tert-butyl (2S)-2-amino-3-[4-(benzyloxy)phenyl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】26717

【品名】tert-butyl (2S)-2-amino-3-[4-(benzyloxy)phenyl]propanoate

【CA登记号】

【分子式】C₂₀H₂₅NO₃

【分子量】327.42344

【元素组成】C 73.37% H 7.7% N 4.28% O 14.66%

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：(VIII)

By condensation of N-(perhydroazepin-1-ylcarbonyl)-L-leucine (V) with 4-O-benzyl-L-tyrosine tert-butyl ester (VIII) by means of HOBT and diisopropylethylamine in DMF. The two peptide intermediates (V) and (VIII) have been obtaines a follows: L-Leucine fragment (V): The carbonatation of perhydroazepine (I) with CO2 and pyridine followed by reaction with SOCl2 gives perhydroazepin-1-ylcarbonyl chloride (II), which is condensed with L-leucine benzyl ester (III) yielding the N-acylated leucine ester (IV). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in THF to afford the target intermediate (V). Tyrosine fragment (VIII): By esterification of 4-O-benzyl-L-tyrosine (VI) with isobutylene (VII) by means of sulfuric acid in dioxane.

参考文献中间体

合成目标

【1】 Malone, T.; et al.; Identification and SAR studies of PD 151307, a novel N-type calcium channel blocker. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 122.
【2】 Roth, B.D.; Connor, D.T.; Malone, T.C.; Hamilton, H.W.; Rafferty, M.F.; Hu, L.-Y.; Cody, W.L.; He, J.X.; Nadasdi, L.; Brogley, L.; Urge, L.; Silva, D.F.; Song, Y.; Szoke, B.G.; Booth, R.J.; Lescosky, J. (Neurex Corp.; Pfizer Inc.); Peptidyl calcium channel blockers. US 6423689 .

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)	18672	azepane	111-49-9	C₆H₁₃N	详情	详情
(II)	26713	1-azepanecarbonyl chloride		C₇H₁₂ClNO	详情	详情
(III)	22252	Benzyl (2S)-2-amino-4-methylpentanoate; Benzyl (S)-leucinate		C₁₃H₁₉NO₂	详情	详情
(IV)	26714	benzyl (2S)-2-[(1-azepanylcarbonyl)amino]-4-methylpentanoate		C₂₀H₃₀N₂O₃	详情	详情
(V)	26715	(2S)-2-[(1-azepanylcarbonyl)amino]-4-methylpentanoic acid		C₁₃H₂₄N₂O₃	详情	详情
(VI)	26716	(2S)-2-amino-3-[4-(benzyloxy)phenyl]propionic acid	16652-64-5	C₁₆H₁₇NO₃	详情	详情
(VII)	15926	2-methyl-1-propene; isobutylene	115-11-7	C₄H₈	详情	详情
(VIII)	26717	tert-butyl (2S)-2-amino-3-[4-(benzyloxy)phenyl]propanoate		C₂₀H₂₅NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Hydrogenation of 6-methylpyridine-2-carboxylic acid (I) over Pd/C in aqueous ammonia afforded the corresponding piperidine (II). Subsequent condensation of (II) with isovaleraldehyde (III), followed by catalytic hydrogenation with Pd/C provided the N-isopentyl piperidine (IV), which was finally coupled with O-benzyltyrosine tert-butyl ester (V) in the presence of benzotriazolyl tetramethyluronium hexafluorophosphate (HBTU) to furnish the target amide.

参考文献中间体

合成目标

【1】 Szoke, B.G.; Hu, L.-Y.; Millerman, E.; Nikam, S.S.; Rafferty, M.F.; Ryder, T.R.; Synthesis and biological evaluation of substituted 4-(OBz)phenylalanine derivatives as novel N-type calcium channel blockers. Bioorg Med Chem Lett 1999, 9, 8, 1121.
【2】 Hu, L.-Y.; et al.; PD 151307 analogs: Synthesis and biological evaluation of substituted 4-(OBz)phenylalanine derivatives as novel N-type calcium channel blockers. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 119.

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)	30380	6-methyl-2-pyridinecarboxylic acid	934-60-1	C₇H₇NO₂	详情	详情
(II)	30381	6-methyl-2-piperidinecarboxylic acid		C₇H₁₃NO₂	详情	详情
(III)	26052	3-methylbutanal	590-86-3	C₅H₁₀O	详情	详情
(IV)	30382	1-isopentyl-6-methyl-2-piperidinecarboxylic acid		C₁₂H₂₃NO₂	详情	详情
(V)	26717	tert-butyl (2S)-2-amino-3-[4-(benzyloxy)phenyl]propanoate		C₂₀H₂₅NO₃	详情	详情

Extended Information