ethyl (2R)-2-amino-5-phenylpentanoate -Drug Synthesis Database

【结构式】

【分子编号】35761

【品名】ethyl (2R)-2-amino-5-phenylpentanoate

【CA登记号】

【分子式】C₁₃H₁₉NO₂

【分子量】221.2994

【元素组成】C 70.56% H 8.65% N 6.33% O 14.46%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VII)

The alkylation of diethyl acetamidomalonate (II) with 1-bromo-3-phenylpropane (I) by means of NaOEt provided the substituted malonate (III), which upon hydrolysis and further decarboxylation gave rise to racemic 2-(acetylamino)-5-phenylpentanoic acid (IVa-b). Kinetic resolution employing Acylase I in the presence of CoCl2 produced a mixture of the (S)-amino acid (V) and the unaltered (R)-amide (VI), which were separated by differential solubility. The desired (R)-amide (VI) was hydrolyzed with aqueous HCl and then treated with EtOH to produce aminoester (VII). Subsequent coupling of (VII) with N-Boc-alpha-aminoisobutyric acid (VIII) employing 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) yielded the protected dipeptide (IX). Basic hydrolysis of the ethyl ester of (IX) afforded the intermediate (X).

参考文献中间体

合成目标

【1】 Growth hormone secretagogues. EP 0933365; WO 9908699 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IVa),(VI)	35759	(2R)-2-(acetamido)-5-phenylpentanoic acid		C₁₃H₁₇NO₃	详情	详情
(IVb)	35775	(2S)-2-(acetamido)-5-phenylpentanoic acid		C₁₃H₁₇NO₃	详情	详情
(I)	20884	1-(3-bromopropyl)benzene	637-59-2	C₉H₁₁Br	详情	详情
(II)	16710	Diethyl 2-(acetamido)malonate; Diethyl acetamidomalonate	1068-90-2	C₉H₁₅NO₅	详情	详情
(III)	35758	diethyl 2-(acetamido)-2-(3-phenylpropyl)malonate		C₁₈H₂₅NO₅	详情	详情
(V)	35760	(2S)-2-amino-5-phenylpentanoic acid		C₁₁H₁₅NO₂	详情	详情
(VII)	35761	ethyl (2R)-2-amino-5-phenylpentanoate		C₁₃H₁₉NO₂	详情	详情
(VIII)	18471	N-(tert-butoxycarbonyl)-2-methylalanine	30992-29-1	C₉H₁₇NO₄	详情	详情
(IX)	35762	ethyl (2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoate		C₂₂H₃₄N₂O₅	详情	详情
(X)	18473	(2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoic acid		C₂₀H₃₀N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Alkylation of diethyl acetamidomalonate (I) with 1-bromo-3-phenylpropane (II) in the presence of NaOEt afforded phenylpropyl malonate (III). Hydrolysis and subsequent decarboxylation of malonate ester (III) yielded racemic 2-(acetylamino)-5-phenylpentanoic acid (IV). Kinetic resolution was achieved by enantioselective hydrolysis of the (S)-acetamide to give amino acid (VI). The desired (R)-enantiomer (V) was then hydrolyzed with HCl and further esterified with HCl-EtOH to provide amino ester (VII). Coupling with N-Boc-alpha-aminoisobutyric acid (VIII) via activation with 2-chloro-4,6-dimethoxy-1,3,5-triazine (IX) furnished dipeptide (X). The ethyl ester group of (X) was then hydrolyzed to acid (XI) using LiOH.

参考文献中间体

合成目标

【1】 Growth hormone secretagogues. EP 0933365; WO 9908699 .

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)	16710	Diethyl 2-(acetamido)malonate; Diethyl acetamidomalonate	1068-90-2	C₉H₁₅NO₅	详情	详情
(II)	20884	1-(3-bromopropyl)benzene	637-59-2	C₉H₁₁Br	详情	详情
(III)	35758	diethyl 2-(acetamido)-2-(3-phenylpropyl)malonate		C₁₈H₂₅NO₅	详情	详情
(IV)	38799	N-acetyl-5-phenylnorvaline		C₁₃H₁₇NO₃	详情	详情
(V)	35759	(2R)-2-(acetamido)-5-phenylpentanoic acid		C₁₃H₁₇NO₃	详情	详情
(VI)	35760	(2S)-2-amino-5-phenylpentanoic acid		C₁₁H₁₅NO₂	详情	详情
(VII)	35761	ethyl (2R)-2-amino-5-phenylpentanoate		C₁₃H₁₉NO₂	详情	详情
(VIII)	18471	N-(tert-butoxycarbonyl)-2-methylalanine	30992-29-1	C₉H₁₇NO₄	详情	详情
(IX)	38798	2-chloro-4,6-dimethoxy-1,3,5-triazine; 4-chloro-6-methoxy-1,3,5-triazin-2-yl methyl ether	3140-73-6	C₅H₆ClN₃O₂	详情	详情
(X)	35762	ethyl (2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoate		C₂₂H₃₄N₂O₅	详情	详情
(XI)	18473	(2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoic acid		C₂₀H₃₀N₂O₅	详情	详情

Extended Information