5-(4-Chloro-phen-yl)-1-methyl-3-phenyl-3,6,8,9-tetra-hydro-pyrazolo-[3,4-b]thio-pyrano[4,3-d]pyridine.

The title compound, C(22)H(18)ClN(3)S, was synthesized by the reaction of 4-chloro-benzaldehyde, tetra-hydro-thio-pyran-4-one and 3-methyl-1-phenyl-1H-pyrazol-5-amine in acetic acid without a catalyst. The pyridine and pyrazole rings are almost coplanar, the dihedral angle between their mean planes being 2.50 (1)°. The thio-pyran ring exhibits an envelope conformation. The crystal packing is stabilized by inter-molecular C-H⋯Cl hydrogen bonds and by C-H⋯π and π-π inter-actions [centroid-centroid distances of 3.825 (2) Å between pyridine rings and 3.557 (2) Å between pyrazole and pyridine rings.

Related literature

The pyrazolo­[3,4-b]pyridine system represents the core skeleton of a pharmaceutically important class of heterocyclic compounds that possess a broad range of biological activity, see: Beutner et al. (2009 ▶); Hamblin et al. (2008 ▶); Jiang et al. (2011 ▶); Lynck et al. (1988 ▶); Manetti et al. (2005 ▶); Meiners & Salama (1982 ▶); Revesz et al. (2006 ▶); Witherington et al. (2003 ▶). For related structures, see: Chebanov et al. (2007 ▶); Lee & Park (2009 ▶); Quiroga et al. (2001 ▶).

Experimental

Crystal data

C22H18ClN3S

M = 391.90

Monoclinic,

a = 8.8731 (9) Å

b = 19.9044 (18) Å

c = 10.5292 (11) Å

β = 96.689 (1)°

V = 1846.9 (3) Å3

Z = 4

Mo Kα radiation

μ = 0.33 mm−1

T = 298 K

0.48 × 0.19 × 0.18 mm

Data collection

Bruker SMART CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996) ▶ T min = 0.857, T max = 0.943

9193 measured reflections

3264 independent reflections

1988 reflections with I > 2σ(I)

R int = 0.049

Refinement

R[F 2 > 2σ(F 2)] = 0.046

wR(F 2) = 0.118

S = 1.02

3264 reflections

245 parameters

H-atom parameters constrained

Δρmax = 0.24 e Å−3

Δρmin = −0.32 e Å−3

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; 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: SHELXTL.

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811033514/zq2115sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811033514/zq2115Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811033514/zq2115Isup3.cml

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

C22H18ClN3S	F(000) = 816
Mr = 391.90	Dx = 1.409 Mg m−3
Monoclinic, P21/c	Melting point = 473–475 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 8.8731 (9) Å	Cell parameters from 2113 reflections
b = 19.9044 (18) Å	θ = 2.2–26.7°
c = 10.5292 (11) Å	µ = 0.33 mm−1
β = 96.689 (1)°	T = 298 K
V = 1846.9 (3) Å3	Solid, yellow
Z = 4	0.48 × 0.19 × 0.18 mm

Bruker SMART CCD area-detector diffractometer	3264 independent reflections
Radiation source: fine-focus sealed tube	1988 reflections with I > 2σ(I)
graphite	Rint = 0.049
φ and ω scans	θmax = 25.0°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −10→10
Tmin = 0.857, Tmax = 0.943	k = −23→23
9193 measured reflections	l = −12→10

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)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.118	H-atom parameters constrained
S = 1.02	w = 1/[σ2(Fo2) + (0.0492P)2 + 0.3375P] where P = (Fo2 + 2Fc2)/3
3264 reflections	(Δ/σ)max < 0.001
245 parameters	Δρmax = 0.24 e Å−3
0 restraints	Δρmin = −0.32 e Å−3

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'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 > σ(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
Cl1	0.44021 (11)	0.63561 (4)	1.01417 (8)	0.0593 (3)
N1	0.7485 (3)	0.54523 (11)	0.4998 (2)	0.0332 (6)
N2	0.8363 (3)	0.55347 (11)	0.2913 (2)	0.0357 (6)
N3	0.8983 (3)	0.51019 (11)	0.2085 (2)	0.0387 (6)
S1	0.67456 (11)	0.30052 (4)	0.63061 (9)	0.0578 (3)
C1	0.8091 (3)	0.51924 (13)	0.4001 (2)	0.0306 (7)
C2	0.8559 (3)	0.45316 (13)	0.3864 (3)	0.0318 (7)
C3	0.9106 (3)	0.45062 (14)	0.2642 (3)	0.0369 (7)
C4	0.9691 (4)	0.39328 (14)	0.1935 (3)	0.0523 (9)
H4A	0.9980	0.4090	0.1136	0.079*
H4B	0.8912	0.3598	0.1775	0.079*
H4C	1.0557	0.3741	0.2436	0.079*
C5	0.7208 (4)	0.38381 (14)	0.6887 (3)	0.0447 (8)
H5A	0.6339	0.4023	0.7245	0.054*
H5B	0.8038	0.3810	0.7571	0.054*
C6	0.7656 (3)	0.43144 (13)	0.5871 (2)	0.0331 (7)
C7	0.8341 (3)	0.40722 (13)	0.4839 (3)	0.0328 (7)
C8	0.8818 (4)	0.33513 (14)	0.4683 (3)	0.0457 (8)
H8A	0.8294	0.3184	0.3886	0.055*
H8B	0.9895	0.3348	0.4598	0.055*
C9	0.8542 (4)	0.28645 (15)	0.5730 (3)	0.0574 (10)
H9A	0.9344	0.2911	0.6433	0.069*
H9B	0.8574	0.2409	0.5406	0.069*
C10	0.7281 (3)	0.50130 (13)	0.5927 (2)	0.0317 (7)
C11	0.6564 (3)	0.53181 (13)	0.7005 (2)	0.0316 (7)
C12	0.5455 (3)	0.58021 (14)	0.6731 (3)	0.0368 (7)
H12	0.5153	0.5916	0.5883	0.044*
C13	0.4789 (3)	0.61196 (14)	0.7682 (3)	0.0382 (7)
H13	0.4048	0.6445	0.7480	0.046*
C14	0.5232 (4)	0.59506 (14)	0.8936 (3)	0.0374 (7)
C15	0.6343 (4)	0.54796 (14)	0.9245 (3)	0.0392 (8)
H15	0.6645	0.5372	1.0096	0.047*
C16	0.7009 (3)	0.51666 (13)	0.8279 (3)	0.0375 (7)
H16	0.7767	0.4849	0.8487	0.045*
C17	0.8084 (3)	0.62075 (13)	0.2522 (2)	0.0328 (7)
C18	0.7261 (3)	0.66428 (14)	0.3209 (3)	0.0406 (8)
H18	0.6893	0.6498	0.3954	0.049*
C19	0.6992 (4)	0.72906 (15)	0.2776 (3)	0.0473 (8)
H19	0.6441	0.7581	0.3238	0.057*
C20	0.7524 (4)	0.75172 (16)	0.1675 (3)	0.0503 (9)
H20	0.7331	0.7954	0.1388	0.060*
C21	0.8344 (4)	0.70828 (15)	0.1010 (3)	0.0489 (9)
H21	0.8706	0.7230	0.0264	0.059*
C22	0.8645 (3)	0.64352 (14)	0.1420 (3)	0.0405 (8)
H22	0.9218	0.6152	0.0963	0.049*

