Literature DB >> 24860393

3-Bromo-2-[4-(methyl-sulfan-yl)phen-yl]-5,6,7,8-tetra-hydro-1,3-benzo-thia-zolo[3,2-a]imidazole.

Alexander S Bunev¹, Elena V Sukhonosova², Vladimir E Statsyuk¹, Gennady I Ostapenko¹, Victor N Khrustalev³.

Abstract

In the title mol-ecule, C16H15BrN2S2, the central imidazo[2,1-b]thia-zole fragment is almost planar (r.m.s. deviation = 0.012 Å), and the fused 5,6,7,8-tetra-hydro-benzene ring adopts an unsymmetrical half-chair conformation. The dihedral angle between the imidazo[2,1-b]thia-zole and benzene planes is 18.25 (4)°. The terminal methyl-sulfanyl substituent lies practically within the benzene plane [the dihedral angle between the corresponding planes is 7.20 (10)°] and is turned toward the C-Br bond. In the crystal, mol-ecules form infinite chains along [100] via secondary Br⋯N inter-actions [3.1861 (16) Å]. The chains are arranged at van der Waals distances.

Entities: Chemical Disease Gene Species

Year: 2014 PMID： 24860393 PMCID： PMC4011264 DOI： 10.1107/S1600536814008976

Source DB: PubMed Journal: Acta Crystallogr Sect E Struct Rep Online ISSN： 1600-5368

Related literature

For applications of imidazo[2,1-b][1,3]benzothiazoles, see: Ager et al. (1988 ▶); Sanfilippo et al. (1988 ▶); Barchéchath et al. (2005 ▶); Andreani et al. (2008 ▶); Chao et al. (2009 ▶); Kumbhare et al. (2011 ▶); Chandak et al. (2013 ▶). For the crystal structures of related compounds, see: Landreau et al. (2002 ▶); Adib et al. (2008 ▶); Fun, Asik et al. (2011 ▶); Fun, Hemamalini et al. (2011 ▶); Ghabbour et al. (2012 ▶); Bunev et al. (2013 ▶, 2014 ▶).

Experimental

Crystal data

C16H15BrN2S2 M = 379.34 Triclinic, a = 7.3132 (3) Å b = 7.5663 (3) Å c = 14.4543 (7) Å α = 95.033 (1)° β = 97.188 (1)° γ = 101.938 (1)° V = 771.03 (6) Å3 Z = 2 Mo Kα radiation μ = 2.93 mm−1 T = 120 K 0.15 × 0.10 × 0.10 mm

Data collection

Bruker APEXII CCD diffractometer Absorption correction: multi-scan (SADABS; Bruker, 2003 ▶) T min = 0.668, T max = 0.758 10352 measured reflections 4508 independent reflections 3927 reflections with I > 2σ(I) R int = 0.025

Refinement

R[F 2 > 2σ(F 2)] = 0.030 wR(F 2) = 0.073 S = 1.05 4508 reflections 191 parameters H-atom parameters constrained Δρmax = 0.67 e Å−3 Δρmin = −0.32 e Å−3 Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL. Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814008976/rk2426sup1.cif Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814008976/rk2426Isup2.hkl Click here for additional data file. Supporting information file. DOI: 10.1107/S1600536814008976/rk2426Isup3.cml CCDC reference: 998505 Additional supporting information: crystallographic information; 3D view; checkCIF report

C₁₆H₁₅BrN₂S₂	Z = 2
M_r = 379.34	F(000) = 384
Triclinic, P1	D_x = 1.634 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.3132 (3) Å	Cell parameters from 4428 reflections
b = 7.5663 (3) Å	θ = 2.8–32.3°
c = 14.4543 (7) Å	µ = 2.93 mm⁻¹
α = 95.033 (1)°	T = 120 K
β = 97.188 (1)°	Prism, colourless
γ = 101.938 (1)°	0.15 × 0.10 × 0.10 mm
V = 771.03 (6) Å³

