Synthesis of tert-butyl 3-(2-(4-amino-3-(2-aminobenzo[d]oxazole-5-yl)-1H-pyrazole[3,4-d] pyrimidine-1-yl) ethoxy) propionate
DOI:
https://doi.org/10.54097/hset.v2i.591Keywords:
mTOR, Synthetic, Condition optimization, PROTAC, Suzuki-Miyaura coupling reactionAbstract
Tert-butyl 3-(2-(4-amino-3-(2-aminobenzo[d]oxazol-5-yl)-1H-pyrazole[3,4-d] pyrimidine-1-yl) ethoxy) propionate plays an important role in the whole synthesis route as an intermediate of target mTOR targeted PROTAC molecule PRO1. In this experiment, palladium catalyzed Suzuki reaction was used, the target compound tert-butyl 3-(2-(4-amino-3-(2-aminobenzo[d]oxazol-5-yl)-1H-pyrazole[3,4-d]pyrimidine-1-yl)ethoxy)propionate (compound 3) was synthesized from 5-(4,4,5,5-tetramethyl-1,3,2-dioxobenzaldehyde-2-yl) benzo[d]oxazole-2-amine (compound 1) and 3-(2-{4-amino-3-iodine-1H-pyrazole[3,4-d]pyrimidine -1-ethoxy}propionic acid) tert-butyl ester (compound 2). The structure of the product was confirmed by 1H NMR, 13C NMR and HRMS. When the reaction time is 6 hours, the ratio of reactants n (compound 1): n (compound 2) = 1:2, the reaction solvent is DME: H2O (2:1, volume ratio), the reaction temperature is 90°C, the catalyst is Pd (PPh3)4, the base condition is Na2CO3, the best reaction condition can be obtained, and the yield is 96.7%.
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