Browse Prior Art Database

CRYSTALLINE FORM OF (3aR, 4S, 7R, 7aS)-2-{(1R, 2R)-2-[4-(1, 2- BENZISOTHIAZOL-3-YL) PIPERAZIN -1- YLMETHYL] CYCLOHEXYLMETHYL} HEXAHYDRO-1H-4, 7-METHANISOINDOLE-1, 3-DIONE HYDROCHLORIDE)

IP.com Disclosure Number: IPCOM000211101D
Publication Date: 2011-Sep-20
Document File: 3 page(s) / 84K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 51% of the total text.

Page 01 of 3

    CRYSTALLINE FORM OF (3aR, 4S, 7R, 7aS)-2-{(1R, 2R)-2-[4-(1, 2- BENZISOTHIAZOL-3-YL) PIPERAZIN -1- YLMETHYL] CYCLOHEXYLMETHYL} HEXAHYDRO-1H-4, 7-METHANISOINDOLE-1, 3-

DIONE HYDROCHLORIDE)

    (3aR, 4S, 7R, 7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl) piperazin-1- yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione hydrochloride, referred to as 'Compound L', has the following formula:

(This page contains 00 pictures or other non-text object)

HCl

Described hereinafter, are solid state physical properties of Compound L.

Crystalline form of Compound L:

The crystalline form of Compound L can be characterized by data selected from a group consisting of: X-ray powder diffraction pattern, having peaks at about 11.5, 13.9, 17.1,
19.6 and 22.0 ± 0.2 degrees two-theta; an X-ray powder diffraction pattern substantially as depicted in Figure 1; and combinations thereof.

Figure 1: XRPD pattern of crystalline Form of Compound L. Peak at 28.48 °2θ belongs to silicon.

(This page contains 01 pictures or other non-text object)


Page 02 of 3

The crystalline form of Compound L can be further characterized by data selected from a group consisting of: X-ray powder diffraction pattern, having peaks at about 8.9, 14.5,
18.0, 21.2 and 24.2 ± 0.2 degrees two-theta.

Method:

PXRD method
After being powdered using mortar and pestle, sample was applied directly on a silicon plate holder. The X-ray powder diffraction pattern was measured with a Philips X'Pert PRO X-ray powder diffractometer, equipped with a Cu irradiation source = 1.54184 Ǻ (Ǻngström), X'Celerator (2.022º 2θ) detector. Scanning parameters: angle range: 3-40 deg., step size 0.0167, time per step 37 s, continuous scan. The described peak positions were determined using silicon powder as an internal standard in an admixture with the sample measured. The position of the silicon (Si) peak was corrected to silicone theoretical peak: 28.45 degrees two theta, and the positions of the measured peaks were corrected respectively. No correction was performed on the diffractogram depicted in the figure.

Example 1: Preparation of crystalline form of Compound L (3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl) piperazin-1- yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione (3.5 g) was dissolved in acetone (43 ml) by heating at 55-60 °C. Obtained solution was cooled at 50- 55°C and water was added (1.5 ml). Then, 10 % aqueous solution of hydrochloric acid (3.3 ml) was added drop wise during 10 minutes. Obtained suspension was stirred for 15


Page 03 of 3

minutes at 50-55°C and then cooled down to 0-5°C during 1 h...