【结 构 式】 |
【分子编号】39488 【品名】3-(4-chlorophenyl)-3-hydroxy-2-methyl-1-isoindolinone 【CA登记号】 |
【 分 子 式 】C15H12ClNO2 【 分 子 量 】273.71852 【元素组成】C 65.82% H 4.42% Cl 12.95% N 5.12% O 11.69% |
合成路线1
该中间体在本合成路线中的序号:(X)Compound can be prepared in several different ways: 1) The reduction of 2-bromomethyl-4'-chlorobenzophenone (I) with NaBH4 in methanol gives 2-bromomethyl-4'-chlorobenzhydrol (II), which is then treated with methylamine in methanol. 2) The reduction of 2-cyano-4'-chlorobenzophenone (III) with LiAlH4 in THF gives 2-aminomethyl-4'-chlorobenzhydrol (IV), which is acylated with p-toluenesulfonyl chloride in pyridine and methylated with methyl iodide and NaOH in ethanol to give 2-(N-methyl-N-tosylaminomethyl)-4'-chlorobenzhydrol (V). Finally, this compound is hydrolyzed with H2SO4 water at 180 C. 3) The reaction of 3-(4-chlorophenyl)phthalide (VI) with methylamine in benzene gives 2-methylaminocarbonyl-4'-chlorobenzhydrol (VII), which is then reduced with LiAlH4 in THF. 4) The Grignard reaction of N-methylphthalimide (VIII) with 4-chlorophenylmagnesium bromide (IX) gives 1-(4'-chlorophenyl)-1-hydroxy-2-methyl-3-oxoisoindoline (X), which is reduced with LiAlH4 affording 1-(4'-chlorophenyl)-2-methylisoindoline (XI). The treatment of (XI) with refluxing acetic anhydride yields 2-[(N-methyl-N-acetylamino)methyl]-4'-chloro-O-acetylbenzhydrol (XII), which is finally hydrolyzed with KOH in refluxing ethylene glycol.
【1】 Goetz, M.; Freter, K.; 2-(Aminomethyl)benzhydrols. Can J Chem 1970, 48, 11, 1670-76. |
【2】 Freter, K.; et al.; ZA 6902707 . |
【3】 Freter, K.; et al.; US 3728460 . |
【4】 Boehringer, C.H.; Sohn; US 3635974 . |
【5】 Freter, K.; et al.; CA 982608 . |
【6】 Freter, K.; et al.; New group of anorexigenic compounds. J Med Chem 1970, 13, 6, 1228-30. |
【7】 Hillier, K.; Setazindol. Drugs Fut 1979, 4, 5, 365. |
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) | 39480 | [2-(bromomethyl)phenyl](4-chlorophenyl)methanone | C14H10BrClO | 详情 | 详情 | |
(II) | 39481 | [2-(bromomethyl)phenyl](4-chlorophenyl)methanol | C14H12BrClO | 详情 | 详情 | |
(III) | 39482 | 2-(4-chlorobenzoyl)benzonitrile | C14H8ClNO | 详情 | 详情 | |
(IV) | 39483 | [2-(aminomethyl)phenyl](4-chlorophenyl)methanol | C14H14ClNO | 详情 | 详情 | |
(V) | 39484 | N-[2-[(4-chlorophenyl)(hydroxy)methyl]benzyl]-N,4-dimethylbenzenesulfonamide | C22H22ClNO3S | 详情 | 详情 | |
(VI) | 39485 | 6-chloro-3-(4-chlorophenyl)-2-benzofuran-1(3H)-one | C14H8Cl2O2 | 详情 | 详情 | |
(VII) | 39486 | 2-[(4-chlorophenyl)(hydroxy)methyl]-N-methylbenzamide | C15H14ClNO2 | 详情 | 详情 | |
(VIII) | 39487 | 2-methyl-1H-isoindole-1,3(2H)-dione | 550-44-7 | C9H7NO2 | 详情 | 详情 |
(IX) | 25127 | bromo(4-chlorophenyl)magnesium | 873-77-8 | C6H4BrClMg | 详情 | 详情 |
(X) | 39488 | 3-(4-chlorophenyl)-3-hydroxy-2-methyl-1-isoindolinone | C15H12ClNO2 | 详情 | 详情 | |
(XI) | 39489 | 1-(4-chlorophenyl)-2-methylisoindoline | C15H14ClN | 详情 | 详情 | |
(XII) | 39490 | (2-[[acetyl(methyl)amino]methyl]phenyl)(4-chlorophenyl)methyl acetate | C19H20ClNO3 | 详情 | 详情 |