Browse Prior Art Database

Amorphous tert-butyl (S)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1- yl)piperidine-1-carboxylate

IP.com Disclosure Number: IPCOM000237097D
Publication Date: 2014-Jun-02
Document File: 2 page(s) / 32K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 84% of the total text.

Page 01 of 2

 

Amorphous tert-butyl (S)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1- yl)piperidine-1-carboxylate

     Provided herein is a process for preparing amorphous tert-butyl (S)-3-(4-amino-3-(4- phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate, referred herein as Compound I. The process is described in Example 1.

Compound I may be used for preparing (S)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-
d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.

Example 1: A process for preparing amorphous tert-butyl (S)-3-(4-amino-3-(4-phenoxyphenyl)-1H- pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate

    Into 250ml reactor were loaded under stream of nitrogen: (4-phenoxyphenyl)boronic acid
(14.45g), tert-butyl (S)-3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1- carboxylate (10g) , K2CO3 (9.33g) and DMF (100ml). The mixture was degassed for 10 min then heated to 150 C and stirred for 3h. The reaction was cooled to 80 C followed by addition of EtOAc (100ml) and filtered on Hyflo. The cake was washed with hot EtOAc (80 ml) and the filtrate was extracted with water and brine. The concentrated residue was purified by column chromatography (EtOAc/Hexane) to obtain 5.75g of a solid, which was analyzed by XRPD and found to be amorphous as shown in Figure 1.

X-ray powder diffraction method (XRPD) method:

    The analysis was performed on ARL (SCINTAG) powder X-Ray diffractometer model X'TRA equipped with a solid state detector....