摘要
以对甲基苯甲酸为起始原料,与氯化亚砜反应得对甲基苯甲酰氯(2),酰氯直接与异丙胺反应得对甲苯甲酰异丙胺(3);化合物3经硝酸铈铵(CAN)氧化得4-甲酰基苯甲酰异丙胺(4);以氰基硼氢化钠为还原剂,化合物4与甲基肼硫酸盐在碱性条件下经经缩合还原反应生成目标化合物丙卡巴肼.该工艺路线共4步反应,总收率44.7%,每个单元反应收率71%~86%.所有化合物的结构均经1H-NMR、13C-NMR和MS确认.
Procarbazine has been prepared through a four-steps process. Firstly,4-methylbenzoyl chloride was synthesized by reaction of 4-methylbenzoic acid with dimethyl sulfoxide. The direct reaction of this chloride with isopropylamine form N-isopropyl-4-methylbenzamide. The amide was then oxidized to4-formyl-N-isopropylbenzamide by using ammonium ceric nitrate as oxidant. Afterwards,this intermediate condensed with methylhydrazine sulfate and then reduced by sodium cyanoborohydride under basic condition to offer the target compound. The overall yield was 44. 7%. The yield of each unit reaction was 71%to 86%. All the intermediates and target product were identified by1 H NMR,13 C NMR and mass spectroscopy( MS).
引文
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