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

Shang, Z.; Tao, X.; Ha, J.; Yu, F.

doi:10.1107/S160053681204233X

organic compounds

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ISSN: 2056-9890

Volume 68| Part 11| November 2012| Page o3175

doi:10.1107/S160053681204233X

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

Zhenhua Shang,^a ^* Xiao Tao,^b Jing Ha ^c and Fuda Yu ^d

^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 ). 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

Crystal data

C₁₈H₂₁N₃O₆
M_r = 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 ) T_min = 0.979, T_max = 0.987
12669 measured reflections
4184 independent reflections
2889 reflections with I > 2σ(I)
R_int = 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
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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); cell refinement: CrystalClear; data reduction: CrystalClear; 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).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681204233X/bh2453sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053681204233X/bh2453Isup2.hkl

Supporting information file. DOI: 10.1107/S160053681204233X/bh2453Isup3.cml

checkCIF report

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.

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

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

C₁₈H₂₁N₃O₆	F(000) = 792
M_r = 375.38	D_x = 1.414 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 5478 reflections
a = 10.540 (2) Å	θ = 2.1–27.9°
b = 12.927 (3) Å	µ = 0.11 mm⁻¹
c = 13.751 (3) Å	T = 113 K
β = 109.74 (3)°	Plate, colourless
V = 1763.5 (6) Å³	0.20 × 0.16 × 0.12 mm
Z = 4

Data collection top

Rigaku Saturn diffractometer	4184 independent reflections
Radiation source: rotating anode	2889 reflections with I > 2σ(I)
Confocal monochromator	R_int = 0.032
Detector resolution: 7.31 pixels mm^-1	θ_max = 27.9°, θ_min = 2.1°
ω and ϕ scans	h = −13→13
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)	k = −16→16
T_min = 0.979, T_max = 0.987	l = −18→10
12669 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.093	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	w = 1/[σ²(F_o²) + (0.0545P)²] where P = (F_o² + 2F_c²)/3
4184 reflections	(Δ/σ)_max = 0.001
255 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.20 e Å⁻³
0 constraints

Crystal data top

C₁₈H₂₁N₃O₆	V = 1763.5 (6) Å³
M_r = 375.38	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 10.540 (2) Å	µ = 0.11 mm⁻¹
b = 12.927 (3) Å	T = 113 K
c = 13.751 (3) Å	0.20 × 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)
T_min = 0.979, T_max = 0.987	R_int = 0.032
12669 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	0 restraints
wR(F²) = 0.093	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	Δρ_max = 0.28 e Å⁻³
4184 reflections	Δρ_min = −0.20 e Å⁻³
255 parameters

