2,4-Diamino-5-benzylpyrimidines and analogs as antibacterial agents. 3. C-Benzylation of aminopyridines with phenolic Mannich bases. Synthesis of 1- and 3-deaza analogs of trimethoprim
作者:Barbara S. Rauckman、Barbara Roth
DOI:10.1021/jm00178a008
日期:1980.4
-4-[(N,N-dimethylamino)methyl]phenols and by halogens (bromine and fluorine) produces 3-benzyl and 3-halo derivatives, plus a small amount of disubstitution at the 3,5 positions. Treatment of a 2,4-diamino-3-halopyridine with phenolic Mannich bases gives 5- and N-benzylation. 2,4-Diamino-3-bromo-5-(4-hydroxy-3,5-dimethoxybenzyl)pyridine was methylated on the phenolic group in good yield and dehalogenated
2,4-二氨基-4-[(N,N-二甲基氨基)甲基]苯酚和卤素(溴和氟)的2,4-二氨基吡啶亲电取代产生3-苄基和3-卤代衍生物,以及少量衍生物在3,5职位上的混乱状况。用酚曼尼希碱处理2,4-二氨基-3-卤代吡啶得到5-和N-苄基化。2,4-二氨基-3-溴-5-(4-羟基-3,5-二甲氧基苄基)吡啶在酚基上甲基化,产率高,然后脱卤生成3-脱氮杂甲氧苄啶[2,4-二氨基-5-( 3,4,5-三甲氧基苄基)吡啶]。该化合物作为大肠杆菌二氢叶酸还原酶抑制剂的活性比甲氧苄氨嘧啶低约300倍。2,6-二氨基吡啶很容易被酚曼尼希碱在3,5位以及氨基上二苄基化;使用四倍过量的吡啶以50%的产率提供了3-苄基化的2,6-二氨基吡啶。在10(-4)M时,它不能作为二氢叶酸还原酶的抑制剂。在此处报道的条件下,2-氨基吡啶和4-氨基吡啶不会产生C-苄基化产物。