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

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ISSN: 2056-9890

Methyl 2-[2-(benzyl­oxycarbon­ylamino)­propan-2-yl]-5-hy­dr­oxy-1-methyl-6-oxo-1,6-di­hydro­pyrimidine-4-carboxyl­ate

aCollege of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Hebei Research Center of Pharmaceutical and Chemical Engineering, State Key Laboratory Breeding Base-Hebei Province, Key Laboratory of Molecular Chemistry for Drugs, Shijiazhuang 050018, People's Republic of China, bCollege of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, People's Republic of China, cZhongqi Pharmacy (Shijiazhang), Shijiazhuang Pharmaceutical Group Co., Ltd (CSPC), Shijiazhuang 050051, People's Republic of China, and dDepartment of Neurosurgery, Shijiazhuang Center Hospital, Shijiazhuang 050011, People's Republic of China
*Correspondence e-mail: zhenhuashang@yahoo.com.cn

(Received 23 August 2012; accepted 9 October 2012; online 20 October 2012)

The title pyrimidine derivative, C18H21N3O6, was obtained by the reaction of methyl 2-[2-(benzyl­oxycarbon­yl)amino­propan-2-yl]-5-hy­droxy-6-oxo-1,6-dihydro­pyrimidine-4-carboxyl­ate with dimethyl sulfate in dimethyl sulfoxide. The mol­ecule has a V-shaped structure, the phenyl and the pyrimidine rings making a dihedral angle of 43.1 (1)°. The methyl group substituting the pyrimidine ring deviates slightly from the ring mean-plane [C—N—C—C torsion angle = 5.49 (15)°], and the methyl ester substituent has a conformation suitable for the formation of an intra­molecular O—H⋯O hydrogen bond with the hydroxyl functionality. In the crystal, molecules are linked into chains along the b axis by N—H⋯O hydrogen bonds.

Related literature

For the anti­retroviral drug raltegravir [systematic name: N-(2-(4-(4-fluoro­benzyl­carbamo­yl)-5-hy­droxy-1-methyl-6-oxo-1,6-dihydro­pyrimidin-2-yl)propan-2-yl)], see: Steigbigel et al. (2008[Steigbigel, R. T. et al. (2008). N. Engl. J. Med. 359, 339-354.]). For the synthesis of raltegravir, see: Belyk et al. (2006[Belyk, K. M., Morrison, H. G., Jones, P. & Summa, V. (2006). Patent No. WO 2006/06712 A2.]); For related structures, see: Fun et al. (2011[Fun, H.-K., Sumangala, V., Prasad, D. J., Poojary, B. & Chantrapromma, S. (2011). Acta Cryst. E67, o274.]); Shang, Ha, Yu & Zhao (2011[Shang, Z., Ha, J., Yu, Y. & Zhao, X. (2011). Acta Cryst. E67, o1336.]); Shang, Qi, Tao & Zhang (2011[Shang, Z., Qi, S., Tao, X. & Zhang, G. (2011). Acta Cryst. E67, o1335.]).

[Scheme 1]

Experimental

Crystal data
  • C18H21N3O6

  • Mr = 375.38

  • Monoclinic, P 21 /n

  • a = 10.540 (2) Å

  • b = 12.927 (3) Å

  • c = 13.751 (3) Å

  • β = 109.74 (3)°

  • V = 1763.5 (6) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.11 mm−1

  • T = 113 K

  • 0.20 × 0.16 × 0.12 mm

Data collection
  • Rigaku Saturn diffractometer

  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA.]) Tmin = 0.979, Tmax = 0.987

  • 12669 measured reflections

  • 4184 independent reflections

  • 2889 reflections with I > 2σ(I)

  • Rint = 0.032

Refinement
  • R[F2 > 2σ(F2)] = 0.035

  • wR(F2) = 0.093

  • S = 1.00

  • 4184 reflections

  • 255 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.28 e Å−3

  • Δρmin = −0.20 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O2—H2⋯O3 0.876 (13) 1.782 (14) 2.5879 (12) 151.9 (14)
N3—H3⋯O1i 0.875 (15) 2.118 (15) 2.9854 (16) 170.9 (12)
Symmetry code: (i) [x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}].

Data collection: CrystalClear (Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear and CrystalStructure. 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: CrystalStructure (Rigaku/MSC, 2005[Rigaku/MSC (2005). CrystalClear and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA.]).

