Browse Prior Art Database

A Process for Preparing and crystallizing 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide

IP.com Disclosure Number: IPCOM000223798D
Publication Date: 2012-Nov-29
Document File: 4 page(s) / 92K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 52% of the total text.

A Process for Preparing and crystallizing 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide

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

Provided is a process for preparing and crystallizing its intermediate: 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide.

6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide

1 L glass reactor was charged with the ethyl 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (30 g) in 480 ml MeOH. Ammonia was bubbled to the mixture for 3 h. The yellow slurry was mixed and heated to 74oC during 1 h. The reaction was mixed over night under these conditions, (18.5 h total). Orange clear solution was obtained. Then, the reaction mixture was cooled down to 25oC, the reactor was washed with N2, and HPLC monitoring was tested. The slurry was concentrated to 150 ml of solvent and the solid was filtrated and washed with additional 2V of MeOH. The product was dried at the oven under reduced pressure at 50 oC over night. The resulting product was analyzed by XRPD to give a pattern of 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide crystalline Form C.

The XRPD pattern is presented in the following representative X-ray diffractogram:

Main XRD peaks of 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4- c]pyridine-3-carboxamide form C are: 6.7, 7.8, 8.3, 9.6, 10.5, 11.2, 11.7, 12.1, 12.6, 13.7, 14.4, 14.7, 15.1, 15.7, 17.2, 17.8, 18.4, 19.0, 19.9, 20.6, 21.1, 21.7, 22.7, 23.6, 24.4, 25.0, 25.8, 26.3, 27.1, 27.4, 28.4, 29.0, 29.4, 30.2, 31.4, 32.1, 33.4, 33.9, 34.2, 34.8, 35.5, 37.0 and 38.6 ± 0.2 degrees 2-theta.

6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide

1 L glass reactor was charged with the ethyl 6-(4-aminophenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (20 g) in 480 ml MeOH and 20 ml NMP. Ammonia was bubbled into the mixture for 3 h. The yellow slurry was mixed and heated to 74oC during 1 h. The reaction was mixed over night under these conditions, (18.5 h total). Orange clear solution was obtained. Then, the reaction mixture was cooled down to 25oC, the reactor was washed with N2, and HPLC monitoring was tested. The slurry was concentrated to 100 ml of solvents and the solid was filtrated and washed with additional 40 ml of MeOH. The product was dried at the oven u...