【结 构 式】 |
【分子编号】48026 【品名】tert-butyl (1S)-1-[chloro(hydroxyimino)methyl]-2-methylpropylcarbamate 【CA登记号】 |
【 分 子 式 】C10H19ClN2O3 【 分 子 量 】250.72524 【元素组成】C 47.91% H 7.64% Cl 14.14% N 11.17% O 19.14% |
合成路线1
该中间体在本合成路线中的序号:(IV)Swern oxidation of N-Boc-S-valinol (I) provided aldehyde (II). After conversion of (II) to the corresponding oxime (III) upon treatment with hydroxylamine, chlorination with N-chlorosuccinimide gave the hydroximinoyl chloride (IV). Reaction of ethyl 2-(bromomethyl)acrylate (V) with phenyllithium (VI) in the presence of CuCN produced ethyl 2-benzylacrylate (VII). The dipolar cycloaddition of the nitrile oxide generated from (IV) to acrylate (VII) furnished the isoxazoline (VIII) as a diastereomeric mixture. The N-Boc protecting group of (VIII) was then cleaved with trifluoroacetic acid to give amine (IX), which was coupled with 2-naphthoic acid (X), yielding amide (XI). The carboxylic acid (XII), resulting from the basic hydrolysis of ethyl ester (XI), was then coupled with the glutamate ester (XIII) to give (XIV).
【1】 Chung, H.-H.; Park, M.-J.; Min, C.-H.; Kang, C.-Y.; Park, T.-K.; Chang, H.-K.; Lee, T.-H.; Moon, K.-Y.; Kim, E.E.-K.; Oh, Y.-L.; Kim, Y.-M. (LG Chem Ltd.); Caspase inhibitor. WO 0121599; WO 0121600 . |
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) | 48024 | tert-butyl (1S)-1-(hydroxymethyl)-2-methylpropylcarbamate | C10H21NO3 | 详情 | 详情 | |
(II) | 47805 | tert-butyl (1S)-1-formyl-2-methylpropylcarbamate | C10H19NO3 | 详情 | 详情 | |
(III) | 48025 | tert-butyl (1S)-1-[(hydroxyimino)methyl]-2-methylpropylcarbamate | C10H20N2O3 | 详情 | 详情 | |
(IV) | 48026 | tert-butyl (1S)-1-[chloro(hydroxyimino)methyl]-2-methylpropylcarbamate | C10H19ClN2O3 | 详情 | 详情 | |
(V) | 11328 | ethyl 2-(bromomethyl)acrylate | 17435-72-2 | C6H9BrO2 | 详情 | 详情 |
(VI) | 24014 | Phenyllithium | 591-51-5 | C6H5Li | 详情 | 详情 |
(VII) | 48027 | ethyl 2-benzylacrylate | C12H14O2 | 详情 | 详情 | |
(VIII) | 48028 | ethyl 5-benzyl-3-[(1S)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-4,5-dihydro-5-isoxazolecarboxylate | C22H32N2O5 | 详情 | 详情 | |
(IX) | 48029 | ethyl 3-[(1S)-1-amino-2-methylpropyl]-5-benzyl-4,5-dihydro-5-isoxazolecarboxylate | C17H24N2O3 | 详情 | 详情 | |
(X) | 10106 | 1-Naphthoic acid | 86-55-5 | C11H8O2 | 详情 | 详情 |
(XI) | 48030 | ethyl 5-benzyl-3-[(1S)-2-methyl-1-(1-naphthoylamino)propyl]-4,5-dihydro-5-isoxazolecarboxylate | C28H30N2O4 | 详情 | 详情 | |
(XII) | 48031 | 5-benzyl-3-[(1S)-2-methyl-1-(1-naphthoylamino)propyl]-4,5-dihydro-5-isoxazolecarboxylic acid | C26H26N2O4 | 详情 | 详情 | |
(XIII) | 48032 | 4-(tert-butyl) 1-methyl (2S)-2-aminobutanedioate | C9H17NO4 | 详情 | 详情 | |
(XIV) | 48033 | 4-(tert-butyl) 1-methyl (2S)-2-[([5-benzyl-3-[(1S)-2-methyl-1-(1-naphthoylamino)propyl]-4,5-dihydro-5-isoxazolyl]carbonyl)amino]butanedioate | C35H41N3O7 | 详情 | 详情 |