521 (3)C15—C161.544 (3)
N1—C181.541 (3)C15—H15A0.9900
N1—C161.559 (3)C15—H15B0.9900
C1—C61.370 (3)C16—H161.0000
C1—C21.407 (3)C17—H17A0.9800
C2—C31.390 (3)C17—H17B0.9800
C2—H20.9500C17—H17C0.9800
C3—C41.390 (3)C18—C191.499 (3)
C3—H30.9500C18—H18A0.9900
C4—C51.386 (3)C18—H18B0.9900
C4—C151.517 (3)C19—C201.509 (3)
C5—C61.374 (3)C19—C211.512 (3)
C5—C121.503 (3)C19—H191.0000
C7—C81.518 (3)C20—C211.504 (3)
C7—C121.557 (3)C20—H20A0.9900
C7—H71.0000C20—H20B0.9900
C8—C91.520 (3)C21—H21A0.9900
C9—C101.539 (3)C21—H21B0.9900
C9—H9A0.9900O5—C221.432 (2)
C9—H9B0.9900O5—H50.8400
C10—C111.533 (3)C22—H22A0.9800
C10—H10A0.9900C22—H22B0.9800
C10—H10B0.9900C22—H22C0.9800
C1—O1—H1109.5C14—C13—H13A109.4
C6—O2—C7103.46 (16)C12—C13—H13A109.4
C11—O4—H4109.5C14—C13—H13B109.4
C17—N1—C14109.55 (18)C12—C13—H13B109.4
C17—N1—C18107.10 (17)H13A—C13—H13B108.0
C14—N1—C18104.24 (17)C13—C14—N1114.19 (19)
C17—N1—C16110.75 (16)C13—C14—H14A108.7
C14—N1—C16112.65 (17)N1—C14—H14A108.7
C18—N1—C16112.23 (17)C13—C14—H14B108.7
O1—C1—C6119.5 (2)N1—C14—H14B108.7
O1—C1—C2124.5 (2)H14A—C14—H14B107.6
C6—C1—C2116.0 (2)C4—C15—C16113.86 (18)
C3—C2—C1122.3 (2)C4—C15—H15A108.8
C3—C2—H2118.9C16—C15—H15A108.8
C1—C2—H2118.9C4—C15—H15B108.8
C2—C3—C4120.8 (2)C16—C15—H15B108.8
C2—C3—H3119.6H15A—C15—H15B107.7
C4—C3—H3119.6C15—C16—N1112.82 (17)
C5—C4—C3115.9 (2)C15—C16—C11111.37 (18)
C5—C4—C15117.3 (2)N1—C16—C11111.05 (17)
C3—C4—C15126.6 (2)C15—C16—H16107.1
C6—C5—C4123.4 (2)N1—C16—H16107.1
C6—C5—C12109.0 (2)C11—C16—H16107.1
C4—C5—C12127.5 (2)N1—C17—H17A109.5
C1—C6—C5121.4 (2)N1—C17—H17B109.5
C1—C6—O2127.3 (2)H17A—C17—H17B109.5
C5—C6—O2111.3 (2)N1—C17—H17C109.5
O2—C7—C8109.7 (2)H17A—C17—H17C109.5
O2—C7—C12104.24 (17)H17B—C17—H17C109.5
C8—C7—C12109.39 (19)C19—C18—N1115.04 (18)
O2—C7—H7111.1C19—C18—H18A108.5
C8—C7—H7111.1N1—C18—H18A108.5
C12—C7—H7111.1C19—C18—H18B108.5
O3—C8—C7123.0 (2)N1—C18—H18B108.5
O3—C8—C9122.4 (2)H18A—C18—H18B107.5
C7—C8—C9114.2 (2)C18—C19—C20114.5 (2)
C8—C9—C10106.51 (18)C18—C19—C21119.6 (2)
C8—C9—H9A110.4C20—C19—C2159.71 (14)
C10—C9—H9A110.4C18—C19—H19116.8
C8—C9—H9B110.4C20—C19—H19116.8
C10—C9—H9B110.4C21—C19—H19116.8
H9A—C9—H9B108.6C21—C20—C1960.22 (14)
C11—C10—C9108.12 (18)C21—C20—H20A117.7
C11—C10—H10A110.1C19—C20—H20A117.7
C9—C10—H10A110.1C21—C20—H20B117.7
C11—C10—H10B110.1C19—C20—H20B117.7
C9—C10—H10B110.1H20A—C20—H20B114.9
H10A—C10—H10B108.4C20—C21—C1960.07 (14)
O4—C11—C12106.82 (18)C20—C21—H21A117.8
O4—C11—C10108.29 (17)C19—C21—H21A117.8
C12—C11—C10111.59 (19)C20—C21—H21B117.8
O4—C11—C16112.36 (19)C19—C21—H21B117.8
C12—C11—C16106.19 (17)H21A—C21—H21B114.9
C10—C11—C16111.52 (18)C22—O5—H5109.5
C5—C12—C11109.64 (19)O5—C22—H22A109.5
C5—C12—C13111.10 (18)O5—C22—H22B109.5
C11—C12—C13107.86 (19)H22A—C22—H22B109.5
C5—C12—C796.89 (19)O5—C22—H22C109.5
C11—C12—C7118.74 (19)H22A—C22—H22C109.5
C13—C12—C7112.16 (19)H22B—C22—H22C109.5
C14—C13—C12110.95 (19)
O1—C1—C2—C3178.9 (2)C10—C11—C12—C13170.80 (17)
C6—C1—C2—C30.5 (3)C16—C11—C12—C1367.5 (2)
C1—C2—C3—C42.2 (3)O4—C11—C12—C776.3 (3)
C2—C3—C4—C50.0 (3)C10—C11—C12—C741.8 (3)
C2—C3—C4—C15173.4 (2)C16—C11—C12—C7163.6 (2)
C3—C4—C5—C64.0 (3)O2—C7—C12—C536.9 (2)
C15—C4—C5—C6170.0 (2)C8—C7—C12—C580.3 (2)
C3—C4—C5—C12180.0 (2)O2—C7—C12—C11153.83 (19)
C15—C4—C5—C125.9 (3)C8—C7—C12—C1136.6 (3)
O1—C1—C6—C5177.2 (2)O2—C7—C12—C1379.2 (2)
C2—C1—C6—C53.4 (3)C8—C7—C12—C13163.55 (19)
O1—C1—C6—O25.4 (4)C5—C12—C13—C1456.7 (3)
C2—C1—C6—O2174.0 (2)C11—C12—C13—C1463.5 (2)
C4—C5—C6—C15.9 (4)C7—C12—C13—C14163.96 (19)
C12—C5—C6—C1177.5 (2)C12—C13—C14—N151.3 (3)
C4—C5—C6—O2171.89 (19)C17—N1—C14—C1379.4 (2)
C12—C5—C6—O24.7 (3)C18—N1—C14—C13166.29 (19)
C7—O2—C6—C1157.3 (2)C16—N1—C14—C1344.4 (3)
C7—O2—C6—C520.3 (2)C5—C4—C15—C1614.7 (3)
C6—O2—C7—C880.8 (2)C3—C4—C15—C16172.0 (2)
C6—O2—C7—C1236.2 (2)C4—C15—C16—N180.4 (2)
O2—C7—C8—O39.7 (3)C4—C15—C16—C1145.3 (3)
C12—C7—C8—O3123.5 (2)C17—N1—C16—C15160.55 (18)
O2—C7—C8—C9162.42 (17)C14—N1—C16—C1576.4 (2)
C12—C7—C8—C948.7 (3)C18—N1—C16—C1540.9 (2)
O3—C8—C9—C10106.3 (2)C17—N1—C16—C1173.6 (2)
C7—C8—C9—C1065.9 (2)C14—N1—C16—C1149.5 (2)
C8—C9—C10—C1167.1 (2)C18—N1—C16—C11166.77 (18)
C9—C10—C11—O461.6 (2)O4—C11—C16—C15177.95 (18)
C9—C10—C11—C1255.7 (2)C12—C11—C16—C1565.6 (2)
C9—C10—C11—C16174.32 (19)C10—C11—C16—C1556.2 (2)
C6—C5—C12—C11149.25 (19)O4—C11—C16—N155.4 (2)
C4—C5—C12—C1127.2 (3)C12—C11—C16—N161.0 (2)
C6—C5—C12—C1391.6 (2)C10—C11—C16—N1177.20 (18)
C4—C5—C12—C1392.0 (3)C17—N1—C18—C1962.6 (2)
C6—C5—C12—C725.4 (2)C14—N1—C18—C19178.7 (2)
C4—C5—C12—C7151.1 (2)C16—N1—C18—C1959.1 (3)
O4—C11—C12—C5173.74 (16)N1—C18—C19—C20163.38 (19)
C10—C11—C12—C568.1 (2)N1—C18—C19—C2195.6 (2)
C16—C11—C12—C553.6 (2)C18—C19—C20—C21111.3 (2)
O4—C11—C12—C1352.6 (2)C18—C19—C21—C20102.8 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O5i0.841.782.613 (2)170
O4—H4···Br10.842.393.2272 (16)175
O5—H5···Br1ii0.842.423.2376 (16)165
Symmetry codes: (i) x+2, y1/2, z+3/2; (ii) x+1/2, y+3/2, z+2.

Experimental details

Crystal data
Chemical formulaC21H26NO4+·Br·CH4O
Mr468.38
Crystal system, space groupOrthorhombic, P212121
Temperature (K)113
a, b, c (Å)7.3335 (11), 12.956 (2), 21.506 (3)
V3)2043.4 (5)
Z4
Radiation typeMo Kα
µ (mm1)2.05
Crystal size (mm)0.20 × 0.18 × 0.12
Data collection
DiffractometerRigaku Saturn CCD area-detector
diffractometer
Absorption correctionMulti-scan
(CrystalClear; Rigaku/MSC, 2005)
Tmin, Tmax0.685, 0.791
No. of measured, independent and
observed [I > 2σ(I)] reflections
15852, 4179, 3287
Rint0.042
(sin θ/λ)max1)0.625
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.024, 0.047, 0.90
No. of reflections4179
No. of parameters267
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.41, 0.23
Absolute structureFlack (1983), 1768 Friedel pairs
Absolute structure parameter0.010 (6)

Computer programs: CrystalClear (Rigaku/MSC, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O5i0.841.782.613 (2)170.2
O4—H4···Br10.842.393.2272 (16)175.1
O5—H5···Br1ii0.842.423.2376 (16)165.0
Symmetry codes: (i) x+2, y1/2, z+3/2; (ii) x+1/2, y+3/2, z+2.
 

Acknowledgements

This work was supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China (grant No. 2009ZX09501-005)

References

First citationBaker, D. E. (2009). Rev. Gastroenterol. Disord. 9, E84–E93.  Web of Science PubMed Google Scholar
First citationCrabtree, B. L. (1984). Clin. Pharm. 3, 273–280.  CAS PubMed Web of Science Google Scholar
First citationDoshan, H. D. & Perez, J. (2006). WO Patent WO 2006127899.  Google Scholar
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationRigaku/MSC (2005). CrystalClear. Rigaku/MSC, 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

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.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds