2-(3-{(3R,4R)-4-Methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}oxetan-3-yl)acetonitrile monohydrate

In the title compound, C18H24N6O·H2O, the piperidine ring adopts a chair conformation with an N—C—C—C torsion angle of 39.5 (5)° between the cis-related substituents. The pyrrole N—H group forms a water-mediated intermolecular hydrogen bond to one of the N atoms of the annelated pyrimidine ring. The water molecule connects two organic molecules and is disorderd over two positions (occupancies of 0.48 and 0.52). The crystal packing shows zigzag chains of alternating organic and water molecules running parallel to the a axis.

In the title compound, C 18 H 24 N 6 OÁH 2 O, the piperidine ring adopts a chair conformation with an N-C-C-C torsion angle of 39.5 (5) between the cis-related substituents. The pyrrole N-H group forms a water-mediated intermolecular hydrogen bond to one of the N atoms of the annelated pyrimidine ring. The water molecule connects two organic molecules and is disorderd over two positions (occupancies of 0.48 and 0.52). The crystal packing shows zigzag chains of alternating organic and water molecules running parallel to the a axis.
In the crystal structure of the title compound, C 18 H 24 N 6 O, the exocyclic amino substituent is oriented almost coplanar to the heteroaromatic ring system with a torsion angle of 0.6 (2)° for C11-N10-C5-C4. The piperidine ring adopts a chair conformation with a torsion angle of 39.5 (5) ° between the cis substituents. One of the protons (H23B) of the methylene group between the oxetane ring and the nitrile function is involved in an intermolecular C-H···π interaction while the other methylene proton forms an intermolecular C-H···N interaction with the nitrile group. The oxygen atom of the oxetane ring makes two intermolecular C-H···O contacts with two H atoms (H13A and H15B) of the piperidine ring.
The heterocyclic pyrrol N-H forms an intermolecular water mediated hydrogen bond to one of the nitrogen atoms (N8) in the 6-membered pyrmidine heterocycle with a length of 2.78 (2) Å for the N-H···O and 2.86 (8) Å for the O-H···N contact. The water molecule connecting two molecules is disorderd over two positions (s.o.f. 0.48/0.52). The crystal packing is shows N-H···OH···N hydrogen bonds resulting in infinite chains parallel to the a axis.
Crystals of the title compound were obtained by slow evaporation of a solution in chloroform + 10% methanol at 298 K.

Refinement
Site occupation factors of the disordered water molecule were fixed assuming similar isotropic displacement parameters with C-H = 0.95 Å (aromatic) or 0.99-1.00 Å (sp 3 C-atom). All H atoms were refined with isotropic displacement parameters (set at 1.2-1.5 times of the U eq of the parent atom). One of the H atoms of the disordered water molecule could be position to make a hydrogen bond to an N atom. The other one was positioneded with idealized geometric with respect to the first one. The absolute configuration was assigned according to the synthesis.

Figure 1
Crystal structure of the title compound with labeling and displacement ellipsoids drawn at the 50% probability level.

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (