Synthesis, spectroscopic (FT–IR and UV–Vis), crystallographic and theoretical studies, and a mol­ecular docking simulation of an imatinib-like template

The aim of the present study was to report the crystal structure and spectroscopic, electronic, supra­molecular and electrostatic properties of a new polymorph of 4-(pyridin-2-yl)pyrimidin-2-amine (C₉H₈N₄). The com­pound was synthesized under microwave irradiation. The single-crystal X-ray structure analysis revealed an angle of 13.36 (8)° between the planes of the rings, as well as mol­ecules linked by Nsp²—H...N hydrogen bonds forming dimers along the crystal. The material was analyzed by FT–IR vibrational spectroscopy, while a com­putational approach was used to elucidate the vibrational frequency couplings. The existence of Nsp²—H...N hydrogen bonds in the crystal was confirmed spectroscopically by the IR peaks from the N—H stretching vibration shifting to lower wavenumbers in the solid state relative to those in the gas phase. The supra­molecular studies confirmed the formation of centrosymmetric R₂²(8) rings, which correspond to the formation of dimers that stack parallel to the b direction. Other weak C—H...π inter­actions, essential for crystal growth, were found. The UV–Vis spectroscopic analysis showed a donor–acceptor process, where the amino group acts as a donor and the pyridine and pyrimidine rings act as acceptors. The reactive sites of the mol­ecule were identified and their qu­anti­tative values were defined using the electrostatic potential model proposed in the multifunctional wave function analyzer multiwfn. The calculated inter­action energies between pairs of mol­ecules were used to visualize the electrostatic terms as the leading factors against the dispersion factors in the crystal-growth process. The docking results showed that the amino group of the pyrimidine moiety was simultaneously anchored by hydrogen-bonding inter­actions with the Asp427 and His407 protein residues. This com­pound could be key for the realization of a series of syntheses of mol­ecules that could be used as possible inhibitors of chronic myelogenous leukemia.

Computing details

Data collection: DATCOL (Bruker, 2006); cell refinement: EVALCCD (Duisenberg et al., 2003); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEP-3 (Farrugia, 2012), Mercury (Macrae et al., 2008) and CrystalExplorer (McKinnon et al., 2004); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b).

4-(Pyridin-2-yl)pyrimidin-2-amine

Crystal data

C9H8N4	Dx = 1.388 Mg m^−3
Mr = 172.19	Melting point: 413 K
Monoclinic, I2/a	Mo Kα radiation, λ = 0.71073 Å
a = 11.4608 (15) Å	Cell parameters from 4441 reflections
b = 5.3791 (9) Å	θ = 3.1–30.0°
c = 26.740 (4) Å	µ = 0.09 mm^−1
β = 91.457 (12)°	T = 293 K
V = 1647.9 (4) Å^3	Block, colourless
Z = 8	0.40 × 0.23 × 0.20 mm
F(000) = 720

Data collection

Bruker Enraf–Nonius KappaCCD diffractometer	2379 independent reflections
Radiation source: 0.2 x 2mm^2 focus rotating anode	1688 reflections with I > 2σ(I)
Detector resolution: 18.02 pixels mm^-1	Rint = 0.020
CCD φ– and ω–scans	θmax = 30.0°, θmin = 3.1°
Absorption correction: gaussian (SADABS; Bruker, 2012)	h = −16→11
Tmin = 0.624, Tmax = 0.995	k = −7→7
4441 measured reflections	l = −31→37

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.046	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.134	w = 1/[σ^2(Fo^2) + (0.0583P)^2 + 0.5919P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
2379 reflections	Δρmax = 0.22 e Å^−3
126 parameters	Δρmin = −0.22 e Å^−3

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.

Refinement. The crystal structure was solved with SHELXT (Sheldrick, 2014) and refined with SHELXL (Sheldrick, 2014). Anisotropic atomic displacement parameters were introduced for all non-hydrogen atoms.

