2,2-diethyl 4-methyl (4R,5S)-5-[[[(1R,2R)-2-(1,3-benzodioxol-5-yl)-1-methyl-4-oxobutyl](2-naphthylmethyl)amino]carbonyl]-1,3-dioxolane-2,2,4-tricarboxylate -Drug Synthesis Database

【结构式】

【分子编号】28481

【品名】2,2-diethyl 4-methyl (4R,5S)-5-[[[(1R,2R)-2-(1,3-benzodioxol-5-yl)-1-methyl-4-oxobutyl](2-naphthylmethyl)amino]carbonyl]-1,3-dioxolane-2,2,4-tricarboxylate

【CA登记号】

【分子式】C₃₅H₃₇NO₁₂

【分子量】663.67832

【元素组成】C 63.34% H 5.62% N 2.11% O 28.93%

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：(XVI)

Partial hydrolysis of dimethyl D-tartrate (XI), followed by esterification with diphenyldiazomethane provided benzhydryl methyl tartrate (XII). Subsequent condensation of (XII) with diethyl dibromomalonate in the presence of NaH produced dioxolane (XIII). Hydrogenolytic removal of the benzhydryl ester of (XIII) using Pd/C gave carboxylic acid (XIV), which was coupled with the intermediate amine (X) by means of 2-chloro-1,3-dimethylimidazolium chloride (DMC) to furnish amide (XV). Acid hydrolysis of the diethyl acetal of (XV) gave aldehyde (XVI). This was condensed with the benzoxazolylmethyl phosphonium salt (XVII) in the presence of NaH to yield the trans olefin (XVIII). Finally, hydrolysis of the ester groups of (XVIII) with LiOH provided the title tricarboxylic acid.

参考文献中间体

合成目标

【1】 Aoyama, T.; et al.; A new class of highly potent farnesyl diphosphate-competitive inhibitors of farnesyltransferase. J Med Chem 1998, 41, 2, 143.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	28475	(2R,3R)-3-(1,3-benzodioxol-5-yl)-5,5-diethoxy-N-(2-naphthylmethyl)-2-pentanamine	C₂₇H₃₃NO₄	详情	详情
(XI)	28476	dimethyl (2S,3S)-2,3-dimethylbutanedioate	C₆H₁₀O₆	详情	详情
(XII)	28477	1-benzhydryl 4-methyl (2S,3S)-2,3-dimethylbutanedioate	C₁₈H₁₈O₆	详情	详情
(XIII)	28478	4-benzhydryl 2,2-diethyl 5-methyl (4S,5R)-1,3-dioxolane-2,2,4,5-tetracarboxylate	C₂₅H₂₆O₁₀	详情	详情
(XIV)	28479	(4S,5R)-2,2-bis(ethoxycarbonyl)-5-(methoxycarbonyl)-1,3-dioxolane-4-carboxylic acid	C₁₂H₁₆O₁₀	详情	详情
(XV)	28480	2,2-diethyl 4-methyl (4R,5S)-5-[[[(1R,2R)-2-(1,3-benzodioxol-5-yl)-4,4-diethoxy-1-methylbutyl](2-naphthylmethyl)amino]carbonyl]-1,3-dioxolane-2,2,4-tricarboxylate	C₃₉H₄₇NO₁₃	详情	详情
(XVI)	28481	2,2-diethyl 4-methyl (4R,5S)-5-[[[(1R,2R)-2-(1,3-benzodioxol-5-yl)-1-methyl-4-oxobutyl](2-naphthylmethyl)amino]carbonyl]-1,3-dioxolane-2,2,4-tricarboxylate	C₃₅H₃₇NO₁₂	详情	详情
(XVII)	28482	(1,3-benzoxazol-2-ylmethyl)(triphenyl)phosphonium chloride	C₂₆H₂₁ClNOP	详情	详情
(XVIII)	28483	2,2-diethyl 4-methyl (4R,5S)-5-[[[(1R,2R,4E)-2-(1,3-benzodioxol-5-yl)-5-(1,3-benzoxazol-2-yl)-1-methyl-4-pentenyl](2-naphthylmethyl)amino]carbonyl]-1,3-dioxolane-2,2,4-tricarboxylate	C₄₃H₄₂N₂O₁₂	详情	详情

Extended Information