Methyl 2-[2-(benzyl­oxycarbonyl­amino)­propan-2-yl]-5-hy­droxy-6-meth­oxy­pyrimidine-4-carboxyl­ate

Hoong-Kun Fun; V Sumangala; D Jagadeesh Prasad; Boja Poojary; Suchada Chantrapromma

doi:10.1107/S160053681005467X

. 2011 Jan 8;67(Pt 2):o274. doi: 10.1107/S160053681005467X

Methyl 2-[2-(benzyloxycarbonylamino)propan-2-yl]-5-hydroxy-6-methoxypyrimidine-4-carboxylate

Hoong-Kun Fun ^a,^*,^‡, V Sumangala ^b, D Jagadeesh Prasad ^b, Boja Poojary ^b, Suchada Chantrapromma ^c,^§

PMCID: PMC3051748 PMID: 21522966

Abstract

In the title compound, C₁₈H₂₁N₃O₆, a pyrimidine derivative, the dihedral angle between the benzene and pyrimidine rings is 52.26 (12)°. The carboxylate unit is twisted with respect to the pyrimidine ring, making a dihedral angle of 12.33 (7)°. In the crystal, molecules are linked by a pair of O—H⋯O hydrogen bonds, forming an inversion dimer. The dimers are stacked into columns along the b axis through weak C—H⋯O interactions.

Related literature

For bond-length data, see: Allen et al. (1987 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For background to and applications of pyrimidine derivatives, see: Cheng & Roth (1971 ▶); Cox (1968 ▶); Eussell (1945 ▶); Jain et al. (2006 ▶); Shinogi (1959 ▶); Tani et al. (1979 ▶).

Experimental

Crystal data

C₁₈H₂₁N₃O₆
M _r = 375.38
Monoclinic,
a = 16.5226 (2) Å
b = 8.5717 (1) Å
c = 13.0944 (2) Å
β = 97.236 (1)°
V = 1839.75 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 297 K
0.57 × 0.52 × 0.39 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.944, T _max = 0.961
20111 measured reflections
5348 independent reflections
4087 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.164
S = 1.04
5348 reflections
256 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.52 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681005467X/is2653sup1.cif

e-67-0o274-sup1.cif^{(21.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681005467X/is2653Isup2.hkl

e-67-0o274-Isup2.hkl^{(261.9KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H1O4⋯O5	0.87 (2)	1.93 (3)	2.6513 (15)	139 (2)
O4—H1O4⋯O2ⁱ	0.87 (2)	2.39 (2)	3.0508 (17)	132 (2)
C7—H7A⋯O5ⁱ	0.97	2.52	3.347 (3)	143
C15—H15A⋯O3ⁱⁱ	0.96	2.49	3.2148 (18)	132
C17—H17A⋯O2	0.96	2.54	3.099 (2)	117

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

VS, DJP and BP thank Mangalore University for a research grant. SC thanks the Prince of Songkla University for generous support. The authors thank Universiti Sains Malaysia for the Research University grant No. 1001/PFIZIK/811160.

supplementary crystallographic information

Comment

Several pyrimidine derivatives have been developed as chemotherapeutic agents and have found wide clinical applications (Jain et al., 2006). The pyrimidine ring is found in vitamins like thiamine, riboflavin and folic acid (Cox, 1968). Barbiton, a pyrimidine derivative, possesses hypnotic, sedative and anticonvulsant (Eussell, 1945) activities. Pyrimidine derivatives of sulfa drugs, namely sulfadiazine, sulfamerazine and sulfadimidine are superior to many other sulfonamides and are used for treatment in some acute UT infections, cerebrospinal meningitis and for patients allergic to pencillins (Shinogi, 1959). 2-Thiouracil and its alkyl analogue, thiobarbital, are effective drugs against hyperthyroidism. Propylthiouracil is used as a drug for hyperthyroidism with minimum side effects (Cheng & Roth, 1971). Afloqualone has been evaluated as a successful anti-inflammatory agent with lower-back-pain patients (Tani et al., 1979). In view of the importance of pyrimidine derivatives, the title compound (I) was synthesized and its crystal structure was reported.

The molecule of (I), (Fig. 1), is a V-shaped structure with the dihedral angle between the benzene and pyrimidine rings being 52.26 (12)°. The oxycarbonylamino unit (atoms C8, N1, O1 and O2) are planar with r.m.s. 0.0035 (1) Å. This unit makes dihedral angles of 62.35 (12) and 65.98 (8)° with the benzyl group (C1—C7) and pyrimidine ring, respectively. The hydroxy group is co-planar with the pyrimidine ring [r.m.s. 0.0190 (1) Å] whereas the methoxy is slightly deviated with the torsion angle C18–O3–C11–C12 = 175.74 (12)°. The carboxylate moiety is planar with r.m.s. 0.0033 (1) Å and makes the dihedral angle of 12.33 (7)° with the pyrimidine ring. The conformation of the carboxylate moiety is indicated by the torsion angles of C15–O6–C14–C13 = 179.53 (11)° and C12–C13–C14–O5 = -10.7 (2)°. Intramolecular O4–H1O4···O5 hydrogen bond generate S(6) ring motif (Bernstein et al., 1995). The bond distances are of normal values (Allen et al., 1987).

In the crystal packing (Fig. 2), the molecules are linked bya pair of O—H···O hydrogen bonds (Table 1), forming an inversion dimer. These dimers are stacked into columns along the b axis through weak C—H···O interactions (Table 1). The crystal is solidated and stabilized by O—H···O hydrogen bonds and C—H···O weak interactions (Table 1).

Experimental

The title compound was synthesized by taking benzyl (1-cyano-1-methylethyl) carbamate (0.10 mole) in xylene and dimethyl acetylene dicarboxylate (0.12 mole) was added. The reaction mixture is heated to 407 K and maintained at the temperature for 10 hrs until the reaction was completed. On cooling, the precipitated product, methyl 2-(1-{[(benzyloxy) carbonyl] amino}-1-methylethyl)-5,6-dihydroxypyrimidine-4-carboxylate, is filtered and washed with hexane. The sample is dried at 313 K for 4–5 hrs. The obtained material is taken in 5 volume of methanol and 0.22 mole of 5% sodium hydroxide in methanol. The mixture was cooled to 288 K and methyl iodide (0.20 mole) was then added and heated to 323 K. After the reaction was over, methanol was distilled off and the product was quenched in water and then filtered to get the title compound. Colorless block-shaped single crystals of the title compound suitable for x-ray structure determination were recrystalized from ethanol by the slow evaporation of the solvent at room temperature after several days, Mp. 391–393 K.