Potassium Carbonate → 4-{4-[5-(2-Amino-pyrimidin-5-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 (82 mg, 0.147 mmol, 1 eq), 2-aminopyrimidine-5-boronic acid pinacol ester (48 mg, 0.22 mmol, 1.5 eq), 1,4-dioxane (4 mL), K2CO3 (61 mg, 0.441 mmol, 3 eq), H2O (1.6 ml) and Pd(PPh3)2Cl2 (10 mg, 0.0147 mmol, 0.1 eq) was heated under microwave irradiation (120° C., 30 min). Solvents were removed and the residue was purified in an Isolute Flash Si II column (0-3% MeOH in DCM). The product obtained was triturated with EtOAc and filtered. The filtrate was evaporated and the residue was triturated with acetone. The filtrate was evaporated. The residue was purified by column chromatography (EtOAc) to give the desired product (11 mg, 14%). HPLC-MS (5-100% B in 8 min at 0.8 mL): tR=5.90 min, [M+H]+ m/z 524.2; 1H NMR (300 MHz, CDCl3) δ 8.86 (s, 2H), 7.43 (m, 2H), 7.36 (dd, J=8.3, 2.1 Hz, 1H), 6.96 (d, J=8.4 Hz, 1H), 5.26 (s, 2H), 4.53 (m, 1H), 3.93 (s, 3H), 3.75 (m, 2H), 3.29 (m, 2H), 1.93 (m, 2H), 1.81 (m, 2H), 1.45 (s, 9H).

Provenance & Evidence