rac-7-[(2E)-But-2-enoyl]-13-chloro-N-cyclohexyl-7,8-dihydro-5H-isochromeno[4,3-c]phenanthridine-8-carboxamide

In the title compound, C31H29ClN2O3, the two heterocyclic rings, belonging to a system of five condensed rings, adopt conformations intermediate between twist-boat and sofa. The secondary amide group is involved in a weak intramolecular N—H⋯N hydrogen bond. In the crystal, molecules are linked by pairs of C—H⋯Cl hydrogen bonds to form inversion dimers. These dimers are linked via a C—H⋯O interaction to form chains propagating along the b-axis direction.

The structure of the title compound has been characterized by spectroscopic methods with further confirmation by X-ray analysis. We report here its crystal structure.
In the molecule of the title compound ( Fig. 1), there are three benzene rings and the middle one was fused with two other benzene rings by CH 2 O and CH 2 N bridges closing six-membered heterocyclic rings. The middle benzene ring is twisted relative to two other benzene rings by 30.7 (3)° and 15.7( 3)°. In the crystal structure, the molecules are linked by two C-H···Cl weak hydrogen bonds into centrosymmetric dimers (Fig. 2).

Experimental
A solution of 2-amino-4-chlorophenol (3.0 mmol) and 2-bromobenzaldehyde (3.0 mmol) in MeOH (5 ml) was stirred at room temperature for 15 min. To the resultant mixture was added (E)-crotonic acid (3.0 mmol) followed by stirring for 5 min at the same temperature. Cyclohexyl isocyanide (3.0 mmol) was then added to the above mixture followed by stirring at 323 K for 48 h. The white precipitate of the U-4CR product was collected by filtration and the solid was washed with methanol (3 ml). The combined filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography over silica gel ] to give additional portion of the U-4CR product. The yield of the U-4CR is 70%. A solution of the above U-4CR product (2.0 mmol), 2-bromobenzyl bromide (2.4 mmol), and K 2 CO 3 (3.0 mmol) in acetone (reagent grade, 10 ml) was heated at 323 K for 2 h. The reaction was allowed to cool to room temperature. After adding water, the mixture was extracted using EtOAc (3 x 10 ml). The combined organic layer was dried over anhydrous Na 2 SO 4 , filtered off, and then evaporated under reduced pressure. The residue was purified by flash column chromatography over silica gel [eluting with 20% EtOAc in PE (b.p. 333-363 K)] to give the O-benzylation product (96%).
A 10-ml pressurized process vial was charged with the above O-benzylation product (0.15 mmol), Pd(OAc) 2 (7.5 x 10 -3 mmol; 5 mol %), K 2 CO 3 (0.3 mmol), and PCy 3 HBF 4 (1.5 x 10 -2 mmol, 10 mol %). The vial was sealed with a cap containing a silicon septum. The vial was evacuated and backfilled with N 2 (repeated for three times) through the cap using a needle. To the degassed vial was added degassed anhydrous MeCN (3 ml) through the cap using a syringe. The loaded vial was then placed into the microwave reactor cavity and was heated at 433 K for 80 min. After cooling to room temperature the reaction mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography over silica gel [eluting with 25% EtOAc in PE (b.p. 333-363 K)] to give the title compound as a yellow solid (49 mg, 63%; m.p. 459-461 K (EtOAc-hexane). Single crystals suitable for X-ray diffraction were grown from a supplementary materials EtOAc/hexane mixture.

Refinement
The H atoms were placed in calculated positions with C-H = 0.93-0.98 Å, N-H = 0.86 Å and included in the refinement as riding on their carrier atoms with U iso (H) =1.2U eq (C,N).

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 40% probability level. H atoms are shown as a small spheres of arbitrary radius.  Centrosymmetric dimers by C-H···Cl hydrogen bonds. Symmetry code:(i) 1 -x, 1 -y, 1 -z.   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 > σ(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.