Bruker APEXII CCD diffractometer	4508 independent reflections
Radiation source: fine-focus sealed tube	3927 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.025
φ and ω scans	θ_max = 30.0°, θ_min = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2003)	h = −10→10
T_min = 0.668, T_max = 0.758	k = −10→10
10352 measured reflections	l = −20→20

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)] = 0.030	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.073	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0377P)² + 0.1351P] where P = (F_o² + 2F_c²)/3
4508 reflections	(Δ/σ)_max = 0.001
191 parameters	Δρ_max = 0.67 e Å⁻³
0 restraints	Δρ_min = −0.32 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	U_iso*/U_eq
Br1	0.52846 (2)	0.33371 (2)	0.103656 (13)	0.01782 (6)
S1	0.31673 (8)	0.75383 (8)	0.55165 (4)	0.02712 (12)
N1	−0.0318 (2)	0.3490 (2)	0.10823 (11)	0.0169 (3)
C2	0.1565 (3)	0.3866 (2)	0.15151 (13)	0.0150 (3)
C3	0.2697 (2)	0.3284 (2)	0.09002 (13)	0.0146 (3)
N4	0.1494 (2)	0.2541 (2)	0.00724 (10)	0.0136 (3)
C4A	0.1551 (3)	0.1754 (2)	−0.08424 (13)	0.0147 (3)
C5	0.3302 (3)	0.1399 (2)	−0.11797 (13)	0.0159 (3)
H5A	0.3921	0.0696	−0.0739	0.019*
H5B	0.4195	0.2568	−0.1199	0.019*
C6	0.2819 (3)	0.0326 (3)	−0.21646 (14)	0.0194 (4)
H6A	0.3978	0.0462	−0.2464	0.023*
H6B	0.2372	−0.0981	−0.2106	0.023*
C7	0.1308 (3)	0.0964 (3)	−0.27918 (13)	0.0208 (4)
H7A	0.1110	0.0295	−0.3429	0.025*
H7B	0.1735	0.2276	−0.2844	0.025*
C8	−0.0560 (3)	0.0635 (3)	−0.23845 (13)	0.0186 (4)
H8A	−0.1458	0.1253	−0.2726	0.022*
H8B	−0.1133	−0.0684	−0.2457	0.022*
C8A	−0.0175 (3)	0.1366 (2)	−0.13656 (13)	0.0154 (3)
S9	−0.19453 (6)	0.18940 (6)	−0.07481 (3)	0.01700 (10)
C9A	−0.0272 (2)	0.2722 (2)	0.02379 (13)	0.0153 (3)
C10	0.2059 (3)	0.4782 (2)	0.24789 (13)	0.0164 (3)
C11	0.0607 (3)	0.4836 (3)	0.30255 (14)	0.0191 (4)
H11	−0.0658	0.4267	0.2767	0.023*
C12	0.0991 (3)	0.5705 (3)	0.39362 (14)	0.0204 (4)
H12	−0.0014	0.5733	0.4291	0.024*
C13	0.2850 (3)	0.6542 (3)	0.43388 (13)	0.0199 (4)
C14	0.4292 (3)	0.6527 (3)	0.37994 (14)	0.0232 (4)
H14	0.5554	0.7108	0.4058	0.028*
C15	0.3898 (3)	0.5664 (3)	0.28802 (14)	0.0217 (4)
H15	0.4900	0.5676	0.2520	0.026*
C16	0.5684 (3)	0.8198 (3)	0.58283 (16)	0.0302 (5)
H16A	0.6001	0.8615	0.6502	0.045*
H16B	0.6187	0.9185	0.5472	0.045*
H16C	0.6242	0.7154	0.5682	0.045*

