CGP-68730A

Chemical Name: 2-[9-Bromo-5,6-dioxo-2,3,6,7-tetrahydro-5H-[1,4]thiazino[4,3,2-de]quinoxalin-3(R)-yl]acetic acid sodium salt
CAS No. 177537-85-8 (free acid), 177537-84-7 (free acid, (S)-isomer), 177537-39-2 (free acid, undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator)
合成路线:Benzothiazin (III) was prepared by condensation of 2-aminothiophenol (I) with ethyl 4-bromoacetoacetate (II).Subsequent reduction of (III) with NaBH3CN provided (IV),which was brominated using N-bromosuccinimide to afford (V).This was coupled with ethyl oxalyl chloride to give amide (VI).Nitration of (VI) was then performed with HNO3 in H2SO4 at -10 C.Further reduction of the nitro group of (VII) with concomitant cyclization produced the tricyclic compound (VIII).After resolution by chiral preparative HPLC,the required (R)-enantiomer was hydrolyzed with NaOH to afford carboxylic acid (IX).This compound was finally isolated as the sodium salt upon treatment with aqueous NaHCO3,followed by lyophilization.