• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】48271

【品名】ethyl (Z)-3-(2-chlorophenyl)-2-[2-(2-iodoethoxy)acetyl]-2-propenoate

【CA登记号】

【 分 子 式 】C15H16ClIO4

【 分 子 量 】422.64681

【元素组成】C 42.63% H 3.82% Cl 8.39% I 30.03% O 15.14%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VI)

The reaction of ethyl 4-bromoacetoacetate (I) with 2-chloroethanol (II) by means of NaH in THF gives ethyl 4-(2-chloroethoxy)acetoacetate (III), which is treated with NaI in refluxing acetone to yield the corresponding 2-iodoethoxy derivative (IV). The condensation of (IV) with 2-chlorobenzaldehyde (V) by means of piperidine acetate in isopropanol affords ethyl 2-(2-chlorobenzylidene)-4-(2-iodoethoxy)acetoacetate (VI), which is cyclized with methyl 3-aminocrotonate (VII) in refluxing isopropanol to provide the dihydropyridine (VIII). The reaction of (VIII) with hexamethylenetetramine (IX) in hot acetonitrile gives the aminium salt (X), which is finally treated with benzenesulfonic acid in refluxing butanol (methanol)/water. Alternatively, the intermediate dihydropyridine (VIII) can be obtained as follows: The condensation of ethyl 4-(2-chloroethoxy)acetoacetate (III) with the aldehyde (V) by means of piperidine acetate in isopropanol gives ethyl 2-(2-chlorobenzylidene)-4-(2-chloroethoxy)acetoacetate (XI), which is cyclized with methyl 3-aminocrotonate (VII) in refluxing isopropanol to yield the corresponding dihydropyridine (XII). Finally, this compound is treated with NaI in refluxing isopropanol to afford the target intermediate dihydropyridine (VIII).

1 Németh, N.; Vereczkey, G.D.; Krasznai, G.; Koványi, G.; Német, G.; Blask, G.; Tömpe, P.; Nagy, K.; Bozsing, D.; Simig, G. (Egis Pharmaceuticals Ltd.); A process and intermediate cpds. for the preparation of amlodipine benzene sulphonate. EP 0902016 .
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) 36651 Ethyl (bromoacetyl)acetate;ethyl 4-bromo-3-oxobutanoate 13176-46-0 C6H9BrO3 详情 详情
(II) 10384 2-Chloro-1-ethanol; Ethylene chlorohydrin 107-07-3 C2H5ClO 详情 详情
(III) 48269 ethyl 4-(2-chloroethoxy)-3-oxobutanoate C8H13ClO4 详情 详情
(IV) 48270 ethyl 4-(2-iodoethoxy)-3-oxobutanoate C8H13IO4 详情 详情
(V) 24114 2-chlorobenzaldehyde 89-98-5 C7H5ClO 详情 详情
(VI) 48271 ethyl (Z)-3-(2-chlorophenyl)-2-[2-(2-iodoethoxy)acetyl]-2-propenoate C15H16ClIO4 详情 详情
(VII) 11372 Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate C5H9NO2 详情 详情
(VIII) 48272 3-ethyl 5-methyl 4-(2-chlorophenyl)-2-[(2-iodoethoxy)methyl]-6-methyl-1,4-dihydro-3,5-pyridinedicarboxylate C20H23ClINO5 详情 详情
(IX) 34873 1,3,5,7-tetraazatricyclo[3.3.1.1(3,7)]decane 100-97-0 C6H12N4 详情 详情
(X) 48273 1-(2-[[4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydro-2-pyridinyl]methoxy]ethyl)-3,5,7-triaza-1-azoniatricyclo[3.3.1.1(3,7)]decane iodide C26H35ClIN5O5 详情 详情
(XI) 48274 ethyl (Z)-2-[2-(2-chloroethoxy)acetyl]-3-(2-chlorophenyl)-2-propenoate C15H16Cl2O4 详情 详情
(XII) 48275 3-ethyl 5-methyl 2-[(2-chloroethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydro-3,5-pyridinedicarboxylate C20H23Cl2NO5 详情 详情
Extended Information