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【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%

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:(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
Extended Information