【结 构 式】 |
【分子编号】56261 【品名】(2S)-1-(tert-butoxycarbonyl)-4-(1-furo[3,2-c]pyridin-2-yl-1-methylethyl)-2-piperazinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C20H27N3O5 【 分 子 量 】389.4516 【元素组成】C 61.68% H 6.99% N 10.79% O 20.54% |
合成路线1
该中间体在本合成路线中的序号:(XIII)(S)-Piperazine-2-carboxylic acid (I) was sequentially protected as the 4-Boc derivative (II) and then as the 1-Alloc-4-Boc-piperazine (III). After conversion of (III) to benzyl ester (IV), its N-Boc group was selectively removed by treatment with trifluoroacetic acid. The resultant 4-deprotected piperazine (V) was then alkylated with 3-chloro-3-methyl-1-butyne (VI) yielding (VII). Copper-promoted coupling of 4-hydroxy-3,5-diiodopyridine (IX) prepared by halogenation of 4-hydroxypyridine (VIII) with N-iodosuccinimide with the propargyl piperazine (VII) gave rise to the furo[3,2-c]pyridine derivative (X). The N-Alloc protecting group was then replaced by the N-Boc group to yield (XII) via palladium catalyzed deprotection of (X), followed by treatment of the resultant piperazine (XI) with Boc2O. Simultaneous hydrogenolysis of the benzyl ester and the iodo substituent of (XII) led to acid (XIII). After coupling of (XIII) with 2,2,2-trifluoroethylamine, acidic cleavage of the N-Boc group furnished the piperazine-2-carboxamide (XIV).
【1】 gamma-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides as HIV protease inhibitors. EP 1242426; WO 0138332 . |
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) | 16266 | (2S)-hexahydro-2-pyrazinecarboxylic acid; (S)-Piperazine-2-carboxylic acid | C5H10N2O2 | 详情 | 详情 | |
(II) | 51591 | (2R)-4-(tert-butoxycarbonyl)-2-piperazinecarboxylic acid | C10H18N2O4 | 详情 | 详情 | |
(III) | 56252 | (2S)-1-[(allyloxy)carbonyl]-4-(tert-butoxycarbonyl)-2-piperazinecarboxylic acid | C14H22N2O6 | 详情 | 详情 | |
(IV) | 56253 | 1-allyl 2-benzyl 4-(tert-butyl) (2S)-1,2,4-piperazinetricarboxylate | C21H28N2O6 | 详情 | 详情 | |
(V) | 56254 | 1-allyl 2-benzyl (2S)-1,2-piperazinedicarboxylate | C16H20N2O4 | 详情 | 详情 | |
(VI) | 22416 | 3-chloro-3-methyl-1-butyne | 1111-97-3 | C5H7Cl | 详情 | 详情 |
(VII) | 56255 | 1-allyl 2-benzyl (2S)-4-(1,1-dimethyl-2-propynyl)-1,2-piperazinedicarboxylate | C21H26N2O4 | 详情 | 详情 | |
(VIII) | 56256 | 4-Hydroxypyridine; 4-Pyridinol; 4(1H)-Pyridone; 4-Pyridol; 4-Pyridone; gamma-Pyridone | 626-64-2 | C5H5NO | 详情 | 详情 |
(IX) | 56257 | 3,5-diiodo-4-pyridinol | C5H3I2NO | 详情 | 详情 | |
(X) | 56258 | 1-allyl 2-benzyl (2S)-4-[1-(7-iodofuro[3,2-c]pyridin-2-yl)-1-methylethyl]-1,2-piperazinedicarboxylate | C26H28IN3O5 | 详情 | 详情 | |
(XI) | 56259 | benzyl (2S)-4-[1-(7-iodofuro[3,2-c]pyridin-2-yl)-1-methylethyl]-2-piperazinecarboxylate | C22H24IN3O3 | 详情 | 详情 | |
(XII) | 56260 | 2-benzyl 1-(tert-butyl) (2S)-4-[1-(7-iodofuro[3,2-c]pyridin-2-yl)-1-methylethyl]-1,2-piperazinedicarboxylate | C27H32IN3O5 | 详情 | 详情 | |
(XIII) | 56261 | (2S)-1-(tert-butoxycarbonyl)-4-(1-furo[3,2-c]pyridin-2-yl-1-methylethyl)-2-piperazinecarboxylic acid | C20H27N3O5 | 详情 | 详情 | |
(XIV) | 56262 | (2S)-4-(1-furo[3,2-c]pyridin-2-yl-1-methylethyl)-N-(2,2,2-trifluoroethyl)-2-piperazinecarboxamide | C17H21F3N4O2 | 详情 | 详情 |