Liquid-phase synthesis of combinatorial libraries based on 7-trifluoromethyl-substituted pyrazolo[1,5-a]pyrimidine scaffold.
The parallel solution-phase synthesis of more than 2200 7-trifluoromethyl-substituted pyrazolo[1,5-a]pyrimidine and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine carboxamides on a 50-100-mg scale has been accomplished. Key reactions include assembly of the pyrazolo[1,5-a]pyrimidine ring by condensation of 5-aminopyrazole derivatives with the corresponding trifluoromethyl-beta-diketones. The libraries from libraries were then obtained in good yields and purities using solution-phase acylation and reduction methodologies. Simple manual techniques for parallel reactions using special CombiSyn synthesizers were coupled with easy purification procedures (crystallization from the reaction mixtures) to give high-purity final products. The scope and limitations of the developed approach are discussed.
Dalinger
Igor L
IL
Zelinski Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospekt, 47, 119991, Moscow, Russian Federation.
Vatsadse
Irina A
IA
Shevelev
Svyatoslav A
SA
Ivachtchenko
Alexandre V
AV
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry
D011720:Pyrazoles; D011743:Pyrimidines