Synthesis of KIF18A inhibitor

The present invention relates to an improved preparation of a KIF18A inhibitor having the following chemical structure: Compound (1) # imgabs0 # or a salt thereof: Compound 1a # imgabs1 # wherein HA is as defined herein; and a key intermediate thereof having the following formula: Compound (2a), Compound (3a), Compound (5) or a salt thereof, and Compound (6a) or a hydrate thereof: Compound (2a) # imgabs2 compound (3a) # imgabs3 compound (5) # imgabs4 compound or a salt thereof; and Compound (6a) # imgabs5 # or a hydrate thereof, preferably Compound (6a-1) # imgabs6 #. The invention further relates to a solid form of Compound (6a), preferably a crystalline hydrate form of Compound (6a-1). 本发明涉及具有以下化学结构的KIF18A抑制剂的改进的制备：化合物(1)#imgabs0#或其盐，即化合物1a#imgabs1#其中HA如本文所定义；以及其具有下式的关键中间体，即化合物(2a)、化合物(3a)、化合物(5)或其盐以及化合物(6a)或其水合物：化合物(2a)#imgabs2#化合物(3a)#imgabs3#化合物(5)#imgabs4#或其盐；和化合物(6a)#imgabs5#或其水合物，优选地化合物(6a-1)#imgabs6#本发明进一步涉及化合物(6a)的固体形式，优选地化合物(6a-1)的结晶水合物形式。