This work describes a solid-phase synthetic method for building a compound library of N-alkyl-4-alkylamino-1-aryl-1H-pyrazolo[3,4-d]pyrimidine-6-carboxamide derivatives, that are based on the biologically active 1-aryl-1H-pyrazolo[3,4-d]pyrimidine scaffold. In the first step of this synthetic sequence, condensation reactions of ethyl 5-amino-1-aryl-1H-pyrazole-4-carboxylates with methyl cyanoformate resulted in the formation of esters that underwent hydrolysis to give 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one-6-carboxylic acids. The coupling reaction of these carboxylic acids with primary alkylamine-loaded acid-sensitive methoxybenzaldehyde (AMEBA) resins was followed by amination reactions mediated by benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP). Subsequent cleavage from the solid support resulted in the formation of the target N-alkyl-4-alkylamino-1-aryl-1H-pyrazolo[3,4-d]pyrimidine-6-carboxamide derivatives. The reaction conditions for solid-phase transformations were optimized using a solution-phase model study with 2,4-dimethoxybenzyl-protected isobutylamine as a reactant in place of the AMEBA resin-loaded isobutylamine. The progress of the solid-phase reactions was monitored by on-bead ATR-FTIR spectroscopy. Diversification experiments were performed by using 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one-6-carboxylic acids and a variety of primary and secondary amine building blocks to build the target compound library.

这项工作描述了一种固相合成方法，该方法基于N-烷基-4-烷基氨基-1-芳基-1 H-吡唑并[3,4- d ]嘧啶-6-羧酰胺衍生物建立化合物库。具有生物活性的1-芳基-1 H-吡唑并[3，4- d ]嘧啶骨架。在该合成步骤的第一步中，5-氨基-1-芳基-1 H-吡唑-4-羧酸乙酯与氰基甲酸酯的缩合反应导致形成酯，将其水解后得到1-芳基-4,5。 -二氢-1 H-吡唑并[3,4- d]嘧啶-4-酮-6-羧酸。这些羧酸与负载伯烷基胺的对酸敏感的甲氧基苯甲醛（AMEBA）树脂进行偶联反应，然后进行苯并三唑-1-基氧基三（二甲氨基）phosph六氟磷酸（（BOP）介导的胺化反应。随后从固体载体上裂解导致形成目标N-烷基-4-烷基氨基-1-芳基-1 H-吡唑并[3,4- d]嘧啶-6-羧酰胺衍生物。使用溶液相模型研究优化了固相转化的反应条件，该溶液相模型研究以2,4-二甲氧基苄基保护的异丁胺为反应物，代替了装有AMEBA树脂的异丁胺。固相反应的进程通过珠上ATR-FTIR光谱进行监测。通过使用1-芳基-4,5-二氢-1 H-吡唑并[3,4- d ]嘧啶-4-one-6-羧酸和各种伯胺和仲胺结构单元来进行分散实验目标化合物库。