Reaction Steps
N-Isopropyl-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (0.300 g, 0.574 mmol), Xphos (Strem Chemicals, Newburyport, Mass., 16 mg, 0.034 mmol), Pd2(dba)3 (Strem Chemicals, Newburyport, Mass., 16 mg, 0.017 mmol), potassium phosphate (0.366 g, 1.723 mmol) and 2-chloro-N-cyclopropylpyrimidine-4-carboxamide (0.136 g, 0.689 mmol) were weighed into a 5 mL glass microwave tube. The tube was purged with argon, the solids were treated with dioxane (3 mL) and water (0.30 mL) and the tube was heated at 130° C. for 20 min in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden). The reaction mixture was treated with water and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography using an ISCO Combiflash Rf(25 g Thomson Single Step silica gel column; 0-10% MeOH in DCM) to give N-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-4-carboxamide (284 mg, 0.509 μmol, 89% yield) as a light brown tar. MS (ESI, pos. ion) m/z: 558.0 (M+H)+. N-Cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)pyrimidine-4-carboxamide (284 mg, 0.509 mmol) was weighed into a 20 mL glass microwave tube, and was treated with dioxane (5.0 mL) and 1 N NaOH (1.5 mL). The solution was heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 10 min. The reaction mixture was treated with water (20 mL) and extracted with EtOAc (30 mL). The organic layer was concentrated in vacuo. The crude residue was dissolved in DMSO (4.0 mL) and purified using a Gilson automated platform (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 20-95% 0.1% TFA/CH3CN in 0.1% TFA/water by volume over 10 min), then dried in a Genevac Series II Evaporator affording the title compound (31.5 mg, 0.061 mmol, 11.95% yield) as a light yellow amorphous solid. MS (ESI, pos. ion) m/z: 404.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.12-12.22 (m, 1H), 9.04 (d, J=5.1 Hz, 1H), 8.98 (s, 1H), 8.93 (d, J=4.5 Hz, 1H), 8.84 (d, J=2.9 Hz, 1H), 7.83 (d, J=7.0 Hz, 1H), 7.71 (dd, J=8.5, 1.7 Hz, 1H), 7.67 (d, J=4.9 Hz, 1H), 7.63 (d, J=8.4 Hz, 1H), 3.76 (dq, J=13.2, 6.4 Hz, 1H), 2.87-3.00 (m, 1H), 1.24 (d, J=6.5 Hz, 6H), 0.73-0.84 (m, 4H). 19F NMR (376 MHz, DMSO-d6) δ ppm −74.84 (s, 3F).
