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【结 构 式】

【分子编号】55787

【品名】tert-butyl 2-(3-{2-[((1S)-2-methyl-1-{[(2S)-2-({[(1S)-3,3,3-trifluoro-1-isopropyl-2-oxopropyl]amino}carbonyl)pyrrolidinyl]carbonyl}propyl)amino]-2-oxoethyl}-2-oxo-1-imidazolidinyl)acetate

【CA登记号】

【 分 子 式 】C27H42F3N5O7

【 分 子 量 】605.6551896

【元素组成】C 53.54% H 6.99% F 9.41% N 11.56% O 18.49%

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:(XI)

The reaction of N-(benzyloxycarbonyl)-L-valine (I) with paraformaldehyde and Ts-OH gives the oxazolidinone (II), which is treated with trimethyl trifluoromethylsilane and CsF in THF to yield the trifluoromethyloxazolidine (III). The cleavage of the oxazolidine ring of (III) by means of ZnCl2 and NaBH4 in t-butyl methyl ether affords the protected aminoalcohol (IV), which is deprotected by means of H2 over Pd(OH)2 in ethyl acetate to provide the free aminoalcohol (V). The condensation of (V) with N-(benzyloxycarbonyl)-L-valyl-L-proline (VI) by means of EDC in dichloromethane gives the protected tripeptide analogue (VII), which is deprotected with H2 over Pd(OH)2 in ethanol to yield the tripeptide analogue (VIII). The condensation of (VIII) with the imidazolidinoneacetic acid derivative (IX) by means of EDC, as before, affords the acylated tripeptide (X), which is oxidized with DMP in dichloromethane to provide the acylated-L-valyl-L-prolyl-L-valyl-trifluoromethane (XI). Finally, this compound is deprotected with TFA in dichloromethane to give the target peptide analogue. The imidazolidinoneacetic acid derivative (IX) intermediate is obtained as follows: the reaction of 2-imidazolidinone (XII) with tert-butyl 2-bromoacetate (XIII) by means of lithium tert-butoxide in DMF gives the bis tert-butyl acetate (XIV), which is selectively monohydrolyzed by means of KOH in hot ethanol/water to afford the target imidazolidinoneacetic acid derivative (IX).

1 Sato, F.; Inoue, Y.; Honda, S.; Komiya, M.; Takemura, T.; Omodani, T.; Shiratake, R. (Dainippon Pharmaceutical Co., Ltd.); Heterocyclic cpds., intermediates thereof and elastase inhibitors. EP 1157998; JP 2000256396; WO 0052032 .
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) 18092 (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutyric acid C13H17NO4 详情 详情
(II) 55779 benzyl (4S)-4-isopropyl-5-oxo-1,3-oxazolidine-3-carboxylate C14H17NO4 详情 详情
(III) 55780 benzyl (4S,5R)-5-hydroxy-4-isopropyl-5-(trifluoromethyl)-1,3-oxazolidine-3-carboxylate C15H18F3NO4 详情 详情
(IV) 55781 benzyl (1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropylcarbamate C14H18F3NO3 详情 详情
(V) 55782 (2S,3S)-3-amino-1,1,1-trifluoro-4-methyl-2-pentanol C6H12F3NO 详情 详情
(VI) 22787 (2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylic acid C18H24N2O5 详情 详情
(VII) 55783 benzyl (1S)-2-methyl-1-{[(2S)-2-({[(1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl]amino}carbonyl)pyrrolidinyl]carbonyl}propylcarbamate C24H34F3N3O5 详情 详情
(VIII) 55784 (2S)-1-[(2S)-2-amino-3-methylbutanoyl]-N-[(1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl]-2-pyrrolidinecarboxamide C16H28F3N3O3 详情 详情
(IX) 55785 2-{3-[2-(tert-butoxy)-2-oxoethyl]-2-oxo-1-imidazolidinyl}acetic acid C11H18N2O5 详情 详情
(X) 55786 tert-butyl 2-(3-{2-[((1S)-2-methyl-1-{[(2S)-2-({[(1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl]amino}carbonyl)pyrrolidinyl]carbonyl}propyl)amino]-2-oxoethyl}-2-oxo-1-imidazolidinyl)acetate C27H44F3N5O7 详情 详情
(XI) 55787 tert-butyl 2-(3-{2-[((1S)-2-methyl-1-{[(2S)-2-({[(1S)-3,3,3-trifluoro-1-isopropyl-2-oxopropyl]amino}carbonyl)pyrrolidinyl]carbonyl}propyl)amino]-2-oxoethyl}-2-oxo-1-imidazolidinyl)acetate C27H42F3N5O7 详情 详情
(XII) 36228 2-imidazolidinone 120-93-4 C3H6N2O 详情 详情
(XIII) 17430 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate 5292-43-3 C6H11BrO2 详情 详情
(XIV) 55788 tert-butyl 2-{3-[2-(tert-butoxy)-2-oxoethyl]-2-oxo-1-imidazolidinyl}acetate C15H26N2O5 详情 详情
Extended Information