The dicyclohexylamine salt of RG108 (N-phthalyl-l-tryptophan), a potential epigenetic modulator

The dicyclohexylamine salt of RG108 (N-phthalyl-l-tryptophan) co-crystallizes with a water molecule and a disordered molecule of dimethylformamide (DMF), viz. dicyclohexylaminium (S)-2-(1,3-dioxoisoindolin-2-yl)-3-(1H-indol-3-yl)propanoate dimethylformamide solvate monohydrate, C12H24N+·C19H13N2O4 −·C3H7NO·H2O. The conformation of the deprotonated compound is constrained by charge-assisted strong hydrogen bonds with the dicyclohexylaminium ion and a dense hydrogen-bond network involving co-crystallized solvent molecules. The dihedral angle between the fused ring systems in the anion is 58.35 (4)°.

Isomer S (C9) of RG108 is obtained starting from L-tryptophan and phthalic anhydride in DMF.
A water molecule (O5) has co-crystallized and is involved in the stability of the packing as it forms a network of H-bonds connecting the N-H (N2) of the indole ring of RG108 with a carbonyl function (O1) of the phtalimide ring of a symmetryrelated molecule and the oxygen atom (O99) of a molecule of DMF solvent (Table 1).
In addition to H-bonding to the water, the extra (disordered) co-crystallized solvent molecule of DMF is thightly packed in a cavity formed by the aromatic heterocycles of RG108 (the phtalimide and the indole rings).
As a consequence of the dense packing (salt bridge, H-bonds and van der Waals interactions), the two aromatic, planar, heterocycles of RG108 are perpendicular (acute angle between the planes defined by the phtalimide and the indole rings = 58.35 (4)°).

Experimental
Synthesis of the compound was made by micro-ave heating of L-tryptophane and phthalic anhydride in DMF by adapting the procedure described by Brueckner et al. (2005).
Crystals were obtained by evaporation at room temperature of a solution in mixture of methylene chloride and methanol (9/1).

Refinement
The two H atoms of the water molecule and the two H atoms on (protonated) nitrogen N5 were located from ΔF Fourier difference maps and their position refined. All other H atoms were placed at idealized positions and allowed to ride on their parent atoms.
supplementary materials sup-2 Atoms of a DMF molecule were refined isotropically. Disorder has been taken into account by refining two sets of coordinates (0.7 and 0.3 occupancies respectively) for each atom of the DMF molecule. Bond lengths and valence angles were restrained to be similar in both disordered parts. Fig. 1. ORTEP view (with atom numbering) of the title compound. Only selected H atoms have been retained for clarity (on the chiral carbon, on the protonated nitrogen, and H involved in H-bonds). Displacement ellipsoids for non-H atoms are drawn at the 30% probability level.