Crystal structure of ethyl 2-cyano-3-[(1-eth-oxy-ethyl-idene)amino]-5-(3-meth-oxy-phen-yl)-7-methyl-5H-1,3-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.

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-meth-oxy-phenyl ring, at the chiral C atom opposite the other N atom, is positioned axially and is inclined to the thia-zolo-pyrimidine ring with a dihedral angle of 83.88 (7)°. The thia-zole ring is essentially planar (r.m.s. deviation = 0.0034 Å). In the crystal, pairs of weak C-H⋯O hydrogen bonds link mol-ecules related by twofold rotation axes to form R 2 (2)(8) rings, which in turn are linked by weak C-H⋯N inter-actions, forming ribbons along [-110]. In addition, π-π stacking inter-actions [centroid-centroid distance = 3.5744 (15) Å] connect the ribbons, forming slabs lying parallel to (001).

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 ▸).

Experimental

Crystal data

C22H24N4O4S

M = 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

Δρmax = 0.49 e Å−3

Δρmin = −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 ▸).

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

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

Click here for additional data file.

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

Click here for additional data file.

. 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.

. 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

C22H24N4O4S	F(000) = 1856
Mr = 440.51	Dx = 1.356 Mg m−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 3793 reflections
a = 14.371 (3) Å	θ = 1.8–25.0°
b = 13.368 (3) Å	µ = 0.19 mm−1
c = 22.771 (6) Å	T = 100 K
β = 99.325 (5)°	Block, yellow
V = 4316.9 (16) Å3	0.16 × 0.12 × 0.10 mm
Z = 8

Bruker SMART APEX CCD detector diffractometer	3793 independent reflections
Radiation source: fine-focus sealed tube	2882 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.052
ω scans	θmax = 25.0°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 1998)	h = −17→17
Tmin = 0.967, Tmax = 0.971	k = −15→15
11002 measured reflections	l = −27→19

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.149	H-atom parameters constrained
S = 1.01	w = 1/[σ2(Fo2) + (0.1696P)2] where P = (Fo2 + 2Fc2)/3
3793 reflections	(Δ/σ)max < 0.001
285 parameters	Δρmax = 0.49 e Å−3
0 restraints	Δρmin = −0.31 e Å−3

