(R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol → (2R)-4-[1-(2-aminopyrimidin-4-yl)-2-(2-fluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol

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Reaction Steps

A solution of 4-[2-(2-fluoroethoxy)-6-iodo-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (130 mg, 0.33 mmol), (2R)-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol (148 mg, 0.97 mmol), bis(triphenylphosphine)palladium(II) dichloride (34 mg, 0.05 mmol) in triethylamine (1 mL) and dimethylsulfoxide (1 mL) was irradiated with microwave radiation under nitrogen in a 8-mL vial at 90° C. for 30 min. The resulting solution was cooled to room temperature and diluted with 30 mL of ethyl acetate. The solid material was removed by filtration. The residue was concentrated under vacuum then purified on a silica gel column (ethyl acetate/petroleum ether, 2:1) to give 10 mg (7%) of (2R)-4-[1-(2-aminopyrimidin-4-yl)-2-(2-fluoroethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-methyl-1,2,4-oxadiazol-3-yl)but-3-yn-2-ol as a light brown solid. 1H NMR (400 MHz, MeOD) delta 8.47 (s, 1H), 8.35 (d, J=5.6 Hz, 1H), 7.44 (d, J=8.4 Hz, 1H), 7.39-7.36 (m, 1H), 7.15 (d, J=5.6 Hz, 1H), 4.95-4.90 (m, 2H), 4.85-4.81 (m, 2H), 2.63 (s, 3H), 1.96 (s, 3H); LC-MS: m/z=+424 (M+H)+.

Provenance & Evidence