GS-7340

替诺福韦艾拉酚胺 替诺福韦艾拉酚胺富马酸盐 Chemical Name: N-[[S(P)]-[2-(Adenin-9-yl)-1(R)-methylethoxymethyl](phenoxy)phosphoryl]-L-alanine isopropyl ester
CAS No. 379270-37-8, 379270-38-9 (fumarate)
项目整合开发状态: Discontinued
项目研究机构: Gilead (Originator)
合成路线:Alkylation of adenine (I) by means of (R)-propylene carbonate (II) in the presence of NaOH in hot DMF provided (R)-9-(2-hydroxypropyl)adenine (III).This was condensed with tosylate (IV) using magnesium tert-butoxide to furnish the alkoxymethylphosphonate (V).Phosphonic acid (VI) was then obtained by hydrolysis of the phosphate ester groups with bromotrimethylsilane.Monophenyl phosphonate (IX) was prepared by either coupling of acid (VI) with phenol (VII) in the presence of DCC or by previous activation of (VI) with SOCl2,and then coupling with phenoxytrimethylsilane (VIII).Further activation of (IX) with SOCl2 to give (X),followed by its condensation with L-alanine isopropyl ester (XI),yielded phosphonamide (XII) as a mixture of diastereomers.The title isomer was then isolated by several alternative procedures,including column chromatography over various supports and fractional crystallization.