Polymorph of an intermediate for palbociclib synthesis
The present disclosure provides a novel polymorph of an intermediate useful in the preparation of palbociclib. The polymorph has enhanced properties that influence process ability of the intermediate and synthesis of palbociclib.
1. Crystalline Form M of a compound of Formula-2
characterized by a powder X-ray diffraction pattern having peaks at 6.0 and 8.7±0.2°2θ.
2. The crystalline Form M of Formula-2 as in claim 1 further characterized by a powder X-ray diffraction pattern having peaks at 6.0, 6.3, 8.7, 12.0, 15.3, 19.1, and 22.6±0.2°2θ.
3. The crystalline Form M of Formula-2 as in claim 1 , further characterized by the powder X-ray diffraction pattern of in FIG. 1 .
4. A process for the preparation of crystalline Form M of Formula-2, as in claim 1 , comprising the steps of:
a) dissolving a compound of Formula-2 in a solvent selected from the group consisting of alcohols, tetrahydrofuran, and mixtures thereof to form a reaction mixture;
b) heating the reaction mixture;
c) optionally adding a seed of Form M of Formula-2;
d) slowly cooling the reaction mixture; and
3 ) isolating crystalline Form M of Formula-2.
5. The process of claim 4 , wherein the alcohol is selected from the group consisting of methanol, ethanol, isopropanol, and mixtures thereof.
6. The process of claim 4 , wherein the reaction mixture is heated to 110° C. in the heating step and wherein the reaction mixture is cooled to 15° C. in the cooling step.
7. Crystalline Form M of Formula-2 prepared according to the process pf claim 4 , further having a purity of 99.0%.