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
N1	0.06467 (9)	0.00568 (6)	0.24005 (7)	0.0175 (2)
N2	0.12798 (9)	0.17823 (6)	0.22657 (8)	0.0184 (2)
N3	0.23993 (10)	0.16037 (7)	0.45582 (8)	0.0200 (2)
O1	0.01828 (8)	0.27591 (6)	0.08460 (7)	0.0245 (2)
O2	−0.13087 (8)	0.11324 (6)	−0.01134 (6)	0.02320 (19)
H2	−0.1711 (14)	0.0529 (10)	−0.0243 (12)	0.035*
O3	−0.18898 (8)	−0.07843 (6)	0.00815 (7)	0.0248 (2)
O4	−0.07643 (7)	−0.16439 (5)	0.15296 (6)	0.02110 (19)
O5	0.01416 (8)	0.16353 (6)	0.42853 (7)	0.0296 (2)
O6	0.16194 (8)	0.26344 (6)	0.55086 (7)	0.0251 (2)
C1	0.13702 (11)	0.08557 (8)	0.28038 (9)	0.0170 (2)
C2	0.03246 (11)	0.19213 (8)	0.12974 (9)	0.0184 (2)
C3	−0.04554 (11)	0.10083 (8)	0.08528 (9)	0.0180 (2)
C4	−0.02494 (10)	0.01226 (8)	0.14162 (9)	0.0168 (2)
C5	0.21999 (12)	0.26756 (8)	0.26136 (10)	0.0272 (3)
H5A	0.2792	0.2719	0.2198	0.041*
H5B	0.2747	0.2586	0.3343	0.041*
H5C	0.1671	0.3313	0.2531	0.041*
C6	−0.10441 (11)	−0.08065 (8)	0.09481 (9)	0.0188 (2)
C7	−0.15552 (12)	−0.25469 (9)	0.10665 (10)	0.0263 (3)
H7A	−0.2505	−0.2422	0.0978	0.039*
H7B	−0.1230	−0.3147	0.1517	0.039*
H7C	−0.1465	−0.2681	0.0391	0.039*
C8	0.23999 (11)	0.07215 (8)	0.38845 (9)	0.0191 (2)
C9	0.38107 (12)	0.06442 (9)	0.37925 (11)	0.0272 (3)
H9A	0.3937	0.1212	0.3362	0.041*
H9B	0.3899	−0.0018	0.3475	0.041*
H9C	0.4495	0.0689	0.4482	0.041*
C10	0.21098 (13)	−0.02658 (8)	0.43885 (10)	0.0257 (3)
H10A	0.2773	−0.0336	0.5084	0.038*
H10B	0.2169	−0.0866	0.3971	0.038*
H10C	0.1202	−0.0227	0.4432	0.038*
C11	0.12831 (11)	0.19193 (8)	0.47419 (9)	0.0212 (3)
C12	0.05270 (13)	0.30190 (10)	0.58204 (12)	0.0345 (3)
H12A	0.0272	0.2496	0.6247	0.041*
H12B	−0.0271	0.3166	0.5204	0.041*
C13	0.09959 (12)	0.39926 (9)	0.64339 (10)	0.0244 (3)
C14	0.01477 (13)	0.48439 (10)	0.62565 (11)	0.0355 (3)
H14	−0.0716	0.4813	0.5736	0.043*
C15	0.05509 (15)	0.57377 (10)	0.68321 (12)	0.0389 (4)
H15	−0.0034	0.6319	0.6701	0.047*
C16	0.17894 (14)	0.57887 (9)	0.75897 (11)	0.0332 (3)
H16	0.2059	0.6402	0.7987	0.040*
C17	0.26443 (12)	0.49493 (9)	0.77748 (10)	0.0269 (3)
H17	0.3503	0.4983	0.8301	0.032*
C18	0.22509 (11)	0.40592 (9)	0.71942 (10)	0.0225 (3)
H18	0.2849	0.3486	0.7318	0.027*
H3	0.3174 (15)	0.1854 (10)	0.4951 (12)	0.034 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0181 (4)	0.0182 (5)	0.0144 (5)	0.0006 (4)	0.0032 (4)	−0.0008 (4)
N2	0.0202 (5)	0.0163 (4)	0.0165 (5)	−0.0014 (4)	0.0036 (4)	0.0010 (4)
N3	0.0203 (5)	0.0181 (5)	0.0179 (6)	−0.0007 (4)	0.0015 (4)	−0.0041 (4)
O1	0.0277 (4)	0.0203 (4)	0.0230 (5)	0.0020 (3)	0.0052 (4)	0.0066 (4)
O2	0.0259 (4)	0.0229 (4)	0.0154 (5)	0.0030 (4)	0.0000 (4)	0.0016 (4)
O3	0.0215 (4)	0.0273 (4)	0.0199 (5)	−0.0012 (3)	−0.0006 (4)	−0.0012 (4)
O4	0.0229 (4)	0.0179 (4)	0.0205 (5)	−0.0035 (3)	0.0048 (4)	−0.0013 (3)
O5	0.0224 (4)	0.0287 (5)	0.0340 (6)	−0.0044 (3)	0.0046 (4)	−0.0112 (4)
O6	0.0226 (4)	0.0261 (4)	0.0266 (5)	−0.0024 (3)	0.0082 (4)	−0.0108 (4)
C1	0.0183 (5)	0.0157 (5)	0.0162 (6)	0.0022 (4)	0.0048 (5)	0.0004 (5)
C2	0.0191 (5)	0.0194 (5)	0.0165 (6)	0.0033 (4)	0.0058 (5)	0.0018 (5)
C3	0.0170 (5)	0.0217 (6)	0.0142 (6)	0.0044 (4)	0.0039 (5)	0.0003 (5)
C4	0.0159 (5)	0.0182 (5)	0.0154 (6)	0.0019 (4)	0.0040 (5)	−0.0004 (5)
C5	0.0293 (6)	0.0217 (6)	0.0260 (7)	−0.0075 (5)	0.0033 (6)	0.0011 (5)
C6	0.0174 (5)	0.0214 (6)	0.0175 (6)	0.0020 (4)	0.0056 (5)	−0.0007 (5)
C7	0.0293 (6)	0.0217 (6)	0.0270 (8)	−0.0084 (5)	0.0083 (6)	−0.0034 (5)
C8	0.0218 (5)	0.0157 (5)	0.0161 (6)	0.0017 (4)	0.0016 (5)	−0.0016 (5)
C9	0.0219 (6)	0.0276 (6)	0.0264 (7)	0.0045 (5)	0.0008 (6)	−0.0051 (6)
C10	0.0346 (6)	0.0174 (6)	0.0182 (7)	0.0016 (5)	0.0000 (6)	0.0008 (5)
C11	0.0248 (6)	0.0156 (5)	0.0209 (7)	−0.0010 (4)	0.0047 (5)	−0.0004 (5)
C12	0.0265 (6)	0.0389 (7)	0.0416 (9)	−0.0076 (6)	0.0162 (7)	−0.0178 (7)
C13	0.0228 (5)	0.0272 (6)	0.0248 (7)	−0.0021 (5)	0.0102 (5)	−0.0060 (5)
C14	0.0261 (6)	0.0450 (8)	0.0305 (8)	0.0079 (6)	0.0031 (6)	−0.0096 (7)
C15	0.0456 (8)	0.0335 (7)	0.0368 (9)	0.0159 (6)	0.0129 (7)	−0.0038 (6)
C16	0.0455 (8)	0.0265 (6)	0.0318 (8)	−0.0058 (6)	0.0185 (7)	−0.0094 (6)
C17	0.0254 (6)	0.0351 (7)	0.0214 (7)	−0.0069 (5)	0.0095 (6)	−0.0034 (5)
C18	0.0231 (6)	0.0236 (6)	0.0229 (7)	0.0012 (5)	0.0106 (5)	0.0020 (5)

