Formic Acid → (1R,5R,6S)-6-[4-(4-Amino-5-oxo-7,8-dihydro-5H-9-oxa-1,3,6-triaza-benzo cyclohepten-6-yl)-phenyl]-tricyclo[3.2.1.0*2,4*]octane-3-carboxylic Acid Methyl Ester

Participants

Reaction Steps

The named was prepared as follows. A slurry of 4-amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one (340 mg, 0.89 mmol), tricycle[3.2.1.0*2,4*]oct-6-ene-3-carboxylic acid ethyl ester (240 mg, 1.35 mmol), tetrabutylammonium iodide (67 mg, 0.18 mmol), piperidine (230 mg, 2.7 mmol), formic acid (170 mg, 0.14 mmol) and dichlorobis(acetonitrile) palladium(II) (23 mg, 0.09 mmol) in DMF (0.36 mL) was stirred at 125° C. for 16 hours. The reaction mixture was cooled, diluted into EtOAc, washed with water, saturated aqueous brine, dried over magnesium sulfate and concentrated in vacuo to afford an oil. Chromatography (20 g of silica gel, 1-5% methanol:chloroform) afforded a solid, 127 mg. IC50 78.3 nM.

Provenance & Evidence