Ethyl 3-eth­oxy­carbonyl­methyl-7-methyl-5-phenyl-5H-thia­zolo[3,2-a]pyrimidine-6-carboxyl­ate

H Nagarajaiah; Noor Shahina Begum

doi:10.1107/S1600536812037828

. 2012 Sep 8;68(Pt 10):o2878. doi: 10.1107/S1600536812037828

Ethyl 3-ethoxycarbonylmethyl-7-methyl-5-phenyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate

H Nagarajaiah ^a, Noor Shahina Begum ^a,^*

PMCID: PMC3470232 PMID: 23125676

Abstract

In the title compound, C₂₀H₂₂N₂O₄S, the central pyrimidine ring incorporating a chiral C atom is significantly puckered and adopts a slight boat conformation with C atom bearing the phenyl ring and the N atom opposite displaced by 0.367 (2) and 0.107 (2) Å, respectively, from the plane formed by the remaining ring atoms. The benzene ring is positioned axially to the pyrimidine ring, making a dihedral angle of 88.99 (5)°. The thiazole ring is essentially planar (r.m.s. deviation = 0.0033 Å). In the crystal, pairs of C—H⋯O interactions result in centrosymmetric dimers with graph-set motifs R ₁ ²(7) and R ₂ ²(8). A weak C—H⋯π contact is also observed.

Related literature

For the therapeutic potential of thiazolopyrimidine derivatives, see: Zhi et al. (2008 ▶). For the synthesis of the title compound, see: Nagarajaiah et al. (2012 ▶). For a related structure, see: Nagarajaiah & Begum (2011) ▶. For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For carbonyl–π interactions, see: Gautrot et al. (2006 ▶).

Experimental

Crystal data

C₂₀H₂₂N₂O₄S
M _r = 386.46
Monoclinic,
a = 10.0861 (4) Å
b = 7.7954 (3) Å
c = 23.4088 (10) Å
β = 95.000 (3)°
V = 1833.52 (13) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 296 K
0.18 × 0.16 × 0.16 mm

Data collection

Bruker SMART APEX CCD detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1998 ▶) T _min = 0.964, T _max = 0.968
11747 measured reflections
3982 independent reflections
3102 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.118
S = 1.00
3982 reflections
247 parameters
H-atom parameters constrained
Δρ_max = 0.50 e Å⁻³
Δρ_min = −0.29 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 (Farrugia, 1997 ▶) and CAMERON (Watkin et al., 1996) ▶; software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812037828/pv2584sup1.cif

e-68-o2878-sup1.cif^{(21.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812037828/pv2584Isup2.hkl

e-68-o2878-Isup2.hkl^{(191.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812037828/pv2584Isup3.cml

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

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

Cg is the centroid of the thiazolopyrimidine ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C17—H17A⋯O2ⁱ	0.97	2.47	3.415 (3)	164
C5—H5⋯O2ⁱ	0.98	2.59	3.429 (2)	144
C4—H4C⋯Cg1ⁱⁱ	0.96	3.03	3.897 (4)	151

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

Acknowledgments

NSB is thankful to the University Grants Commission (UGC), India, for financial assistance and HN thanks for the fellowship.

supplementary crystallographic information

Comment

Thiazolo[3,2-a]pyrimidine derivatives may be to generate enzyme inhibitors as novel therapeutical entities for severe neurodegenerative diseases (Zhi et al., 2008). In continuation to our research interests on thiazolo[3,2-a]pyrimidine derivatives (Nagarajaiah & Begum, 2011; Nagarajaiah et al. 2012), we report the crystal structure of the title compound.

In the title molecule (Fig. 1), the benzene ring is positioned axially and lies almost perpendicular to the pyrimidine ring (N1/N2/C5/C6/C7/C9) with dihedral angle of 88.99 (5)°. The pyrimidine ring substituted with C5 chiral carbon atom is significantly puckered and adopts a slight boat conformation with N2 and C5 atoms displaced by 0.107 (2) and 0.367 (2) Å, respectively, from the plane formed by the remaining ring atoms. The thiazole ring (S1/N1/C2/C3/C9) is essentially planar with r.m.s.d 0.0033 Å for the fitted atoms. The ethyl carboxylate at C6 is almost co–planar with the thiazolopyrimidine ring with a dihedral angle of 13.40 (5)°, where as the other ethyl carboxylate group at C17 is inclined at an angle of 80.57 (4)° with the thiazolopyrimidine ring and is positioned almost parallel to the benzene ring. This is because of intramolecular carbonyl—π interaction of aryl ring with the ethyl carboxylate group (Gautrot et al., 2006). The exocyclic ester at C8 adopts a cis orientation with respect to C8═C9 double bond. The N1—C3 bond length (1.403 (2) Å) in the thiazole ring is longer than that of a typical C═N bond but shorter than a C—N single bond, indicating electron delocalization in the ring. The bond distances and angles in the title compound agree very well with the corresponding bond distances and angles reported in a closely related compound (Nagarajaiah & Begum, 2011).

The crystal structure is stabilized by C—H···O intermolecular interactions involving carbonyl O2 atom, resulting in centrosymmetric dimers; the seven and eight membered rings thus resulting from these interaction can be described as R²₁(7) and R²₂(8) motifs in graph–set notations (Bernstein et al., 1995). In addition π–ring interaction of the type C—H···Cg (Cg being the centroid of the thiazolopyrimidine ring) is also observed in the crystal structure (Table 1 and Fig. 2).

Experimental

The synthesis of the title compound has already been reported (Nagarajaiah et al., 2012). The crystals suitable for X-ray crystallographic analysis were grown from a solution of ethylacetate.