Potassium Carbonate → 4-{4-[5-(6-Amino-5-trifluoromethyl-pyridin-3-yl)-imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-methoxy-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[4-(5-iodo-imidazo[2,1-b][1,3,4]thiadiazol-2-yl)-2-methoxy-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (94 mg, 0.169 mmol, 1 eq), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (73 mg, 0.253 mmol, 1.5 eq), 1,4-dioxane (5 ml), K2CO3 (70 mg, 0.507 mmol, 3 eq), H2O (2 ml) and Pd(PPh3)2Cl2 (12 mg, 0.0169 mmol, 0.1 eq) was heated under microwave irradiation (120° C., 30 min). Solvents were removed and the residue was partitioned between H2O and EtOAc. The organic layer was dried, filtered and evaporated. The residue was purified in an Isolute Flash Si II column (10-25% EtOAc in c-hexane and 20% MeOH in DCM) and by HPLC-prep to give the desired product (7 mg) as a yellow solid. The aqueous phase was further extracted with MeOH/DCM 1:9, the organic layers were dried, filtered and evaporated. The residue was triturated with MeOH/DMSO, filtered and washed with CH3CN to give the desired product (18 mg, overall yield: 25%). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=2.95 min, [M+H]+ m/z 591.2; 1H NMR (300 MHz, DMSO) δ 8.86 (d, J=1.8 Hz, 1H), 8.43 (d, J=2.1 Hz, 1H), 7.77 (s, 1H), 7.49 (m, 2H), 7.27 (d, J=9.2 Hz, 1H), 6.73 (s, 2H), 4.67 (m, 1H), 3.89 (s, 3H), 3.68 (m, 2H), 3.21 (m, 2H), 1.92 (m, 2H), 1.57 (m, 2H), 1.41 (s, 9H).

Provenance & Evidence