Crystal structure of ethyl 2-cyano-3-[(1-eth­oxy­ethyl­idene)amino]-5-(3-meth­oxy­phen­yl)-7-methyl-5H-1,3-thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate

M S Krishnamurthy; Noor Shahina Begum

doi:10.1107/S2056989015005241

. 2015 Mar 25;71(Pt 4):o256–o257. doi: 10.1107/S2056989015005241

Crystal structure of ethyl 2-cyano-3-[(1-ethoxyethylidene)amino]-5-(3-methoxyphenyl)-7-methyl-5H-1,3-thiazolo[3,2-a]pyrimidine-6-carboxylate

M S Krishnamurthy ^a, Noor Shahina Begum ^a,^*

PMCID: PMC4438835 PMID: 26029443

Abstract

In the title compound, C₂₂H₂₄N₄O₄S, the central pyrimidine ring adopts a sofa conformation with the ring-junction N atom displaced by 0.2358 (6) Å from the mean plane of the remaining ring atoms. The 3-methoxyphenyl ring, at the chiral C atom opposite the other N atom, is positioned axially and is inclined to the thiazolopyrimidine ring with a dihedral angle of 83.88 (7)°. The thiazole ring is essentially planar (r.m.s. deviation = 0.0034 Å). In the crystal, pairs of weak C—H⋯O hydrogen bonds link molecules related by twofold rotation axes to form R ₂ ²(8) rings, which in turn are linked by weak C—H⋯N interactions, forming ribbons along [-110]. In addition, π–π stacking interactions [centroid—centroid distance = 3.5744 (15) Å] connect the ribbons, forming slabs lying parallel to (001).

Keywords: crystal structure; pyrimidine; thiazolopyrimidine; thiazolo[3,2-a]pyrimidine; hydrogen bonding; π–π stacking interactions

Related literature

For background and pharmacological properties of pyrimidine and thiazolopyrimidine derivatives, see: Singh et al. (2011 ▸); Ozair et al. (2010a ▸,b ▸); Sayed et al. (2010 ▸); Zhi et al. (2008 ▸); Mobinikhaledi et al. (2005 ▸). For related crystal structures, see: Krishnamurthy & Begum (2014 ▸); Krishnamurthy et al. (2014 ▸); Nagarajaiah & Begum (2011 ▸). graphic file with name e-71-0o256-scheme1.jpg

Experimental

Crystal data

C₂₂H₂₄N₄O₄S
M _r = 440.51
Monoclinic,
a = 14.371 (3) Å
b = 13.368 (3) Å
c = 22.771 (6) Å
β = 99.325 (5)°
V = 4316.9 (16) Å³
Z = 8
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 100 K
0.16 × 0.12 × 0.10 mm

Data collection

Bruker SMART APEX CCD detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ▸) T _min = 0.967, T _max = 0.971
11002 measured reflections
3793 independent reflections
2882 reflections with I > 2σ(I)
R _int = 0.052

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.149
S = 1.01
3793 reflections
285 parameters
H-atom parameters constrained
Δρ_max = 0.49 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Data collection: SMART (Bruker, 1998 ▸); cell refinement: SAINT-Plus (Bruker, 1998 ▸); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸) and CAMERON (Watkin et al., 1996 ▸); software used to prepare material for publication: WinGX (Farrugia, 2012 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015005241/su5092sup1.cif

e-71-0o256-sup1.cif^{(22.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015005241/su5092Isup2.hkl

e-71-0o256-Isup2.hkl^{(182.3KB, hkl)}

Click here for additional data file.^{(8.4KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015005241/su5092Isup3.cml

Click here for additional data file.^{(1.4MB, tif)}

. DOI: 10.1107/S2056989015005241/su5092fig1.tif

The molecular structure of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Click here for additional data file.^{(1.4MB, tif)}

. DOI: 10.1107/S2056989015005241/su5092fig2.tif

Crystal packing of the title compound viewed along the b axis, showing the intermolecular interactions as dashed lines (see Table 1). H-atoms not involved in hydrogen bonding have been omitted for clarity.

CCDC reference: 1054504

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
C13H13N4ⁱ	0.95	2.67	3.396(4)	134
C21H21AN2ⁱⁱ	0.99	2.65	3.538(2)	149
C20H20BO4ⁱⁱⁱ	0.98	2.68	3.249(5)	117

Open in a new tab

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

Acknowledgments

MSK is thankful to the University Grants Commission (UGC), India, for a UGC–BSR meritorious fellowship.

supplementary crystallographic information

S1. Comment

Pyrimidine has been subjected to a variety of structural modifications in order to synthesize derivatives (Singh et al., 2011) with different biological properties, among which, a thiazole ring fused to a pyrimidine ring, viz. a thiazolopyrimidine, has been found to be more active (Ozair et al., 2010a,b; Sayed et al., 2010). Thiazolo[3,2-a]pyrimidine derivatives act as potential enzyme inhibitors and are novel therapeutic entities for severe neurodegenerative diseases (Zhi et al., 2008). In continuation of our research interests on thiazolo[3,2-a]pyrimidine derivatives (Krishnamurthy & Begum, 2014; Krishnamurthy et al., 2014), we attempted to synthesize tricyclic thiazolopyrimidine derivatives (Mobinikhaledi et al., 2005). The title compound, an intermediate, was isolated and we report herein on its crystal structure.

The molecular structure of the title compound is shown in Fig. 1. The 3-methoxy phenyl ring at chiral carbon C5 is positioned axially and exactly bisects the thiazolopyrimidine ring with a dihedral angle of 83.88 (7)°. The pyrimidine ring adopts a flattened sofa conformation with atom N1 displaced by 0.2358 (6) Å from the mean plane of the other five atoms (C5/C6/C7/N2/C9). The carbonyl group of the exocyclic ester at C6 adopts a cis orientation with respect to C6—C7 double bond. The 3-methoxy phenyl ring adopts a syn periplanar conformation with respect to C5—H5 bond of the pyrimidine ring. The thiazole ring is essentially planar (r.m.s. deviation = 0.0034 Å).

In the crystal, pairs of weak C—H···O hydrogen bonds link molecules related by twofold rotation axes to form R₂²(8) rings, which are in turn linked by weak C—H···N interactions to form ribbons along [110]; Table 1 and Fig. 2. In addition, π–π stacking interactions with a centroid—centroid distance of 3.5744 (15) Å connect the ribbons to form slabs lying parallel to (001); [Cg1···.Cg1ⁱ where Cg1 is the centroid of ring S1/N1/C2/C3/C9; symmetry code: (i) -x, y, -z+1/2].

S2. Experimental

A mixture of ethyl 3-amino-2-cyano-5-(3-methoxyphenyl)-7-methyl-5H- thiazolo[3,2 a] pyrimidine-6-carboxylate (1.85 g, 5 mmol) and triethylorthoacetate (2 ml) was heated under reflux in acetic anhydride for 6 h. Excess triethylorthoacetate and acetic anhydride was removed. The residue was treated with petroleum ether. The solid that separated was filtered, washed and recrystallized from petroleum ether by slow evaporation, yielding light-greenish yellow crystals suitable for X-ray diffraction studies (yield 83%; m.p.: 384 K).