2-Methylcarbamoyl-4-{4-[3-(trifluoromethyl)benzamido]phenoxy}pyridinium 4-methylbenzenesulfonate monohydrate

The asymmetric unit of the title compound, C21H17F3N3O3 +·C7H7O3S−·H2O, contains two formula units. In one of the cations, the pyridinium and trifluoromethyl benzene rings form dihedral angles of 87.42 (8) and 45.92 (8)°, respectively, with the central benzene ring [79.56 (8) and 43.52 (8)° in the other cation]. In the crystal structure, N—H⋯O, O—H⋯O and C—H⋯O hydrogen bonds link the ions and water molecules, forming a three-dimensional network.

The asymmetric unit of the title compound, C 21 H 17 F 3 N 3 O 3 + Á-C 7 H 7 O 3 S À ÁH 2 O, contains two formula units. In one of the cations, the pyridinium and trifluoromethyl benzene rings form dihedral angles of 87.42 (8) and 45.92 (8) , respectively, with the central benzene ring [79.56 (8) and 43.52 (8) in the other cation]. In the crystal structure, N-HÁ Á ÁO, O-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds link the ions and water molecules, forming a three-dimensional network.

Related literature
For general background to the use of small molecule inhibitors of Raf kinase activity in the treatment of cancer, see: Lowinger et al. (2002). For bond-length data, see: Allen et al. (1987). H atoms treated by a mixture of independent and constrained refinement Á max = 0.36 e Å À3 Á min = À0.40 e Å À3 Table 1 Hydrogen-bond geometry (Å , ).

Comment
There are many small molecule inhibitors of Raf kinase activity for the treatment of cancer (Lowinger et al., 2002). The title compound is one of the important agents in our synthetic investigations of antitumor drugs. We report here its crystal structure.
The asymmetric unit of the title compound contains two cationic units, two anionic units and two water molecules. One of the independent units of all constituents are shown in Fig.1 In the crystal structure, N-H···O, O-H···O and C-H···O hydrogen bonds link the ionic units and water molecules into a three-dimensional network.

Experimental
A mixture of 4-methylbenzenesulfonic acid (2.4 g, 14 mmol), ethyl acetate (30 ml) and water (5 ml) was added to a solution of N-methyl-4-[4-(3-(trifluoromethyl)benzamido)phenoxy]picolinamide (5 g, 12 mmol) in ethyl acetate (120 ml). The resulting mixture was stirred for 2 h under reflux, then cooled to ambient temperature. The precipitate was collected by filtration and washed with cold ethyl acetate to yield the title compound as a white solid (6.6 g, 91%). Crystals suitable for X-ray analysis were obtained by slow evaporation of a ethyl acetate-water (26:1) solution.

Refinement
H atoms of the amino group and water molecules were located in a difference map and refined freely. The reminaing H atoms were positioned geometrically (C-H = 0.95-0.98 Å) and refined using a riding model, with U iso (H) = 1.2-1.5U eq (C). Fig. 1 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 Rfactors(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.