|
【结 构 式】 
|
【分子编号】20392 【品名】methyl 3-(bromomethyl)benzoate 【CA登记号】1129-28-8 |
【 分 子 式 】C9H9BrO2 【 分 子 量 】229.07326 【元素组成】C 47.19% H 3.96% Br 34.88% O 13.97% |
合成路线1
该中间体在本合成路线中的序号：(II)The key intermediate alpha-(2-chloro-4-nitrophenoxy)-m-toluic acid (IV) is prepared from methyl m-toluate (I) by bromination with N-bromosuccinimide in the presence of benzoyl peroxide, then condensation with 2-chloro-4-nitrophenol, followed by basic hydrolysis. The carboxylic acid group of compound (IV) is converted to dimethylamide (VI) via acyl chloride (V). The nitro intermediate (VI) is hydrogenated over platinum oxide in 2-methoxyethanol. The resulting amine (VII) is then condensed with cyanoguanidine and acetone in the presence of ethanesulfonic acid to give triazinate.
| 【1】 Baker, B.R.; Ashton, W.T.; Irreversible enzyme inhibitors. CLXXIX. Active-site-directed irreversible enzyme inhibitors of dihydrofolate reductase from 1-(3-chlorophenyl)-4, 6-diamino-1,2-dihydro-2,2-dimethyl-s-triazine with oxyamine bridges to a terminal sulfonyl flouride. J Med Chem 1970, 13, 1165-70. |
| 【2】 Chang, P.; TRIAZINATE. Drugs Fut 1989, 14, 2, 138. |
| 【3】 Baker, B.R.; Ashton, W.T.; Water-soluble reversible inhibitors of dihydrofolate reductase with potent antitumor activity derived from 4,6-diamino-1,2-dihydro-2, 2-dimethyl-1-phenyl-s-triazine. J Med Chem 1973, 16, 209-14. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 23611 | N-cyanoguanidine | 461-58-5 | C2H4N4 | 详情 | 详情 | |
| 49872 | 1-Chloro-2-Hydroxy-5-Nitrobenzene; 2-Chloro-4-nitrophenol; 4-Nitro-2-chlorophenol; p-Nitro-o-chlorophenol | 619-08-9 | C6H4ClNO3 | 详情 | 详情 | |
| (I) | 20391 | methyl 3-methylbenzoate | 99-36-5 | C9H10O2 | 详情 | 详情 |
| (II) | 20392 | methyl 3-(bromomethyl)benzoate | 1129-28-8 | C9H9BrO2 | 详情 | 详情 |
| (III) | 20393 | methyl 3-[(2-chloro-4-nitrophenoxy)methyl]benzoate | C15H12ClNO5 | 详情 | 详情 | |
| (IV) | 20394 | 3-[(2-chloro-4-nitrophenoxy)methyl]benzoic acid | C14H10ClNO5 | 详情 | 详情 | |
| (V) | 20395 | 3-[(2-chloro-4-nitrophenoxy)methyl]benzoyl chloride | C14H9Cl2NO4 | 详情 | 详情 | |
| (VI) | 20396 | 3-[(2-chloro-4-nitrophenoxy)methyl]-N,N-dimethylbenzamide | C16H15ClN2O4 | 详情 | 详情 | |
| (VII) | 20397 | 3-[(4-amino-2-chlorophenoxy)methyl]-N,N-dimethylbenzamide | C16H17ClN2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)2,6-Dichlorobenzaldehyde (I) was converted to oxime (II) and then chlorinated with N-chlorosuccinimide to afford the oximidoyl chloride (III). The cycloaddition reaction between ketoester (IV) and the nitrile oxide resulting from (III) in the presence of NaOMe gave rise to the isoxazole system (V). The ester group of (V) was then reduced to alcohol (VI) employing diisobutylaluminium hydride. Subsequent coupling of alcohol (VI) with 2-chloro-4-hydroxybenzaldehyde (VII) under Mitsunobu conditions provided ether (VIII). Phosphonate (X) was prepared by heating methyl 3-(bromomethyl)benzoate (IX) with triethyl phosphite at 185 C. Horner-Emmons condensation of aldehyde (VIII) with phosphonate (X) in the presence of NaH in THF furnished the stilbene derivative (XI). The methyl ester group of (XI) was finally hydrolyzed by means of LiOH in aqueous THF.
| 【1】 Lehmann, J.; Stimmel, J.B.; Blanchard, S.G.; Kliewer, S.A.; Willson, T.M.; Parks, D.J. (Glaxo Group Ltd.); Assays for ligands for nuclear receptors. WO 0037077 . |
| 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) | 27507 | 2,6-dichlorobenzaldehyde | 83-38-5 | C7H4Cl2O | 详情 | 详情 |
| (II) | 43329 | 2,6-dichlorobenzaldehyde oxime | C7H5Cl2NO | 详情 | 详情 | |
| (III) | 43330 | 2,6-dichloro-N-hydroxybenzenecarboximidoyl chloride | C7H4Cl3NO | 详情 | 详情 | |
| (IV) | 43331 | methyl 4-methyl-3-oxopentanoate | 42558-54-3 | C7H12O3 | 详情 | 详情 |
| (V) | 43332 | methyl 3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolecarboxylate | C14H13Cl2NO3 | 详情 | 详情 | |
| (VI) | 43333 | [3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolyl]methanol | C13H13Cl2NO2 | 详情 | 详情 | |
| (VII) | 43334 | 2-chloro-4-hydroxybenzaldehyde | C7H5ClO2 | 详情 | 详情 | |
| (VIII) | 43335 | 2-chloro-4-[[3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolyl]methoxy]benzaldehyde | C20H16Cl3NO3 | 详情 | 详情 | |
| (IX) | 20392 | methyl 3-(bromomethyl)benzoate | 1129-28-8 | C9H9BrO2 | 详情 | 详情 |
| (X) | 43336 | methyl 3-[(diethoxyphosphoryl)methyl]benzoate | C13H19O5P | 详情 | 详情 | |
| (XI) | 43337 | methyl 3-[(E)-2-(2-chloro-4-[[3-(2,6-dichlorophenyl)-5-isopropyl-4-isoxazolyl]methoxy]phenyl)ethenyl]benzoate | C29H24Cl3NO4 | 详情 | 详情 |