Stepwise synthesis of 2,6-difunctionalized ethyl pyrazolo[1,5-a]pyrimidine-3-carboxylate via site-selective cross-coupling reactions: experimental and computational studies

Abstract

A variety of novel disubstituted 2-(alknyl, aryl and arylamine)-6-alkynylpyrazolo[1,5-a]pyrimidine derivatives was prepared via sequential site-selective cross-coupling reactions from 2,6-dibromopyrazolo[1,5-a]pyrimidine 3. The regio-controlled Sonogashira-type coupling of 3 with a wide range...

Regioselective Suzuki–Miyaura Reactions of Ethyl 2,6-Dibromo­pyrazolo[1,5-a]pyrimidine-3-carboxylate

“…30 According to our recent procedure, 31 the condensation between brominated aminoazole 2 and commercially available bromomalonaldehyde afforded the corresponding key intermediate 3 in 74% yield (Scheme 1). 29 Scheme 1 Synthesis of 2,6-dibromopyrazolo[1,5-a]pyrimidine 3.…”

“…Synthesis of ethyl 3-amino-5-bromo-1H-pyrazole-4-carboxylate (2) 29 The ethyl 3-amino-5-bromo-1H-pyrazole-4-carboxylate 2 was synthesized following a slightly modified procedure adopted from the literature. 26 oven-dried 100 mL round-bottom flask equipped with a stir bar was charged with 3-amino-1H-pyrazole-4-carboxylate 1 (1.0 g, 5.8 mmol) and dry MeCN (50 mL).…”

“…1 H NMR (300 MHz, DMSO-d6): δ = 12.15 (s, 1H), 6.27 (s, 2H), 4.18 (q, J = 7.1 Hz, 2H), 1.25 (t, J = 7.1 Hz, 3H). 29 To a mixture of ethyl 3-amino-5-bromo-1H-pyrazole-4-carboxylate 2 (1.00 g, 4.2 mmol) in solvent mixture EtOH/AcOH (4/1) (30 mL) was added 2-bromomalonaldehyde (0.69 g, 4.6 mmol). The reaction mixture This article is protected by copyright.…”

“…30 According to our recent procedure, 31 the condensation between brominated aminoazole 2 and commercially available bromomalonaldehyde afforded the corresponding key intermediate 3 in 74% yield (Scheme 2 ). 29 2,6-Dibromopyrazolo[1,5- a ]pyrimidine 3 was subsequently used as a key intermediate to promote a wide range of functionalization at the C2 and C6 positions.…”

“…Ethyl 3-Amino-5-bromo-1H-pyrazole-4-carboxylate (2) 29 For the synthesis of 2, a slightly modified procedure adopted from the literature was used. 26 An oven-dried 100 mL round-bottom flask equipped with a stir bar was charged with 1 (1.0 g, 5.8 mmol) and anhydrous MeCN (50 mL).…”