Olanzapinium dipicrate

Abstract

The asymmetric unit of the title salt [systematic name: 2-methyl-4-(4-methyl­piperazin-4-ium-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepinium bis­(2,4,6-trinitro­phenolate)], C17H22N4S2+·2C6H2N3O7 −, consists of a diprotonated olanzapinium cation and two independent picrate anions. In the cation, the piperazine ring adopts a distorted chair conformation and contains a positively charged N atom with quaternary character and the N atom in the seven-membered 1,5-diazepine ring, which adopts a boat configuration, is also protonated. The dihedral angle between the benzene and thiene rings flanking the diazepine ring is 58.8 (1)°. In one of the picrate anions, a nitro group is disordered over two sets of sites in a 0.748 (5):0.252 (5) ratio, and the benzene ring has a flat envelope conformation with the O− C atom displaced from the mean plane of the other five C atoms [maximum deviation 0.0151 (14) Å] by 0.1449 (14) Å. In the crystal, N—H⋯O hydrogen bonds and weak inter­molecular C—H⋯S and C—H⋯O inter­actions link the components, forming a three-dimensional network.

Crystal structure and Hirshfeld surface analysis of 1-methyl-4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-ium 2,5-dihydroxybenzoate propan-2-ol monosolvate

“…The bond lengths and bond angles of the thiene and piperazine rings of compound (I) are also comparable with the values observed for related structures (Kavitha et al, 2013;Ravikumar et al, 2005). The superimposed fit (Gans & Shalloway, 2001) of the olazapine group of (I) (atoms C1-C8, N1, O1 and O2) gives an r.m.s deviation of 1.179 Å with olanzapinium dipicrate (II) (Kavitha et al, 2013) (Fig. 2) and 1.175 Å with olazipinium nicotinate (III) (Ravikumar et al, 2005) (Fig.…”

“…, with pyrazinoic acid (SUKPAS; Sarmah et al, 2020) and with other carboxylic acids (AMIYUR and AMIZAY; Thakuria et al, 2011a andSarmah et al, 2020;FABKAX and FABKEB;Sarmah et al, 2016;FHIRYUE, HIRZAL, HIRZEP and HIRZIT;Thakuria et al, 2013;JIXROY;Sridhar & Ravikumar, 2007;LESQIL;Kavitha et al, 2013;PEWPUF, PEWQAM and PEWQEQ;Sarmah et al, 2018;TAQNUV;Ravikumar et al, 2005). Among them, the crystal structures of PEWQEQ, PEWQAM, HIRZIT, FABJUQ, SUKPIA, SUKPOG, FABKEB, HIRZEP and PEWQAM contain solvent molecules.…”

Olanzapine Form IV: Discovery of a New Polymorphic Form Enabled by Computed Crystal Energy Landscapes

“…A Rietveld refinement was performed on the model (Figure 3), with bond lengths restrained to an error of 0.1 Å and bond angles to an error of 1.0°, confirming that the crystal structure of model A1 and form IV were equivalent. 1548.2 71586.9(4) 1671.28 (12) The crystal structure of form IV does not contain the SC0 dimer motif seen in the other anhydrous forms of olanzapine and the vast majority of its solvates. Instead, the packing involved ladder-like hydrogen bonding interactions between the olanzapine molecules, whereby each molecule is involved in two hydrogen bonds to two adjacent molecules between the piparizine N4 atom and protonated N1 atom (Figure 4).…”

“…The crystallization of olanzapine (Chart a), a former blockbuster antipsychotic drug licensed for the treatment of schizophrenia, has been intensely investigated. Three anhydrous polymorphic forms of olanzapine (forms I, II, and III) have been characterized as well as many (>60) hydrates, solvates, cocrystals, and salts. − The prolific solvate formation of olanzapine is attributed to the low packing efficiency of the drug molecules in the solid state . It is noteworthy that while there are over 60 forms of olanzapine with full structural details on the Cambridge Structural Database (CSD), they all contain the same SC 0 dimer packing motif (Chart b), with the exception of some doubly ionized forms and one hydroquinone toluene cocrystal. , …”

Olanzapine Salts and Diversity in Molecular Packing

“…This family of drugs has very low solubility and belongs to the BCS class II category where solid-state modification is essential in order to get better efficacy as well as efficiency. An extensive amount of study has been carried out on the OLN molecule that includes six anhydrous polymorphs − (two polymorphs with 3D coordinates determined; others confirmed using PXRD), three polymorphic dihydrates, two sesquihydrate polymorphs, several solvates, − hydrates, mixed solvated forms, − salts, − ,, cocrystals, − and one amorphous form. , Zaworotko et al studied a few quaternary solvated cocrystals of OLN and categorized them in four different classes of crystal packing arrangement. Apart from the study of highly soluble olanzapinium salts, Thakuria and Nangia extended the paradigm of olanzapine structure and discovered a few disalts with new crystal packing arrangement.…”