N-(3-Meth­oxy­phen­yl)-4-{4-methyl-2-[(meth­yl)(4-methyl­phen­yl)amino]-1,3-thia­zol-5-yl}pyrimidin-2-amine

Hai-Bo Shi; Hai-Bo Li; Wei-Xiao Hu

doi:10.1107/S1600536810053559

. 2011 Jan 8;67(Pt 2):o261. doi: 10.1107/S1600536810053559

N-(3-Methoxyphenyl)-4-{4-methyl-2-[(methyl)(4-methylphenyl)amino]-1,3-thiazol-5-yl}pyrimidin-2-amine

Hai-Bo Shi ^a,^b, Hai-Bo Li ^c, Wei-Xiao Hu ^b

PMCID: PMC3051738 PMID: 21522954

Abstract

The asymmetric unit of the title compound, C₂₃H₂₃N₅OS, contains two independent molecules. In one molecule, the thiazole and pyrimidine rings are almost co-planar, making a dihedral angle of 2.48 (8)°. In the other molecule, the corresponding dihedral angle is 12.82 (8)°. The crystal structure is stabilized by weak intermolecular N—H⋯N and C—H⋯O interactions that extend along the b axis.

Related literature

For general background to the biological activity of thiazole derivatives, see: Narayana et al. (2004 ▶). For the synthesis of the title compound, see: Bredereck et al. (1964 ▶).

Experimental

Crystal data

C₂₃H₂₃N₅OS
M _r = 417.52
Triclinic,
a = 10.280 (3) Å
b = 12.413 (2) Å
c = 17.671 (4) Å
α = 74.290 (9)°
β = 87.96 (1)°
γ = 68.281 (7)°
V = 2011.3 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 153 K
0.40 × 0.40 × 0.23 mm

Data collection

Rigaku AFC10/Saturn724+ diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2008 ▶) T _min = 0.929, T _max = 0.958
19475 measured reflections
9061 independent reflections
6741 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.115
S = 1.03
9061 reflections
551 parameters
H-atom parameters constrained
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2008 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810053559/ng5080sup1.cif

e-67-0o261-sup1.cif^{(34.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810053559/ng5080Isup2.hkl

e-67-0o261-Isup2.hkl^{(434.2KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N5—H0⋯N3′ⁱ	0.88	2.27	3.151 (2)	177
N5′—H0′⋯N3ⁱ	0.88	2.24	3.089 (2)	164
C22—H22B⋯O1ⁱⁱ	0.98	2.57	3.500 (2)	159

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We are very thankful to the Natural Science Foundation of Ningbo City (grant No. 2009 A610185) for financial support. We are also grateful to the Beijing Institute of Technology for the X-ray diffraction measurements.

supplementary crystallographic information

Comment

Thiazole derivatives are found to be associated with various biological activities (Narayana et al., 2004). In order to further study the structure-activity relationship (SAR) of the thiazolyl-pyrimidine derivatives, we introduced arylamino group into 2-position of thiazole ring of thiazolyl-pyrimidine according to the general pyrimidine condensation method of Bredereck (Bredereck et al., 1964). But, it was found that the obtained compound was not desired compound that confirmed by ¹H NMR, MS. So, the structure of (I) was further determined using single-crystal X-ray diffraction.

The molecular structure of (I) is illustrated in Fig. 1. The benzene ring makes opposite angles with thiazole-pyrimidine ring. The thiazole ring (S1/C7/N2/C8/C9) and the pyrimidine ring (C10/C11/C12/N3/C13/N4) are almost planar, with a dihedral angle of 2.48 (8)°. The aniline rings (C1/C2/C3/C4/C5/C6/N1) and (C14/C15/C16/C17/C18/C19/N5) make dihedral angles of 53.06 (8) Å and 19.21 (8) Å with the thiazole ring, respectively. In contrast, in the other independent molecule, the thiazole ring (S1'/C7'/N2'/C8'/C9') and the pyrimidine ring (C10'/C11'/C12'/N3'/C13'/N4') make a dihedral angle of 12.82 (8)°. The aniline rings (C1'/C2'/C3'/C4'/C5'/C6'/N1') and (C14'/C15'/C16'/C17'/C18'/C19'/N5') make dihedral angles of 51.09 (9) Å and 29.07 (9) Å with the thiazole ring, respectively. Moreover, there exist different bond lengths in the two independent molecules due to different intermolecular hydrogen bonding interactions (Table 1). The crystal structure is stabilized by intermolecular weak N—H···N and C—H···O interactions, which extending down b axis.

Experimental

A mixture of

3-Dimethylamino-1-[2-(methyl-p-tolyl-amino)-4-methyl-thiazol-5-yl]-propenone (1.575 g, 5 mmol) and NaOH (0.2 g, 5 mmol) in 2-methoxylethanol (35 ml) was treated with N-(3-Methoxy-phenyl)-guanidine carbonate (1.476 g, 6.5 mmol). The reaction mixture was heated at 383 K under N₂ for 11 h. After concentration, the residue was filtered and washed liberally with ethanol and water. Recrystallization from THF affored the title compound as brown-yellow crystals, 0.97 g, m.p.453–456 K, yield 46.7%.Since the crystal product was not found to be suitable for X-ray diffraction studies,a few crystals were dissolved in 2-butanone, which was allowed to evaporate slowly to give yellow crystals of (I) suitable for X-ray diffraction studies. ¹H NMR(CDCl₃, TMS, 400 MHz, δp.p.m.): 8.27 (s, 1H, J = 4.8 Hz, py—H), 7.53 (s, 1H, Ar—H), 7.29–7.07 (m, 5H, Ar—H), 6.87 (d, 1H,J = 8.0 Hz, Ar—H), 6.83 (d, 1H, J = 5.2 Hz, py—H), 6.54 (d, 1H, J = 8.0 Hz, Ar—H), 3.64 (s, 3H, OCH₃), 3.54 (s, 3H, CH₃), 2.60 (s, 3H, CH₃), 2.41 (s, 3H, CH₃). EIMS m/z (%): 417 (M⁺,100), 402 (7), 311 (12), 105 (9), 91 (10), 73 (12), 57 (17).