Z-203, T-0632

盐(S)-1-(2-氟苯基)-3-(3-异喹啉基碳杂草酰氨基)-6-甲氧基-2-羰基-1H-吲哚-3-丙酸钠Chemical Name: (S)-1-(2-Fluorophenyl)-3-(3-isoquinolinylcarboxamido)-6-methoxy-2-oxo-1H-indole-3-propionic acid sodium salt
CAS No. 169042-78-8
项目整合开发状态: Phase I
项目研究机构: Tanabe Seiyaku (Originator), Zeria (Licensee)
合成路线:The condensation of 3-amino-1-(2-fluorophenyl)-6-methoxyindolin-2-one (I) with isoquinolin-3-ylcarbonyl chloride (II) by means of NaHCO3 in chloroform/dichloromethane/water gives the corresponding amide (III),which is condensed with methyl acrylate (IV) by means of K2CO3 in acetone to yield the propionic ester derivative (V).Finally,the ester group of (V) is hydrolyzed with NaOH in ethanol to afford the target propionic acid derivative as a racemic compound.

合成路线:The condensation of 3-amino-1-(2-fluorophenyl)-6-methoxyindolin-2-one (I) with acrylonitrile (II) by means of K2CO3 in DMSO gives the propionitrile derivative (III),which was submitted to optical resolution with (+)-dibenzoyl tartaric acid to yield enantiomer (IV).The condensation of (IV) with isoquinoline-3-carboxylic acid (V) by means of DEC and HOBt in DMF affords the carboxamide (VI),which is treated with HCl in methanol to provide the propionic ester (VII).Finally,this compound is hydrolyzed with NaOH in methanol/water to furnish the target sodium propionate derivative as a pure enantiomer.