Supporting information


Comment top

Pyrimidine derivatives are important chemotherapeutic agents, and Raltegravir (MK-0518, brand name Isentress), an antiretroviral drug produced by Merck & Co, used to treat HIV infection (Steigbigel et al., 2008), is one of the representatives. When methyl 2-[2-(benzyloxycarbonyl)aminopropan-2-yl]-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate was reacted with dimethyl sulfate and magnesium methoxide as catalyst in dimethyl sulfoxide (Belyk et al., 2006), as we designed, in order to synthesize the title compound as the key intermediate of Raltegravir, two products appeared unfortunately. The products were separated by flash chromatography and the structure of the title compound was confirmed by NMR and X-ray analysis. The X-ray results (Fig. 1) showed that the phenyl and pyrimidine rings are not in a common plane, as found in related compounds (Fun et al., 2011; Shang, Ha, Yu & Zhao, 2011; Shang, Qi, Tao & Zhang, 2011). The dihedral angle between the two aromatic rings is 43.1 (1)°. The carbamate unit (atoms C11, N3, O5 and O6) is planar. The methyl group bonded to N2 is slightly deviated from the pyrimidine mean-plane, with the torsion angle C5—N2—C1—C8 = 5.49 (15)°. The conformation of the carboxylate in the methyl ester group is indicated by torsion angles C7—O4—C6—C4 = 179.58 (8)° and C3—C4—C6—O3 = -1.39 (15)°. The crystal structure is stabilized mainly through intermolecular N—H···O and intramolecular O—H···O hydrogen bonds.

Related literature top

For background to the antiretroviral drug raltegravir [systematic name: N-(2-(4-(4-fluorobenzylcarbamoyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)], see: Steigbigel et al. (2008). For the synthesis of raltegravir, see: Belyk et al. (2006); For related structures, see: Fun et al. (2011); Shang, Ha, Yu & Zhao (2011); Shang, Qi, Tao & Zhang (2011).

Experimental top

To a slurry of methyl 2-[2-(benzyloxycarbonyl)aminopropan-2-yl]-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.5 g) and magnesium methoxide (2.1 g) in dimethyl sulfoxide (15 ml) at 70 °C, dimethyl sulfate (3.1 g) was added droply. After addition, the mixture was heated at the same temperature for 8 h. The reaction mixture was then added to 40 ml of HCl 2 N, and then to 100 ml of water. A solid phase appeared when the mixture was stirred with ice-water bath. The products were filtered and separated by flash chromatography. The title compound (50 mg) was dissolved in 50 ml of ethanol at room temperature and the solvent was slowly evaporated over 10 days, affording colourless single crystals suitable for X-ray analysis. 1H-NMR (500 MHz, CDCl3): 1.75 (s, 6H), 4.05 (s, 3H), 4.07 (s, 3H), 5.12 (s, 2H), 6.58 (bs, 1H), 7.26–7.38 (m, 5H, J=18.5 Hz), 10.46 (s, 1H). IR (KBr) 1150, 1240, 1282, 1492, 1454, 1694, 1738, 2975, 3233, 3398 cm-1.

Refinement top

All H atoms attached to C atoms were placed geometrically and treated as riding atoms, with C—H = 0.95 (aromatic), 0.98 (methyl CH3 group), or 0.99 Å (methlyene group), with Uiso(H)=1.2Ueq(carrier C), or Uiso(H)=1.5Ueq(carrier C). The positions for atoms H2 and H3, bonded to O2 and N3, were refined freely with bond lengths converging to N3—H3 = 0.875 (15) Å and O2—H2 = 0.876 (13) Å.

