Crystal structures of 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(2,4-dimethylphenyl)acetamide and 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(3-methoxyphenyl)acetamide

Two 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamide derivatives have folded conformations with the pyrimidine ring being inclined to the benzene ring by 58.64 (8) and 78.33 (9)°.

In the title compounds, C 14 H 17 N 5 OS (I) and C 13 H 15 N 5 O 2 S (II), the dihedral angle between the pyrimidine and benzene rings is 58.64 (8) in (I) and 78.33 (9) in (II). In both compounds, there is an intramolecular C-HÁ Á ÁO hydrogen bond, and in (II) there is also an intramolecular N-HÁ Á ÁN hydrogen bond present. In the crystals of both compounds, a pair of N-HÁ Á ÁN hydrogen bonds links the individual molecules to form inversion dimers with R 2 2 (8) ring motifs. In (I), the dimers are linked by N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds, enclosing R 2 1 (14), R 2 1 (11) and R 2 1 (7) ring motifs, forming layers parallel to the (100) plane. There is also an N-HÁ Á Á interaction present within the layer. In (II), the inversion dimers are linked by N-HÁ Á ÁO hydrogen bonds enclosing an R 4 4 (18) ring motif. The presence of N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds generate an R 2 1 (6) ring motif. The combination of these various hydrogen bonds results in the formation of layers parallel to the (111) plane.

Chemical context
Diaminopyrimidine derivatives have been proved to be an important class of compounds because of their therapeutic and pharmacological properties. One such important property is its inhibition potency against cancer targets. As a result of the limited capacity of drugs that can cure or at least prolong the survival of cancer patients, there is always an strong requirement for new chemotherapeutics. It has been reported that diaminopyrimidines show inhibition against cyclindependent kinases (cdks), thus arresting cell proliferation in cancer cells (Mesguiche et al., 2003). 2,4-Diaminopyrimidine derivatives have also shown effective suppression of anaplastic lymphoma kinase (ALK), one of the receptor tyrosine kinases that is involved in a variety of tumours (Achary et al., 2017). 2,4-Diaminopyrimidine derivatives have also been reported to exhibit potent inhibitory activity against influenza viruses (Kimura et al., 2006) and have anti-retroviral activity (Hocková et al., 2004), anti-bacterial (Kandeel et al., 1994) and potential anti-microbial properties (Holla et al., 2006). Several diaminopyrimidine derivatives have shown good activity, efficiency against the malarial parasite Plasmodium falciparum K1 strain (Phuangsawai et al., 2016;Chiang et al., 2009). Interestingly, they also act as calcium channel blocking agents (Manjula et al., 2004;Singh et al., 2009). As part of our own studies in this area, we report herein on the syntheses and ISSN 2056-9890 crystal structure analyses of the title compounds, 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(2,4-dimethylphenyl)acetamide (I) and [2-((4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(3methoxyphenyl)acetamide (II).

Figure 2
The molecular structure of (II), showing the atom labelling and displacement ellipsoids drawn at 50% probability level. The N-HÁ Á ÁN and C-HÁ Á ÁO contacts are shown as dashed lines (see Table 2).

Figure 1
The molecular structure of (I), showing the atom labelling and displacement ellipsoids drawn at 50% probability level. The C-HÁ Á ÁO contact is shown as a dashed line (see Table 1). Table 1 Hydrogen-bond geometry (Å , ) for (I).

