【结 构 式】 |
【分子编号】53498 【品名】1-[4-(4-ethyl-2-hydroxyphenyl)-3,6-dihydro-1(2H)-pyridinyl]-1-ethanone 【CA登记号】n/a |
【 分 子 式 】C15H19NO2 【 分 子 量 】245.3214 【元素组成】C 73.44% H 7.81% N 5.71% O 13.04% |
合成路线1
该中间体在本合成路线中的序号:(V)The condensation of 3-ethylphenol (I) with 4-piperidone (II) by means of gaseous HCl in acetic acid gives 5-ethyl-2-(1,2,3,6-tetrahydropyridin-4-yl)phenol (III), which is treated with acetic anhydride in pyridine to yield the diacetyl derivative (IV). The selective hydrolysis of the O-acetyl group of (IV) by means of K2CO3 in methanol affords the phenol derivative (V), which is hydrogenated with H2 over Pd/C in methanol to provide the acetyl piperidine (VI). The alkylation of the phenolic group of (VI) with ethyl iodide and Cs2CO3 in refluxing acetone gives 1-acetyl-4-(2-ethoxy-4-ethylphenyl)piperidine (VII), which is deacetylated by means of NaOH in refluxing methanol to yield 4-(2-ethoxy-4-ethylphenyl)piperidine (VIII). The alkylation of the piperidine (VIII) with N-(4-bromobutyl)phthalimide (IX) by means of Cs2CO3 in refluxing acetone affords the adduct (X), which is cleaved with hydrazine in hot methanol to provide 1-(4-aminobutyl)-4-(2-ethoxy-4-ethylphenyl)piperidine (XI). Finally, this amine is condensed with 4-(4-chlorobenzamido)benzoic acid (XII) by means of EDC, HOBT and TEA in DMF to give the target diamide. The intermediate 4-(4-chlorobenzamido)benzoic acid (XII) is obtained as follows: The condensation of 4-aminobenzoic acid ethyl ester (XIV) with 4-chlorobenzoyl chloride (XIII) by means of TEA and DMAP gives 4-(4-chlorobenzamido)benzoic acid ethyl ester (XV), which is finally hydrolyzed with NaOH to afford the target benzoic acid intermediate (XII).
【1】 Grand-Perret, T.A.R.; Issandou, M. (GlaxoSmithKline plc); Binding competition of SREBP-cleavage activating protein (SCAP) antagonists. WO 0106261 . |
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) | 53495 | 3-Ethyl phenol; m-Ethyl phenol | 620-17-7 | C8H10O | 详情 | 详情 |
(II) | 27115 | 4-piperidinone | 40064-34-4 | C5H9NO | 详情 | 详情 |
(III) | 53496 | 5-ethyl-2-(1,2,3,6-tetrahydro-4-pyridinyl)phenol | n/a | C13H17NO | 详情 | 详情 |
(IV) | 53497 | 2-(1-acetyl-1,2,3,6-tetrahydro-4-pyridinyl)-5-ethylphenyl acetate | n/a | C17H21NO3 | 详情 | 详情 |
(V) | 53498 | 1-[4-(4-ethyl-2-hydroxyphenyl)-3,6-dihydro-1(2H)-pyridinyl]-1-ethanone | n/a | C15H19NO2 | 详情 | 详情 |
(VI) | 53499 | 1-[4-(4-ethyl-2-hydroxyphenyl)-1-piperidinyl]-1-ethanone | n/a | C15H21NO2 | 详情 | 详情 |
(VII) | 53500 | 1-[4-(2-ethoxy-4-ethylphenyl)-1-piperidinyl]-1-ethanone | n/a | C17H25NO2 | 详情 | 详情 |
(VIII) | 53501 | 4-(2-ethoxy-4-ethylphenyl)piperidine; ethyl 5-ethyl-2-(4-piperidinyl)phenyl ether | n/a | C15H23NO | 详情 | 详情 |
(IX) | 17163 | N-(4-Bromobutyl)phthalimide; 2-(4-Bromobutyl)-1H-isoindole-1,3(2H)-dione | 5394-18-3 | C12H12BrNO2 | 详情 | 详情 |
(X) | 53502 | 2-{4-[4-(2-ethoxy-4-ethylphenyl)-1-piperidinyl]butyl}-1H-isoindole-1,3(2H)-dione | n/a | C27H34N2O3 | 详情 | 详情 |
(XI) | 53503 | 4-[4-(2-ethoxy-4-ethylphenyl)-1-piperidinyl]-1-butanamine; 4-[4-(2-ethoxy-4-ethylphenyl)-1-piperidinyl]butylamine | n/a | C19H32N2O | 详情 | 详情 |
(XII) | 53504 | 4-[(4-chlorobenzoyl)amino]benzoic acid | n/a | C14H10ClNO3 | 详情 | 详情 |
(XIII) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
(XIV) | 16498 | Benzocaine; ethyl 4-aminobenzoate | 94-09-7 | C9H11NO2 | 详情 | 详情 |
(XV) | 53505 | Ethyl 4-(4-chlorobenzamido)benzoate | n/a | C16H14ClNO3 | 详情 | 详情 |