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: CrystalStructure (Rigaku/MSC, 2005).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, drawn with 30% probability ellipsoids.
Methyl 2-[2-(benzyloxycarbonylamino)propan-2-yl]-5-hydroxy-1-methyl-6-oxo-1,6- dihydropyrimidine-4-carboxylate top
Crystal data top
C18H21N3O6F(000) = 792
Mr = 375.38Dx = 1.414 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 5478 reflections
a = 10.540 (2) Åθ = 2.1–27.9°
b = 12.927 (3) ŵ = 0.11 mm1
c = 13.751 (3) ÅT = 113 K
β = 109.74 (3)°Plate, colourless
V = 1763.5 (6) Å30.20 × 0.16 × 0.12 mm
Z = 4
Data collection top
Rigaku Saturn
diffractometer
4184 independent reflections
Radiation source: rotating anode2889 reflections with I > 2σ(I)
Confocal monochromatorRint = 0.032
Detector resolution: 7.31 pixels mm-1θmax = 27.9°, θmin = 2.1°
ω and ϕ scansh = 1313
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
k = 1616
Tmin = 0.979, Tmax = 0.987l = 1810
12669 measured reflections
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)] = 0.035Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.093H atoms treated by a mixture of independent and constrained refinement
S = 1.00 w = 1/[σ2(Fo2) + (0.0545P)2]
where P = (Fo2 + 2Fc2)/3
4184 reflections(Δ/σ)max = 0.001
255 parametersΔρmax = 0.28 e Å3
0 restraintsΔρmin = 0.20 e Å3
0 constraints
Crystal data top
C18H21N3O6V = 1763.5 (6) Å3
Mr = 375.38Z = 4
Monoclinic, P21/nMo Kα radiation
a = 10.540 (2) ŵ = 0.11 mm1
b = 12.927 (3) ÅT = 113 K
c = 13.751 (3) Å0.20 × 0.16 × 0.12 mm
β = 109.74 (3)°
Data collection top
Rigaku Saturn
diffractometer
4184 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2005)
2889 reflections with I > 2σ(I)
Tmin = 0.979, Tmax = 0.987Rint = 0.032
12669 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0350 restraints
wR(F2) = 0.093H atoms treated by a mixture of independent and constrained refinement
S = 1.00Δρmax = 0.28 e Å3
4184 reflectionsΔρmin = 0.20 e Å3
255 parameters
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.06467 (9)0.00568 (6)0.24005 (7)0.0175 (2)
N20.12798 (9)0.17823 (6)0.22657 (8)0.0184 (2)
N30.23993 (10)0.16037 (7)0.45582 (8)0.0200 (2)
O10.01828 (8)0.27591 (6)0.08460 (7)0.0245 (2)
O20.13087 (8)0.11324 (6)0.01134 (6)0.02320 (19)
H20.1711 (14)0.0529 (10)0.0243 (12)0.035*
O30.18898 (8)0.07843 (6)0.00815 (7)0.0248 (2)
O40.07643 (7)0.16439 (5)0.15296 (6)0.02110 (19)
O50.01416 (8)0.16353 (6)0.42853 (7)0.0296 (2)
O60.16194 (8)0.26344 (6)0.55086 (7)0.0251 (2)
C10.13702 (11)0.08557 (8)0.28038 (9)0.0170 (2)
C20.03246 (11)0.19213 (8)0.12974 (9)0.0184 (2)
C30.04554 (11)0.10083 (8)0.08528 (9)0.0180 (2)
C40.02494 (10)0.01226 (8)0.14162 (9)0.0168 (2)
C50.21999 (12)0.26756 (8)0.26136 (10)0.0272 (3)
H5A0.27920.27190.21980.041*
H5B0.27470.25860.33430.041*
H5C0.16710.33130.25310.041*
C60.10441 (11)0.08065 (8)0.09481 (9)0.0188 (2)
C70.15552 (12)0.25469 (9)0.10665 (10)0.0263 (3)
H7A0.25050.24220.09780.039*
H7B0.12300.31470.15170.039*
H7C0.14650.26810.03910.039*
C80.23999 (11)0.07215 (8)0.38845 (9)0.0191 (2)
C90.38107 (12)0.06442 (9)0.37925 (11)0.0272 (3)
H9A0.39370.12120.33620.041*
H9B0.38990.00180.34750.041*
H9C0.44950.06890.44820.041*
C100.21098 (13)0.02658 (8)0.43885 (10)0.0257 (3)
H10A0.27730.03360.50840.038*
H10B0.21690.08660.39710.038*
H10C0.12020.02270.44320.038*
C110.12831 (11)0.19193 (8)0.47419 (9)0.0212 (3)
