HCID 67019715, compound → HCID 86725118, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 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 (150 mg, 0.287 mmol), 78 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide, Pd2(dba)3 (Strem Chemicals, 8 mg, 8.6 μmol), Xphos (Stem Chemicals, cat #15-1152, 9 mg, 17 μmol), potassium phosphate (183 mg, 0.861 mmol) in dioxane (2.5 mL) and water (0.5 mL) was heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 130° C. for 25 min. LCMS indicated the presence of desired product (M+1=563.0), as well as a significant amount of the starting 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. To the reaction mixture was added Pd(PPh3)4 (Strem Chemicals, cat #46-2150, 10 mg) and 50 mg of the 1:1 mixture of 2-bromo-N-cyclopropylthiazole-5-carboxamide and 2-chloro-N-cyclopropylthiazole-5-carboxamide. It was heated again at 130° C. for 15 min in an Initiator microwave reactor. The reaction mixture was treated with water (5 mL) and extracted with EtOAc (2×25 mL). The organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica gel flash chromatography using a gradient of 20-100% EtOAc in hexanes to give N-cyclopropyl-2-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1-tosyl-1H-indol-3-yl)thiazole-5-carb oxamide (60 mg, in 75% purity) as a brown amorphous solid. MS (ESI, pos. ion) m/z: 563.0 (M+1).

Provenance & Evidence