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【结 构 式】

【药物名称】Ontazolast, BIRM-270, BI-RM-270

【化学名称】N-[2-Cyclohexyl-1(S)-(2-pyridyl)ethyl]-5-methylbenzoxazol-2-amine

【CA登记号】147432-77-7

【 分 子 式 】C21H25N3O

【 分 子 量 】335.4529

【开发单位】Boehringer Ingelheim (Originator)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Leukotriene Synthesis Inhibitors

合成路线1

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.

1 Roth, G.P.; et al.; Optimization and scale-up of an asymetric route to the LTB4 inhibitor ontazolast. Org Process Res Dev 1997, 1, 5, 331.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 16643 Poly-alpha-pinene; (1S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene 7785-26-4 C10H16 详情 详情
(II) 31762 (1S,2R,5S)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]heptan-3-one C10H16O2 详情 详情
(III) 13582 2-Pyridinylmethanamine; 2-Pyridinylmethylamine; 2-(Aminomethyl)pyridine 3731-51-9 C6H8N2 详情 详情
(IV) 31763 (1S,2R,5S)-2,6,6-trimethyl-3-[(2-pyridinylmethyl)imino]bicyclo[3.1.1]heptan-2-ol C16H22N2O 详情 详情
(V) 31767 1-(bromomethyl)cyclohexane 2550-36-9 C7H13Br 详情 详情
(VI) 31764 (1S,2R,5S)-3-[[(1S)-2-cyclohexyl-1-(2-pyridinyl)ethyl]imino]-2,6,6-trimethylbicyclo[3.1.1]heptan-2-ol C23H34N2O 详情 详情
(VII) 31765 (1S)-2-cyclohexyl-1-(2-pyridinyl)ethylamine; (1S)-2-cyclohexyl-1-(2-pyridinyl)-1-ethanamine C13H20N2 详情 详情
(VIII) 31766 2-chloro-5-methyl-1,3-benzoxazole C8H6ClNO 详情 详情
Extended Information