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CRYSTALLINE FORMS OF A 4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3,4-c]PYRIDINE DERIVATIVE

IP.com Disclosure Number: IPCOM000243579D
Publication Date: 2015-Oct-02
Document File: 5 page(s) / 178K

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             CRYSTALLINE FORMS OF A 4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3,4-c]PYRIDINE DERIVATIVE

Ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4- c]pyridine-3-carboxylate, compound (I), has the following chemical structure:


(I)

The present document discloses two new crystalline forms of ethyl 1-(4-methoxyphenyl) -7-oxo-6-[4- (2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate.

Crystalline form X of ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7- tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate is characterized by a DSC pattern having a sharp endothermic peak at 111ºC as shown in Figure 1 and an IR spectra as shown in Figure 2.

Crystalline form X of ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7- tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate is also characterized by an XRPD pattern having characteristics peaks at 5.5, 7.3, 7.9, 11.1, 11.5, 12.3, 12.7, 15.9, 16.3, 16.6, 17.2, 17.9, 18.6, 22.5,
23.7, 24.1, 26.1, 26.4, 26.7 and 30.2 ± 0.2º 2-theta, a powder XRD pattern substantially as depicted in Figure 3, or a combination thereof.

Crystalline form Y of ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7- tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate is characterized by DSC having a sharp endothermic peak at 164ºC as shown in Figure 4 and an IR spectra as shown in Figure 5.

Crystalline form Y of ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7- tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate is also characterized by an XRPD pattern having characteristics peaks at 6.1, 9.8, 11.9, 13.4, 14.2, 15.1, 16.2, 17.3, 18.3, 18.9, 19.3, 19.5, 19.8, 20.1,
20.7, 21.6, 23.9, 25.3, 25.8, 26, 26.6, 26.9, 27.2, 27.5 and 28.6 ± 0.2º 2-theta, a powder XRD pattern substantially as depicted in Figure 6, or a combination thereof.

Experimental Conditions

The DSC thermogram was done on a Mettler Toledo differential scanner calorimeter at a heating rate of 10ºC/min. The IR spectrum was recorded on a Perkin Elmer spectrophotometer using the attenuated total reflectance (ATR) technique. Powder diffraction patterns were acquired using a

1


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PANalytical, X'Pert diffractometer using CuKalpha-radiation. The system configured in theta-theta, transmission geometry and equipped with a focusing X-ray mirror and divergence (0.5º), anti-scatter
(0.5º) and soller (0.02 rad) slits. The PIXcel detector was equipped with anti-scatter (0.5º) and soller
(0.02 rad) slits. Approximately 10-20 mg of sample was mounted between two layers of cellophane film using standard sample holders for a spinning reflection/transmission sample platform. Data was collected using X´Pert Data Collector (version 2.2g).

Example 1: Synthesis of crystalline form X of ethyl 1-(4-methoxyphenyl)-7-oxo-6-[4- (2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3- carboxylat...