	U11	U22	U33	U12	U13	U23
Cl1	0.0792 (7)	0.0579 (6)	0.0456 (5)	0.0061 (5)	0.0279 (5)	−0.0081 (4)
N1	0.0386 (15)	0.0337 (13)	0.0286 (13)	0.0005 (11)	0.0092 (11)	0.0007 (11)
N2	0.0452 (16)	0.0333 (13)	0.0306 (13)	0.0045 (12)	0.0128 (12)	0.0004 (11)
N3	0.0455 (17)	0.0405 (15)	0.0323 (14)	0.0043 (12)	0.0138 (12)	−0.0038 (11)
S1	0.0621 (7)	0.0369 (5)	0.0795 (7)	−0.0095 (4)	0.0298 (5)	0.0017 (4)
C1	0.0312 (17)	0.0326 (16)	0.0290 (15)	−0.0012 (13)	0.0078 (13)	0.0014 (12)
C2	0.0328 (18)	0.0292 (15)	0.0344 (16)	0.0003 (13)	0.0079 (13)	−0.0012 (13)
C3	0.0383 (19)	0.0375 (17)	0.0357 (17)	0.0037 (15)	0.0078 (14)	−0.0023 (14)
C4	0.065 (3)	0.0421 (19)	0.055 (2)	0.0025 (17)	0.0255 (18)	−0.0082 (16)
C5	0.057 (2)	0.0361 (17)	0.0434 (19)	−0.0031 (15)	0.0166 (16)	0.0052 (14)
C6	0.0335 (18)	0.0341 (16)	0.0316 (16)	−0.0033 (13)	0.0037 (13)	0.0019 (12)
C7	0.0310 (18)	0.0292 (16)	0.0380 (17)	−0.0027 (13)	0.0038 (14)	−0.0009 (13)
C8	0.051 (2)	0.0375 (18)	0.0502 (19)	0.0060 (15)	0.0119 (16)	0.0012 (15)
C9	0.066 (3)	0.0341 (18)	0.076 (2)	0.0056 (17)	0.024 (2)	0.0087 (17)
C10	0.0328 (18)	0.0338 (16)	0.0286 (15)	−0.0036 (13)	0.0042 (13)	0.0009 (13)
C11	0.0362 (18)	0.0294 (15)	0.0301 (16)	−0.0054 (13)	0.0082 (13)	0.0003 (12)
C12	0.042 (2)	0.0404 (17)	0.0286 (16)	0.0015 (15)	0.0056 (14)	0.0029 (13)
C13	0.0327 (19)	0.0422 (17)	0.0406 (18)	0.0041 (14)	0.0077 (15)	−0.0011 (14)
C14	0.046 (2)	0.0352 (17)	0.0329 (17)	−0.0074 (15)	0.0150 (15)	−0.0065 (13)
C15	0.053 (2)	0.0380 (17)	0.0281 (16)	−0.0046 (16)	0.0099 (15)	0.0036 (13)
C16	0.043 (2)	0.0341 (16)	0.0364 (17)	0.0026 (14)	0.0080 (15)	0.0028 (13)
C17	0.0382 (19)	0.0301 (15)	0.0303 (16)	−0.0019 (14)	0.0043 (14)	0.0011 (12)
C18	0.052 (2)	0.0391 (18)	0.0326 (17)	0.0015 (16)	0.0128 (15)	0.0020 (14)
C19	0.056 (2)	0.0372 (18)	0.050 (2)	0.0063 (16)	0.0115 (17)	0.0008 (15)
C20	0.056 (2)	0.0395 (19)	0.056 (2)	−0.0026 (17)	0.0088 (18)	0.0091 (16)
C21	0.059 (2)	0.048 (2)	0.0416 (19)	−0.0107 (17)	0.0136 (17)	0.0130 (16)
C22	0.043 (2)	0.0444 (19)	0.0361 (17)	−0.0007 (15)	0.0131 (15)	0.0029 (14)

