N-(1-Acetyl-5-benzoyl-1,4,5,6-tetra­hydro­pyrrolo­[3,4-c]pyrazol-3-yl)benzamide

Xiao-Guang Bai; Ju-Xian Wang; Yu-Cheng Wang

doi:10.1107/S1600536812019708

. 2012 May 12;68(Pt 6):o1677. doi: 10.1107/S1600536812019708

N-(1-Acetyl-5-benzoyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)benzamide

Xiao-Guang Bai ^a, Ju-Xian Wang ^a, Yu-Cheng Wang ^a,^*

PMCID: PMC3379273 PMID: 22719471

Abstract

In the molecule of the title compound, C₂₁H₁₈N₄O₃, the fused pyrrolo[3,4-c]pyrazole ring system is approximately planar [maximum deviation = 0.0486 (16) Å] and forms dihedral angles of 87.21 (8) and 35.46 (7)° with the phenyl rings. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds and weak C—H⋯π interactions link the molecules into chains parallel to [201].

Related literature

For background to potential anticancer kinase inhibitors, see: Fancelli et al. (2005 ▶); Gadekar et al. (1968 ▶). For the structures of related compounds synthesized by our group, see: Guo et al. (2010 ▶); Xia et al. (2011 ▶).

Experimental

Crystal data

C₂₁H₁₈N₄O₃
M _r = 374.39
Monoclinic,
a = 5.32163 (11) Å
b = 21.1878 (5) Å
c = 16.4585 (3) Å
β = 96.9378 (17)°
V = 1842.16 (7) Å³
Z = 4
Cu Kα radiation
μ = 0.76 mm⁻¹
T = 293 K
0.25 × 0.22 × 0.18 mm

Data collection

Oxford Diffraction Xcalibur Atlas Gemini ultra diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.819, T _max = 1.000
10256 measured reflections
3276 independent reflections
2856 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.150
S = 1.07
3276 reflections
254 parameters
H-atom parameters constrained
Δρ_max = 0.62 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812019708/rz2745sup1.cif

e-68-o1677-sup1.cif^{(21KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812019708/rz2745Isup2.hkl

e-68-o1677-Isup2.hkl^{(160.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812019708/rz2745Isup3.cml

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

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

Cg1 is the centroid of the C16–C21 phenyl ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H4⋯O1ⁱ	0.86	2.23	2.997 (2)	148
C20—H20⋯O1ⁱⁱ	0.93	2.49	3.359 (3)	156
C5—H5A⋯Cg1ⁱⁱ	0.97	2.64	3.508 (3)	150

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

Acknowledgments

This work was supported by the National Natural Science Foundation (81072577).

supplementary crystallographic information

Comment

In our ongoing project (Guo et al., 2010; Xia et al., 2011) devoted to the development of potential anticancer kinase inhibitors (Fancelli et al., 2005; Gadekar et al., 1968), we have synthesized the title compound and report its crystal structure herein.

In the molecule of the title compound (Fig. 1), bond lengths and angles have normal values. The fused pyrrole-pyrazole ring system is approximately planar (maximum deviation 0.0486 (16) Å for atom N3), the dihedral angle between the two five-membered rings being 1.32 (14)°. The phenyl rings C9–C14 and C16–C21 form dihedral angles of 87.21 (8) and 35.46 (7)°, respectively, with the mean plane through C1/N1/N2/C3/C2/C4/N3/C5. In the crystal structure (Fig. 2), molecules are linked by intermolecular N—H···O and C—H···O hydrogen bonds (Table 1) and by weak C—H···π interactions to form chains running parallel to the [2 0 1] direction.

Experimental

A solution of benzoyl chloride (3.37 g, 24 mmol) in THF (20 ml) was added slowly to a mixture of 5-tert-butyl 1-ethyl 3-aminopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate (6.5 g, 21.8 mmol) and DIEA (N,N-diisopropylethylamine; 24 ml, 130.8 mmol) in THF (250 ml) at 0–5 °C for 12 h, the resulting suspension was evaporated under vacuum to dryness, and the residual was taken up with AcOEt and water, the organic layer was separated and stayed for 2 h to form white solid in the solution, separated by filtration and washed with Et2O, to give 7.37 g (84.5%) of 5-tert-butyl 1-ethyl 3-benzamidopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate as a white solid. A suspension of 5-tert-butyl 1-ethyl 3-benzamidopyrrolo[3,4-c]pyrazole-1,5(4H,6H)-dicarboxylate (7.6 g, 19 mmol) in DCM (300 ml) was pumped dried hydrochloride gas under room temperature for 3 h, filtered, extensively washed with Et2O, and dried under vacuum at 40 °C to give 6.37 g (100%) of ethyl 3-benzamido-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate hydrochloride as white powder. A solution of benzoyl chloride (3.04 g, 21.6 mmol) in THF (20 ml) was added slowly to a suspension of ethyl 3-benzamido-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate hydrochloride (6.05 g, 18 mmol) and DIEA (17.8 ml, 108 mmol) in THF (200 ml) at 0–5 °C, The resulting suspension was evaporated under vacuum to dryness, and the residual was taken up with AcOEt and water, the organic layer was separated and stayed for 2 h to form white solid in the solution, separated by filtration and washed with Et2O, to give 7.1 g (97.6%) of ethyl 3-benzamido-5-benzoyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate as a white solid. A solution of ethyl 3-benzamido-5-benzoyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate (6.8 g, 16.8 mmol) in MeOH (300 ml) and Et3N (30 ml) was stirred at room temperature for 2 h. The resulting mixture was evaporated to dryness and dried under vacuum to give 5.47 g (98%) of N-(5-benzoyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)benzamide as white powder. A solution of acetyl chloride (0.424 g, 5.4 mmol) in THF (10 ml) was added slowly to a mixture of N-(5-benzoyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)benzamide (1.5 g, 4.5 mmol) and DIEA (4.5 ml, 27 mmol) in THF (80 ml) at 0–5 °C for 12 h, the resulting suspension was evaporated under vacuum to dryness, and the residual was taken up with AcOEt and water, the organic layer was separated and stayed for 2 h to form white solid in the solution, separated by filtration and washed with Et2O, to give 1.5 g (89%) of N-(1-acetyl-5-benzoyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)benzamide as a white solid. Colourless block crystals suitable for X-ray diffraction were obtained in 6 days by slow envaporation of a mixed solution (1:1 v/v) of dichloromethane and ethyl acetate.