US 12,145,910 B2
Method for synthesizing 3-spiro three-membered ring indolinone derivative
Xiaoping Xu, Suzhou (CN); Shunjun Ji, Suzhou (CN); and Ruiying Zhang, Suzhou (CN)
Assigned to SOOCHOW UNIVERSITY, Suzhou (CN)
Appl. No. 17/613,472
Filed by SOOCHOW UNIVERSITY, Suzhou (CN)
PCT Filed Oct. 26, 2020, PCT No. PCT/CN2020/123620
§ 371(c)(1), (2) Date Nov. 22, 2021,
PCT Pub. No. WO2022/082817, PCT Pub. Date Apr. 28, 2022.
Claims priority of application No. 202011125496.7 (CN), filed on Oct. 20, 2020.
Prior Publication US 2022/0315533 A1, Oct. 6, 2022
Int. Cl. C07D 209/96 (2006.01)
CPC C07D 209/96 (2013.01) 10 Claims
 
1. A method for synthesizing a 3-spiro three-membered ring indolinone derivative, comprising steps of:
under a protective atmosphere, reacting a compound of formula (I) or formula (III) at 20-60° C. in the presence of an additive and an organic base in an organic solvent, to obtain a compound of formula (II) or formula (IV) after the reaction is complete, wherein the additive is N-bromosuccinimide (NBS) or N-chlorosuccinimide (NCS); and
the reaction routes are as follows, wherein the formula (I) is exclusive of the formula (III):

OG Complex Work Unit Chemistry
wherein in formulas (I)-(IV), R1 is selected from hydrogen, C1-C4 alkyl or halo; R2 is hydrogen, C1-C4 alkyl, benzyl or phenyl; Ar is selected from phenyl, substituted phenyl or thienyl, in which the substituent on the substituted phenyl is selected from the group consisting of halo, C1-C4 alkyl, C1-C4 alkoxy or any combination thereof; and X is chloro or bromo.