(R)-N-Methyl-4-[2-(methylsulfanyl)pyrimidin-4-yl]-1-(tetrahydrofuran-3-yl)-1H-pyrazol-5-amine

The chiral center at the substituted atom of the tetrahydrofuranyl ring in the title compound, C13H17N5OS, has an R configuration. The methylsulfanylpyrimidine group and the pyrazole ring are almost coplanar [the maximum deviation from this plane is 0.070 (4) Å], the N—Me substituent being displaced from the methylsulfanylpyrimidine-pyrazole plane by 0.880 (4) Å. The secondary amine group participates in an intramolecular hydrogen bond with the pyrimidine N atom in position 3.

The chiral center at the substituted atom of the tetrahydrofuranyl ring in the title compound, C 13 H 17 N 5 OS, has an R configuration. The methylsulfanylpyrimidine group and the pyrazole ring are almost coplanar [the maximum deviation from this plane is 0.070 (4) Å ], the N-Me substituent being displaced from the methylsulfanylpyrimidine-pyrazole plane by 0.880 (4) Å . The secondary amine group participates in an intramolecular hydrogen bond with the pyrimidine N atom in position 3.

Related literature
For the structures of related pyrimidine derivatives with similar intramolecular hydrogen bonds, see: Golic et al. (1993).

Data collection
The methylsulfanylpyrimidine group and pyrazolyl ring lie approximately in one plane. The maximum deviation from this plane being 0.070 (4) Å for the C13 atom; the displacement of methyl-C8 atom from this plane is 0.880 (4) Å. The orientation of the tetrahydrofuran ring can be characterized by the dihedral angle of 98.1 (3)° formed by the pyrimidine-pyrazolyl plane with the C2-C3-C4 plane.
The secondary amino group forms an intramolecular hydrogen bond with the N5 atom of the pyrimidine ring, Table 1, the geometry of this bond is similar to that observed in ethyl (Z)-2-amino-3-(4-pyrimidinyl)propenoate (Golic et al., 1993).

Experimental
A solution of -(2-(methylsulfanyl)pyrimidin-4-yl)-1-(tetrahydrofuran-2-yl)-1H-pyrazol-5-amine (8.32 g, 30.0 mmol) in anhydrous THF (80 ml) was added dropwise to a suspension of hexane-washed NaH (60% dispersion in mineral oil, 1.92 g, 48.0 mmol) in anhydrous THF (20 ml) at room temperature. The resulting orange reaction mixture was stirred under nitrogen for 30 minutes; thereafter MeI (5.96 g, 42.0 mmol) was added dropwise. The reaction mixture was stirred at room temperature under nitrogen overnight and then quenched with aqueous NH 4 Cl (100 ml). EtOAc (200 ml) was added and layers were separated. The organic extract was washed with brine, dried over sodium sulfate, and concentrated to give the crude product, which was purified by flash chromatography using 20-50% EtOAc in hexane to afford 5.85 g (67%) of yellow solid. The racemic product thus obtained was subjected to chiral chromatography on Chiralpak AS-H 21.2 x 250 mm column with 15% IPA in CO 2 at 140 bar as eluent (temp = 35°C; flow = 60 ml/min; UV detection at 260 nm). Two fractions corresponding to each of the enantiomers (Peak1 and Peak2) were collected and evaporated to dryness; specific rotation [α] D 20 was measured in methanol solution and yielded the values of -191.4° and +224.1°, respectively. The enantiomer collected as Peak 1 was recrystallized from EtOAc/hexane to yield single crystals.

Refinement
All H atoms bonded to C atoms were placed in geometrically calculated positions (C-H 0.95 Å, 0.98 Å, 0.99 Å, and 1.00 Å for aromatic-, methyl-, methylene-and methyine-H atoms, respectively) and included in the refinement in the riding model The U iso (H) were set to 1.2U eq of the carrying atom for non-methyl and amine, and 1.5U eq for methyl-H atoms. Fig. 1. Molecular structure of (I), showing 50% probability displacement ellipsoids and atom numbering scheme. H atoms are drawn as circles with arbitrary small radius.