Cl1—C14	1.739 (3)	C9—H9A	0.9700
N1—C1	1.339 (3)	C9—H9B	0.9700
N1—C10	1.339 (3)	C10—C11	1.493 (4)
N2—C1	1.378 (3)	C11—C12	1.383 (4)
N2—N3	1.384 (3)	C11—C16	1.387 (4)
N2—C17	1.414 (3)	C12—C13	1.374 (4)
N3—C3	1.322 (3)	C12—H12	0.9300
S1—C9	1.792 (3)	C13—C14	1.375 (4)
S1—C5	1.798 (3)	C13—H13	0.9300
C1—C2	1.392 (4)	C14—C15	1.372 (4)
C2—C7	1.405 (4)	C15—C16	1.382 (4)
C2—C3	1.428 (4)	C15—H15	0.9300
C3—C4	1.489 (4)	C16—H16	0.9300
C4—H4A	0.9600	C17—C18	1.389 (4)
C4—H4B	0.9600	C17—C22	1.391 (4)
C4—H4C	0.9600	C18—C19	1.379 (4)
C5—C6	1.517 (4)	C18—H18	0.9300
C5—H5A	0.9700	C19—C20	1.378 (4)
C5—H5B	0.9700	C19—H19	0.9300
C6—C7	1.391 (4)	C20—C21	1.373 (4)
C6—C10	1.433 (4)	C20—H20	0.9300
C7—C8	1.511 (4)	C21—C22	1.375 (4)
C8—C9	1.509 (4)	C21—H21	0.9300
C8—H8A	0.9700	C22—H22	0.9300
C8—H8B	0.9700
C1—N1—C10	114.9 (2)	C8—C9—H9B	109.2
C1—N2—N3	109.7 (2)	S1—C9—H9B	109.2
C1—N2—C17	131.9 (2)	H9A—C9—H9B	107.9
N3—N2—C17	118.4 (2)	N1—C10—C6	123.5 (2)
C3—N3—N2	107.3 (2)	N1—C10—C11	113.3 (2)
C9—S1—C5	94.73 (15)	C6—C10—C11	123.2 (2)
N1—C1—N2	125.9 (2)	C12—C11—C16	117.9 (3)
N1—C1—C2	126.7 (2)	C12—C11—C10	118.7 (2)
N2—C1—C2	107.3 (2)	C16—C11—C10	123.3 (3)
C1—C2—C7	118.1 (2)	C13—C12—C11	121.6 (3)
C1—C2—C3	105.3 (2)	C13—C12—H12	119.2
C7—C2—C3	136.5 (3)	C11—C12—H12	119.2
N3—C3—C2	110.4 (2)	C12—C13—C14	119.2 (3)
N3—C3—C4	118.7 (3)	C12—C13—H13	120.4
C2—C3—C4	130.8 (3)	C14—C13—H13	120.4
C3—C4—H4A	109.5	C15—C14—C13	120.8 (3)
C3—C4—H4B	109.5	C15—C14—Cl1	119.9 (2)
H4A—C4—H4B	109.5	C13—C14—Cl1	119.3 (2)
C3—C4—H4C	109.5	C14—C15—C16	119.4 (3)
H4A—C4—H4C	109.5	C14—C15—H15	120.3
H4B—C4—H4C	109.5	C16—C15—H15	120.3
C6—C5—S1	113.9 (2)	C15—C16—C11	121.0 (3)
C6—C5—H5A	108.8	C15—C16—H16	119.5
S1—C5—H5A	108.8	C11—C16—H16	119.5
C6—C5—H5B	108.8	C18—C17—C22	119.5 (3)
S1—C5—H5B	108.8	C18—C17—N2	121.6 (2)
H5A—C5—H5B	107.7	C22—C17—N2	118.9 (2)
C7—C6—C10	119.6 (2)	C19—C18—C17	119.5 (3)
C7—C6—C5	120.6 (3)	C19—C18—H18	120.2
C10—C6—C5	119.8 (2)	C17—C18—H18	120.2
C6—C7—C2	117.1 (2)	C20—C19—C18	121.4 (3)
C6—C7—C8	124.6 (2)	C20—C19—H19	119.3
C2—C7—C8	118.3 (2)	C18—C19—H19	119.3
C9—C8—C7	117.3 (3)	C21—C20—C19	118.5 (3)
C9—C8—H8A	108.0	C21—C20—H20	120.8
