【结 构 式】 |
【分子编号】36782 【品名】 【CA登记号】 |
【 分 子 式 】C38H52ClN7O10S 【 分 子 量 】834.39076 【元素组成】C 54.7% H 6.28% Cl 4.25% N 11.75% O 19.17% S 3.84% |
合成路线1
该中间体在本合成路线中的序号:(XIII)Condensation of L-phenylalanine methyl ester (I) with benzaldehyde gave aldimine (II). Then, alkylation of (II) with allyl bromide in the presence of LDA, and subsequent imine hydrolysis afforded the racemic alpha-allylphenylalanine methyl ester (III), which was protected as the N-Boc derivative (IV) upon treatment with Boc2O. Ozonolysis of the olefin group of (IV), followed by reductive workup with Me2S yielded the aldehyde ester (V). This was cyclized with hydrazine, affording pyridazinone (VI), which was further hydrogenated over PtO2 to give (VII). The 1,3-dipolar cycloaddition of the iminium ion (VIII), formed by treatment of (VII) with formaldehyde, with boiling ethyl acrylate furnished a mixture of pyrazolopyridazines (IXa-b). After chromatographic isolation of the racemic cis amino ester, hydrolysis with LiOH yielded carboxylic acid (X), which was activated as the mixed anhydride (XI) with isobutyl chloroformate. Coupling of racemic anhydride (XI) with the L-arginine analogue (XII) provided a diastereomeric mixture of amides, from which the desired isomer (XIII) was isolated by column chromatography. Finally, deprotection of (XIII) by means of trifluoroacetic acid furnished the title compound.
【1】 Nakanishi, H.; Ogbu, C.O.; Shea, J.P.; Cao, B.; Kahn, M.; Boatman, P.D.; Kim, H.-O.; Eguchi, M.; Secondary structure peptide mimetics: Design, synthesis, and evaluation of beta-strand mimetic thrombin inhibitors. J Med Chem 1999, 42, 8, 1367. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 | |
11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 | |
(IXa) | 36777 | methyl (1S,7S)-7-benzyl-7-[(tert-butoxycarbonyl)amino]-8-oxohexahydro-1H-pyrazolo[1,2-a]pyridazine-1-carboxylate | C21H29N3O5 | 详情 | 详情 | |
(IXb) | 36778 | methyl (1R,7S)-7-benzyl-7-[(tert-butoxycarbonyl)amino]-8-oxohexahydro-1H-pyrazolo[1,2-a]pyridazine-1-carboxylate | C21H29N3O5 | 详情 | 详情 | |
(I) | 12324 | methyl (2R)-2-amino-3-phenylpropanoate | 21685-51-8 | C10H13NO2 | 详情 | 详情 |
(II) | 36770 | methyl (2S)-3-phenyl-2-[[(E)-benzylidene]amino]propanoate | C17H17NO2 | 详情 | 详情 | |
(III) | 36771 | methyl 2-amino-2-benzyl-4-pentenoate | C13H17NO2 | 详情 | 详情 | |
(IV) | 36772 | methyl 2-benzyl-2-[(tert-butoxycarbonyl)amino]-4-pentenoate | C18H25NO4 | 详情 | 详情 | |
(V) | 36773 | methyl 2-benzyl-2-[(tert-butoxycarbonyl)amino]-4-oxobutanoate | C17H23NO5 | 详情 | 详情 | |
(VI) | 36774 | tert-butyl 4-benzyl-3-oxo-2,3,4,5-tetrahydro-4-pyridazinylcarbamate | C16H21N3O3 | 详情 | 详情 | |
(VII) | 36775 | tert-butyl 4-benzyl-3-oxohexahydro-4-pyridazinylcarbamate | C16H23N3O3 | 详情 | 详情 | |
(VIII) | 36776 | 4-benzyl-4-[(tert-butoxycarbonyl)amino]-1-methylene-3-oxohexahydropyridazin-1-ium | C17H24N3O3 | 详情 | 详情 | |
(X) | 36779 | (1S,7S)-7-benzyl-7-[(tert-butoxycarbonyl)amino]-8-oxohexahydro-1H-pyrazolo[1,2-a]pyridazine-1-carboxylic acid | C20H27N3O5 | 详情 | 详情 | |
(XI) | 36780 | C25H35N3O7 | 详情 | 详情 | ||
(XII) | 36781 | [[[[(4S)-4-amino-6-chloro-5-oxohexyl]amino](imino)methyl]amino](4-methoxy-2,3,6-trimethylphenyl)dioxo-lambda(6)-sulfane | C17H27ClN4O4S | 详情 | 详情 | |
(XIII) | 36782 | C38H52ClN7O10S | 详情 | 详情 |