Ontazolast, BIRM-270, BI-RM-270

昂唑司特Chemical Name: N-[2-Cyclohexyl-1(S)-(2-pyridyl)ethyl]-5-methylbenzoxazol-2-amine
CAS No. 147432-77-7
项目整合开发状态: Phase II
项目研究机构: Boehringer Ingelheim (Originator)
合成路线:The required chiral auxiliary hydroxyketone (II) was prepared from (S)-alpha-pinene (I) either by dihydroxylation with K2OsO4 and NMO,followed by Swern oxidation of the secondary alcohol,or by direct oxidation using KMnO4 under phase-transfer conditions.Condensation of (II) with 2-(aminomethyl)pyridine (III) in the presence of titanium isopropoxide or thionyl chloride as the dehydrating reagents provided the chiral imine (IV),which was estereoselectively alkylated with cyclohexylmethyl bromide (V) and n-BuLi,yielding (VI).Cleavage of the chiral auxiliary of (VI) was carried out by treatment with hydroxylamine hydrochloride.Enantiomeric enrichment of the resulting (S)-pyridylamine was achieved by recrystallization of the corresponding L-tartrate salt (VII).Finally,the amine was condensed with chlorobenzoxazole (VIII) in the presence of NaOAc and Na2CO3 in refluxing methylcyclohexane.