AG-13736, AG-013736

阿西替尼Chemical Name: N-Methyl-2-[3-[2-(2-pyridyl)vinyl]-1H-indazol-6-ylsulfanyl]benzamide
CAS No. 319460-85-0
项目整合开发状态: Phase I
项目研究机构: Agouron (Originator)
合成路线:6-Nitroindazole (I) is iodinated to (II) employing iodine in the presence of NaOH.Subsequent reaction of 3-iodo-6-nitroindazole (II) with 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) under phase-transfer conditions furnishes the N-protected indazole (III).Suzuki coupling of iodoindazole (III) with styrylboronic acid gives rise to the styryl indazole (IV).The nitro group of (IV) is then reduced employing SnCl2 to produce amine (V).This is converted to the iodoindazole (VI) via diazotization,followed by reaction with KI.Ozonization of the styryl moiety of (VI) leads to aldehyde (VII).This is then subjected to Wittig reaction with 2-picolyltriphenylphosphonium chloride (VIII) to produce (IX).

合成路线:Displacement of iodoindazole (IX) with methyl 2-sulfanylbenzoate (X) in the presence of Cs2CO3 and Pd catalyst leads to thioether (XI).After alkaline hydrolysis of the methyl ester group of (XI),the resultant carboxylic acid (XII) is coupled to methylamine in the presence of HATU to furnish amide (XIII).Finally,removal of the SEM protecting group employing tetrabutylammonium fluoride and ethylenediamine yields the title compound.