【结 构 式】 |
【分子编号】17635 【品名】tert-butyl (1S)-1-[[4-(aminocarbonyl)anilino]carbonyl]-3-(methylsulfanyl)propylcarbamate 【CA登记号】 |
【 分 子 式 】C17H25N3O4S 【 分 子 量 】367.46932 【元素组成】C 55.57% H 6.86% N 11.44% O 17.42% S 8.73% |
合成路线1
该中间体在本合成路线中的序号:(III)The condensation of 4-aminobenzamide (I) with N-(tert-butoxycarbonyl)-L-methionine (II) by means of 2-chloro-1-methylpyridinium iodide (CMPI) and N-methylmorpholine (NMM) in DMF gives the corresponding methioninamide (III), which is cyclized by means of trimethylsulfonium iodide and K2CO3 in hot DMSO yielding the pyrrolidinone (IV). The dehydration of (IV) with trifluoroacetic anhydride in THF affords the corresponding nitrile (V), which is deprotected with dry HCl in ethyl acetate giving the amine (VI). The condensation of (VI) with beta-alanine ethyl ester (VII) and carbonyl diimidazole (CDI) in pyridine yields the substituted urea (VIII), which is treated with hydroxylamine hydrochloride and triethylamine in ethyl acetate to afford the N-hydroxybenzamidine (IX). Finally, this compound is hydrogenated with H2 over Pd/C in acetic acid.
【1】 Castañer, J.; Merlos, M.; Leeson, P.A.; Orbofiban Acetate. Drugs Fut 1998, 23, 11, 1190-1198. |
【2】 Abood, N.A.; Flynn, D.L.; Laneman, S.A.; Nosal, R.; Schretzman, L.A. (Pharmacia Corp.); Process for the preparation of amidino phenyl pyrrolidine betal-alanine urea analogs. US 5484946 . |
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) | 16778 | 4-aminobenzamide; p-aminobenzamide | 2835-68-9 | C7H8N2O | 详情 | 详情 |
(II) | 17634 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-(methylsulfanyl)butyric acid; N-alpha-t-BOC-L-methionine | 2488-15-5 | C10H19NO4S | 详情 | 详情 |
(III) | 17635 | tert-butyl (1S)-1-[[4-(aminocarbonyl)anilino]carbonyl]-3-(methylsulfanyl)propylcarbamate | C17H25N3O4S | 详情 | 详情 | |
(IV) | 17636 | tert-butyl (3S)-1-[4-(aminocarbonyl)phenyl]-2-oxopyrrolidinylcarbamate | C16H21N3O4 | 详情 | 详情 | |
(V) | 17637 | tert-butyl (3S)-1-(4-cyanophenyl)-2-oxopyrrolidinylcarbamate | C16H19N3O3 | 详情 | 详情 | |
(VI) | 17638 | 4-[(3S)-3-amino-2-oxopyrrolidinyl]benzonitrile | C11H11N3O | 详情 | 详情 | |
(VII) | 17639 | beta-Alanine, ethyl ester; ethyl 3-aminopropanoate | 924-73-2 | C5H11NO2 | 详情 | 详情 |
(VIII) | 17640 | ethyl 3-[([[(3S)-1-(4-cyanophenyl)-2-oxopyrrolidinyl]amino]carbonyl)amino]propanoate | C17H20N4O4 | 详情 | 详情 | |
(IX) | 17641 | ethyl 3-([[((3S)-1-[4-[amino(hydroxyimino)methyl]phenyl]-2-oxopyrrolidinyl)amino]carbonyl]amino)propanoate | C17H23N5O5 | 详情 | 详情 |