【结 构 式】 |
【分子编号】33873 【品名】2-[5-(benzyloxy)-6-(hydroxymethyl)-2-pyridinyl]-N-(tert-butyl)-2-hydroxyacetamide 【CA登记号】 |
【 分 子 式 】C19H24N2O4 【 分 子 量 】344.41064 【元素组成】C 66.26% H 7.02% N 8.13% O 18.58% |
合成路线1
该中间体在本合成路线中的序号:(V)The reaction of 3-hydroxypyridine (I) first with formaldehyde and NaOH in water, and then with benzyl bromide (A) in ethanol gives 3-benzyloxy-2,6-bis(hydroxymethyl)pyridine hydrochloride (II), which is oxidized with MnO2 in refluxing benzene yielding 2-hydroxmethyl-3-benzyloxy-6-pyridincarboxaldehyde (III). The condensation of (III) with tertbutylisonitrile (B) and acetic acid in refluxing CHCl3 affords N-tertbutyl-2-(5-benzyloxy-6-hydroxymethyl-2-pyridil)-2-acetoxyacetamide (IV), which is hydrolyzed with 12N HCl yielding N-tertbutyl-2-(5-benzyloxy-6-hydroxymethyl-2-pyridil)-2-hydroxyacetamide (V). The reduction of the amide group of (V) with diborane in THF gives 2-hydroxymethyl-3-benzyloxy-6-(1-hydroxy-2-tertbutylaminoethyl)pyridine (VI), which is finally debenzylated with H2 over Pd/C in methanol.
【1】 Barth, W.; 2-Hydroxymethyl-3-hydroxy-6-(1-hydroxy-2-aminoethyl)pyridines. DE 2204195; FR 2125309; GB 1367668; GB 1367669; US 3700681; US 3763173 . |
【2】 Castaner, J.; Thorpe, P.; Pirbuterol. Drugs Fut 1977, 2, 1, 60. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
(B) | 33871 | pivalonitrile | 630-18-2 | C5H9N | 详情 | 详情 |
(I) | 12911 | 3-Hydroxypyridine; 3-Pyridinol | 109-00-2 | C5H5NO | 详情 | 详情 |
(II) | 33869 | [3-(benzyloxy)-6-(hydroxymethyl)-2-pyridinyl]methanol | C14H15NO3 | 详情 | 详情 | |
(III) | 33870 | 5-(benzyloxy)-6-(hydroxymethyl)-2-pyridinecarbaldehyde | C14H13NO3 | 详情 | 详情 | |
(IV) | 33872 | 1-[5-(benzyloxy)-6-(hydroxymethyl)-2-pyridinyl]-2-(tert-butylamino)-2-oxoethyl acetate | C21H26N2O5 | 详情 | 详情 | |
(V) | 33873 | 2-[5-(benzyloxy)-6-(hydroxymethyl)-2-pyridinyl]-N-(tert-butyl)-2-hydroxyacetamide | C19H24N2O4 | 详情 | 详情 | |
(VI) | 33874 | 1-[5-(benzyloxy)-6-(hydroxymethyl)-2-pyridinyl]-2-(tert-butylamino)-1-ethanol | C19H26N2O3 | 详情 | 详情 |