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【结 构 式】

【分子编号】37939

【品名】(2S,3S)-3-(dibenzylamino)-1-(isobutylamino)-4-phenyl-2-butanol

【CA登记号】

【 分 子 式 】C28H36N2O

【 分 子 量 】416.60672

【元素组成】C 80.73% H 8.71% N 6.72% O 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:(XXIa)

An alternative procedure for the preparation of the intermediate urea (IX) has been reported. Alkylation of L-phenylalanine (XIV) with benzyl bromide provided the N,N-dibenzyl amine (XV), which was reduced to amino alcohol (XVI) using DIBAL in cold toluene. In an improved large-scale process, amino alcohol (XVI) was prepared by benzylation of L-phenylalaninol (XVII). Swern oxidation of the alcohol function of (XVI) afforded aldehyde (XVIII). Subsequent reaction of (XVIII) with chloromethyllithium at low temperature furnished the desired epoxide (XX) along with minor amounts of its diastereoisomer (XIX). Opening of this mixture with isobutyl amine (V) gave diamino alcohol (XXIa-b). After coupling of (XXIa-b) with tert-butyl isocyanate (VII) to produce the corresponding ureas (XXIIa-b) [the required isomer (XXIIb) was isolated by recrystallization]. Removal of the benzyl protecting groups of (XXIIb) then yielded the target intermediate (IX).

1 Talley, J.J.; Getman, D.P.; DeCrescenzo, G.A.; Lin, K.-O.; Vazquez, M.L.; Mueller, R.A.; Reed, K.L.; Heintz, R.M.; Clare, M.; Freskos, J.N.; Sun, E.T. (Pharmacia Corp.); Urea-containing hydroxyethylamine cpds. as retroviral protease inhibitors. JP 1995508041; WO 9323368 .
2 Liu, C.; et al.; Development of large-scale process for an HIV protease inhibitor. Org Process Res Dev 1997, 1, 1, 45.
3 Getman, D.P.; et al.; Discovery of a novel class of potent HIV-1 protease inhibitors containing the (R)-(hydroxyethyl)urea isostere. J Med Chem 1993, 36, 2, 288.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
(XXIa) 37939 (2S,3S)-3-(dibenzylamino)-1-(isobutylamino)-4-phenyl-2-butanol C28H36N2O 详情 详情
(XXIb) 37940 (2R,3S)-3-(dibenzylamino)-1-(isobutylamino)-4-phenyl-2-butanol C28H36N2O 详情 详情
(XXIIa) 37941 N'-(tert-butyl)-N-[(2S,3S)-3-(dibenzylamino)-2-hydroxy-4-phenylbutyl]-N-isobutylurea C33H45N3O2 详情 详情
(XXIIb) 37942 N'-(tert-butyl)-N-[(2R,3S)-3-(dibenzylamino)-2-hydroxy-4-phenylbutyl]-N-isobutylurea C33H45N3O2 详情 详情
(V) 13306 2-Methyl-1-propanamine; Isobutylamine 78-81-9 C4H11N 详情 详情
(VII) 16976 tert-butylisocyanate; tert-butyl isocyanate; 2-isocyanato-2-methylpropane 1609-86-5 C5H9NO 详情 详情
(IX) 37931 N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N'-(tert-butyl)-N-isobutylurea C19H33N3O2 详情 详情
(XIV) 13952 (S)-(-)-Phenylalanine; L-Phenylalanine 63-91-2 C9H11NO2 详情 详情
(XV) 37935 (2S)-2-(dibenzylamino)-3-phenylpropionic acid C23H23NO2 详情 详情
(XVI) 30457 (2S)-2-(dibenzylamino)-3-phenyl-1-propanol 111060-52-7 C23H25NO 详情 详情
(XVII) 28523 (2S)-2-amino-3-phenyl-1-propanol; L-phenylalanilol; (S)-2-amino-3-phenyl-1-propanol 5267-64-1 C9H13NO 详情 详情
(XVIII) 37936 (2S)-2-(dibenzylamino)-3-phenylpropanal C23H23NO 详情 详情
(XIX) 37937 N,N-dibenzyl-N-[(1S)-1-[(2R)oxiranyl]-2-phenylethyl]amine; (1S)-N,N-dibenzyl-1-[(2R)oxiranyl]-2-phenyl-1-ethanamine C24H25NO 详情 详情
(XX) 37938 N,N-dibenzyl-N-[(1S)-1-[(2S)oxiranyl]-2-phenylethyl]amine; (1S)-N,N-dibenzyl-1-[(2S)oxiranyl]-2-phenyl-1-ethanamine C24H25NO 详情 详情
Extended Information