【结 构 式】 |
【分子编号】44825 【品名】(1S)-1-furo[2,3-b]pyridin-2-yl-2-[(4-nitrophenethyl)amino]-1-ethanol 【CA登记号】 |
【 分 子 式 】C17H17N3O4 【 分 子 量 】327.3398 【元素组成】C 62.38% H 5.23% N 12.84% O 19.55% |
合成路线1
该中间体在本合成路线中的序号:(VIII)Oxidation of aldehyde (I) with AgNO3 in EtOH/H2O in the presence of KOH provides carboxylic acid (II), which is then converted into acid chloride (III) by means of (COCl)2 in CH2Cl2 and catalytic DMF. Treatment of (III) with trimethylsilyl diazomethane (TMSCH2N2) in Et2O followed by HCl(g) in Et2O furnishes chloro derivative (IV), which is then enantioselectively reduced by means of (-)-Dip-Cl to afford alcohol (V). Treatment of (V) with NaOH in THF/H2O induces formation of epoxy derivative (VI), which is then condensed with amine (VII) to yield compound (VIII). N-Protection of (VIII) by reaction with Boc2O in CH2Cl2, followed by reduction of the nitro moiety by hydrogenation over Pd(OH)2 in MeOH, gives amine (IX). Amine (IX) is converted into sulfonamide (XI) by reaction with sulfonyl chloride (X) in CH2Cl2 in the presence of pyridine. Finally, the Boc group of (XI) is removed by means of TFA in CH2Cl2 to furnish the desired product.
【1】 Lambert, M.H.; Xu, H.E.; Collins, J.L.; Willson, T.M.; Henke, B.R.; Oplinger, J.A.; Brown, P.J.; PPAR agonists for metabolic diseases. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 197. |
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) | 44819 | furo[2,3-b]pyridine-2-carbaldehyde | C8H5NO2 | 详情 | 详情 | |
(II) | 44820 | furo[2,3-b]pyridine-2-carboxylic acid | C8H5NO3 | 详情 | 详情 | |
(III) | 44821 | furo[2,3-b]pyridine-2-carbonyl chloride | C8H4ClNO2 | 详情 | 详情 | |
(IV) | 44822 | 2-chloro-1-furo[2,3-b]pyridin-2-yl-1-ethanone | C9H6ClNO2 | 详情 | 详情 | |
(V) | 44823 | (1R)-2-chloro-1-furo[2,3-b]pyridin-2-yl-1-ethanol | C9H8ClNO2 | 详情 | 详情 | |
(VI) | 44824 | 2-[(2S)oxiranyl]furo[2,3-b]pyridine | C9H7NO2 | 详情 | 详情 | |
(VII) | 26560 | 4-nitrophenethylamine | 24954-67-4 | C8H10N2O2 | 详情 | 详情 |
(VIII) | 44825 | (1S)-1-furo[2,3-b]pyridin-2-yl-2-[(4-nitrophenethyl)amino]-1-ethanol | C17H17N3O4 | 详情 | 详情 | |
(IX) | 44826 | tert-butyl 4-aminophenethyl[(2S)-2-furo[2,3-b]pyridin-2-yl-2-hydroxyethyl]carbamate | C22H27N3O4 | 详情 | 详情 | |
(X) | 44827 | 4-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]benzenesulfonyl chloride | C16H9ClF3NO2S2 | 详情 | 详情 | |
(XI) | 44828 | tert-butyl (2S)-2-furo[2,3-b]pyridin-2-yl-2-hydroxyethyl(4-[[(4-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]phenyl)sulfonyl]amino]phenethyl)carbamate | C38H35F3N4O6S2 | 详情 | 详情 |