Efficient Access to 3,5-Disubstituted 7-(Trifluoromethyl)pyrazolo[1,5-<i>a</i>]pyrimidines Involving S<i><sub>N</sub></i>Ar and Suzuki Cross-Coupling Reactions
Badr Jismy,
Abdellatif Tikad,
Mohamed Akssira,
Gérald Guillaumet,
Mohamed Abarbri
Affiliations
Badr Jismy
Laboratoire de Physico-Chimie des Matériaux et des Electrolytes pour l’Energie (PCM2E), EA 6299, Avenue Monge, Faculté des Sciences, Université de Tours, Parc de Grandmont, 37200 Tours, France
Abdellatif Tikad
Laboratoire de Chimie Moléculaire et Substances Naturelles, Faculté des Sciences, Université Moulay Ismail, B.P. 11201, Zitoune, Meknès 50050, Morocco
Mohamed Akssira
Laboratoire de Chimie Physique & de Chimie Bioorganique, URAC 22, Université Hassan II de Casablanca, B.P. 146, Mohammedia 28800, Morocco
Gérald Guillaumet
Institut de Chimie Organique et Analytique (ICOA), Université d’Orléans, UMR CNRS 7311, BP 6759, Rue de Chartres, CEDEX 2, 45067 Orléans, France
Mohamed Abarbri
Laboratoire de Physico-Chimie des Matériaux et des Electrolytes pour l’Energie (PCM2E), EA 6299, Avenue Monge, Faculté des Sciences, Université de Tours, Parc de Grandmont, 37200 Tours, France
An efficient and original synthesis of various 3,5-disubstituted 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines is reported. A library of compounds diversely substituted in C-3 and C-5 positions was easily prepared from a common starting material, 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-one. In C-5 position, a SNAr type reaction was achieved by first activating the C–O bond of the lactam function with PyBroP (Bromotripyrrolidinophosphonium hexafluorophosphate), followed by the addition of amine or thiol giving monosubstituted derivatives, whereas in C-3 position, arylation was performed via Suzuki–Miyaura cross-coupling using the commercially available aromatic and heteroaromatic boronic acids. Moreover, trifluoromethylated analogues of potent Pim1 kinase inhibitors were designed following our concise synthetic methodology.
