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Crystalline forms of 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide and salts thereof

IP.com Disclosure Number: IPCOM000234712D
Publication Date: 2014-Jan-30
Document File: 4 page(s) / 98K

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The IP.com Prior Art Database

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Crystalline forms of 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-

tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide and salts thereof

Disclosed herein after is crystalline Form G of 6-(4-aminophenyl)-1-(4- methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3- carboxamide ("compound I").

Figure 1: a powder XRD pattern of crystalline Form G of compound I:

Sample ID: Analyst:Ayelet sg, Sample name: APX KG-418 7d 100%RH , Temp: 25.0°C Date: 05/19/13 11:00 Step : 0.050° Integration Time: 1.000 sec

Date: 05/16/13 14:13 Step : 0.050° Integration Time: 1.000 sec

Vert. Scale Unit: [CPS]

Range: 2.000 - 40.000° Cont. Scan Rate: 3.000 [°/min]

Horz. Scale Unit: [deg]

6000

4000

2000

0


2.0


6.0


10.0


14.0


18.0


22.0


26.0


30.0


34.0


38.0

degrees 2-theta

Main XRD peaks of crystalline Form G of compound I are: 6.0, 7.5, 8.4, 9.4,


9.7, 10.3, 10.7, 11.3, 12.9, 14.2, 14.8, 16.3, 16.9, 17.7, 18.5, 18.9, 19.4, 19.9,


20.5, 21.3, 22.6, 23.7, 24.3, 24.8, 25.6, 26.3, 26.6, 27.0, 27.7, 28.5, 28.9, 29.6,


30.2, 30.7, 30.2, 30.7, 31.0, 32.3, 32.9, 33.8, 34.3, 35.0, 37.3 and 37.9 ± 0.2 degrees 2-theta.

X-Ray Power Diffraction:

The analysis was performed on ARL (SCINTAG) powder X-Ray diffractometer model X'TRA equipped with a solid state detector. Copper radiation of 1.5418 Å was used. Scanning parameters: range: 2-40 degrees two-theta; scan mode: continuous scan; step size: 0.05°.; and a rate of 3 deg/min.

Example:


10 L SS reactor was charged with solution of ethyl 6-(4-aminophenyl)-1-(4- methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3- carboxylate in 4200 ml MeOH (15V), the mixture was stirred and bubbled with


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ammonia (saturated solution of 13.5% ammonia was obtained by titration). The yellow slurry was heated to 75oC and stirred over night. The reaction mixture was then cooled down to 25oC, washed with N2, and HPLC monitoring was tested. N2 was bubbled into the mixture and the crude mixture was cooled to


1.3oC over night. Then, the mixture was cooled to -7.7oC for few hours, and the product was filtrated and washed with additional 3V of cold MeOH. The yellow product was dried at the oven under reduced pressure at 50oC over night. The resulting product was analyzed by XRPD to give a pattern of crystalline Form E of compound I.

A sample of Form E of compound I was exposed to 100% RH in RT for 7 days. The sample was analyzed by XRD to give crystalline Form G of compound I.

Disclosed herein after is crystalline Form H of compound I

Figure 2: a powder XRD pattern of crystalline Form H of compound I:

Sample ID: Analyst: Ayelet sg, Sample name: APX GP-6630-1, Temp: 25.0°C Date: 11/27/13 12:12 Step : 0.050° Integration Time: 1.000 sec
Range: 2.000 - 40.000° Cont. Scan Rate: 3.000 [°/min] Date: 05/20/13 17:24 Step : 0.050° Integration Time: 1.000 sec
10.0 14.0 18.0 22.0 26.0 30.0 34.0 38.0

degrees 2-theta

Main XRD peaks of crystalline Form H of compound I are: 5.2, 6.0, 7.8, 8.6,


9.1, 9.7, 10.6, 11.9,...