Liquid‐Phase Synthesis of Combinatorial Libraries Based on 7‐Trifluoromethyl‐Substituted Pyrazolo[1,5‐a]pyrimidine Scaffold.

Abstract

Fused pyrimidine derivatives R 0515Liquid-Phase Synthesis of Combinatorial Libraries Based on 7-Trifluoromethyl-Substituted Pyrazolo[1,5-a]pyrimidine Scaffold. -More than 2200 carboxamides of type (V), (VI), (IX), and (X) are prepared on a 50-100-mg scale using special CombiSyn synthesizers. Key reactions include assembly of the pyrazolo[1,5-a]pyrimidine ring by condensation of 5-aminopyrazole derivatives with trifluoromethyl-β-diketones. Target carboxamides are obtained from the condensation products by conversion into acid chlorides, treatment of the latter with amines, and for the appropriate cases, selective reduction of the pyrimidine ring by NaBH4. -(DALINGER, I. L.; VATSADSE, I. A.; SHEVELEV, S. A.; IVACHTCHENKO*, A. V.; J. Comb. Chem. 7 (2005) 2, 236-245; Chem. Div. Labs, Inc., San Diego, CA 92121, USA; Eng.) -Klein 32-152

Discovery of an Oral Respiratory Syncytial Virus (RSV) Fusion Inhibitor (GS-5806) and Clinical Proof of Concept in a Human RSV Challenge Study

“…Pyrazolo[1,5- a ]pyrimidine analogues in which the keto group is removed can be readily accessed through the synthesis routes described in Scheme . Replacing the keto ester that was condensed with pyrazole 9 in Scheme , with diketones, generates the corresponding pyrazolo[1,5- a ]pyrimidine intermediates 13 – 15 directly . These intermediates were readily converted to the final compounds 16a – b , 17 , and 18 by BOC deprotection and amide bond coupling.…”

“…Replacing the keto ester that was condensed with pyrazole 9 in Scheme 1, with diketones, generates the corresponding pyrazolo[1,5-a]pyrimidine intermediates 13− 15 directly. 26 These intermediates were readily converted to the final compounds 16a−b, 17, and 18 by BOC deprotection and amide bond coupling. Replacing the 2-methylacetoacetate ester described in Scheme 1 with alternative keto esters allows the formation of different 4H-pyrazolo[1,5-a]pyrimidin-7-ones, which upon treatment with POCl 3 provided the 7-chloro intermediates 19 and 20.…”

Synthesis of n-alkylated derivatives of 1-(4-methoxyphenyl)-1,5-dihydro-4h-pyrazolo[3,4-d]pyrimidin-4-ones as potential anticonvulsants

“…As psychotropic agents, a special attention deserve azolopyrimidine derivatives, including pyrazolopyrimidines. Thus, the compounds with antiepileptic, anticonvulsant, sedative, anxiolytic activity (1,2), ligands of benzodiazepine site of GABA receptors (3) were found among the pyrazolopyrimidine derivatives.…”

Discovery of Tetrahydropyrazolopyrimidine Carboxamide Derivatives As Potent and Orally Active Antitubercular Agents

“…The general synthesis of tetrahydropyrazolopyrimidine carboxamide derivatives is shown in Scheme . − Condensation of the aminopyrazole 2 with the corresponding diketones 1 in acetic acid yielded the pyrazolopyrimidines 3 as single regioisomer at the 5,7-position. Reduction of the pyrimidine ring with sodium borohydride (NaBH 4 ) afforded only the 5,7-cis isomer of the tetrahydropyridimine analogue 4 .…”