Supramolecular features
The hydrogen-bonding geometry of compounds (I) and (II) are given in Tables 1 and 2, respectively. In compound (I), atom O1 is a triple acceptor of hydrogen bonds. The N5-H5Á Á ÁO1 ii hydrogen bonds form a chain running along the caxis direction. The N2-H2AÁ Á ÁO1 ii and C13-H13CÁ Á ÁO1 ii hydrogen bonds generate an R 1 2 (14) ring motif, and the N2-H2AÁ Á ÁO1 ii and N5-H5Á Á ÁO1 ii hydrogen bonds form an R 1 2 (11) ring motif, and N5-H5Á Á ÁO1 ii and C13-H13Á Á ÁO1 ii hydrogen bonds generate an R 1 2 (7) ring motif (Table 1 and Fig. 3). There is also a N2-H2BÁ Á Á interaction present within the layer (Table 1 and Fig. 4), with the separation distance between the donor and acceptor, Cg1, being 3.4851 (1) Å . The N1-H1AÁ Á ÁN3 i hydrogen bond generates an inversion dimer with an R 2 2 (8) ring motif (Table 1 and The crystal packing of (I), viewed along the b axis, C-HÁ Á ÁO and N-HÁ Á ÁO hydrogen bonds generate R 1 2 (14), R 1 2 (11) and R 1 2 (7) ring motifs. In this and subsequent figures, the hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 4
A partial view of the crystal packing of (I), viewed approximately along the c axis, showing the N-HÁ Á Á interactions.

Figure 5
A view along the b axis of the crystal packing of (I), showing the N-HÁ Á ÁN hydrogen bonds that generate an R 2 2 (8) ring motif.

Figure 7
A partial view along the a axis of the crystal packing of (II). The N-HÁ Á ÁN hydrogen bonds generate an R 2 2 (8) ring motif and N-HÁ Á ÁO and N-HÁ Á ÁN hydrogen bonds an R 4 4 (18) ring motif.
In compound (II), atom O2 is a double acceptor of hydrogen bonds. The N2-H2BÁ Á ÁO2 iii hydrogen bond forms an R 2 2 (26) ring motif and hydrogen bond C2-H2Á Á ÁO2 iii generates an R 2 2 (26) ring motif (Table 2 and Fig. 6). These two intermolecular hydrogen bonds generate an R 1 2 (6) ring motif, which is shown in Fig. 6. Molecules are linked by a pair of N1-H1AÁ Á ÁN3 i hydrogen bonds, forming an inversion dimer with an R 2 2 (8) ring motif, and hydrogen bonds N1-H1BÁ Á ÁO1 ii and N1-H1AÁ Á ÁN3 i generate an R 4 4 (18) ring motif (Table 2 and Fig. 7). The combination of these various hydrogen bonds results in the formation of layers parallel to (111).

Synthesis and crystallization
Compound (I): To a solution of 4,6-diamino-pyrimidine-2thiol (0.5 g, 3.52 mmol) in 25 ml of ethanol in a round-bottom flask, potassium hydroxide (0.2 g, 3.52 mmol) was added and the mixture was refluxed for 30 min. 2,4-Dimethylphenyl acetamide (3.52 mmol) was added and the mixture was refluxed for 3 h. At the end of the reaction (observed by TLC), the ethanol was evaporated under vacuum and cold water was added. The precipitate formed was filtered and dried to give compound (I) as a crystalline powder (yield 67%). After purification, the compound was recrystallized from ethanol solution by slow evaporation of the solvent.
Compound (II): To a solution of 4,6-diamino-pyrimidine-2thiol (0.5 g, 3.52 mmol) in 25 ml of ethanol in a round-bottom flask was added potassium hydroxide (0.2 g, 3.52 mmol) and the mixture was refluxed for 30 min. 3-Methoxyphenyl acetamide (3.52 mmol) was added and the mixture was refluxed for 3 h. At the end of the reaction (observed by TLC), the ethanol was evaporated under vacuum and cold water was added, and the precipitate formed was filtered and dried to give compound (II) as a shiny powder (yield 73%). After purification, the compound was recrystallized from ethanol solution by slow evaporation of the solvent.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. For both compounds the hydrogen atoms were placed in calculated positions and refined using the riding model: C-H = 0.93-0.97 Å and N-H = 0.86 Å , with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (N,C) for other H atoms.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

(II) 2-[(4,6-Diaminopyrimidin-2-yl)sulfanyl]-N-(3-methoxyphenyl)acetamide
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.