POLYMORPHS OF ETV AND PROCESSES FOR PREPARATION THEREOF

POLYMORPHS OF ETV

AND PROCESSES FOR PREPARATION THEREOF

    4-(6-amino-5-bromo-2-(4-cyanophenylamino)pyrimidin-4-yloxy)-3,5- dimethylbenzonitrile (referred as ETV) of the following chemical structure:

is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) used for the treatment of patients with HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTI's.

Crystalline forms of ETV are described herein below.

Crystalline ETV form C

    The crystalline form, designated form C, is characterized by data selected from a group consisting of at least one of: powder XRD pattern having peaks at about
8.4, 12.8, 20.4 and 25.3 ± 0.2 degrees two-theta; a PXRD pattern depicted in Figure 1; and any combination thereof.

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Figure 1: A PXRD pattern of crystalline ETV form C

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    The above crystalline form C can be further characterized by data selected from the group consisting of: a powder XRD pattern with peaks at about 8.8, 11.4,
16.8 and 22.5 ± 0.2 degrees 2-theta, and a DSC curve characterized by two thermal events; first endoterm with maxima at about 164 °C, and the second one at about 263 °C corresponding the melting that takes place parallel with degradation process as shown in Figure 2; a DSC thermogram as depicted in Figure 2; and combination thereof.

Figure 2: A DSC thermogram of crystalline ETV form C

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Crystalline ETV form F

    The crystalline form, designated form F, is characterized by data selected from a group consisting of at least one of: powder XRD pattern having peaks at about 9.2,
16.2, 18.4 and 22.0 ± 0.2 degrees two-theta; a PXRD pattern depicted in Figure 3; and any combination thereof.

Figure 3: A PXRD pattern of crystalline ETV form F

    The above crystalline form can be further characterized by data selected from the group consisting of: a powder XRD pattern with peaks at about 8.8, 13.5, 19.4 and
23.5± 0.2 degrees 2-theta, and a DSC curve characterized by a thermal event at about 258 °C corresponding the melting that takes place parallel to degradation process of ETV as shown in Figure 4; a DSC thermogram as depicted in Figure 4; and combination thereof.

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Figure 4: A DSC thermogram of crystalline ETV form F

Crystalline ETV form I

    The crystalline form, designated form I, is characterized by data selected from a group consisting of at least one of: powder XRD pattern having peaks at about 7.4,
12.5, 17.1 and 29.2 ± 0.2 degrees two-theta; a PXRD pattern depicted in Figure 5; and any combination thereof.

Figure 5: A PXRD pattern of crystalline ETV form I

    The above crystalline form can be further chara...