(1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(cyclopropylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate -Drug Synthesis Database

【结构式】

【分子编号】37613

【品名】(1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(cyclopropylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate

【CA登记号】

【分子式】C₂₇H₄₃NO₅

【分子量】461.64216

【元素组成】C 70.25% H 9.39% N 3.03% O 17.33%

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：(III)

A cost-efficient synthesis of simvastatin has been reported: 1) The reaction of lovastatin (mevinolin) (I) with cyclopropylamine (II) gives the corresponding amide (III), which is methylated by means of BuLi, methyl iodide and pyrrolidine in THF yielding the dimethylbutyryl derivative (IV). Hydrolysis of (IV) with NaOH in refluxing methanol, followed by a treatment with NH4OH in methanol affords the ammonium salt (V), which is finally lactonized in acidic medium. 2) The cyclopropylamide (III) can also be obtained by reaction of mevinolinic acid ammonium salt (VI) with cyclopropylamine in hot toluene.

参考文献中间体

合成目标

【1】 Thaper, R.K.; Misra, S.; Kumar, Y.; Kumar, S.M.D.; Khanna, J.M.; A cost-efficient synthesis of simvastatin via high-conversion methylation of an alkoxide ester enolate. Org Process Res Dev 1999, 3, 6, 476.

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)	64415	(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate		C₂₄H₃₆O₅	详情	详情
(II)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情
(III)	37613	(1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(cyclopropylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate		C₂₇H₄₃NO₅	详情	详情
(IV)	37616	ammonium (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-[(2,2-dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydro-1-naphthalenyl]-3,5-dihydroxyheptanoate		C₂₅H₄₃NO₆	详情	详情
(V)	37615	(1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(cyclopropylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate		C₂₈H₄₅NO₅	详情	详情
(VI)	37614	ammonium (3R,5R)-7-((1S,2S,6R,8S,8aR)-2,6-dimethyl-8-[[(2S)-2-methylbutanoyl]oxy]-1,2,6,7,8,8a-hexahydro-1-naphthalenyl)-3,5-dihydroxyheptanoate		C₂₄H₄₁NO₆	详情	详情

Extended Information