C7—C8—H8A	108.0	C19—C20—H20	120.8
C9—C8—H8B	108.0	C20—C21—C22	121.7 (3)
C7—C8—H8B	108.0	C20—C21—H21	119.2
H8A—C8—H8B	107.2	C22—C21—H21	119.2
C8—C9—S1	111.9 (2)	C21—C22—C17	119.5 (3)
C8—C9—H9A	109.2	C21—C22—H22	120.3
S1—C9—H9A	109.2	C17—C22—H22	120.3
C1—N2—N3—C3	−0.4 (3)	C1—N1—C10—C6	−0.8 (4)
C17—N2—N3—C3	−178.7 (2)	C1—N1—C10—C11	−178.4 (2)
C10—N1—C1—N2	177.7 (3)	C7—C6—C10—N1	3.4 (4)
C10—N1—C1—C2	−2.2 (4)	C5—C6—C10—N1	−172.5 (3)
N3—N2—C1—N1	−179.4 (3)	C7—C6—C10—C11	−179.2 (3)
C17—N2—C1—N1	−1.4 (5)	C5—C6—C10—C11	5.0 (4)
N3—N2—C1—C2	0.5 (3)	N1—C10—C11—C12	37.0 (4)
C17—N2—C1—C2	178.4 (3)	C6—C10—C11—C12	−140.7 (3)
N1—C1—C2—C7	2.3 (4)	N1—C10—C11—C16	−139.5 (3)
N2—C1—C2—C7	−177.5 (2)	C6—C10—C11—C16	42.9 (4)
N1—C1—C2—C3	179.5 (3)	C16—C11—C12—C13	−1.0 (4)
N2—C1—C2—C3	−0.4 (3)	C10—C11—C12—C13	−177.6 (3)
N2—N3—C3—C2	0.1 (3)	C11—C12—C13—C14	−0.2 (4)
N2—N3—C3—C4	177.6 (3)	C12—C13—C14—C15	1.1 (4)
C1—C2—C3—N3	0.1 (3)	C12—C13—C14—Cl1	179.5 (2)
C7—C2—C3—N3	176.5 (3)	C13—C14—C15—C16	−0.8 (4)
C1—C2—C3—C4	−176.9 (3)	Cl1—C14—C15—C16	−179.2 (2)
C7—C2—C3—C4	−0.6 (6)	C14—C15—C16—C11	−0.4 (4)
C9—S1—C5—C6	57.4 (3)	C12—C11—C16—C15	1.3 (4)
S1—C5—C6—C7	−29.2 (4)	C10—C11—C16—C15	177.8 (3)
S1—C5—C6—C10	146.6 (2)	C1—N2—C17—C18	−7.6 (5)
C10—C6—C7—C2	−3.1 (4)	N3—N2—C17—C18	170.2 (3)
C5—C6—C7—C2	172.8 (3)	C1—N2—C17—C22	172.7 (3)
C10—C6—C7—C8	178.7 (3)	N3—N2—C17—C22	−9.5 (4)
C5—C6—C7—C8	−5.4 (4)	C22—C17—C18—C19	1.0 (4)
C1—C2—C7—C6	0.5 (4)	N2—C17—C18—C19	−178.7 (3)
C3—C2—C7—C6	−175.6 (3)	C17—C18—C19—C20	0.0 (5)
C1—C2—C7—C8	178.8 (3)	C18—C19—C20—C21	−0.4 (5)
C3—C2—C7—C8	2.8 (5)	C19—C20—C21—C22	−0.2 (5)
C6—C7—C8—C9	−0.6 (4)	C20—C21—C22—C17	1.1 (5)
C2—C7—C8—C9	−178.8 (3)	C18—C17—C22—C21	−1.5 (4)
C7—C8—C9—S1	40.3 (4)	N2—C17—C22—C21	178.2 (3)
C5—S1—C9—C8	−62.7 (3)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···Cl1i	0.97	3.00	3.608 (3)	122.
C9—H9A···Cg1ii	0.97	2.84	3.778 (4)	163.

Table 1

Hydrogen-bond geometry (Å, °)

Please define Cg1 is the centroid of the C17–C22 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5A⋯Cl1i	0.97	3.00	3.608 (3)	122
C9—H9A⋯Cg1ii	0.97	2.84	3.778 (4)	163

Symmetry codes: (i) ; (ii) .