US 11,858,928 B2
Process for making palbociclib
Petr Mitas, Blansko (CZ); and Oldrich Smekal, Blansko (CZ)
Assigned to Synthon B.V., Nijmegen (NL)
Appl. No. 17/057,425
Filed by SYNTHON B.V., Nijmegen (NL)
PCT Filed May 21, 2019, PCT No. PCT/EP2019/063085
§ 371(c)(1), (2) Date Nov. 20, 2020,
PCT Pub. No. WO2019/224194, PCT Pub. Date Nov. 28, 2019.
Claims priority of application No. 18174119 (EP), filed on May 24, 2018.
Prior Publication US 2021/0206761 A1, Jul. 8, 2021
Int. Cl. C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) 22 Claims
 
1. A process for the preparation of a compound of formula (1) or a salt thereof,

OG Complex Work Unit Chemistry
the process comprising:
(a) reacting compound of formula (3) and compound of formula (4) to provide compound of formula (2),

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
in a solvent mixture comprising methanol and butanol;
(b) adding water;
(c) isolating solid crystalline form of compound of formula (2) characterized by XRPD pattern having 2θ values 5.5°, 7.5°, 9.7°, 10.1°, 14.5°, 15.9°, 18.1°, 20.2° and 21.5° degrees 2 theta (±0.2 degrees 2 theta); and
(d) transforming the compound of formula (2) into the compound of formula (1).