【结 构 式】 |
【分子编号】30777 【品名】4-[((3R)-1-[[5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl]piperidinyl)oxy]benzaldehyde 【CA登记号】 |
【 分 子 式 】C33H39NO4 【 分 子 量 】513.677 【元素组成】C 77.16% H 7.65% N 2.73% O 12.46% |
合成路线1
该中间体在本合成路线中的序号:(VII)The known benzofuran carbinol (I) was converted to mesylate (II) upon treatment with methanesulfonyl chloride and triethylamine and then condensed with (S)-prolinol (III) at 120 C to afford adduct (IV). Subsequent chlorination of (IV) with concomitant rearrangement by means of thionyl chloride in benzene produced the 3-chloropiperidine derivative (V). The reaction of (V) with 4-hydroxybenzaldehyde (VI) in the presence of K2CO3 in DMF at 80 C furnished a mixture of six- and five-membered ring products (VII) and (VIII), which were separated by column chromatography. Condensation of the required aldehyde (VIII) with thiazolidinedione (IX) using piperidinium benzoate in refluxing toluene provided the target benzylidene thiazolidine, which was finally converted to the corresponding maleate salt.
【1】 Reddy, K.A.; Lohray, B.B.; Brushan, V.; et al.; Novel antidiabetic and hypolipidemic agents. 3. Benzofuran-containing thiazolidinediones. J Med Chem 1999, 42, 11, 1927. |
【2】 Ramanujam, R.; Chakrabarti, R.; Lohray, B.B.; Bajji, A.C.; Lohray, V.B.; Alla, S.R. (Dr. Reddy's Research Foundation); Heterocyclic cpds. having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compsns. containing them. US 5889032 . |
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) | 30773 | [5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methanol | C21H26O3 | 详情 | 详情 | |
(II) | 30774 | [5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl methanesulfonate | C22H28O5S | 详情 | 详情 | |
(III) | 21347 | (2S)pyrrolidinylmethanol | 23356-96-9 | C5H11NO | 详情 | 详情 |
(IV) | 30775 | ((2S)-1-[[5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl]pyrrolidinyl)methanol | C26H35NO3 | 详情 | 详情 | |
(V) | 30776 | (3R)-1-[[5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl]-3-chloropiperidine; benzyl 3-[[(3R)-3-chloropiperidinyl]methyl]-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl ether | C26H34ClNO2 | 详情 | 详情 | |
(VI) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
(VII) | 30777 | 4-[((3R)-1-[[5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl]piperidinyl)oxy]benzaldehyde | C33H39NO4 | 详情 | 详情 | |
(VIII) | 30778 | 4-[((2S)-1-[[5-(benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-yl]methyl]pyrrolidinyl)methoxy]benzaldehyde | C33H39NO4 | 详情 | 详情 | |
(IX) | 10883 | 1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione | 2295-31-0 | C3H3NO2S | 详情 | 详情 |