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

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
S1	0.13934 (4)	0.70794 (4)	0.20570 (3)	0.0237 (2)
O1	0.10595 (11)	1.16153 (12)	0.30234 (7)	0.0258 (4)
O2	0.12547 (12)	1.21281 (12)	0.21099 (8)	0.0309 (5)
O3	0.33654 (13)	1.03011 (15)	0.48409 (8)	0.0406 (5)
O4	0.11827 (12)	0.80604 (12)	0.46167 (7)	0.0277 (4)
N1	0.11799 (13)	0.86522 (14)	0.26730 (8)	0.0204 (5)
N2	0.13810 (13)	0.89673 (15)	0.16753 (9)	0.0240 (5)
N3	0.08826 (13)	0.80714 (14)	0.36078 (9)	0.0219 (5)
N4	0.12362 (15)	0.52819 (16)	0.33506 (10)	0.0319 (5)
C1	0.11149 (19)	1.05852 (19)	0.12197 (11)	0.0336 (7)
H1A	0.1037	1.1294	0.1311	0.050*
H1B	0.0551	1.0346	0.0957	0.050*
H1C	0.1667	1.0505	0.1021	0.050*
C2	0.12358 (16)	0.69605 (17)	0.28022 (11)	0.0216 (5)
C3	0.11295 (15)	0.78635 (17)	0.30573 (10)	0.0200 (5)
C4	0.0977 (2)	1.2676 (2)	0.38543 (12)	0.0420 (7)
H4A	0.0383	1.2355	0.3905	0.063*
H4B	0.0978	1.3371	0.3992	0.063*
H4C	0.1505	1.2315	0.4087	0.063*
C5	0.13384 (16)	0.96962 (16)	0.28873 (10)	0.0197 (5)
H5	0.0840	0.9878	0.3128	0.024*
C6	0.12340 (16)	1.03689 (17)	0.23357 (10)	0.0211 (5)
C7	0.12523 (15)	0.99914 (18)	0.17838 (10)	0.0225 (6)
C8	0.10788 (18)	1.26578 (17)	0.32076 (11)	0.0275 (6)
H8A	0.0555	1.3031	0.2968	0.033*
H8B	0.1682	1.2973	0.3151	0.033*
C9	0.13237 (15)	0.83739 (18)	0.21150 (10)	0.0208 (5)
C10	0.11810 (16)	1.14516 (19)	0.24543 (11)	0.0245 (6)
C11	0.23017 (16)	0.97772 (17)	0.32810 (10)	0.0216 (5)
C12	0.31098 (16)	0.95397 (16)	0.30541 (11)	0.0238 (6)
H12	0.3070	0.9350	0.2649	0.029*
C13	0.39864 (18)	0.95799 (18)	0.34235 (12)	0.0299 (6)
H13	0.4543	0.9425	0.3267	0.036*
C14	0.40474 (18)	0.98420 (19)	0.40119 (12)	0.0329 (7)
H14	0.4644	0.9862	0.4262	0.039*
C15	0.32356 (19)	1.00781 (19)	0.42400 (11)	0.0301 (6)
C16	0.23615 (17)	1.00501 (18)	0.38753 (10)	0.0256 (6)
H16	0.1807	1.0217	0.4031	0.031*
C17	0.2546 (2)	1.0463 (2)	0.51025 (12)	0.0491 (8)
H17A	0.2234	1.1080	0.4943	0.074*
H17B	0.2726	1.0524	0.5535	0.074*
H17C	0.2114	0.9897	0.5011	0.074*
C18	0.12295 (16)	0.60302 (18)	0.31003 (11)	0.0227 (6)
C19	0.14560 (17)	0.79047 (17)	0.40873 (11)	0.0239 (6)
C20	0.24524 (17)	0.7560 (2)	0.41573 (11)	0.0318 (6)
H20A	0.2485	0.6850	0.4267	0.048*
H20B	0.2838	0.7951	0.4470	0.048*
H20C	0.2690	0.7651	0.3781	0.048*
C21	0.01889 (18)	0.8272 (2)	0.46214 (12)	0.0316 (6)
H21A	−0.0065	0.8681	0.4270	0.038*
H21B	0.0122	0.8659	0.4983	0.038*
C22	−0.0361 (2)	0.7323 (2)	0.46124 (13)	0.0427 (7)
H22A	−0.0306	0.6946	0.4250	0.064*
H22B	−0.1025	0.7479	0.4619	0.064*
H22C	−0.0112	0.6920	0.4962	0.064*

