	US 12,459,948 B2
	Processes and intermediates for preparing a Btk inhibitor
Philip James Pye, Bridgewater, NJ (US); Andras Horvath, Turnhout (BE); Laurent Lefort, Zoersel (BE); Bernardus Kaptein, Sittard (NL); Gerardus Karel Maria Verzijl, Well (NL); Yuanyuan Yuan, Changzhou (CN); and Jinxiong Su, Changzhou (CN)
Assigned to Janssen Pharmaceutica NV, Beerse (BE)
Appl. No. 17/612,034
Filed by JANSSEN PHARMACEUTICA NV, Beerse (BE)
PCT Filed May 20, 2020, PCT No. PCT/EP2020/064119 § 371(c)(1), (2) Date Nov. 17, 2021, PCT Pub. No. WO2020/234379, PCT Pub. Date Nov. 26, 2020.
Claims priority of application No. PCT/CN2019/087804 (WO), filed on May 21, 2019.
Prior Publication US 2022/0235058 A1, Jul. 28, 2022
Int. Cl. C07D 211/02 (2006.01); C07D 211/56 (2006.01); C07D 487/04 (2006.01)

CPC C07D 487/04 (2013.01) [C07D 211/56 (2013.01)]

9 Claims

1. A process for preparing a compound of formula (I):

or a pharmaceutically acceptable salt thereof, in an enantioenriched form, wherein:

R¹is hydrogen or a nitrogen protecting group;

* is a chiral centre of an (R) configuration;

and the process comprises reductive hydrazination of a compound of formula (II):

or a salt thereof, with a compound of formula (III):

H₂N—N(H)—R² (III)

or a salt thereof, wherein R²is hydrogen or a nitrogen protecting group to form a compound of formula (IV):

or a salt thereof, followed by, in any order at least one of:

optionally deprotecting R²(when R²is a nitrogen protecting group),

optionally introducing R¹at the NH moiety of the piperidinyl ring (when R¹is a nitrogen protecting group) to form a product, and

optionally resolving the product.