Reaction Steps
A mixture of methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate (5-1, 3.00 g, 13.6 mmol, 1 equiv), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (3.80 g, 15.0 mmol, 1.10 equiv), potassium acetate (4.10 g, 41.8 mmol, 3.07 equiv), and 1,1′-bis(diphenylphophino)-ferrocene)dichloropalladium (360 mg, 0.44 mmol, 0.032 equiv) in DMF (50 mL) was heated at 80° C. for 4 hours. The reaction mixture was concentrated and the residue was partitioned between aqueous half-saturated sodium bicarbonate solution and ethyl acetate (150 mL). The organic layer was dried over sodium sulfate and concentrated. A solution of this residue, 6-bromo-3-phenylpyrazolo[1,5-a]pyrimidine (1-3, 1.90 g, 6.93 mmol, 0.510 equiv), and tetrakis(triphenylphosphine)palladium (400 mg, 0.350 mmol, 0.025 equiv) in a mixture of dioxane and aqueous sodium carbonate solution (2M, 7 mL, 14 mmol, 1.0 equiv) was heated at reflux for 20 hours. The reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated. The residue was suspended in methanol and filtered to give methyl 4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)thiophene-2-carboxylate (5-2) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.86 (d, 1H, J=2.4 Hz), 8.80 (d, 1H, J=2.2 Hz), 8.46 (s, 1H), 8.07 (d, 1H, J=1.6 Hz), 8.05 (br d, 2H, J=7.8 Hz), 7.75 (d, 1H, J=1.6 Hz), 7.47 (br t, 2H, J=7.7 Hz), 7.30 (t, 1H, J=7.5 Hz), 3.95 (s, 3H).
