Sodium Carbonate → tert-Butyl 2-(5-(2-(benzyloxy)-6-fluoro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 2-(5-(2-(benzyloxy)-4-bromo-6-fluorophenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (150 mg, 0.254 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (74 mg, 0.382 mmol) in dioxane (2 mL) was stirred under nitrogen atmosphere. To this suspension was added Pd(PPh3)4 (15 mg, 0.013 mmol) followed by a solution of Na2CO3 (81 mg, 0.763 mmol) in water (0.5 mL). The reaction mixture was sealed and heated at 120° C. for 1 hour under microwave irradiation. A further 1.5 eq of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (74 mg, 0.382 mmol) was added and the reaction was heated for an additional hour at 120° C. under microwave irradiation. A further 1.5 eq of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (74 mg, 0.382 mmol) was added, followed by an additional 0.05 eq of Pd(PPh3)4 (15 mg, 0.013 mmol) and the reaction mixture was heated for 1 hour at 120° C. under microwave irradiation. The reaction mixture was diluted with water (15 mL) and extracted with DCM (20 mL). The organic phase was concentrated in vacuo to afford the crude product as a pale brown oil. The crude material was purified by flash chromatography using a 24 g silica cartridge running a MeOH/DCM gradient to afford a pale brown oil. The oil was purified using a 24 g silica running an EtOAc/heptane gradient to afford the title compound as a clear glass-like solid (86 mg, 58% yield). MS m/z 577.2 [M+H]+, 1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H), 8.39 (d, J=1.8 Hz, 1H), 8.09 (d, J=2.0 Hz, 1H), 7.47-7.57 (m, 2H), 7.33-7.44 (m, 4H), 7.28 (dd, J=11.6, 1.5 Hz, 1H), 5.35 (s, 2H), 3.82 (s, 4H), 3.18-3.32 (m, 4H), 1.63-1.77 (m, 4H), 1.40 (s, 9H).

Provenance & Evidence