C120.05270 (13)0.30190 (10)0.58204 (12)0.0345 (3)
H12A0.02720.24960.62470.041*
H12B0.02710.31660.52040.041*
C130.09959 (12)0.39926 (9)0.64339 (10)0.0244 (3)
C140.01477 (13)0.48439 (10)0.62565 (11)0.0355 (3)
H140.07160.48130.57360.043*
C150.05509 (15)0.57377 (10)0.68321 (12)0.0389 (4)
H150.00340.63190.67010.047*
C160.17894 (14)0.57887 (9)0.75897 (11)0.0332 (3)
H160.20590.64020.79870.040*
C170.26443 (12)0.49493 (9)0.77748 (10)0.0269 (3)
H170.35030.49830.83010.032*
C180.22509 (11)0.40592 (9)0.71942 (10)0.0225 (3)
H180.28490.34860.73180.027*
H30.3174 (15)0.1854 (10)0.4951 (12)0.034 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0181 (4)0.0182 (5)0.0144 (5)0.0006 (4)0.0032 (4)0.0008 (4)
N20.0202 (5)0.0163 (4)0.0165 (5)0.0014 (4)0.0036 (4)0.0010 (4)
N30.0203 (5)0.0181 (5)0.0179 (6)0.0007 (4)0.0015 (4)0.0041 (4)
O10.0277 (4)0.0203 (4)0.0230 (5)0.0020 (3)0.0052 (4)0.0066 (4)
O20.0259 (4)0.0229 (4)0.0154 (5)0.0030 (4)0.0000 (4)0.0016 (4)
O30.0215 (4)0.0273 (4)0.0199 (5)0.0012 (3)0.0006 (4)0.0012 (4)
O40.0229 (4)0.0179 (4)0.0205 (5)0.0035 (3)0.0048 (4)0.0013 (3)
O50.0224 (4)0.0287 (5)0.0340 (6)0.0044 (3)0.0046 (4)0.0112 (4)
O60.0226 (4)0.0261 (4)0.0266 (5)0.0024 (3)0.0082 (4)0.0108 (4)
C10.0183 (5)0.0157 (5)0.0162 (6)0.0022 (4)0.0048 (5)0.0004 (5)
C20.0191 (5)0.0194 (5)0.0165 (6)0.0033 (4)0.0058 (5)0.0018 (5)
C30.0170 (5)0.0217 (6)0.0142 (6)0.0044 (4)0.0039 (5)0.0003 (5)
C40.0159 (5)0.0182 (5)0.0154 (6)0.0019 (4)0.0040 (5)0.0004 (5)
C50.0293 (6)0.0217 (6)0.0260 (7)0.0075 (5)0.0033 (6)0.0011 (5)
C60.0174 (5)0.0214 (6)0.0175 (6)0.0020 (4)0.0056 (5)0.0007 (5)
C70.0293 (6)0.0217 (6)0.0270 (8)0.0084 (5)0.0083 (6)0.0034 (5)
C80.0218 (5)0.0157 (5)0.0161 (6)0.0017 (4)0.0016 (5)0.0016 (5)
C90.0219 (6)0.0276 (6)0.0264 (7)0.0045 (5)0.0008 (6)0.0051 (6)
C100.0346 (6)0.0174 (6)0.0182 (7)0.0016 (5)0.0000 (6)0.0008 (5)
C110.0248 (6)0.0156 (5)0.0209 (7)0.0010 (4)0.0047 (5)0.0004 (5)
C120.0265 (6)0.0389 (7)0.0416 (9)0.0076 (6)0.0162 (7)0.0178 (7)
C130.0228 (5)0.0272 (6)0.0248 (7)0.0021 (5)0.0102 (5)0.0060 (5)
C140.0261 (6)0.0450 (8)0.0305 (8)0.0079 (6)0.0031 (6)0.0096 (7)
C150.0456 (8)0.0335 (7)0.0368 (9)0.0159 (6)0.0129 (7)0.0038 (6)
C160.0455 (8)0.0265 (6)0.0318 (8)0.0058 (6)0.0185 (7)0.0094 (6)
C170.0254 (6)0.0351 (7)0.0214 (7)0.0069 (5)0.0095 (6)0.0034 (5)
C180.0231 (6)0.0236 (6)0.0229 (7)0.0012 (5)0.0106 (5)0.0020 (5)
Geometric parameters (Å, º) top
N1—C11.2923 (13)C7—H7B0.9800
N1—C41.3667 (15)C7—H7C0.9800
N2—C21.3833 (15)C8—C101.5317 (15)
N2—C11.3943 (13)C8—C91.5376 (15)
N2—C51.4797 (14)C9—H9A0.9800
N3—C111.3473 (14)C9—H9B0.9800
N3—C81.4694 (14)C9—H9C0.9800
N3—H30.875 (15)C10—H10A0.9800
O1—C21.2320 (13)C10—H10B0.9800
O2—C31.3390 (14)C10—H10C0.9800
O2—H20.876 (13)C12—C131.5028 (17)
O3—C61.2239 (15)C12—H12A0.9900
O4—C61.3187 (13)C12—H12B0.9900
O4—C71.4507 (13)C13—C181.3843 (18)
O5—C111.2109 (14)C13—C141.3865 (17)
O6—C111.3562 (14)C14—C151.3838 (19)
O6—C121.4457 (14)C14—H140.9500
C1—C81.5255 (17)C15—C161.369 (2)
C2—C31.4503 (16)C15—H150.9500
C3—C41.3581 (15)C16—C171.3781 (17)
C4—C61.4813 (15)C16—H160.9500
C5—H5A0.9800C17—C181.3819 (16)
C5—H5B0.9800C17—H170.9500
C5—H5C0.9800C18—H180.9500
C7—H7A0.9800
C1—N1—C4119.05 (10)C1—C8—C9108.47 (10)
C2—N2—C1121.31 (9)C10—C8—C9109.24 (9)
C2—N2—C5113.23 (9)C8—C9—H9A109.5
C1—N2—C5125.38 (10)C8—C9—H9B109.5
C11—N3—C8122.65 (10)H9A—C9—H9B109.5