	U11	U22	U33	U12	U13	U23
S1	0.0270 (4)	0.0215 (3)	0.0222 (4)	−0.0008 (2)	0.0033 (3)	−0.0006 (2)
O1	0.0300 (10)	0.0192 (9)	0.0288 (10)	0.0005 (7)	0.0063 (8)	−0.0008 (7)
O2	0.0403 (11)	0.0223 (10)	0.0297 (11)	0.0001 (8)	0.0042 (8)	0.0083 (8)
O3	0.0430 (12)	0.0532 (13)	0.0230 (11)	−0.0142 (10)	−0.0023 (9)	−0.0023 (9)
O4	0.0325 (10)	0.0313 (10)	0.0188 (10)	0.0022 (8)	0.0031 (8)	0.0003 (7)
N1	0.0228 (11)	0.0190 (10)	0.0192 (11)	−0.0003 (8)	0.0026 (8)	0.0009 (8)
N2	0.0269 (11)	0.0222 (11)	0.0228 (12)	−0.0013 (9)	0.0038 (9)	−0.0004 (9)
N3	0.0249 (11)	0.0218 (11)	0.0195 (11)	0.0000 (8)	0.0049 (9)	0.0013 (8)
N4	0.0347 (13)	0.0252 (12)	0.0358 (14)	−0.0007 (10)	0.0057 (10)	0.0041 (10)
C1	0.0477 (17)	0.0295 (15)	0.0225 (14)	−0.0074 (13)	0.0017 (12)	0.0030 (11)
C2	0.0189 (12)	0.0208 (13)	0.0247 (14)	−0.0007 (10)	0.0024 (10)	0.0008 (10)
C3	0.0145 (12)	0.0232 (13)	0.0213 (13)	−0.0011 (10)	0.0006 (10)	0.0044 (10)
C4	0.061 (2)	0.0289 (15)	0.0363 (18)	−0.0040 (14)	0.0081 (15)	−0.0063 (13)
C5	0.0239 (13)	0.0141 (12)	0.0215 (13)	0.0001 (9)	0.0048 (10)	−0.0019 (9)
C6	0.0206 (13)	0.0182 (12)	0.0240 (14)	−0.0013 (9)	0.0020 (10)	0.0040 (10)
C7	0.0181 (12)	0.0257 (13)	0.0234 (14)	−0.0003 (10)	0.0019 (10)	0.0021 (10)
C8	0.0292 (14)	0.0169 (12)	0.0362 (16)	0.0005 (11)	0.0042 (12)	−0.0046 (11)
C9	0.0168 (12)	0.0265 (13)	0.0181 (13)	−0.0013 (10)	0.0003 (10)	−0.0015 (10)
C10	0.0169 (12)	0.0290 (14)	0.0270 (14)	0.0028 (10)	0.0017 (10)	0.0032 (11)
C11	0.0263 (13)	0.0146 (12)	0.0235 (14)	−0.0010 (10)	0.0029 (10)	0.0034 (10)
C12	0.0269 (14)	0.0185 (12)	0.0252 (14)	0.0000 (10)	0.0020 (11)	−0.0014 (10)
C13	0.0239 (14)	0.0252 (14)	0.0398 (17)	0.0018 (11)	0.0028 (12)	−0.0015 (11)
C14	0.0306 (15)	0.0237 (14)	0.0401 (18)	−0.0022 (11)	−0.0070 (13)	0.0011 (12)
C15	0.0365 (16)	0.0254 (14)	0.0262 (15)	−0.0052 (12)	−0.0017 (12)	−0.0003 (11)
C16	0.0268 (14)	0.0257 (14)	0.0235 (14)	−0.0032 (11)	0.0015 (11)	0.0014 (11)
C17	0.057 (2)	0.065 (2)	0.0247 (16)	−0.0221 (17)	0.0049 (14)	−0.0069 (14)
C18	0.0241 (13)	0.0210 (13)	0.0231 (14)	−0.0013 (10)	0.0041 (11)	−0.0016 (11)
C19	0.0281 (13)	0.0211 (13)	0.0220 (14)	−0.0015 (10)	0.0026 (11)	0.0019 (10)
C20	0.0316 (15)	0.0353 (15)	0.0269 (15)	0.0035 (12)	−0.0005 (12)	0.0032 (12)
C21	0.0371 (16)	0.0339 (15)	0.0251 (15)	0.0042 (12)	0.0094 (12)	−0.0019 (11)
C22	0.0474 (18)	0.0475 (18)	0.0355 (17)	−0.0082 (15)	0.0139 (14)	−0.0015 (14)