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.01313 (9)	0.02030 (10)	0.01932 (10)	0.00599 (7)	−0.00109 (6)	−0.00219 (7)
S1	0.0271 (3)	0.0327 (3)	0.0173 (2)	0.0007 (2)	0.0029 (2)	−0.0057 (2)
N1	0.0157 (7)	0.0163 (7)	0.0187 (8)	0.0026 (6)	0.0042 (6)	0.0015 (6)
C2	0.0154 (8)	0.0140 (8)	0.0158 (8)	0.0029 (7)	0.0033 (7)	0.0023 (6)
C3	0.0134 (8)	0.0155 (8)	0.0154 (8)	0.0051 (7)	0.0010 (6)	0.0008 (6)
N4	0.0109 (7)	0.0153 (7)	0.0145 (7)	0.0034 (6)	0.0011 (5)	0.0010 (6)
C4A	0.0145 (8)	0.0121 (8)	0.0175 (9)	0.0030 (6)	0.0023 (7)	0.0016 (6)
C5	0.0140 (8)	0.0160 (8)	0.0186 (9)	0.0050 (7)	0.0036 (7)	0.0004 (7)
C6	0.0195 (9)	0.0217 (9)	0.0179 (9)	0.0083 (8)	0.0030 (7)	−0.0010 (7)
C7	0.0221 (9)	0.0247 (10)	0.0159 (9)	0.0070 (8)	0.0025 (7)	−0.0004 (7)
C8	0.0178 (9)	0.0193 (9)	0.0167 (9)	0.0036 (7)	−0.0016 (7)	−0.0013 (7)
C8A	0.0136 (8)	0.0140 (8)	0.0182 (8)	0.0025 (7)	0.0028 (7)	0.0007 (6)
S9	0.01080 (19)	0.0210 (2)	0.0186 (2)	0.00355 (17)	0.00092 (16)	0.00057 (17)
C9A	0.0119 (8)	0.0160 (8)	0.0186 (8)	0.0030 (7)	0.0033 (7)	0.0031 (7)
C10	0.0192 (9)	0.0129 (8)	0.0167 (8)	0.0027 (7)	0.0028 (7)	0.0010 (6)
C11	0.0176 (9)	0.0174 (9)	0.0208 (9)	0.0017 (7)	0.0021 (7)	0.0001 (7)
C12	0.0211 (9)	0.0208 (9)	0.0193 (9)	0.0037 (8)	0.0051 (7)	0.0010 (7)
C13	0.0252 (10)	0.0187 (9)	0.0145 (8)	0.0037 (8)	0.0019 (7)	−0.0011 (7)
C14	0.0196 (9)	0.0252 (10)	0.0208 (10)	−0.0006 (8)	0.0014 (7)	−0.0028 (8)
C15	0.0205 (9)	0.0235 (10)	0.0194 (9)	0.0009 (8)	0.0063 (7)	−0.0012 (8)
C16	0.0286 (11)	0.0311 (12)	0.0249 (11)	−0.0003 (9)	−0.0030 (9)	−0.0030 (9)

Br1—C3	1.8693 (18)	C7—H7B	0.9900
S1—C13	1.7673 (19)	C8—C8A	1.498 (3)
S1—C16	1.793 (2)	C8—H8A	0.9900
N1—C9A	1.312 (2)	C8—H8B	0.9900
N1—C2	1.400 (2)	C8A—S9	1.7529 (19)
C2—C3	1.391 (2)	S9—C9A	1.7354 (19)
C2—C10	1.467 (3)	C10—C15	1.399 (3)
C3—N4	1.391 (2)	C10—C11	1.405 (3)
N4—C9A	1.374 (2)	C11—C12	1.387 (3)
N4—C4A	1.411 (2)	C11—H11	0.9500
C4A—C8A	1.349 (2)	C12—C13	1.403 (3)
C4A—C5	1.492 (2)	C12—H12	0.9500
C5—C6	1.537 (3)	C13—C14	1.389 (3)
C5—H5A	0.9900	C14—C15	1.396 (3)
C5—H5B	0.9900	C14—H14	0.9500
C6—C7	1.524 (3)	C15—H15	0.9500
C6—H6A	0.9900	C16—H16A	0.9800
C6—H6B	0.9900	C16—H16B	0.9800
C7—C8	1.537 (3)	C16—H16C	0.9800
C7—H7A	0.9900

