【结 构 式】 |
【分子编号】17951 【品名】methyl (2S)-4-(methylsulfanyl)-2-[(6-nitro-1-naphthoyl)amino]butanoate 【CA登记号】 |
【 分 子 式 】C17H18N2O5S 【 分 子 量 】362.4064 【元素组成】C 56.34% H 5.01% N 7.73% O 22.07% S 8.85% |
合成路线1
该中间体在本合成路线中的序号:(V)Treatment of 3-nitro-1,8-naphthalic anhydride (I) with mercuric oxide and aqueous sodium acetate, and then with refluxing concentrated HCl provided a mixture of decarboxylation products (II) and (III). Condensation of this mixture with L-methionine methyl ester (IV) in the presence of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole, followed by chromatographic separation of isomers, yielded the desired 6-nitronaphthalenecarboxamide (V). Further reduction of the nitro group with SnCl2 in ethanol gave amine (VI), which was reductively condensed with S-triphenylmethyl-N-Boc-cysteinal (VII) in the presence of sodium cyanoborohydride, acetic acid, and molecular sieves to afford (VIII). Then, hydrolysis of methyl ester with lithium hydroxide in THF-water gave acid (IX), and finally, deprotection of trityl and tert-butoxycarbonyl groups with an excess of trifluoroacetic acid in the presence of ethanedithiol provided the title compound as the trifluoroacetate salt.
【1】 Ito, Y.; Kato, H.; Yasuda, S.; Iwasaki, N.; Nishino, H.; Takeshita, M. (Hokuriku Seiyaku Co., Ltd.); Benzamide deriv.. EP 0640601; US 5395832; US 5500422; WO 9214705 . |
【2】 Baudoin, B.; Burns, C.; Commercon, A.; Guitton, J.-D. (Aventis Pharma SA); Novel farnesyl transferase inhibitors, their preparation and pharmaceutical compsns. containing same. JP 1998501259; WO 9534535 . |
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) | 15864 | 5-nitro-1H,3H-benzo[de]isochromene-1,3-dione; 3-Nitro-1,8-naphthalic anhydride | 3027-38-1 | C12H5NO5 | 详情 | 详情 |
(II) | 17948 | 6-nitro-1-naphthoic acid | C11H7NO4 | 详情 | 详情 | |
(III) | 17949 | 3-nitro-1-naphthoic acid | 4507-84-0 | C11H7NO4 | 详情 | 详情 |
(IV) | 17950 | D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride | 21691-49-6 | C6H13NO2S | 详情 | 详情 |
(V) | 17951 | methyl (2S)-4-(methylsulfanyl)-2-[(6-nitro-1-naphthoyl)amino]butanoate | C17H18N2O5S | 详情 | 详情 | |
(VI) | 17952 | methyl (2S)-2-[(6-amino-1-naphthoyl)amino]-4-(methylsulfanyl)butanoate | C17H20N2O3S | 详情 | 详情 | |
(VII) | 17953 | tert-butyl (1R)-1-formyl-2-(tritylsulfanyl)ethylcarbamate | C27H29NO3S | 详情 | 详情 | |
(VIII) | 17954 | methyl (2S)-2-[(6-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propyl]amino]-1-naphthoyl)amino]-4-(methylsulfanyl)butanoate | C44H49N3O5S2 | 详情 | 详情 | |
(IX) | 17955 | (2S)-2-[(6-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propyl]amino]-1-naphthoyl)amino]-4-(methylsulfanyl)butyric acid | C43H47N3O5S2 | 详情 | 详情 |