S1—C9	1.740 (2)	C5—H5	1.0000
S1—C2	1.755 (3)	C6—C7	1.359 (3)
O1—C10	1.353 (3)	C6—C10	1.476 (3)
O1—C8	1.454 (3)	C8—H8A	0.9900
O2—C10	1.213 (3)	C8—H8B	0.9900
O3—C15	1.383 (3)	C11—C12	1.382 (3)
O3—C17	1.419 (3)	C11—C16	1.391 (3)
O4—C19	1.343 (3)	C12—C13	1.398 (3)
O4—C21	1.458 (3)	C12—H12	0.9500
N1—C9	1.371 (3)	C13—C14	1.374 (4)
N1—C3	1.380 (3)	C13—H13	0.9500
N1—C5	1.484 (3)	C14—C15	1.388 (4)
N2—C9	1.291 (3)	C14—H14	0.9500
N2—C7	1.409 (3)	C15—C16	1.390 (3)
N3—C19	1.277 (3)	C16—H16	0.9500
N3—C3	1.385 (3)	C17—H17A	0.9800
N4—C18	1.151 (3)	C17—H17B	0.9800
C1—C7	1.496 (3)	C17—H17C	0.9800
C1—H1A	0.9800	C19—C20	1.488 (3)
C1—H1B	0.9800	C20—H20A	0.9800
C1—H1C	0.9800	C20—H20B	0.9800
C2—C3	1.359 (3)	C20—H20C	0.9800
C2—C18	1.418 (3)	C21—C22	1.492 (4)
C4—C8	1.503 (4)	C21—H21A	0.9900
C4—H4A	0.9800	C21—H21B	0.9900
C4—H4B	0.9800	C22—H22A	0.9800
C4—H4C	0.9800	C22—H22B	0.9800
C5—C11	1.526 (3)	C22—H22C	0.9800
C5—C6	1.532 (3)
C9—S1—C2	89.92 (11)	O2—C10—C6	126.9 (2)
C10—O1—C8	115.58 (18)	O1—C10—C6	110.6 (2)
C15—O3—C17	117.4 (2)	C12—C11—C16	120.0 (2)
C19—O4—C21	117.78 (18)	C12—C11—C5	120.1 (2)
C9—N1—C3	114.3 (2)	C16—C11—C5	119.8 (2)
C9—N1—C5	121.45 (19)	C11—C12—C13	119.7 (2)
C3—N1—C5	122.10 (19)	C11—C12—H12	120.1
C9—N2—C7	115.8 (2)	C13—C12—H12	120.1
C19—N3—C3	121.0 (2)	C14—C13—C12	120.4 (2)
C7—C1—H1A	109.5	C14—C13—H13	119.8
C7—C1—H1B	109.5	C12—C13—H13	119.8
H1A—C1—H1B	109.5	C13—C14—C15	119.9 (2)
C7—C1—H1C	109.5	C13—C14—H14	120.1
H1A—C1—H1C	109.5	C15—C14—H14	120.1
H1B—C1—H1C	109.5	O3—C15—C14	115.6 (2)
C3—C2—C18	124.4 (2)	O3—C15—C16	124.1 (2)
C3—C2—S1	111.95 (18)	C14—C15—C16	120.2 (2)
C18—C2—S1	123.66 (18)	C15—C16—C11	119.7 (2)
C2—C3—N1	112.8 (2)	C15—C16—H16	120.1
C2—C3—N3	128.9 (2)	C11—C16—H16	120.1
N1—C3—N3	117.9 (2)	O3—C17—H17A	109.5
C8—C4—H4A	109.5	O3—C17—H17B	109.5
C8—C4—H4B	109.5	H17A—C17—H17B	109.5
H4A—C4—H4B	109.5	O3—C17—H17C	109.5
C8—C4—H4C	109.5	H17A—C17—H17C	109.5
H4A—C4—H4C	109.5	H17B—C17—H17C	109.5
H4B—C4—H4C	109.5	N4—C18—C2	178.8 (3)
N1—C5—C11	109.64 (18)	N3—C19—O4	119.9 (2)
N1—C5—C6	107.05 (18)	N3—C19—C20	128.5 (2)
C11—C5—C6	113.51 (19)	O4—C19—C20	111.6 (2)
N1—C5—H5	108.8	C19—C20—H20A	109.5
C11—C5—H5	108.8	C19—C20—H20B	109.5
C6—C5—H5	108.8	H20A—C20—H20B	109.5
C7—C6—C10	122.9 (2)	C19—C20—H20C	109.5
C7—C6—C5	121.8 (2)	H20A—C20—H20C	109.5