C13—S1—C16	103.71 (10)	C8A—C8—H8B	109.9
C9A—N1—C2	104.13 (15)	C7—C8—H8B	109.9
C3—C2—N1	110.13 (16)	H8A—C8—H8B	108.3
C3—C2—C10	130.54 (17)	C4A—C8A—C8	124.20 (17)
N1—C2—C10	119.33 (16)	C4A—C8A—S9	113.31 (14)
C2—C3—N4	106.03 (15)	C8—C8A—S9	122.44 (13)
C2—C3—Br1	131.99 (14)	C9A—S9—C8A	89.99 (9)
N4—C3—Br1	121.98 (13)	N1—C9A—N4	114.32 (16)
C9A—N4—C3	105.38 (15)	N1—C9A—S9	134.58 (14)
C9A—N4—C4A	114.32 (15)	N4—C9A—S9	111.08 (13)
C3—N4—C4A	140.26 (16)	C15—C10—C11	117.62 (17)
C8A—C4A—N4	111.27 (16)	C15—C10—C2	123.61 (17)
C8A—C4A—C5	124.77 (17)	C11—C10—C2	118.73 (17)
N4—C4A—C5	123.97 (16)	C12—C11—C10	121.15 (18)
C4A—C5—C6	110.25 (15)	C12—C11—H11	119.4
C4A—C5—H5A	109.6	C10—C11—H11	119.4
C6—C5—H5A	109.6	C11—C12—C13	120.61 (18)
C4A—C5—H5B	109.6	C11—C12—H12	119.7
C6—C5—H5B	109.6	C13—C12—H12	119.7
H5A—C5—H5B	108.1	C14—C13—C12	118.75 (18)
C7—C6—C5	112.55 (15)	C14—C13—S1	124.86 (16)
C7—C6—H6A	109.1	C12—C13—S1	116.38 (15)
C5—C6—H6A	109.1	C13—C14—C15	120.45 (19)
C7—C6—H6B	109.1	C13—C14—H14	119.8
C5—C6—H6B	109.1	C15—C14—H14	119.8
H6A—C6—H6B	107.8	C14—C15—C10	121.38 (18)
C6—C7—C8	110.44 (16)	C14—C15—H15	119.3
C6—C7—H7A	109.6	C10—C15—H15	119.3
C8—C7—H7A	109.6	S1—C16—H16A	109.5
C6—C7—H7B	109.6	S1—C16—H16B	109.5
C8—C7—H7B	109.6	H16A—C16—H16B	109.5
H7A—C7—H7B	108.1	S1—C16—H16C	109.5
C8A—C8—C7	109.02 (15)	H16A—C16—H16C	109.5
C8A—C8—H8A	109.9	H16B—C16—H16C	109.5
C7—C8—H8A	109.9

