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CRYSTALLINE FORMS OF TETRAHYDROBENZAZEPINE COMPOUNDS

IP.com Disclosure Number: IPCOM000238513D
Publication Date: 2014-Sep-01
Document File: 4 page(s) / 145K

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The IP.com Prior Art Database

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CRYSTALLINE FORMS OF TETRAHYDROBENZAZEPINE COMPOUNDS

[0001]          The present document discloses crystalline Form I of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride, which is represented by Formula (I):

 (I)

[0002]          Crystalline Form I of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine  hydrochloride (compound I) is characterized by an XRPD pattern having characteristic peaks at 6.1, 10.5, 12.2, 14.6, 16.4, 16.9, 17.3, 17.6, 18.3, 19.4, 20.3, 20.7, 21.1, 21.8, 22.1, 23.8, 24.5, 24.9, 25.9, 26.2, 27.5, 28.9, 30.0, 30.8, 31.3, 31.8, 33.2, 33.5, 34.0 and 34.6º ± 0.2 degrees 2-theta, more characteristic peaks being at 6.1, 12.2, 16.4, 18.3, 19.4, 22.1 and 24.5º ± 0.2 degrees 2-theta, and even more characteristic peaks being at 6.1, 12.2 and 24.5º ± 0.2 degrees 2-theta. Figure 1 illustrates the XRPD pattern of Form I of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (compound I).

[0003]          The present document further discloses crystalline Form I of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, which is represented by Formula (II):

(II)

[0004]          Crystalline Form I of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (compound II) is characterized by an XRPD pattern having characteristic peaks at 8.4, 11.1, 12.8, 15.2, 16.2, 17.8, 18.2, 19.3, 20.7, 21.0, 22.3, 22.6, 23.5, 23.9, 24.6, 25.5, 25.8, 26.1, 26.5, 27.2, 27.6, 28.3, 29.4, 30.1, 30.8, 31.6, 32.7, 33.5 and 34.2º ± 0.2 degrees 2-theta, more characteristic peaks being at 12.8, 17.8, 19.3, 22.3, 23.5, 23.9 and 25.8º ± 0.2 degrees 2-theta, and even more characteristic peaks being at 12.8, 17.8 and 22.3º ± 0.2 degrees 2-theta. Figure 2 illustrates the XRPD pattern of Form I of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (compound II).

[0005]          The N-[2-(4-chlorophenyl)ethyl]-N-(2-chloropropyl)ammonium chloride which is used as starting material in the below experimental example can be prepared for example by the procedure disclosed in Example 2 of US 8,501,935 B2.

General Experimental Conditions:

X-Ray Powder Diffraction (XRPD):

[0006]          The XRPD pattern was recorded on a Siemens D5000 diffractometer equipped with two symmetrically mounted vertical goniometers (Bragg-Brentano geometry) with horizontal sample stages, a X-ray tube, a high voltage generator (working at 45 kV and 35 mA) and standard scintillation detectors. Ni-filtered Cu-anode source was used and diffracted radiation was further monochromatized with a graphite crystal to avoid fluorescence effects [(l(Ka) = 1.54056 Å]. The diffraction pattern was recorded including values of 2θ that range from 2 to 50º with a sampling rate of 0.02º per second and a step time of 1 second per step. The powdered sample was pressed between two glass plates, forming a film. DIFFRAC Plus measurement software with EVA evaluation software (Bruker) was used to record the data and for a primary analysis of the diffraction pattern. The equipment was periodically calibrated using quartz an...