6-溴甲基-3,4-二氢-2-甲基-4-氧代喹唑啉的合成

Synthesis of 6-bromomethyl-3,4-dihydro-2-methyl-4-oxoquinazoline

用对甲基苯胺与水合三氯乙醛、盐酸羟胺反应制得对甲基 (N 肟基乙酰 )苯胺 ,再与浓硫酸反应生成 5 甲基靛红 ,后经碱性过氧化氢氧化 ,制得 2 氨基 5 甲基苯甲酸。将 2 氨基 5 甲基苯甲酸与硫代乙酰胺反应生成的 3 ,4 二氢 2 ,6 二甲基 4 氧代喹唑啉 ,经N 溴代琥珀酰亚胺溴化得到标题化合物 ,其结构经IR、MS、1HNMR和元素分析确证 ,5步反应总收率为 2 3 1 %。

Bromomethyl-3,4-dihydro-2-methyl-4-oxoquinazoline is the key intermediate for the synthesis of some anti-cancer drugs inhibiting thymidylate synthase.In this paper,2-amino-5-methylbenzoic acid was prepared through reacting p-toluidine with chloral hydrate and hydroxylamine hydrochloride,treated with concentrated sulfuric acid,followed by alkaline H 2O 2 oxidation of the resulted 5-methylisatin.Then,heating 2-amino-5-methylbenzoic acid with thioacetamide yielded 3,4-dihydro-2,6-dimethyl-4-oxoquinazoline which was brominated with N-bromosuccinimide in the presence of benzoyl peroxide to give the title compound in 23.1% overall yield.IR, 1HNMR ,MS and elemental analysis of two intermediates and the final product are consistent with their structures.