Potassium Fluoride → 4-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-benzo [2,1,3]thiadiazole

Participants

Reaction Conditions

Reaction Steps

Add 4-iodo-[2,1,3]-benzothiadiazole (Maybridge; 350 mg, 1.3 mmol), 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 300 mg, 1.3 mmol), potassium fluoride (250 mg, 4.3 mmol), and THF (6.0 mL) to a flask under nitrogen. Purge the system with nitrogen for 10 min and add tris(dibenzylideneacetone) dipalladium(0) (120 mg, 0.13 mmol) and tri-tert-butylphosphonium tetrafluoroborate (Strem; 100 mg, 0.039 mmol). Purge the system with nitrogen for 2 min and stir for 48 h at 45° C. Filter the reaction through Celite®, rinse with chloroform/methanol, and concentrate in vacuo. Purify by flash column chromatography followed by reverse-phase preparative HPLC. Collect the pure fractions from the HPLC, concentrate in vacuo, take up the residue in methanol, and treat with MP-carbonate beads. Filter and concentrate in vacuo to provide the title compound (46 mg, 11%) as a pale yellow solid. Melting Range: 140-142° C. MS APCI m/e 320 (M+1). 1H NMR (CDCl3): δ 8.44-8.37 (m, 1H), 7.95-7.89 (m, 1H), 7.60-7.49 (m, 3H), 7.48-7.41 (m, 1H), 7.12-7.02 (m, 1H), 4.37-4.28 (m, 2H), 3.09-2.99 (m, 2H), 2.72-2.60 (m, 2H). HPLC: 98.3%, Rt=15.03 min. TLC (SiO2): Rf0.3 (1:1 [80:18:2 chloroform/methanol/concentrated aqueous ammonium hydroxide]/dichloromethane).

Provenance & Evidence