C11—N3—H3117.7 (9)C8—C9—H9C109.5
C8—N3—H3118.5 (9)H9A—C9—H9C109.5
C3—O2—H2102.2 (10)H9B—C9—H9C109.5
C6—O4—C7114.62 (10)C8—C10—H10A109.5
C11—O6—C12116.08 (9)C8—C10—H10B109.5
N1—C1—N2122.28 (11)H10A—C10—H10B109.5
N1—C1—C8116.74 (9)C8—C10—H10C109.5
N2—C1—C8120.89 (9)H10A—C10—H10C109.5
O1—C2—N2121.61 (10)H10B—C10—H10C109.5
O1—C2—C3123.23 (11)O5—C11—N3126.06 (11)
N2—C2—C3115.13 (10)O5—C11—O6124.26 (10)
O2—C3—C4126.26 (10)N3—C11—O6109.67 (10)
O2—C3—C2114.58 (10)O6—C12—C13108.10 (9)
C4—C3—C2119.14 (11)O6—C12—H12A110.1
C3—C4—N1122.78 (10)C13—C12—H12A110.1
C3—C4—C6118.53 (11)O6—C12—H12B110.1
N1—C4—C6118.69 (10)C13—C12—H12B110.1
N2—C5—H5A109.5H12A—C12—H12B108.4
N2—C5—H5B109.5C18—C13—C14118.59 (11)
H5A—C5—H5B109.5C18—C13—C12121.68 (11)
N2—C5—H5C109.5C14—C13—C12119.71 (12)
H5A—C5—H5C109.5C15—C14—C13120.45 (13)
H5B—C5—H5C109.5C15—C14—H14119.8
O3—C6—O4123.35 (10)C13—C14—H14119.8
O3—C6—C4121.54 (10)C16—C15—C14120.33 (12)
O4—C6—C4115.10 (10)C16—C15—H15119.8
O4—C7—H7A109.5C14—C15—H15119.8
O4—C7—H7B109.5C15—C16—C17119.91 (12)
H7A—C7—H7B109.5C15—C16—H16120.0
O4—C7—H7C109.5C17—C16—H16120.0
H7A—C7—H7C109.5C16—C17—C18119.93 (13)
H7B—C7—H7C109.5C16—C17—H17120.0
N3—C8—C1111.98 (9)C18—C17—H17120.0
N3—C8—C10108.59 (9)C17—C18—C13120.79 (11)
C1—C8—C10110.51 (9)C17—C18—H18119.6
N3—C8—C9107.98 (9)C13—C18—H18119.6
C4—N1—C1—N20.69 (14)N1—C4—C6—O42.56 (13)
C4—N1—C1—C8177.17 (9)C11—N3—C8—C156.33 (14)
C2—N2—C1—N15.48 (15)C11—N3—C8—C1065.98 (14)
C5—N2—C1—N1170.84 (10)C11—N3—C8—C9175.69 (11)
C2—N2—C1—C8178.18 (9)N1—C1—C8—N3136.08 (10)
C5—N2—C1—C85.49 (15)N2—C1—C8—N347.39 (13)
C1—N2—C2—O1175.31 (9)N1—C1—C8—C1014.88 (13)
C5—N2—C2—O17.95 (14)N2—C1—C8—C10168.59 (9)
C1—N2—C2—C36.35 (14)N1—C1—C8—C9104.85 (10)
C5—N2—C2—C3170.39 (9)N2—C1—C8—C971.68 (12)
O1—C2—C3—O22.85 (15)C8—N3—C11—O511.11 (19)
N2—C2—C3—O2175.46 (8)C8—N3—C11—O6170.45 (10)
O1—C2—C3—C4178.65 (10)C12—O6—C11—O53.79 (17)
N2—C2—C3—C43.04 (14)C12—O6—C11—N3177.74 (10)
O2—C3—C4—N1179.76 (9)C11—O6—C12—C13164.02 (10)
C2—C3—C4—N11.45 (15)O6—C12—C13—C1845.05 (16)
O2—C3—C4—C61.11 (16)O6—C12—C13—C14136.37 (12)
C2—C3—C4—C6179.41 (9)C18—C13—C14—C150.22 (19)
C1—N1—C4—C32.74 (15)C12—C13—C14—C15178.41 (12)
C1—N1—C4—C6178.12 (9)C13—C14—C15—C160.5 (2)
C7—O4—C6—O30.77 (14)C14—C15—C16—C170.6 (2)
C7—O4—C6—C4179.58 (8)C15—C16—C17—C180.13 (19)
C3—C4—C6—O31.39 (15)C16—C17—C18—C130.87 (18)
N1—C4—C6—O3177.78 (9)C14—C13—C18—C170.91 (17)
C3—C4—C6—O4178.27 (9)C12—C13—C18—C17177.69 (10)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2···O30.876 (13)1.782 (14)2.5879 (12)151.9 (14)
N3—H3···O1i0.875 (15)2.118 (15)2.9854 (16)170.9 (12)
Symmetry code: (i) x+1/2, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC18H21N3O6
Mr375.38
Crystal system, space groupMonoclinic, P21/n
Temperature (K)113
a, b, c (Å)10.540 (2), 12.927 (3), 13.751 (3)
β (°) 109.74 (3)
V3)1763.5 (6)
Z4
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.20 × 0.16 × 0.12
Data collection
DiffractometerRigaku Saturn
diffractometer
Absorption correctionMulti-scan
(CrystalClear; Rigaku/MSC, 2005)
Tmin, Tmax0.979, 0.987
No. of measured, independent and
observed [I > 2σ(I)] reflections
12669, 4184, 2889
Rint0.032
(sin θ/λ)max1)0.659
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.093, 1.00
No. of reflections4184
No. of parameters255
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.28, 0.20