C9A—N1—C2—C3	−0.4 (2)	C8—C8A—S9—C9A	−175.86 (16)
C9A—N1—C2—C10	178.60 (16)	C2—N1—C9A—N4	0.5 (2)
N1—C2—C3—N4	0.2 (2)	C2—N1—C9A—S9	−178.31 (16)
C10—C2—C3—N4	−178.66 (17)	C3—N4—C9A—N1	−0.4 (2)
N1—C2—C3—Br1	−178.84 (14)	C4A—N4—C9A—N1	−178.63 (15)
C10—C2—C3—Br1	2.3 (3)	C3—N4—C9A—S9	178.71 (12)
C2—C3—N4—C9A	0.07 (19)	C4A—N4—C9A—S9	0.45 (19)
Br1—C3—N4—C9A	179.24 (12)	C8A—S9—C9A—N1	177.7 (2)
C2—C3—N4—C4A	177.6 (2)	C8A—S9—C9A—N4	−1.11 (14)
Br1—C3—N4—C4A	−3.2 (3)	C3—C2—C10—C15	17.2 (3)
C9A—N4—C4A—C8A	0.7 (2)	N1—C2—C10—C15	−161.53 (18)
C3—N4—C4A—C8A	−176.6 (2)	C3—C2—C10—C11	−164.91 (19)
C9A—N4—C4A—C5	−179.12 (16)	N1—C2—C10—C11	16.3 (3)
C3—N4—C4A—C5	3.5 (3)	C15—C10—C11—C12	−1.1 (3)
C8A—C4A—C5—C6	−6.7 (3)	C2—C10—C11—C12	−179.12 (17)
N4—C4A—C5—C6	173.18 (16)	C10—C11—C12—C13	−0.5 (3)
C4A—C5—C6—C7	39.6 (2)	C11—C12—C13—C14	1.7 (3)
C5—C6—C7—C8	−63.1 (2)	C11—C12—C13—S1	−177.96 (15)
C6—C7—C8—C8A	49.1 (2)	C16—S1—C13—C14	−6.6 (2)
N4—C4A—C8A—C8	175.79 (16)	C16—S1—C13—C12	173.04 (16)
C5—C4A—C8A—C8	−4.3 (3)	C12—C13—C14—C15	−1.2 (3)
N4—C4A—C8A—S9	−1.6 (2)	S1—C13—C14—C15	178.47 (16)
C5—C4A—C8A—S9	178.26 (14)	C13—C14—C15—C10	−0.5 (3)
C7—C8—C8A—C4A	−17.4 (3)	C11—C10—C15—C14	1.7 (3)
C7—C8—C8A—S9	159.79 (14)	C2—C10—C15—C14	179.55 (18)
C4A—C8A—S9—C9A	1.59 (15)

12 in total

1. Synthesis and biological evaluation of novel Mannich bases of 2-arylimidazo[2,1-b]benzothiazoles as potential anti-cancer agents.

Authors: Ravindra M Kumbhare; K Vijay Kumar; M Janaki Ramaiah; Tulshiram Dadmal; S N C V L Pushpavalli; Debasmita Mukhopadhyay; B Divya; T Anjana Devi; Umesh Kosurkar; Manika Pal-Bhadra
Journal: Eur J Med Chem Date: 2011-07-01 Impact factor: 6.514

2. Inhibitors of apoptosis in lymphocytes: synthesis and biological evaluation of compounds related to pifithrin-alpha.

Authors: Sylvie D Barchéchath; Rommel I Tawatao; Maripat Corr; Dennis A Carson; Howard B Cottam
Journal: J Med Chem Date: 2005-10-06 Impact factor: 7.446

3. Inhibitors of apoptosis in testicular germ cells: synthesis and biological evaluation of some novel IBTs bearing sulfonamide moiety.

Authors: Navneet Chandak; Jitender K Bhardwaj; Rajnesh K Sharma; Pawan K Sharma
Journal: Eur J Med Chem Date: 2012-11-20 Impact factor: 6.514

4. Synthesis of (aryloxy)alkylamines. 2. Novel imidazo-fused heterocycles with calcium channel blocking and local anesthetic activity.

Authors: P J Sanfilippo; M Urbanski; J B Press; B Dubinsky; J B Moore
Journal: J Med Chem Date: 1988-11 Impact factor: 7.446

5. Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor.

Authors: Qi Chao; Kelly G Sprankle; Robert M Grotzfeld; Andiliy G Lai; Todd A Carter; Anne Marie Velasco; Ruwanthi N Gunawardane; Merryl D Cramer; Michael F Gardner; Joyce James; Patrick P Zarrinkar; Hitesh K Patel; Shripad S Bhagwat
Journal: J Med Chem Date: 2009-12-10 Impact factor: 7.446

6. New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.

Authors: Aldo Andreani; Silvia Burnelli; Massimiliano Granaiola; Alberto Leoni; Alessandra Locatelli; Rita Morigi; Mirella Rambaldi; Lucilla Varoli; Natalia Calonghi; Concettina Cappadone; Giovanna Farruggia; Maddalena Zini; Claudio Stefanelli; Lanfranco Masotti; Norman S Radin; Robert H Shoemaker
Journal: J Med Chem Date: 2008-02-06 Impact factor: 7.446