2-Chloro-5-fluoro-6-methyl-N-o-tolylpyrimidin-4-amine

In the title compound, C12H11ClFN3, the benzene ring forms a dihedral angle of 72.43 (5)° with the pyrimidine ring. In the crystal, N—H⋯N hydrogen bonds link the molecules into a chain running along the c axis.


Related literature
We are acknowledge the support of Education Department Fund (Y201018689) of Zhejiang Province.

Comment
The fluoro-containning pyrimidine skeleton was found in many biologically active molecules (Riccaboni et al., 2010).
Especially, the 4-anilines-substituted derivatives of 5-fluoropyrimidine were proved possessing obvious antitumor activity in recent years (Lawrence et al., 2012). Owing to our interest in this area, we have prepared a series of 5-fluoropyrimidine derivatives substituted with anilines. In a continuation of our SAR investigations, we present here the crystal structure of the title compound, (1).
In (1) (Fig. 1), the atoms N1/H1 and C6 are co-planar well with the pyrimidine ring [r.m.s. 0.007 (1) Å], indicating a good conjugate system between the atom N1 and pyrimidine. The plane of o-toluidine moiety is torsional toward the pyrimidine ring, showing a dihedral angle of 72.43 (5)°. The amino group is involved in the formation of intermolecular N-H···N hydrogen bond (Table 1). In the crystal (Fig. 2), the intermolecular N-H···N hydrogen bonds link the molecules into one-dimensional chains running along the c axis.

Experimental
In a tube-reactor was added a mixture of 2,4-dichloro-5-fluoro-6-methylpyrimidine (0.181 g, 1.0 mmol), o-toluidine (0.107 g, 1.0 mmol), KHCO 3 (0.1 g, 1.0 mmol) and 1.0 ml DMSO. The mixture was heated at 333 K until the TLC test showed that the reaction is complete. Then the mixture was diluted with 30 ml e thyl acetate, washed with 30 ml water for three times, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 8/1) to give a white solid (0.238 g, yield 94.5%, m.p. 430-432 K). Since the crystal product was not found to be suitable for X-ray diffraction studies, a few solids were dissolved in ethyl acetate, which was allowed to evaporate slowly to give colourless crystals of (1) suitable for X-ray diffraction studies.

Refinement
The amino H atom was found in a difference Fourier map and treated as riding with N-H = 0.86 Å, and with U iso (H) = 1.2U eq (N). The other H atoms were added at calculated positions and refined using a riding model, with C-H = 0.93 Å (or 0.96 Å for methyl H) and U iso (H) = 1.2U eq (C) or 1.5U eq (C methyl ) .  The molecular structure of the title compound with 30% probability displacement ellipsoids.  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.