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【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

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.

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.

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