Geometric parameters (Å, º) top

N1—C1	1.2923 (13)	C7—H7B	0.9800
N1—C4	1.3667 (15)	C7—H7C	0.9800
N2—C2	1.3833 (15)	C8—C10	1.5317 (15)
N2—C1	1.3943 (13)	C8—C9	1.5376 (15)
N2—C5	1.4797 (14)	C9—H9A	0.9800
N3—C11	1.3473 (14)	C9—H9B	0.9800
N3—C8	1.4694 (14)	C9—H9C	0.9800
N3—H3	0.875 (15)	C10—H10A	0.9800
O1—C2	1.2320 (13)	C10—H10B	0.9800
O2—C3	1.3390 (14)	C10—H10C	0.9800
O2—H2	0.876 (13)	C12—C13	1.5028 (17)
O3—C6	1.2239 (15)	C12—H12A	0.9900
O4—C6	1.3187 (13)	C12—H12B	0.9900
O4—C7	1.4507 (13)	C13—C18	1.3843 (18)
O5—C11	1.2109 (14)	C13—C14	1.3865 (17)
O6—C11	1.3562 (14)	C14—C15	1.3838 (19)
O6—C12	1.4457 (14)	C14—H14	0.9500
C1—C8	1.5255 (17)	C15—C16	1.369 (2)
C2—C3	1.4503 (16)	C15—H15	0.9500
C3—C4	1.3581 (15)	C16—C17	1.3781 (17)
C4—C6	1.4813 (15)	C16—H16	0.9500
C5—H5A	0.9800	C17—C18	1.3819 (16)
C5—H5B	0.9800	C17—H17	0.9500
C5—H5C	0.9800	C18—H18	0.9500
C7—H7A	0.9800

C1—N1—C4	119.05 (10)	C1—C8—C9	108.47 (10)
C2—N2—C1	121.31 (9)	C10—C8—C9	109.24 (9)
C2—N2—C5	113.23 (9)	C8—C9—H9A	109.5
C1—N2—C5	125.38 (10)	C8—C9—H9B	109.5
C11—N3—C8	122.65 (10)	H9A—C9—H9B	109.5
C11—N3—H3	117.7 (9)	C8—C9—H9C	109.5
C8—N3—H3	118.5 (9)	H9A—C9—H9C	109.5
C3—O2—H2	102.2 (10)	H9B—C9—H9C	109.5
C6—O4—C7	114.62 (10)	C8—C10—H10A	109.5
C11—O6—C12	116.08 (9)	C8—C10—H10B	109.5
N1—C1—N2	122.28 (11)	H10A—C10—H10B	109.5
N1—C1—C8	116.74 (9)	C8—C10—H10C	109.5
N2—C1—C8	120.89 (9)	H10A—C10—H10C	109.5
O1—C2—N2	121.61 (10)	H10B—C10—H10C	109.5
O1—C2—C3	123.23 (11)	O5—C11—N3	126.06 (11)
N2—C2—C3	115.13 (10)	O5—C11—O6	124.26 (10)
O2—C3—C4	126.26 (10)	N3—C11—O6	109.67 (10)
O2—C3—C2	114.58 (10)	O6—C12—C13	108.10 (9)
C4—C3—C2	119.14 (11)	O6—C12—H12A	110.1
C3—C4—N1	122.78 (10)	C13—C12—H12A	110.1
C3—C4—C6	118.53 (11)	O6—C12—H12B	110.1
N1—C4—C6	118.69 (10)	C13—C12—H12B	110.1
N2—C5—H5A	109.5	H12A—C12—H12B	108.4
N2—C5—H5B	109.5	C18—C13—C14	118.59 (11)
H5A—C5—H5B	109.5	C18—C13—C12	121.68 (11)
N2—C5—H5C	109.5	C14—C13—C12	119.71 (12)
H5A—C5—H5C	109.5	C15—C14—C13	120.45 (13)
H5B—C5—H5C	109.5	C15—C14—H14	119.8
O3—C6—O4	123.35 (10)	C13—C14—H14	119.8
O3—C6—C4	121.54 (10)	C16—C15—C14	120.33 (12)
O4—C6—C4	115.10 (10)	C16—C15—H15	119.8
O4—C7—H7A	109.5	C14—C15—H15	119.8
O4—C7—H7B	109.5	C15—C16—C17	119.91 (12)
H7A—C7—H7B	109.5	C15—C16—H16	120.0
O4—C7—H7C	109.5	C17—C16—H16	120.0
H7A—C7—H7C	109.5	C16—C17—C18	119.93 (13)
H7B—C7—H7C	109.5	C16—C17—H17	120.0
N3—C8—C1	111.98 (9)	C18—C17—H17	120.0
N3—C8—C10	108.59 (9)	C17—C18—C13	120.79 (11)
C1—C8—C10	110.51 (9)	C17—C18—H18	119.6
N3—C8—C9	107.98 (9)	C13—C18—H18	119.6

