SL-65.0155, SL-650155

5-(8-氨基-7-氯-2,3-二氢-1,4-苯并二恶烷-5-基)-3-[1-(2-苯基乙基)哌啶-4-基]-1,3,4-恶二唑-2(3H)-酮盐酸盐Chemical Name: 5-(8-Amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-[1-(2-phenylethyl)piperidin-4-yl]-1,3,4-oxadiazol-2(3H)-one hydrochloride
CAS No. 191023-43-5
项目整合开发状态: Phase II
项目研究机构: Sanofi-Aventis (Originator)
合成路线:4-Amino-benzodioxan-1-carboxylic acid (I) is esterified to (II) employing SOCl2 in EtOH.Subsequent chlorination of benzodioxan (II) with N-chlorosuccinimide furnishes (III).The ethyl ester group of (III) is then displaced by hydrazine hydrate to produce the corresponding hydrazide (IV).Cyclization of hydrazide (IV) with phosgene,followed by quenching with benzyl alcohol leads to the oxadiazole derivative (V).This is then coupled with N-Boc-4-piperidinol (VI) under Mitsunobu conditions to yield the piperidinyl oxadiazole (VII).Selective cleavage of the N-Boc protecting group of (VII) by means of trifluoroacetic acid in CH2Cl2 gives rise to piperidine (VIII).

合成路线:Piperidine (VIII) is alkylated with phenethyl bromide (IX) to furnish (X).The benzyloxycarbonyl protecting group of (X) is finally removed by treatment with HBr in AcOH to provide the title compound.