LY-382924

Chemical Name: 2,6-Di-tert-butyl-4-[4-[4-[2-(N-ethyl-N-methylamino)ethyl]phenoxymethyl]oxazol-2-yl]phenol hydrochloride; 2-(3,5-Di-tert-butyl-4-hydroxyphenyl)-4-[4-[2-(N-ethyl-N-methylamino)ethyl]phenoxymethyl]oxazole hydrochloride
CAS No. 206122-67-0, 206122-66-9 (mono HCl salt)
项目整合开发状态: Preclinical
项目研究机构: Lilly (Originator)
合成路线:1) The N-acylation of DL-serine (I) with 3,5-di-tert-butyl-4-hydroxybenzoic acid by means of carbonyldiimidazole (CDI) in THF gives the acylated serine (III),which is cyclized by means of CBr4/triphenylphosphine/imidazole in acetonitrile to yields the oxazoline (IV).The dehydrogenation of (IV) with activated MnO2 in acetone affords 2-(3,5-di-tert-butyl-4-hydroxyphenyl)oxazole-4-carboxylic acid methyl ester (V),which is reduced with LiBH4 in THF/methanol giving the oxazolylmethnaol (VI).The reaction of (VI) with Br2/triphenylphosphine in acetonitrile yields the bromomethyl derivtive (VII),which is condensed with N-ethyl-N-[2-(4-hydroxyphenyl)ethyl]formamide (VIII) by means of NaH in THF to afford the formylated precursor (IX).Finally,this compound is converted into LY-382924 by reduction of the formyl group with AlH3 (LiAlH4/H2SO4) in THF and treatmnt with HCl gas in CHCl3.2) The intermediate N-ethyl-N-[2-(4-hydroxyphenyl)ethyl]formamide (VIII) has been obtained as follows: The acylation of 2-(4-hydroxyphenyl)ethylamine (X) with acetic anhydride gives the acetamide (XI),which is reduced with LiAlH4 to the secondary amine (XII).Finally,this amine is formylated with formic acid and carbonyldiimidazole (CDI) in THF.