Two scalable processes for the synthesis of 4-amino-5-aminomethyl-2-methylpyrimidine (2) are described. In the first approach, the less expensive 2-cyanoacetamide was reacted with Vilsmeier reagent to afford enamine 18, followed by the condensation with acetamidine to produce the 4-amino-2-methylpyrimidine-5-carbonitrile (6); subsequent hydrogenation gave 2 in 65% overall yield. In the second approach, malononitrile was treated with the ionic salt 21, prepared in situ from DMF and dimethyl sulfate, to give 18, which, without isolation was reacted with acetamidine hydrochloride to afford the common intermediate 6. Overall yield of this approach was 70%. Both methods are performed in a convenient manner suitable for industrial use.

中文翻译：

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两种可扩展合成的4-氨基-5-氨基甲基-2-甲基嘧啶的开发：维生素B _1的关键中间体

描述了合成4-氨基-5-氨基甲基-2-甲基嘧啶（2）的两个可扩展的方法。在第一种方法中，将较便宜的2-氰基乙酰胺与Vilsmeier试剂反应，得到烯胺18，然后与乙am缩合，生成4-氨基-2-甲基嘧啶-5-甲腈（6）；然后将其与乙酰胺缩合。随后的氢化，得到2以65％的总产率。在第二种方法中，丙二腈用由DMF和硫酸二甲酯原位制备的离子盐21处理，得到18，将其不经分离即可与盐酸乙react反应，得到通用中间体6。该方法的总产率为70％。两种方法均以适合工业用途的方便方式进行。