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【结 构 式】

【分子编号】17442

【品名】2-(6-ethynyl-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid

【CA登记号】

【 分 子 式 】C10H14O4

【 分 子 量 】198.21876

【元素组成】C 60.59% H 7.12% O 32.29%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXVIII)

3) The condensation of 3-(trimethylsilyl)propynal (XXIII) with the dialkaline salt of ethylacetoacetate (XXIV) in THF gives 5-hydroxy-3-oxo-7-(trimethylsilyl)-6-heptynoic acid ethyl ester (XXV), which is reduced with NaBH4/diethylmethoxyborane to the racemic 3,5-dihydroxy-7-(trimethylsilyl)-6-heptynoic acid ethyl ester (XXVI). The protection and desilylation of (XXVI) with 2,2-dimethoxypropane and p-toluenesulfonic acid yields the protected heptynoic ester (XXVII), which is saponified to the corresponding acid (XXVIII) with NaOH. The optical resolution of the racemic acid (XXVIII) by treatment with 1(R)-(1-naphthyl)ethylamine (XXIX) and crystallization of the diastereomeric salts affords the protected (3R,5S)-isomer (XXX), which is esterified with ethyl iodide and DBU to the corresponding ester (XXXI). The condensation of (XXXI) with 2-cyclopropyl-4-(4-fluorophenyl)-3-iodoquinoline (XXI, see Scheme 5) by means of disiamylborane, NaOEt and PdCl2 in acetonitrile gives the protected (3R,5S)-NK-104 ethyl ester (XXXII).

1 Castaner, J.; Sorbera, L.A.; Leeson, P.A.; NK-104. Drugs Fut 1998, 23, 8, 847-859.
2 Iwasaki, H.; Miyachi, N.; Yanagawa, Y.; Ohara, Y.; Hiyama, T.; A novel synthetic method of HMG-CoA reductase inhibitor NK-104 via a hydroboration-cross-coupling sequence. Tetrahedron Lett 1993, 34, 51, 8267-70.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXI) 17435 2-cyclopropyl-4-(4-fluorophenyl)-3-iodoquinoline C18H13FIN 详情 详情
(XXIII) 17437 2-butynal C4H4O 详情 详情
(XXIV) 17438 lithium sodium (1E)-1-ethoxy-1,3-butadiene-1,3-diolate C6H8LiNaO3 详情 详情
(XXV) 17439 ethyl 5-hydroxy-3-oxo-7-(trimethylsilyl)-6-heptynoate C12H20O4Si 详情 详情
(XXVI) 17440 ethyl 3,5-dihydroxy-7-(trimethylsilyl)-6-heptynoate C12H22O4Si 详情 详情
(XXVII) 17441 ethyl 2-(6-ethynyl-2,2-dimethyl-1,3-dioxan-4-yl)acetate C12H18O4 详情 详情
(XXVIII) 17442 2-(6-ethynyl-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid C10H14O4 详情 详情
(XXIX) 17443 (1R)-1-(1-naphthyl)ethylamine; (1R)-1-(1-naphthyl)-1-ethanamine 3886-70-2 C12H13N 详情 详情
(XXX) 17444 2-[(4R,6S)-6-ethynyl-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid C10H14O4 详情 详情
(XXXI) 17445 ethyl 2-[(4R,6S)-6-ethynyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate C12H18O4 详情 详情
(XXXII) 17446 ethyl 2-((4R,6S)-6-[(E)-2-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]ethenyl]-2,2-dimethyl-1,3-dioxan-4-yl)acetate C30H32FNO4 详情 详情
Extended Information