Formamidine → HCID 86693531, compound

Participants

Reaction Steps

A solution of ethyl 9-iodo-5H-spiro[benzo[b]pyrazolo[1,5-d][1,4]oxazepine-4,1′-cyclopropane]-2-carboxylate (28 mg, 0.068 mmol) in 2 mL of DMF was treated sequentially with formamidine (0.2 mL) and 25 wt % sodium methoxide in methanol (0.1 mL). The mixture was stirred at room temperature overnight (complete conversion of starting material by LCMS). The mixture was diluted with ammonium chloride solution and extracted with ethyl acetate. The combined organics were dried over sodium sulfate and concentrated by rotoevaporation. Similar to as described elsewhere in the application the crude amide was dissolved in dissolved in DMF/TEA (0.75 mL/0.25 mL) and the mixture sparged with nitrogen. Solid bis(triphenylphosphine)palladium(II)dichloride (4.8 mg, 0.00068 mmol), cuprous iodide (1.3 mg, 0.0068 mmol) and (3R)-3-ethynyl-3-hydroxy-1-methyl-pyrrolidin-2-one (24 mg. 0.17 mmol) was added and the MW vial was sealed. The mixture was heated at 80° C. (sand bath). Complete conversion at 30 min. Purification by reverse phase HPLC gave 7.2 mg of the titled compound as a colorless solid (27% yield).

Provenance & Evidence