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Solid state forms of N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4- pyrimidinyl]-N'-propylsulfamide

IP.com Disclosure Number: IPCOM000236886D
Publication Date: 2014-May-21
Document File: 6 page(s) / 128K

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Solid state forms of N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4- pyrimidinyl]-N'-propylsulfamide 

     N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'- propylsulfamide referred to as Compound I, has the following chemical structure:

 

   

Provided are amorphous and crystalline forms of Compound I.

    Samples of amorphous Compound I were prepared by the processes described in examples 1-3, and were analyzed by X-ray powder diffraction ("XRPD") to provide amorphous form of Compound I. Figure 1 presents the XRPD of the amorphous form.

Figure 1: XRPD of amorphous Compound I 

    Samples of form A of Compound I were prepared by the processes described in examples 4-11, and were analyzed by X-ray powder diffraction ("XRPD") to provide crystalline form A of Compound I. Figure 2 presents the XRPD of form A.


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Figure 2: XRPD of form A of Compound I 

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According to figure 2, form A of Compound I is characterized by XRPD peaks at: 6.3, 8.4,
10.7, 12.2, 17.8, 19.0, 21.2, 21.7, 22.5 and 25.0°2theta ± 0.2 °2theta.

    Samples of form B of Compound I were prepared by the process described in example 12, and were analyzed by X-ray powder diffraction ("XRPD") to provide crystalline form B of Compound I. Figure 3 presents the XRPD of form B.

Figure 3: XRPD of form B of Compound I 

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According to figure 3, form B of Compound I is characterized by XRPD peaks at: 6.6, 8.5,
10.7, 12.3, 13.1, 14.2, 16.7, 18.9, 19.4, 22.5 and 26.3 °2theta ± 0.2 °2theta.

XRPD method:

    After being powdered in a mortar and pestle, the samples were applied directly on a silicon plate holder. The X-ray powder diffraction pattern was measured with Philips X'Pert PRO X-ray powder diffractometer, equipped with Cu irradiation source of 1.54184 Ǻ (Ǻngström) and X'Celerator (2.022º 2θ) detector. Scanning parameters: range: 3-40 degrees two-theta; step size: 0.0167 degrees; time per step: 37 sec.; scan mode: continuous scan.

Example 1: Preparation of amorphous form of Compound I

N-5-(4-bromophenyl)-6-(2-hydroxyethoxy)-4-pyrimidinyl)-N'-propylsulfamide (10.8 g, 25 mM) was dissolved in the mixture of THF (100 ml) and DMF (100 ml).

Lithium amide (1.73 g, 75 mM) was added while stirring at room temperature under nitrogen, and the mixture was stirred for 10 min. 5-bromo-2-chloropyrimidine (7.25 g; 37.5 mM) was added to it and stirred at reflux temperature (70 - 74 °C) for 8 h. The mixture was then diluted with water (300 ml), washed with n-heptane (2x100 ml), treated with charcoal (1.1 g) and the solution was acidified with addition of the mixture of water (200 ml) and acetic acid (7.5 ml) while stirring. A gummy precipitate was formed which solidified upon standing in a refrigerator at 2-8 °C overnight. The solid was collected by filtration...