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

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2···O30.876 (13)1.782 (14)2.5879 (12)151.9 (14)
N3—H3···O1i0.875 (15)2.118 (15)2.9854 (16)170.9 (12)
Symmetry code: (i) x+1/2, y+1/2, z+1/2.
 

Acknowledgements

The project was supported by the Hebei Provincial Natural Science Foundation of the China–Shijiazhuang Pharmaceutical Group (CSPC) Foundation (H2012208045), the Scientific and Technological Major Special Project (Major Creation of New Drugs, No. 2011ZX09202–101–22) and the Program for Innovative Research Team of Hebei University of Science and Technology.

References

First citationBelyk, K. M., Morrison, H. G., Jones, P. & Summa, V. (2006). Patent No. WO 2006/06712 A2.
First citationFun, H.-K., Sumangala, V., Prasad, D. J., Poojary, B. & Chantrapromma, S. (2011). Acta Cryst. E67, o274.  Web of Science CSD CrossRef IUCr Journals
First citationRigaku/MSC (2005). CrystalClear and CrystalStructure. Rigaku/MSC Inc., The Woodlands, Texas, USA.
First citationShang, Z., Ha, J., Yu, Y. & Zhao, X. (2011). Acta Cryst. E67, o1336.  Web of Science CSD CrossRef IUCr Journals
First citationShang, Z., Qi, S., Tao, X. & Zhang, G. (2011). Acta Cryst. E67, o1335.  Web of Science CSD CrossRef IUCr Journals
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSteigbigel, R. T. et al. (2008). N. Engl. J. Med. 359, 339–354.  Web of Science CrossRef PubMed

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