Crystal structure of 2(R)-(5-fluorouracil-1-yI)acetyl-2-phenylglycin dimethylformamide solvate, C14H12FN3O5 • C3H7NO

Abstract

C17H19FN4O6, monoclinic, P121/c1 (no. 14), a = 5.2042(5) A, b = 21.778(2) A, c = 16.932(2) A, = 101.165(2)°, V = 1882.7 A, Z = 4, Rgt(F) = 0.068, wRref(F) = 0.198, T = 298 K. Source of material The starting material 5-fluoro-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-acetic acid was prepared from 5-fluorouracil and bromoacetic acid following the method of the literature [1]. The key intermediate methyl 2(R)-(5-fluorouracil-1-aceto)amino-2phenyl acetatewas synthesized from5-fluorouracil-1-acetic acid, dicyclohexyl carbodiimide (dcc), and 1-hydroxybenzotriazole (btOH). A solution (25 ml) of dcc (0.024 mol) in dimethylformamide (dmf) was dropped in a dmf solution (75 ml) of 5-fluorouracil-1-acetic acid (0.02 mol) and btOH (0.02 mol) at 273 K. After 5 h reaction at room temperature, methyl 2(R)-amino-2phenyl acetate (0.02mol) and triethylamine (0.02mol)were added to the abovemixture.After 4 h stirring, awhite solidmethyl 2(R)(5-fluorouracil-1-aceto)amino-2-phenyl acetate was obtained after filtration, reduced pressure distillation of dmf, and column chromatography separation. The title compound was obtained by hydrolysis with 1 M sodium hydroxide solution. The purified product was dissolved in 95 % ethanol and single crystals were separated after 10 d.Mass, IR, HNMR and CNMR are available in the CIF. Discussion 5-Fluorouracil (5FU) is an antimetabolite with good antitumor activity but has side effects [1-3].Much attention has been paid to the derivatives of 5FU and their anticancer activities [4-6]. In an extension of this research, we report the crystal structure of a peptide derivative of 5FU, 2(R)-(5-fluorouracil-1-yl)acetyl-2-phenylglycin. The atoms (C1, C2, C3, C4, N1 and N2) in the heterocyclic ring and the atoms (C9 – C14) of the benzene ring are essentially planarwith r.m.s. deviations of 0.0104A and 0.0100A, respectively. The dihedral angle between the two rings is 53.8(2)A.Moreover, the N3—C6 bond distance (1.327(5) A) is shorter than a typical C—N bond length (1.443(4) A) [7] indicating the electron delocalization of the atoms O3, C6 and N3. In the crystal structure, 2(R)-(5-fluorouracil-1-yl)acetyl-2-phenylglycin and N,N-dimethylformamide solventmolecules are linked by intermolecular O4–H4···O6, N3–H3···O2 (i: x,–y+ 2,z– 2) and N2–H2···O5 (ii: x,–y+ 2,z– 2) hydrogen bonds to produce a zigzag chain along [001] direction (figure, bottom). Z. Kristallogr. NCS 221 (2006) 39-40 39 © by OldenbourgWissenschaftsverlag,Munchen Crystal: colorless block, size 0.14 × 0.15 × 0.26 mm Wavelength: Mo K radiation (0.71073 A) : 1.13 cm−1 Diffractometer, scan mode: Bruker APEX SMART CCD, / 2 max: 50.02° N(hkl)measured, N(hkl)unique: 9665, 3321 Criterion for Iobs, N(hkl)gt: Iobs > 2 (Iobs), 2514 N(param)refined: 255 Programs: SHELXS-97 [8], SHELXL-97 [9], SHELXTL [10] Table 1. Data collection and handling.