Methyl (3S,10b’S)-5-chloro-9′-fluoro-1-methyl-2-oxo-5′-phenyl-10b’H-spiro[indoline-3,1′-pyrazolo[3,2-a]isoquinoline]-2′-carboxylate

In the title compound, C27H19ClFN3O3, the pyrazole ring has a twist conformation and the six-membered ring to which it is fused has a screw-boat conformation. The mean plane of the pyrazole ring is inclined to the 2-methylindoline ring by 85.03 (9) and by 28.17 (8)° to the mean plane of the isoquinoline ring system. In the crystal, molecules are linked by pairs of C—H⋯F hydrogen bonds, forming inversion dimers. These dimers are linked via C—H⋯O hydrogen bonds, forming a two-dimensional network lying parallel to (10-1).

In the title compound, C 27 H 19 ClFN 3 O 3 , the pyrazole ring has a twist conformation and the six-membered ring to which it is fused has a screw-boat conformation. The mean plane of the pyrazole ring is inclined to the 2-methylindoline ring by 85.03 (9) and by 28.17 (8) to the mean plane of the isoquinoline ring system. In the crystal, molecules are linked by pairs of C-HÁ Á ÁF hydrogen bonds, forming inversion dimers. These dimers are linked via C-HÁ Á ÁO hydrogen bonds, forming a two-dimensional network lying parallel to (101).   Table 1 Hydrogen-bond geometry (Å , ). atoms. During the past years considerable evidence has been accumulated to demonstrate the biological efficacy of pyrazole derivatives, including antibacterial (Patel et al., 1990), antifungal (Zhao et al., 2001), herbicidal (Li et al., 2005, insecticidal (Huang et al., 1996) and other biological activities. A number of pyrazole-containing compounds have been successfully commercialized, such as the blockbuster drugs Viagra, Celebrex, and Acomplia.

Related literature
Among the family of isoquinolines, the fused isoquinolines have attracted much attention owing to their biological activities including potent inhibitor of human topoisomerase I and selective inhibition against HIV-1 integrase in vitro (Aubry et al., 2004;Marco et al., 2005;Reddy et al., 1999). In view of the diverse applications of this class of compounds, and continuing our research on the synthesis and crystal structure analysis of similar compounds (Manivel et al., 2009;Khan et al., 2010a,b,c;Hathwar et al., 2008), we report herein on the crystal structure of the new title isoquinoline pyrazole compound.
The pyrazole ring mean plane forms a dihedral angle of 85.03 (9) ° with the methyldihydroindole ring system. This clearly shows that the pyrazole ring is almost perpendicular to the methyldihydroindole ring system. The dihedral angle between mean planes of the pyrazole ring and the isoquinoline ring system is 28.17 (8)°.

Experimental
General experimental procedure for the silver triflate-catalyzed tandem reaction of N′-(2-alkynylbenzylidene) hydrazide with methyleneindolinones: A mixture of N′-(2-alkynylbenzylidene) hydrazide (0.3 mmol) and AgOTf (10 mol%) in DCE (2.0 mL) was heated at 333 K with vigorous stirring for 1 hour. Then, the methyleneindolinone (0.45 mmol, 1.5 equiv), Cs 2 CO 3 (0.9 mmol, 3.0 equiv) and toluene (2.0 mL) were added. The reaction mixture was refluxed at 353 K until supplementary materials completion of the reaction. The reaction mixture was diluted with ethyl acetate (5.0 mL) and quenched with water (5.0 mL). The organic layer was washed with brine, dried over Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by column chromatography using ethyl acetate and hexane (3:7) as an elutent on neutral alumina to provide the desired product. Block-like crystals, suitable for X-ray diffraction analysis, were obtained by slow evaporation of a solution in ethyl acetate at room temperature.

Refinement
All H atoms were fixed geometrically and allowed to ride on their parent C atom: C-H 0.93-0.97 Å with U iso (H) = 1.5U eq (C-methyl) and = 1.2U eq (C) for other H atoms. The positions of the methyl hydrogens were optimized rotationally.  The molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.  The partial view of the crystal packing of the title compound. The C-H···F and C-H···O hydrogen bonds are shown as dashed lines (see Table 1 for details; Cl green, F yellow). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.25 e Å −3 Δρ min = −0.30 e Å −3

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.