【结 构 式】 |
【分子编号】51935 【品名】methyl (2S)-2-[(butoxycarbonyl)amino]-3-([2-[3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetyl]amino)propanoate 【CA登记号】 |
【 分 子 式 】C21H26N4O6 【 分 子 量 】430.4608 【元素组成】C 58.6% H 6.09% N 13.02% O 22.3% |
合成路线1
该中间体在本合成路线中的序号:(I)The reaction of N-(butoxycarbonyl)-3-[2-[3-(4-cyanophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetamido]-L-alanine methyl ester (I) (intermediate (VII) in scheme no. 22467601a) with hydroxylamine and TEA in hot methanol gives the N-hydroxyamidine compound (II), which is treated with Ac2O in acetic acid to yield the N-acetoxyamidino compound (III). The cyclization of (III) by means of Ac2O in refluxing acetic aid affords the 1,2,4-oxadiazole derivative (IV), which is reduced with H2 over Pd/C in methanol/HOAc to provide the amidino derivative (V). Alternatively, the direct reduction of N-acetoxyamidino derivative (III) with H2 over Pd/C in acetic acid also gives the amidino derivative (V). Finally, the methyl ester group of compound (V) is hydrolyzed with LiOH in THF to yield the target roxifiban acetate.
【1】 Anzalone, L.; Storace, L. Ward, R.; Kauffman, G.S.; Zhang, L.-H.; Ma, P.; The chiral specific synthesis of DMP 754, a platelet GPIIb/IIIa antagonist. Tetrahedron Lett 1996, 37, 26, 4455-8. |
【2】 Confalone, P.N.; Li, H.-Y.; Ma, P. (DuPont Pharmaceuticals Co.); An efficient method for the conversion of nitriles to amidines. WO 9918090 . |
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) | 51935 | methyl (2S)-2-[(butoxycarbonyl)amino]-3-([2-[3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetyl]amino)propanoate | C21H26N4O6 | 详情 | 详情 | |
(II) | 51932 | methyl (2S)-3-[[2-(3-[4-[amino(hydroxyimino)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetyl]amino]-2-[(butoxycarbonyl)amino]propanoate | C21H29N5O7 | 详情 | 详情 | |
(III) | 51933 | methyl (2S)-3-[[2-(3-[4-[[(acetoxy)imino](amino)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetyl]amino]-2-[(butoxycarbonyl)amino]propanoate | C23H31N5O8 | 详情 | 详情 | |
(IV) | 51934 | methyl (2S)-2-[(butoxycarbonyl)amino]-3-[(2-[3-[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-4,5-dihydro-5-isoxazolyl]acetyl)amino]propanoate | C23H29N5O7 | 详情 | 详情 | |
(V) | 51936 | methyl (2S)-3-[[2-(3-[4-[amino(imino)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetyl]amino]-2-[(butoxycarbonyl)amino]propanoate | C21H29N5O6 | 详情 | 详情 |