title: Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction.
abstract: An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.
authors.affiliation: Incyte Corporation, Experimental Station, Route 141 and Henry Clay Road, Wilmington, Delaware 19880, USA. qlin@incyte.com
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Meloni
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Pan
authors.forename: Michael
authors.initials: M
authors.lastname: Xia
authors.forename: James
authors.initials: J
authors.lastname: Rodgers
authors.forename: Stacey
authors.initials: S
authors.lastname: Shepard
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Laurine
authors.initials: L
authors.lastname: Galya
authors.forename: Brian
authors.initials: B
authors.lastname: Metcalf
authors.forename: Tai-Yuen
authors.initials: TY
authors.lastname: Yue
authors.forename: Pingli
authors.initials: P
authors.lastname: Liu
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Zhou
mesh_terms: D001565:Benzoates / Q000737:chemistry; D002384:Catalysis; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009570:Nitriles; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines; D013237:Stereoisomerism
chemical_list: D001565:Benzoates; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases