Synthesis of Voxelotor intermediate ethyl 2-(1-isopropyl-1H-pyrazol-5-yl)nicotinate
The synthesis of Voxelotor intermediate ethyl 2-(1-isopropyl-1H-pyrazol-5-yl)nicotinate(1)was reported.The Suzuki coupling reaction of ethyl 2-chloronicotinate(2)with 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(3)was catalyzed by Pd(PPh3)4.The structure of the product was characterized by 1H NMR and MS.Subsequently,the factors affecting the yield of the product were investigated,the optimum reaction conditions were as follows:n(3)∶n(2)=1.2∶1,the dosage of Pd(PPh3)4 catalyst n(Pd(PPh3)4)∶n(2)= 0.04∶1,the reaction solvent was the mixture of dioxane and water,and the reaction temperature was 100℃,under this reaction conditions,the yield of product was up to 75.7%.
NETL
NSTL
万方数据
维普