Structure pictures were drawn with ORTEP (Farrugia, 2012), Mercury (Macrae et al., 2008) and CrystalExplorer (McKinnon et al., 2004).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.59793 (10)	0.8075 (2)	0.54174 (4)	0.0397 (3)
N2	0.49244 (9)	0.4940 (2)	0.58498 (4)	0.0334 (3)
N3	0.67213 (11)	0.1998 (3)	0.67891 (5)	0.0475 (3)
N4	0.40143 (12)	0.7523 (3)	0.52808 (5)	0.0458 (3)
C1	0.50044 (11)	0.6820 (3)	0.55227 (5)	0.0336 (3)
C2	0.69358 (12)	0.7359 (3)	0.56694 (5)	0.0444 (4)
H2	0.763316	0.816777	0.560470	0.053*
C3	0.69520 (12)	0.5499 (3)	0.60189 (5)	0.0411 (3)
H3	0.763313	0.505318	0.619289	0.049*
C4	0.58989 (11)	0.4316 (2)	0.60997 (5)	0.0320 (3)
C5	0.58070 (11)	0.2278 (2)	0.64725 (5)	0.0325 (3)
C6	0.48303 (12)	0.0784 (3)	0.64859 (5)	0.0369 (3)
H6	0.420375	0.105298	0.626471	0.044*
C7	0.47957 (13)	−0.1109 (3)	0.68304 (5)	0.0420 (3)
H7	0.415261	−0.215904	0.684306	0.050*
C8	0.57305 (14)	−0.1415 (3)	0.71553 (6)	0.0476 (4)
H8	0.573555	−0.268033	0.739234	0.057*
C9	0.66543 (14)	0.0180 (3)	0.71233 (6)	0.0540 (4)
H9	0.727581	−0.002133	0.735011	0.065*
H4A	0.3371 (19)	0.677 (4)	0.5350 (7)	0.066 (6)*
H4B	0.4016 (15)	0.880 (4)	0.5056 (7)	0.057 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0365 (6)	0.0410 (7)	0.0416 (6)	−0.0022 (5)	0.0005 (5)	0.0065 (5)
N2	0.0286 (5)	0.0365 (6)	0.0349 (5)	0.0018 (5)	−0.0007 (4)	0.0024 (4)
N3	0.0353 (6)	0.0509 (8)	0.0555 (7)	−0.0016 (6)	−0.0114 (5)	0.0148 (6)
N4	0.0347 (7)	0.0508 (8)	0.0516 (7)	0.0001 (6)	−0.0058 (5)	0.0169 (6)
C1	0.0319 (6)	0.0356 (7)	0.0332 (6)	0.0022 (5)	0.0003 (5)	−0.0010 (5)
C2	0.0322 (7)	0.0519 (9)	0.0492 (8)	−0.0066 (7)	0.0000 (6)	0.0087 (7)
C3	0.0281 (6)	0.0491 (9)	0.0457 (7)	−0.0006 (6)	−0.0036 (5)	0.0081 (6)
C4	0.0285 (6)	0.0347 (7)	0.0329 (6)	0.0025 (5)	0.0010 (4)	−0.0003 (5)
C5	0.0289 (6)	0.0344 (7)	0.0343 (6)	0.0035 (5)	−0.0004 (4)	0.0005 (5)
C6	0.0329 (6)	0.0405 (8)	0.0372 (6)	−0.0005 (6)	−0.0021 (5)	−0.0017 (6)
C7	0.0411 (7)	0.0396 (8)	0.0457 (7)	−0.0040 (6)	0.0058 (6)	0.0007 (6)
C8	0.0503 (9)	0.0425 (8)	0.0500 (8)	0.0030 (7)	0.0020 (6)	0.0132 (7)
C9	0.0449 (8)	0.0565 (10)	0.0599 (9)	0.0017 (8)	−0.0150 (7)	0.0196 (8)

Geometric parameters (Å, º)

N1—C2	1.3291 (17)	C3—C4	1.3862 (19)
N1—C1	1.3413 (18)	C3—H3	0.9300
N2—C4	1.3297 (16)	C4—C5	1.4875 (18)
N2—C1	1.3420 (17)	C5—C6	1.3792 (19)
N3—C9	1.3286 (19)	C6—C7	1.374 (2)
N3—C5	1.3386 (16)	C6—H6	0.9300
N4—C1	1.3459 (17)	C7—C8	1.372 (2)
N4—H4A	0.87 (2)	C7—H7	0.9300
N4—H4B	0.91 (2)	C8—C9	1.367 (2)
C2—C3	1.369 (2)	C8—H8	0.9300
C2—H2	0.9300	C9—H9	0.9300
C2—N1—C1	115.38 (12)	C3—C4—C5	121.30 (11)
C4—N2—C1	116.56 (11)	N3—C5—C6	122.74 (12)
C9—N3—C5	116.77 (13)	N3—C5—C4	116.04 (12)
C1—N4—H4A	118.6 (13)	C6—C5—C4	121.22 (11)
C1—N4—H4B	120.8 (11)	C7—C6—C5	119.10 (12)
H4A—N4—H4B	120.6 (18)	C7—C6—H6	120.4
N1—C1—N2	125.95 (12)	C5—C6—H6	120.4
N1—C1—N4	117.02 (13)	C8—C7—C6	118.56 (14)
N2—C1—N4	117.03 (12)	C8—C7—H7	120.7
N1—C2—C3	123.68 (13)	C6—C7—H7	120.7
N1—C2—H2	118.2	C9—C8—C7	118.59 (14)
C3—C2—H2	118.2	C9—C8—H8	120.7
C2—C3—C4	116.43 (12)	C7—C8—H8	120.7
C2—C3—H3	121.8	N3—C9—C8	124.21 (14)
C4—C3—H3	121.8	N3—C9—H9	117.9
N2—C4—C3	121.97 (12)	C8—C9—H9	117.9
N2—C4—C5	116.73 (11)
C2—N1—C1—N2	−0.6 (2)	C9—N3—C5—C4	−179.77 (13)
C2—N1—C1—N4	178.87 (13)	N2—C4—C5—N3	−167.20 (12)
C4—N2—C1—N1	1.8 (2)	C3—C4—C5—N3	12.78 (19)
C4—N2—C1—N4	−177.71 (12)	N2—C4—C5—C6	12.77 (19)
C1—N1—C2—C3	−0.8 (2)	C3—C4—C5—C6	−167.24 (13)
N1—C2—C3—C4	0.9 (2)	N3—C5—C6—C7	−1.4 (2)
C1—N2—C4—C3	−1.58 (19)	C4—C5—C6—C7	178.66 (12)
C1—N2—C4—C5	178.40 (11)	C5—C6—C7—C8	1.1 (2)
C2—C3—C4—N2	0.4 (2)	C6—C7—C8—C9	0.2 (2)
C2—C3—C4—C5	−179.61 (13)	C5—N3—C9—C8	1.2 (3)
C9—N3—C5—C6	0.2 (2)	C7—C8—C9—N3	−1.4 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4B···N1^i	0.91 (2)	2.10 (2)	3.0154 (19)	175.8 (16)

Symmetry code: (i) −x+1, −y+2, −z+1.