【结 构 式】 |
【分子编号】27816 【品名】tert-butyl (2S)-3-[[6-(acetamido)-3-pyridinyl]oxy]-2-hydroxypropyl(4-nitrophenethyl)carbamate 【CA登记号】 |
【 分 子 式 】C23H30N4O7 【 分 子 量 】474.51396 【元素组成】C 58.22% H 6.37% N 11.81% O 23.6% |
合成路线1
该中间体在本合成路线中的序号:(VI)The reaction of 2-acetamido-5-hydroxypyridine (I) with (S)-glycidol 3-nitrobenzenesulfonate (II) by means of NaOH in DMF gives 2(S)-(6-acetamido-3-pyridyloxymethyl)oxirane (III), which is condensed with 2-(4-nitrophenyl)ethylamine (IV) by means of triethylamine in refluxing methanol yielding the chiral isopropanol (V). The protection of the secondary amino group of (V) with tert-butoxycarbonyl anhydride affords the carbamate (VI), which is submitted to reduction at the nitro group with H2 over Pd/C in ethyl acetate providing the aniline derivative (VII). The acylation of (VII) with 4-iodobenzenesulfonyl chloride (VIII) and pyridine in dichloromethane affords the sulfonamide (IX), which is finally deprotected with 2N HCl in refluxing methanol.
【1】 Fisher, M.H.; Mathvink, R.J.; Ok, H.O.; Parmee, E.R.; Weber, A.E. (Merck & Co., Inc.); Substd. phenyl sulfonamides as selective beta3 agonists for the treatment of diabetes and obesity. CA 2114712; EP 0611003; JP 1995010827; US 5451677; WO 9418161 . |
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) | 27813 | N-(5-hydroxy-2-pyridinyl)acetamide | C7H8N2O2 | 详情 | 详情 | |
(II) | 16259 | (2S)oxiranylmethyl 3-nitrobenzenesulfonate; (S)-(+)-Glycidyl nosylate | 115314-14-2 | C9H9NO6S | 详情 | 详情 |
(III) | 27814 | N-[5-[(2S)oxiranylmethoxy]-2-pyridinyl]acetamide | C10H12N2O3 | 详情 | 详情 | |
(IV) | 26560 | 4-nitrophenethylamine | 24954-67-4 | C8H10N2O2 | 详情 | 详情 |
(V) | 27815 | N-[5-([(2S)-2-hydroxy-3-[(4-nitrophenethyl)amino]propyl]oxy)-2-pyridinyl]acetamide | C18H22N4O5 | 详情 | 详情 | |
(VI) | 27816 | tert-butyl (2S)-3-[[6-(acetamido)-3-pyridinyl]oxy]-2-hydroxypropyl(4-nitrophenethyl)carbamate | C23H30N4O7 | 详情 | 详情 | |
(VII) | 27817 | tert-butyl (2S)-3-[[6-(acetamido)-3-pyridinyl]oxy]-2-hydroxypropyl(4-aminophenethyl)carbamate | C23H32N4O5 | 详情 | 详情 | |
(VIII) | 28870 | 4-isopropylbenzenesulfonyl chloride | 54997-90-9 | C9H11ClO2S | 详情 | 详情 |
(IX) | 27818 | tert-butyl (2S)-3-[[6-(acetamido)-3-pyridinyl]oxy]-2-hydroxypropyl(4-[[(4-isopropylphenyl)sulfonyl]amino]phenethyl)carbamate | C32H42N4O7S | 详情 | 详情 |