Salcaprozic acid sodium salt, E414(free acid), SNAC, P414, -Drug Synthesis Database

【结构式】

【药物名称】Salcaprozic acid sodium salt, E414(free acid), SNAC, P414

【化学名称】8-(2-Hydroxybenzamido)octanoic acid sodium salt

【CA登记号】183990-46-7 (free acid)

【分子式】C₁₅H₂₀NNaO₄

【分子量】301.32075

【开发单位】Emisphere (Originator)

【药理作用】Absorption Promoters, DRUG DELIVERY, Drug Delivery Systems

合成路线1 合成路线2

合成路线1

The silylation of 8-aminooctanoic acid (I) with Tms-Cl in dichloromethane gives the disilylated compound (II), which is treated with 2-hydroxybenzoyl chloride (III) and TEA to yield the corresponding silylated amide (IV). Finally, this compound is desilylated with NaOH to afford the target sodium salt.

参考文献中间体

【1】 Baughman, R.A.; Salo-Kostmayer, S.; O'Toole, D.; Rosado-Gray, C.; Tai, M.; Mercogliano, F.; Leone-Bay, A.; Freeman, J.; Studies directed at the use of a parallel synthesis matrix to increase throughput in an in vivo assay. J Med Chem 2000, 43, 19, 3573.

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)	47828	8-aminooctanoic acid	1002-57-9	C₈H₁₇NO₂	详情	详情
(II)	47829	trimethylsilyl 8-[(trimethylsilyl)amino]octanoate		C₁₄H₃₃NO₂Si₂	详情	详情
(III)	32668	2-hydroxybenzoyl chloride		C₇H₅ClO₂	详情	详情
(IV)	47830	trimethylsilyl 8-[(2-hydroxybenzoyl)amino]octanoate		C₁₈H₂₉NO₄Si	详情	详情

合成路线2

Full protection of 8-aminooctanoic acid (I) with TMSCl in refluxing CH2Cl2 yields derivative (II), which is then coupled to acetylsalicyloyl chloride (III) by means of Et3N to provide compound (IV). Finally, the desired product is obtained by saponification of (IV) with NaOH. Alternatively, another route can be followed for the synthesis of the target compound: Curtius rearrangement of nonanedioic acid monomethyl ester (V) with DPPA and Et3N in toluene, followed by treatment with tert-BuOH, affords Boc-amino ester (VI), whose Boc group is then removed by means of HCl in dioxane to yield deprotected ester (VII). Coupling of (VII) with acetylsalicyloyl chloride (III) by means of Et3N in THF/DMF gives compound (VIII), which is finally saponified with NaOH.

参考文献中间体

【1】 Baughman, R.A.; Salo-Kostmayer, S.; O'Toole, D.; Rosado-Gray, C.; Tai, M.; Mercogliano, F.; Leone-Bay, A.; Freeman, J.; Studies directed at the use of a parallel synthesis matrix to increase throughput in an in vivo assay. J Med Chem 2000, 43, 19, 3573.
【2】 Leone-Bay, A.; Paton, D.R.; Freeman, J.; et al.; Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin. J Med Chem 1998, 41, 7, 1163.

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)	47828	8-aminooctanoic acid	1002-57-9	C₈H₁₇NO₂	详情	详情
(II)	47829	trimethylsilyl 8-[(trimethylsilyl)amino]octanoate		C₁₄H₃₃NO₂Si₂	详情	详情
(III)	16900	2-(chlorocarbonyl)phenyl acetate; Acetylsalicyloyl chloride	5538-51-2	C₉H₇ClO₃	详情	详情
(IV)	51224	trimethylsilyl 8-[[2-(acetoxy)benzoyl]amino]octanoate		C₂₀H₃₁NO₅Si	详情	详情
(V)	51225	9-methoxy-9-oxononanoic acid		C₁₀H₁₈O₄	详情	详情
(VI)	51226	methyl 8-[(tert-butoxycarbonyl)amino]octanoate		C₁₄H₂₇NO₄	详情	详情
(VII)	51227	8-methoxy-8-oxo-1-octanaminium chloride		C₉H₂₀ClNO₂	详情	详情
(VIII)	51228	methyl 8-[[2-(acetoxy)benzoyl]amino]octanoate		C₁₈H₂₅NO₅	详情	详情

Extended Information