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【结 构 式】

【药物名称】LY-341122

【化学名称】2,6-Di-tert-butyl-4-[4-[2-[4-(N-ethyl-N-methylaminomethyl) phenoxy]ethyl]oxazol-2-yl]phenol

【CA登记号】

【 分 子 式 】C29H40N2O3

【 分 子 量 】464.65375

【开发单位】Lilly

【药理作用】NEUROLOGIC DRUGS, TREATMENT OF CEREBROVASCULAR DISEASES

合成路线1

3,5-Di-tert-butyl-4-hydroxybenzoic acid (I) was converted to amide (III) via activation as the acyl imidazole (II) followed by treatment with aqueous ammonia. Subsequent condensation of (III) with ethyl 4-chloroacetoacetate (IV) produced oxazole (V). Basic hydrolysis of the ethyl ester of (V) yielded carboxylic acid (VI), which was reduced to alcohol (VII) with borane in THF. Treatment of (VII) with methanesulfonyl chloride and triethylamine generated mesylate (VIII). This was coupled with 4-hydroxybenzaldehyde (IX), yielding ether (X). Finally, reductive condensation of (X) with ethyl methylamine in the presence of NaBH3CN furnished the corresponding tertiary amine.

1 Heinz, L.J.; Panetta, J.A.; Phillips, M.L.; Shadle, J.K. (Eli Lilly and Company); Novel cpds. useful as neuro-protective agents. EP 0971709; WO 9815274 .
2 Shannon, H.E.; Panetta, J.A. (Eli Lilly and Company); Method for treating pain. WO 9909980 .
3 Shannon, H.E.; Panetta, J.A. (Eli Lilly and Company); Method for treating neuropathic pain. WO 9909979 .
4 Heinz, L.J.; Panetta, J.A.; Phillips, M.L.; Rieck, J.A.; Rizzo, J.R.; Shadle, J.K.; Varie, D.L.; Anderson, B.A. (Eli Lilly and Company); Oxazoles, thiazoles, oxazolines, oxadiazoles and benzoxazoles useful as neuro-protective agents. EP 0908454; WO 9918091 .
5 Panetta, J.A.; Shannon, H.E. (Eli Lilly and Company); Method for treating pain. WO 9909829 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
40588 N-methyl-1-ethanamine; N-ethyl-N-methylamine 624-78-2 C3H9N 详情 详情
(I) 19980 3,5-di(tert-butyl)-4-hydroxybenzoic acid 1421-49-4 C15H22O3 详情 详情
(II) 35204 [3,5-di(tert-butyl)-4-hydroxyphenyl](1H-imidazol-1-yl)methanone C18H24N2O2 详情 详情
(III) 35205 3,5-di(tert-butyl)-4-hydroxybenzamide C15H23NO2 详情 详情
(IV) 23541 ethyl 4-chloro-3-oxobutanoate;Ethyl 4-chloro-3-oxobutanoate;Ethyl 4-chloroacetoacetate 638-07-3 C6H9ClO3 详情 详情
(V) 35206 ethyl 2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]acetate C21H29NO4 详情 详情
(VI) 35207 2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]acetic acid C19H25NO4 详情 详情
(VII) 35208 2,6-di(tert-butyl)-4-[4-(2-hydroxyethyl)-1,3-oxazol-2-yl]phenol C19H27NO3 详情 详情
(VIII) 35209 2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]ethyl methanesulfonate C20H29NO5S 详情 详情
(IX) 13433 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde 123-08-0 C7H6O2 详情 详情
(X) 35210 4-(2-[2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]ethoxy)benzaldehyde C26H31NO4 详情 详情
Extended Information