C10—C6—C5	115.2 (2)	H20B—C20—H20C	109.5
C6—C7—N2	123.1 (2)	O4—C21—C22	110.6 (2)
C6—C7—C1	125.3 (2)	O4—C21—H21A	109.5
N2—C7—C1	111.6 (2)	C22—C21—H21A	109.5
O1—C8—C4	107.32 (19)	O4—C21—H21B	109.5
O1—C8—H8A	110.2	C22—C21—H21B	109.5
C4—C8—H8A	110.3	H21A—C21—H21B	108.1
O1—C8—H8B	110.3	C21—C22—H22A	109.5
C4—C8—H8B	110.2	C21—C22—H22B	109.5
H8A—C8—H8B	108.5	H22A—C22—H22B	109.5
N2—C9—N1	126.2 (2)	C21—C22—H22C	109.5
N2—C9—S1	122.74 (18)	H22A—C22—H22C	109.5
N1—C9—S1	111.07 (17)	H22B—C22—H22C	109.5
O2—C10—O1	122.5 (2)
C9—S1—C2—C3	0.67 (18)	C5—N1—C9—S1	164.04 (16)
C9—S1—C2—C18	−178.8 (2)	C2—S1—C9—N2	−179.1 (2)
C18—C2—C3—N1	178.9 (2)	C2—S1—C9—N1	−0.59 (17)
S1—C2—C3—N1	−0.6 (3)	C8—O1—C10—O2	−3.5 (3)
C18—C2—C3—N3	−8.9 (4)	C8—O1—C10—C6	174.89 (19)
S1—C2—C3—N3	171.65 (19)	C7—C6—C10—O2	−9.0 (4)
C9—N1—C3—C2	0.1 (3)	C5—C6—C10—O2	166.8 (2)
C5—N1—C3—C2	−163.4 (2)	C7—C6—C10—O1	172.7 (2)
C9—N1—C3—N3	−173.04 (18)	C5—C6—C10—O1	−11.5 (3)
C5—N1—C3—N3	23.4 (3)	N1—C5—C11—C12	59.5 (3)
C19—N3—C3—C2	71.3 (3)	C6—C5—C11—C12	−60.2 (3)
C19—N3—C3—N1	−116.8 (2)	N1—C5—C11—C16	−117.8 (2)
C9—N1—C5—C11	−99.3 (2)	C6—C5—C11—C16	122.5 (2)
C3—N1—C5—C11	63.1 (3)	C16—C11—C12—C13	−0.3 (3)
C9—N1—C5—C6	24.2 (3)	C5—C11—C12—C13	−177.6 (2)
C3—N1—C5—C6	−173.38 (19)	C11—C12—C13—C14	0.8 (4)
N1—C5—C6—C7	−15.6 (3)	C12—C13—C14—C15	−0.6 (4)
C11—C5—C6—C7	105.5 (2)	C17—O3—C15—C14	−174.8 (2)
N1—C5—C6—C10	168.50 (18)	C17—O3—C15—C16	3.1 (4)
C11—C5—C6—C10	−70.4 (3)	C13—C14—C15—O3	178.0 (2)
C10—C6—C7—N2	174.6 (2)	C13—C14—C15—C16	0.0 (4)
C5—C6—C7—N2	−1.0 (3)	O3—C15—C16—C11	−177.3 (2)
C10—C6—C7—C1	−7.2 (4)	C14—C15—C16—C11	0.5 (4)
C5—C6—C7—C1	177.2 (2)	C12—C11—C16—C15	−0.3 (3)
C9—N2—C7—C6	11.2 (3)	C5—C11—C16—C15	177.0 (2)
C9—N2—C7—C1	−167.2 (2)	C3—C2—C18—N4	−50 (14)
C10—O1—C8—C4	−177.4 (2)	S1—C2—C18—N4	130 (13)
C7—N2—C9—N1	−2.1 (3)	C3—N3—C19—O4	−176.35 (19)
C7—N2—C9—S1	176.16 (16)	C3—N3—C19—C20	5.0 (4)
C3—N1—C9—N2	178.8 (2)	C21—O4—C19—N3	9.1 (3)
C5—N1—C9—N2	−17.5 (3)	C21—O4—C19—C20	−172.0 (2)
C3—N1—C9—S1	0.4 (2)	C19—O4—C21—C22	84.7 (3)

D—H···A	D—H	H···A	D···A	D—H···A
C13—H13···N4i	0.95	2.67	3.396 (4)	134
C21—H21A···N2ii	0.99	2.65	3.538 (2)	149
C20—H20B···O4iii	0.98	2.68	3.249 (5)	117

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

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