C4—N1—C1—N2	−0.69 (14)	N1—C4—C6—O4	−2.56 (13)
C4—N1—C1—C8	−177.17 (9)	C11—N3—C8—C1	56.33 (14)
C2—N2—C1—N1	5.48 (15)	C11—N3—C8—C10	−65.98 (14)
C5—N2—C1—N1	−170.84 (10)	C11—N3—C8—C9	175.69 (11)
C2—N2—C1—C8	−178.18 (9)	N1—C1—C8—N3	−136.08 (10)
C5—N2—C1—C8	5.49 (15)	N2—C1—C8—N3	47.39 (13)
C1—N2—C2—O1	175.31 (9)	N1—C1—C8—C10	−14.88 (13)
C5—N2—C2—O1	−7.95 (14)	N2—C1—C8—C10	168.59 (9)
C1—N2—C2—C3	−6.35 (14)	N1—C1—C8—C9	104.85 (10)
C5—N2—C2—C3	170.39 (9)	N2—C1—C8—C9	−71.68 (12)
O1—C2—C3—O2	2.85 (15)	C8—N3—C11—O5	−11.11 (19)
N2—C2—C3—O2	−175.46 (8)	C8—N3—C11—O6	170.45 (10)
O1—C2—C3—C4	−178.65 (10)	C12—O6—C11—O5	3.79 (17)
N2—C2—C3—C4	3.04 (14)	C12—O6—C11—N3	−177.74 (10)
O2—C3—C4—N1	179.76 (9)	C11—O6—C12—C13	−164.02 (10)
C2—C3—C4—N1	1.45 (15)	O6—C12—C13—C18	−45.05 (16)
O2—C3—C4—C6	−1.11 (16)	O6—C12—C13—C14	136.37 (12)
C2—C3—C4—C6	−179.41 (9)	C18—C13—C14—C15	−0.22 (19)
C1—N1—C4—C3	−2.74 (15)	C12—C13—C14—C15	178.41 (12)
C1—N1—C4—C6	178.12 (9)	C13—C14—C15—C16	−0.5 (2)
C7—O4—C6—O3	−0.77 (14)	C14—C15—C16—C17	0.6 (2)
C7—O4—C6—C4	179.58 (8)	C15—C16—C17—C18	0.13 (19)
C3—C4—C6—O3	−1.39 (15)	C16—C17—C18—C13	−0.87 (18)
N1—C4—C6—O3	177.78 (9)	C14—C13—C18—C17	0.91 (17)
C3—C4—C6—O4	178.27 (9)	C12—C13—C18—C17	−177.69 (10)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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+1/2, −y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₈H₂₁N₃O₆
M_r	375.38
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	113
a, b, c (Å)	10.540 (2), 12.927 (3), 13.751 (3)
β (°)	109.74 (3)
V (Å³)	1763.5 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.20 × 0.16 × 0.12

Data collection
Diffractometer	Rigaku Saturn diffractometer
Absorption correction	Multi-scan (CrystalClear; Rigaku/MSC, 2005)
T_min, T_max	0.979, 0.987
No. of measured, independent and observed [I > 2σ(I)] reflections	12669, 4184, 2889
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.659

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.093, 1.00
No. of reflections	4184
No. of parameters	255
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	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···A	D—H	H···A	D···A	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+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

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

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Volume 68| Part 11| November 2012| Page o3175

doi:10.1107/S160053681204233X

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

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

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

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