The twinned crystal structure of (4SR)-7-benzyl-2,4,8,8-tetramethyl-7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione, C₁₆H₂₀N₄O₂

Source of material

The title compound has been obtained by a regioselective N2-alkylation reaction of (4RS)-7-benzyl-4,8,8-trimethyl-7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione with a large excess of methyl iodide (3.0 equiv.) in anhydrous dimethylformamide (1–2 mL per 1.0 equiv. starting material) [6]. The mixture was stirred at room temperature for 72 h in the presence of sodium hydride (1.26 equiv.) as a base. The crude product was purified by column chromatography on silica gel (dichloromethane/methanol, 95:5, R_f = 0.58) followed by RP-HPLC (methanol/water, 70:30) and recrystallization from dichloromethane/petroleum ether (90:10) to give a pure product as a white solid. Clear colorless plate crystals suitable for X-ray structure analysis were obtained after final recrystallization from methanol and crystallization over a period of several days at 268–270 K (m.p. 343–344 K).

Experimantal details

Single crystals of the title compound were multiple non-merohedrically twinned. Four domains were located and integrated. Four domains were taken into account during data integration and refinement. Carbon-bound hydrogen atoms were placed in calculated positions and were included in the refinement in the riding model approximation, with U_iso(H) set to 1.2U_eq(C).

Discussion

The title compound was prepared as a part of our study of regioselective synthesis of novel drug-like small molecules comprising an imidazo[1,2,4]triazine-3,6-dione framework [6]. Numerous biologically active compounds and natural products exhibit a condensed heterobicyclic 1,2,4-triazine scaffold [7], [8], [9].

The asymmetric unit contains two independent molecules of the title compound. The crystal structure contains four symmetry equivalent molecules per unit cell, which show an antiparallel orientation in the crystal packing. The significant shorter bonds C3–N1 = 1.280(7) Å for molecule No. 1 and C19–N5 = 1.282(7) Å for molecule No. 2, respectively, indicate the localization of the double bond in the corresponding six-membered triazine-rings. A methyl group is connected to the imidazotriazine basic structure in the corresponding asymmetric centers C2 and C18 and it is cis to the benzyl substituent in the positions N4 and N8 of the respective molecule No. 1 and 2.

The main imidazotriazine core in both molecules is almost planar including followed atoms for molecule No. 1: N1, N2, N3, N4, C1, C2, C3, C4, C6, C7, C10, O1, O2, and for molecule No. 2: N5, N6, N7, N8, C17, C18, C19, C20, C22, C23, C26, O3 O4 with r.m.s. values of 0.105 Å (for molecule No. 1) and 0.136 Å (for molecule No. 2) of the deviations from the least squares planes.

The benzyl substituent forms a second planar moiety consisting of C10, C11, C12, C13, C14, C15, C16 for molecule No. 1 (r.m.s. = 0.028 Å), and C26, C27, C28, C29, C30, C31, C32 for molecule No. 2 (r.m.s. = 0.026 Å). The tilt angle between the main imidazotriazine planes and the second planar arrangement are 69.0(1)° for molecule No. 1 and 59.7(1)° for molecule No. 2. The benzyl and the imidazotriazine moiety form a bond angle of N4—C10—C11 = 114.6(4)° for molecule No. 1 and N8—C26—C27 = 115.1(4)° for molecule No. 2, respectively.

The distance between the centroid of the two imidazotriazine planes defined above is 3.982(2) Å with a dihedral angle of 22.5(1)°.